2022 Summer Student Research Program

2022 SUMMER STUDENT POSTER DAY

Welcome to the 2022 Poster Day for the Summer Student Research Program. Each year we host this event to showcase unique and innovative research being conducted by undergraduate, medical and graduate students over the summer.

Over the past few years, the COVID-19 pandemic has continued to impact all areas of research on the Oak Street Campus. As the health and safety of the research community is our first priority, we were able to work with our partner organizations to adjust all aspects of the summer program so it could be held both virtually and in-person. Despite the challenges, we realize the important contributions our summer students make each year, and hope the research community at BC Children’s Hospital has provided students with valuable research opportunities and learning experiences.

Since the early 1990s, the Summer Student Research Program has provided students an opportunity to participate in research projects related to children’s and women’s health. It is amazing to see the activities the students are involved with, which range from basic science to clinical and population health research. Poster Day provides a wonderful preview of the interdisciplinary work our students will pursue as they progress into their own careers as scientific and clinical investigators.

We are proud of the students here and we are pleased to be able to help them become leaders in their fields.

Sincerely, Ashley Biggerstaff, Sharon Yau and Laura Christensen Research Education Team, BC Children’s Hospital Research Institute www.bcchr.ca/posterday

Summer Student Poster Day Thursday, July 28, 2022 Morning Sessions

Showcasing the outstanding work of summer students and their contributions to research. Each participant will have 5 minutes to discuss their poster and up to 5 minutes for questions.

10:00 - 11:40 am

Watch Virtually: www.bcchr.ca/posterday Session #1: Clinical & Population Health Session #2: Clinical & Population Health Watch In-Person: Chieng Family Atrium, BCCHR Session #3: Clinical & Population Health Session #4: Basic Science Session #5: Clinical & Population Health

Afternoon Sessions

1:30 - 3:00 pm

Watch Virtually: www.bcchr.ca/posterday Session #6: Clinical & Population Health + Basic Science Session #7: Clinical & Population Health Watch In-Person: Chieng Family Atrium, BCCHR Session #8: Clinical & Population Health + Basic Science Session #9: Basic Science

Awards Ceremony

3:30 - 3:45 pm

Watch Virtually: www.bcchr.ca/posterday OR Watch In-Person: Chan Auditorium, BCCHR Join us in celebrating the accomplishments of our colleagues and the positive impact of research taking place in our community. The award ceremony will feature the poster presentation awards.

Showingcasing excellence in our talented research community!

2022 Poster Participants Participant Evelyn Armour

Research Team Abstract Title Grunau Research Team Early exposure to sedation and analgesia is related to lower brain signaling efficiency and executive functions in children born very preterm at age 8 years Ibreez Asaria Sadarangani Evaluating the Safety and Effectiveness of Research Team Capsular Group B Meningococcal Vaccines In Children Aysha Ayub Rayment & Biggs Impact of early life serum immunoglobulin G Research Teams on pulmonary outcomes in children with cystic fibrosis Fatemeh (Shakiba) Reid Research Team Characterization of Precursor B Cells PreBaharvand leukemic and Leukemic Cells by RNA Sequencing Beenu (Barinder) Bajwa

Arneja Research Team

The Environmental Impact of Ambulatory Surgical Centres Survey

Myriam Beaulieu

Lim Research Team

Role of α6 Integrin Isoforms in Breast Cancer Cell Metastasis

Grace Bernard

Beristain Research Team

TNFα production kinetics following LPS challenge in myeloid cells

Ishmam Bhuiyan

Wang Research Team

Predictive Biomarkers of Successful Immunotherapy for Renal Cell Carcinoma

Laeticia Brice

Woodward Research Team

Vicky Cao

Datta Research Team

Creating an Anatomical and functional Atlas of task-based networks detectable by fMRI: Analyzing a ball squeezing task Infantile Spasms and Trisomy 21: Unfavorable Outcomes with First-line Vigabatrin Therapy

Maria Caray

Polderman Research Team

Anesthetic Management of the Pediatric Patient with Diabetes: A Retrospective Chart Review

Session # Session #5: 10:00 - 11:30 am In-Person Session #2: 10:00 - 11:30 am Virtual Session #5: 10:00 - 11:30 am In-Person Session #4: 10:00 - 11:40 am In-Person Session #1: 10:00 - 11:30 am Virtual Session #6: 1:30 - 3:00 pm Virtual Session #9: 1:30 - 3:00 pm In-Person Session #7: 1:30 - 3:00 pm Virtual Session #1: 10:00 - 11:30 am Virtual Session #5: 10:00 - 11:30 am In-Person Session #3: 10:00 - 11:30 am In-Person

Participant Ella Chan

Research Team Blydt-Hansen Research Team

Abstract Title Bye Bye Biopsies? Implications to the clinical use of CXCL10 in pediatric kidney transplant monitoring

Tiffany Chang

Taubert Research Team

The Role of Mediator Subunit MED15 in Lung Cancer Cell Stress Response

Samantha Coleborn

Beasley Research Team

Antipsychotics Effect on Sirtuin Protein Levels as a Possible Mediator of Metabolic Syndrome

Laura Cunningham Joseph Research Team A Systems Approach for Enhancing Perinatal Care Regionalization Gia Da Roza

Dionne Research Team Cost Savings Analysis of a Clinical Pathway for Diagnostic Testing in Pediatric Hypertension

Mary Daniel

Robinson Research Team

Characterizing X chromosome DNA methylation in the placenta

Nataly El-Bittar

Carlsten Research Team

Effects of wood smoke exposure on human airway epithelial cells

Madeline Elder

Tamber Research Team

Management of Post-Hemorrhagic Ventricular Dilation: When to Intervene

Ria Gill

Pike Research Team

Developing Case Studies for Brain Injury Prevention

Aanisah Golam

Prakash Research Team

Jasleen Grewal

Bush Research Team

Anesthetic techniques for the management of neonatal inguinal hernia repairs: A retrospective audit Immunohistochemical Assessment of Methylation Status in Ewing Sarcoma

Sanya Grover

Loock Research Team

Torin Halvorson

Levings Research Team Insulin receptor engineering in regulatory T cells for enhanced immunosuppressive function in the pancreatic islet microenvironment

Multi-Partner Approach to Place Based Rights Literacy and Action to address Equity, Diversity, and Inclusion

Session # Session #5: 10:00 - 11:30 am In-Person Session #9: 1:30 - 3:00 pm In-Person Session #4: 10:00 - 11:40 am In-Person Session #2: 10:00 - 11:30 am Virtual Session #2: 10:00 - 11:30 am Virtual Session #2: 10:00 - 11:30 am Virtual Session #4: 10:00 - 11:40 am In-Person Session #8: 1:30 - 3:00 pm In-Person Session #9: 1:30 - 3:00 pm In-Person Session #3: 10:00 - 11:30 am In-Person Session #4: 10:00 - 11:40 am In-Person Session #5: 10:00 - 11:30 am In-Person Session #9: 1:30 - 3:00 pm In-Person

Participant Lauren Ho

Research Team Collet Research Team

Abstract Title Assessing the measurement properties of the Child Comprehensive Assessment scale

Parnian Hosseini

Nama Research Team

Describing Canadian infants with BRUE and validating a BRUE risk stratification tool

Kyle Hui

Woodward Research Team

Functional Brain Networks Underlying Deficiencies in Impulse Inhibition in Schizophrenia

Karen Johal

Eslami Research Team

Nicole Katz

Devlin Research Team

Parent versus patient understanding of suicidal crisis: Is a difference in understanding a cause for concern?

The Role Riboflavin in Cardiometabolic Health

Parsa Khanbadr

Maxwell Research Team

Validating an Ex Vivo Model of Alveologenesis in Mouse Mammary Epithelial Organoids

Martina Knappett

Wiens Research Team

Pediatric Discharges in Uganda: Health Worker and Caregiver Perspectives

Emily Mei Yi Kon

Healey & Jacobson Research Teams

The impact of fermentable fibre on disease outcomes in a mouse model of ulcerative colitis

Zoe Kortje

Lang Research Team

Assessing Cerebrovascular Burden in Post-COVID-19 Patients: A Quantitative Rating Scale

Laveniya Kugathasan

Brown Research Team

Does non-invasive microcirculation monitoring using near-infrared spectroscopy during scoliosis correction surgery help inform blood transfusion? – Results of a prospective observational study

Session # Session #7: 1:30 - 3:00 pm Virtual Session #1: 10:00 - 11:30 am Virtual Session #2: 10:00 - 11:30 am Virtual Session #6: 1:30 - 3:00 pm Virtual Session #4: 10:00 - 11:40 am In-Person Session #4: 10:00 - 11:40 am In-Person Session #1: 10:00 - 11:30 am Virtual Session #4: 10:00 - 11:40 am In-Person Session #3: 10:00 - 11:30 am In-Person Session #8: 1:30 - 3:00 pm In-Person

Participant Christina Lam

Research Team Eslami Research Team

Davy Lau

Haji & Henkelman Research Teams

Henry Li

Kobor Research Team

Ying Jie Li

Lavoie Research Team

Rebecca Lim

Beasley Research Team

Abstract Title Responsiveness of children and adolescents to psychiatric crisis stabilisation by Indigeneity and family structure Improving Assessment and Training in Craniosynostosis: The Role of Interactive 3D Models and Multimodal e-Learning Exploring the role of histone SUMOylation in the DNA damage response Characterizing neonatal CD4 T cells expressing mitochondrial biogenesis-related transcription factor, PGC-1α Effect of clozapine on brain complement C5b9 protein levels

Michelle Lisonek

Christoffersen-Deb & Manual Removal of Placenta and Retained Products Vidler Research Teams of Conception in the PRECISE Network in Kenya, The Gambia, and Mozambique: Preliminary Results from Literature Review Caroline McCamus Pouladi Research Team Leukodystrophy-linked mutant claudin-11 sensitizes cells to endoplasmic reticulum stress-induced death Ava Momeni

Woodward Research Team

Functional Brain Networks Underlying Selective Attention in Schizophrenia

Lindy Moxham

Chen Research Team

Colette Newby

Devlin Research Team

Bubble-Blowing as a Method for Distraction During Pediatric IV Insertion: a Randomized Control Trial for Effectiveness Characterizing Vascular Damage at Type 1 Diabetes Diagnosis

Abigail Netanya Tan Ngan

Biggs Research Team

The Molecular and Phenotypic Landscape of Severe Combined Immune Deficiency in British Columbia

Bachviet Nguyen

Doan Research Team

Language barriers and research at the Children and Women’s hospital (C&W): A current state analysis

Tina Nguyen

Sandhu Research Team

Jayne Owston

Turvey Research Team

Integrating Research into Clinical Practice: Developing an Educational Video for Healthcare Professionals in Pediatrics Impacts and the Resulting Burdens of the COVID-19 Pandemic on Employment Changes within Canadian Families with Young Children: Data from the CHILD Cohort Study

Session # Session #3: 10:00 - 11:30 am In-Person Session #8: 1:30 - 3:00 pm In-Person Session #9: 1:30 - 3:00 pm In-Person Session #8: 1:30 - 3:00 pm In-Person Session #6: 1:30 - 3:00 pm Virtual Session #1: 10:00 - 11:30 am Virtual Session #6: 1:30 - 3:00 pm Virtual Session #9: 1:30 - 3:00 pm In-Person Session #5: 10:00 - 11:30 am In-Person Session #4: 10:00 - 11:40 am In-Person Session #3: 10:00 - 11:30 am In-Person Session #5: 10:00 - 11:30 am In-Person Session #7: 1:30 - 3:00 pm Virtual Session #2: 10:00 - 11:30 am Virtual

Participant Samantha Pang

Samantha Pawer

Leora Pearl-Dowler

Research Team Badenhorst Research Team

Abstract Title Self-reported clinical practice and attitudes about cricoid pressure among pediatric anesthesiologists in Canada Görges Research Team Identification of features for a peer support mental health app for adolescents with type 1 diabetes Oberlander Research Team

Sarra Pirmohamed Pike Research Team

Patient engagement in the development and dissemination of a developmentally-informed, home-based research platform Developing a Case Study for Injury Prevention – Vision Zero Surrey

Ariel Qi

Stewart Research Team

COVID-19 Era Psychiatric Illness among Canadians: Exploring Intersectionality of Vulnerability Factors

Maiya Rasheed

Woodward Research Team

Predicting variance in behaviour and cognition from task-based fMRI derived functional brain networks

Deirdre Reynolds

Mahon Research Team Lived Experiences of Adolescents Living With Primary Complex Pain

Fidan Sadig

Robinson Research Team

microRNA Expression In Healthy Human Placenta

Samuel Salitra

Wasserman Research Team

GraphTF: Integrating Transcription Factor Annotation into a Graphical Database

Olivia Scoten

Janssen Research Team

Screening for perinatal anxiety disorders: A randomized controlled trial

Niki Shahraki

Afshar Research Team

Non-Opioid Non-NSAID (NONN) Analgesia for Acute Renal Colic: A Systematic Review

Benjamin Shaw

Richardson Research Team

Rameen Siddiqui

Eslami Research Team

Claire Sie

Vallance Research Team

Meaghan Smith

Vanderwal Research Team

Exams Under Anesthesia (EUA): The Need for Optimized Healthcare in Children with Severe Behavioural Complexities Prevalence and Nature of ADHD Diagnoses Among First-Generation Immigrant Adolescents Visiting CAPE – A Retrospective Cohort Study Modeling bacterial gastroenteritis: Using enteroids to define how epithelial-intrinsic inflammasomes recognize and respond to invading Campylobacter jejuni Graph-based properties of functional connectivity gradients in resting state and movie-fMRI

Session # Session #8: 1:30 - 3:00 pm In-Person Session #1: 10:00 - 11:30 am Virtual Session #7: 1:30 - 3:00 pm Virtual Session #7: 1:30 - 3:00 pm Virtual Session #6: 1:30 - 3:00 pm Virtual Session #5: 10:00 - 11:30 am In-Person Session #2: 10:00 - 11:30 am Virtual Session #6: 1:30 - 3:00 pm Virtual Session #9: 1:30 - 3:00 pm In-Person Session #1: 10:00 - 11:30 am Virtual Session #3: 10:00 - 11:30 am In-Person Session #8: 1:30 - 3:00 pm In-Person Session #7: 1:30 - 3:00 pm Virtual Session #9: 1:30 - 3:00 pm In-Person Session #3: 10:00 - 11:30 am In-Person

Participant Tim Song

Research Team Stewart Research Team

Natalie South

Schaeffer & Mulpuri Research Teams

Valérie Sprockeels

Verchere Research Team

Shambo Basu Thakur

Woodward Research Team

Kaitlyn Treleaven

Glegg Research Team

Andrew Wilk

Goldowitz Research Team

Bernice Wong

Vallance Research Team

The BC Children’s Hospital research community would like to acknowledge the following organizations for supporting training opportunities on the Oak Street Campus:

Abstract Title Improving health outcomes and access to care using digital pediatric mental health services during COVID-19: A systematic review Assessing the Impact of COVID-19 on Health Resource Utilisation by Paediatric Patients with Cerebral Palsy Evaluation of prohormone processing in diabetes

fMRI-CPCA to study the contribution of hyperintensity of functional networks to the blurring of ego boundaries as a characteristic of schizophrenia Implementing KidsAction Coaching using the Theoretical Domains Framework and Behaviour Change Wheel The role of genetics in a choline intervention for fetal alcohol spectrum disorder (FASD) in a mouse model Developing an ex vivo assay to examine composition and functional changes in individual gut microbiome from stool

Session # Session #6: 1:30 - 3:00 pm Virtual Session #1: 10:00 - 11:30 am Virtual Session #9: 1:30 - 3:00 pm In-Person Session #7: 1:30 - 3:00 pm Virtual Session #3: 10:00 - 11:30 am In-Person Session #6: 1:30 - 3:00 pm Virtual Session #6: 1:30 - 3:00 pm Virtual

BC Children’s Hospital Foundation Canucks for Kids Fund Childhood Diabetes Laboratories Community Child Health Endowment Research Themes: Brain, Behaviour & Development Childhood Diseases Healthy Starts Evidence to Innovation

Participant Kendrew Wong

Research Team Cheng Research Team

Abstract Title A retrospective study of pediatric patients treated with proton radiation therapy in Canada

Kenzie Wrightson

Verchere Research Team

Role of carboxypeptidase E in pancreatic beta cells during the development of diabetes

Leo Xu

Taubert Research Team

Justin Yap

Rayar Research Team

Jennifer Yi

Yong Research Team

Investigation of the Role of Lipid Metabolism in the Skin-like Hypodermis of C. elegans During Starvation Current state analysis of best practices and patient education in pediatric allogeneic hematopoietic stem cell transplant (HSCT) Interleukin 1-Beta and Nerve Growth Factor as potential biomarkers in endometriosis

Erica Zeng

Woodward Research Team

Conghao (Tony) Zhang

Vallance Research Team

Annie Zhou

Klein Geltink Research Team

Ted Zhou

Ipsiroglu Research Team

fMRI study of functional brain networks in the working memory task in healthy control & schizophrenia patients Effects of inulin on Muc2-deficient in vitro model

Determining the role of mTOR signaling in rare, devastating infantile-onset liver disease due to LARS1 deficiency Sleep as a Treatment-Emergent Adverse Event in Randomized Controlled Trials Investigating Amphetamines

Session # Session #5: 10:00 - 11:30 am In-Person Session #4: 10:00 - 11:40 am In-Person Session #8: 1:30 - 3:00 pm In-Person Session #3: 10:00 - 11:30 am In-Person Session #8: 1:30 - 3:00 pm In-Person Session #2: 10:00 - 11:30 am Virtual Session #4: 10:00 - 11:40 am In-Person Session #8: 1:30 - 3:00 pm In-Person Session #7: 1:30 - 3:00 pm Virtual

In-Person Presentations: Chieng Family Atrium Finding a Poster

Room 2108

Patio

Session #4

Refreshments

Session #8

Registration

Session #3 Session #3

Session #9

Chan Centre for Family Health Education

Main Entrance

Reception

Session #5

Morning In-Person Sessions: 10:00 - 11:40 am Session #3 | Clinical | Poster - #17 - 25

Afternoon In-Person Sessions: 1:30 - 3:00 pm Session #8 | Clinical & Basic Science | Poster - #62 - 70

Session #4 | Basic Science | Poster - #26 - 35

Session #9 | Basic Science | Poster - #71 - 79

Session #5 | Clinical | Poster - #36 - 44

*This drawing is intended for visual reference only and is not to scale

Since 1987, the Summer Student Research Program has provided 1,500+ students with the opportunity to participate in projects related to child and family health under the supervision of researchers on the Oak Street Campus.

2022 Program Details

123

Registered Summer Student Research Program participants

80 Undergraduate Students 32 Medical Students 11 Alumni & Master’s Students

Participant Affiliations:

34 Brain, Behaviour & 20 Childhood Diseases Development 16 Partner Organizations 23 Healthy Starts 30 Evidence to Innovation

19

Represented universities

123

$127,000+ BCCHR/Partnered Summer Studentship funding awarded

42

Offsite/remote research projects

30+

Hours of professional development

Research projects pursuing new discoveries and innovations to transform the lives of families in BC and beyond

Participant Universities

12 National Universities | 7 International Universities Amherst College British Columbia Institute of Technology Dalhousie University McGill University McMaster University Queen’s University

Royal College Surgeons in Ireland Simon Fraser University Université Pierre et Marie Curie University of Alberta University of British Columbia University of Southern California University of Tehran

www.bcchr.ca/ssrp

University of Toronto University of Victoria University of St. Andrews Vancouver Island University Western University Xi’an Jiaotong University

Session #1: Virtual CLINICAL & POPULATION HEALTH Moderator: Sarah Hutchison Participants: Beenu (Barinder) Bajwa Laeticia Brice Parnian Hosseini Martina Knappett Michelle Lisonek Samantha Pawer Olivia Scoten Natalie South

Watch Virtually: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 10:00 - 11:30 am www.bcchr.ca/posterday

Session #1 | Poster #1 Beenu (Barinder) Bajwa, Medical Student, University of British Columbia Supervisor: Jugpal Arneja, Evidence to Innovation

Congratulations to Beenu on receiving a UBC Faculty of Medicine Summer Studentship

The Environmental Impact of Ambulatory Surgical Centres Survey Beenu Bajwa, Zach Zhang, Young Ji Tuen, Jugpal Arneja

Background: Global warming has emerged as a social, political, and financial crisis; health care facilities are not immune as contributors to climate change. The OR is a significant resource consuming section of health care facilities writ large and thus presents an opportunity to analyze and manage its carbon footprint. Hospitals and physicians can undertake several evidence-based green practices, such as choosing anesthetic gases based on environmental footprint, reducing energy consumption by utilizing LED lights, turning off OR lights and anesthesia machines when not in use and using reusable items.

However, there are numerous barriers to the implementation of green practices, including manufacturer restriction, lack of support from leadership, cost, and inadequate education. Institutional barriers may be lower in non-hospital surgical clinics, where medical directors have a greater capacity to enact measures. Through implementing sustainable practices, non-hospital surgical clinics can do their part to help manage carbon emission.

Study Objectives: 1. To review the current practices and attitudes towards going green for plastic surgery procedures.

2. To determine the barriers that may exist when implementing environmental sustainability efforts.

3. To review and compile strategies and educational initiatives to increase sustainable practice.

Methods: All accredited non-hospital medical surgical facilities in British Columbia will be sent an invitation to complete the survey by mail. The survey will ask questions regarding waste management, anesthetic gases, energy use in the OR, and multidisciplinary OR staff education to measure the level of initiatives private surgical centers are taking to reduce their environmental impact.

Significance: We hope that the findings of our study can provide a province-wide snapshot of current practices and efforts towards environmental sustainability in non-hospital surgical centers. Our results may help inform future environmental sustainability programs and cost-effective best practices.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #1 | Poster #2 Laeticia Brice, Master’s Student, Université Pierre et Marie Curie/University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

Creating an Anatomical and functional Atlas of task-based networks detectable by fMRI: Analyzing a ball squeezing task Todd Woodward, Justin Andrushko, Linda Chen, Chantal Percival, Laeticia Brice

Introduction: Task-based Functional Magnetic Resonance Imaging (fMRI) studies, designed to link brain activity with cognitive functions, rarely measure brain networks, but instead use analytical methods that focus on individual brain regions. The Woodward lab has created an atlas of canonical task-based networks to provide a critical tool for researchers and clinicians, providing common ground for comparison between clinical samples, and associations with individual differences.

Methods: In this project, publicly available data was analyzed. All participants had to first imagine then execute a simple task that was shown on a screen. The task consisted on squeezing a ball with the right hand, left hand or both hands, in response to two hands displayed on the screen. The analysis was carried out using Constrained Principal Component Analysis for fMRI (fMRI-CPCA). fMRI-CPCA revealed brain networks and their blood-oxygendependent (BOLD) responses for this task.

Results: In a first peak, the Response Network activate, followed the Traditional Default Mode Network peaking negatively. For both of these networks the HDR is stronger when both hands are involved and weaker when one hand is involved. Another component shows that, when the right hand is used, the left hemisphere of the brain is activated while the right one is deactivated, and reciprocally for the left hand. Lastly, the Focus on Visual Features Network was inhibited when only one hand is used.

Conclusion: These results show that the response network was precisely retrieved for this task, and observation over task conditions showed that the left-right network differences were appropriately retrieved, with only the opposite hemisphere activated when the ball is squeeze with one hand. In addition, the visual focus network was deactivated during the onehanded conditions only, reflecting the requirement to ignore the non-used hand displayed on the screen.

This provides confirmation that fMRI-CPCA can retrieve all networks necessary to describe the BOLD signal response to this simple task.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #1 | Poster #3 Parnian Hosseini, Medical Student, University of British Columbia Supervisor: Nassr Nama, Evidence to Innovation

Congratulations to Parnian on receiving a BC Children’s Hospital Research Institute Summer Studentship

Describing Canadian infants with BRUE and validating a BRUE risk stratification tool Parnian Hosseini, Zerlyn Lee, Nassr Nama

Introduction: Brief Resolved Unexplained Events (BRUEs) are common amongst infants and a cause for concern in parents. These usually benign and self-limited events pose a diagnostic challenge for healthcare providers attempting to identify events caused by a serious underlying illness. The American Academy of Pediatrics published in guidelines in 2016 for infants categorized at extremely low-risk for recurrence and serious underlying diagnosis. These guidelines inaccurately identify many patients as higher-risk of a serious underlying etiology (positive predictive value 5-15%).

In addition to inflicting psychological stress on caregivers and unnecessary harm to the infant, the admission of otherwise well infants for diagnostic clarity and management is associated with significant healthcare costs.

Recently, new clinical prediction rules have been derived with better discrimination for patients at higher risk of an adverse outcome. However, these rules were validated with data geographically limited to the United States.

The current study will be the first to describe the BRUE population in a Canadian pediatric hospital and the prevalence of serious underlying etiologies. It will also provide external validation of the BRUE clinical prediction rules outside of the cohort from which the rules were derived, specifically assessing their validity in a Canadian context.

Methods and Analysis: This is a multicenter retrospective study, conducted within the Canadian Paediatric Inpatient Research Network (PIRN). Infants (<1 year) presenting with a BRUE at one of ten pediatric Canadian centres between January 1, 2017, and December 31, 2021, will be included. Eligible patients will be identified using diagnostic codes.

The study will look at the presence of a serious underlying medical condition as the primary outcomes. Secondary outcomes will include BRUE recurrence and hospital length of stay. Additionally, variation in demographics and treatment patterns will be assessed across Canada.

Expected Outcomes: We anticipate that in application of the BRUE Clinical Prediction Rule retrospectively, infants who presented with BRUE and had a recurrent event or serious underlying diagnosis uncovered during the course of the admission would be identified with higher sensitivity and specificity than with the AAP Clinical Practice Guidelines.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #1 | Poster #4 Martina Knappett, Master’s Student, University of Victoria Supervisor: Matthew Wiens, Healthy Starts

Pediatric Discharges in Uganda: Health Worker and Caregiver Perspectives

Martina Knappett, Clare Komugisha, Jessica Trawin, Savio Mwaka, Ezrah Bamwesigye, Collins Agaba, Jesca Nsungwa-Sabiiti, Peter Waiswa, J. Mark Ansermino, Niranjan Kissoon, Nathan Kenya Mugisha, Matthew O. Wiens Background: Under-five mortality rates are disproportionately high in low- and middle-income countries (LMICs).

One important, yet neglected, aspect of this disparity is the post-discharge period. Post-discharge mortality rates often exceed in-hospital mortality rates for children living in LMICs; however, much remains to be explored in terms of the specific barriers to improving standards of discharge care. Assessing health worker and caregiver insights will afford a better understanding of the current challenges to improving the health facility discharge process, identify priority areas for improvement in quality of care, and ultimately decrease pediatric post-discharge mortality.

Objective: The objective of this study was to determine health worker and caregiver perceptions of the pediatric discharge process in Uganda.

Methods: 180 health workers and 180 patient-caregivers from 36 nationally representative health facilities in Uganda underwent structured interviews based on the Pediatric Sepsis CoLab Environmental Scan to elicit their satisfaction and experiences with the discharge process.

Results: Training in discharge guidelines was reported by 18(10%) health workers. Eighty-six(48%) health workers perceived the caregiver discharge education provided at their facility as inadequate, and 145(81%) had never contacted a lower-level health facility or community health worker on a patient expected to return for follow-up care. To improve the education process, health workers recommended establishing counselling protocols and providing take-home materials.

Among caregivers, 145(81%) stated that they were informed of their child’s diagnosis during hospitalization. A total of 105(58%) caregivers perceived time spent by health workers preparing them for discharge as adequate, while 147(82%) considered the timing of discharge suitable. For those who felt the timing was poor, the most common concern was having insufficient time to travel home. At the time of discharge, fewer than half (42%) reported having been informed of their child’s vulnerability post-discharge. To improve discharge care, caregivers recommended allowing more time for questions and earlier patient notification of discharge.

Conclusion: There are deficiencies and differing perceptions concerning the adequacy of preparation for discharge at health facilities in Uganda. Implementation of, and training for, standardized discharge protocols may improve both practices and satisfaction with peri-discharge care.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #1 | Poster #5 Michelle Lisonek, Medical Student, University of British Columbia Supervisors: Astrid Christoffersen-Deb & Marianne Vidler, Healthy Starts

Congratulations to Michelle on receiving a UBC Faculty of Medicine Summer Studentship

Manual Removal of Placenta and Retained Products of Conception in the PRECISE Network in Kenya, The Gambia, and Mozambique: Preliminary Results from Literature Review

Michelle Lisonek, Kelly Pickerill, Jeffrey Bone, Peter von Dadelszen, Laura Magee, Rachel Craik, Hannah Blencowe, Veronique Filippi, Hawanatu Jah, Angela Koech, Esperanca Sevene, Salesio Macuacua, Anne Rerimoi Background: The PRECISE Network is a multi-institutional collaborative undertaking that follows a unique cohort of biologically and contextually characterized pregnant people in Kenya, The Gambia, and Mozambique. The incidence of retained placenta occurs in 0.1-3% of all deliveries, however, initial data from the PRECISE pregnancy cohort demonstrate an unexpected number of healthcare workers reporting “manual removal of the placenta and retained products of conception” after delivery (15-30%). Preliminary inquiries with healthcare workers and research staff revealed a regular practice of “vaginal sweeps” after labour to assess for blood and/or blood clots. Vaginal evacuation is not routinely recommended due to risks and patient discomfort.

Objective: To explore if routine practice of vaginal sweep, vaginal evacuation, or manual removal of products of conception have been documented in sub-Saharan Africa and other low-income settings.

Methods: A scoping review was conducted. OvidMEDLINE was searched using terms developed in consultation with a librarian from the UBC Faculty of Medicine, as well as with experts in the field of obstetrics and local clinicians.

Results: Search results revealed no literature describing the phenomenon we have seen in the PRECISE cohort of routine “vaginal sweeps” or “manual removal of products of contraception” during the third stage of labour in subSaharan Africa. Studies from Africa elucidated traditional beliefs regarding blood during and after childbirth including the importance of expelling “bad” blood to avoid complications. In addition, two Nigerian studies reported high manual removal of placenta rates, which may indicate a similar practice of routine vaginal evacuation.

Conclusion and Future Directions: This significant gap in literature will form the basis for the research project. Next steps include assessing correlation between manual removal and relevant pregnancy and delivery outcomes in the PRECISE cohort. Analyses will consider infection postpartum, key neonatal and maternal outcomes, as well as perceived and experienced quality of care. Ultimately the project may contribute to guiding evidence-based clinical care in pregnancy and postpartum in sub-Saharan Africa. Future research can continue to build a context around this practice by investigating the qualitative aspect of routine vaginal evacuation.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #1 | Poster #6 Samantha Pawer, Medical Student, University of British Columbia Supervisor: Matthias Görges, Evidence to Innovation

Congratulations to Samantha on receiving a Community Child Health Endowment Summer Studentship

Identification of features for a peer support mental health app for adolescents with type 1 diabetes Samantha Pawer, Titilola Yakubu, Tricia S. Tang, Matthias Görges

Background: Diabetes distress refers to the invisible emotional burden, ongoing worry, and relentless frustration associated with diabetes. Approximately one-third of adolescents with type 1 diabetes (T1D) experience diabetes distress, and these feelings can lead to poorer diabetes management. Digital health interventions including mobile health applications, phone calls/video conferencing, text messaging, websites, and games for youth with T1D have the potential to reduce this psychological distress. Moreover, interventions involving peer support are particularly desirable to adolescents with T1D. This study explores the perspectives of adolescents with T1D and their parents/guardians, with the goal of tailoring a peer-led digital mental health intervention (REACHOUT) originally designed for adults to fit the unique support preferences and needs of adolescents.

Methods: With REB approval, informed parental consent, and adolescent assent, focus groups with adolescents with T1D and their parents/guardians are being conducted to explore adolescent mental health needs, and identify features for the REACHOUT NexGEN app. Participants were stratified by health region (receiving care at BC Children’s Hospital, or living in either the Interior Health or the Island Health region), and age group (parents/guardians, 15-16-year-olds, and 17-18-year-olds). Participants completed pre-focus group questionnaires for demographic and T1D-specific information. Focus group data were transcribed and coded into themes in NVivo using a thematic analysis approach.

Preliminary Results: Data from pre-focus group questionnaires were available for 7 adolescents and 12 parents/ guardians. Day-to-day management was identified as the most important T1D topic for adolescents, while the impact of T1D on emotional well-being and mental health was identified as the most important T1D topic by parents/guardians.

In the focus group with parents/guardians, the 3 topics that most often came up included challenges and concerns regarding T1D management, family conflicts due to T1D-related issues, and a lack of support for parents.

Conclusion: These preliminary data confirm the need for digital health-enabled mental health support for adolescents with T1D. Once data analysis is complete, focus group data will help inform the co-design of the REACHOUT NexGEN peer support mental health app.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #1 | Poster #7 Olivia Scoten, Medical Student, University of British Columbia Supervisor: Patricia Janssen, Healthy Starts

Congratulations to Olivia on receiving a BC Children’s Hospital Research Institute Healthy Starts Summer Studentship

Screening for perinatal anxiety disorders: A randomized controlled trial Olivia Scoten, Patricia Janssen, Nichole Fairbrother

Background: Anxiety and anxiety related disorders affect one in five pregnant and postpartum people. These disorders are associated with adverse pregnancy outcomes (e.g., preeclampsia, preterm delivery, low birth weight) and prolonged negative effects on the developing infant (e.g., difficult temperament, impaired self-regulation, increased risk of attention-deficit hyperactivity disorder). However, despite a high prevalence and profound impact on maternal and infant health, routine screening for these disorders is rarely conducted. Lack of routine screening means that many who could benefit from treatment may not be identified.

Objectives: To evaluate the effectiveness of perinatal anxiety screening with respect to anxiety symptoms, treatment seeking, and treatment engagement.

Methods: This province-wide, three-armed randomized control trial seeks to recruit 282 English-speaking pregnant/ postpartum participants over the age of 18. Recruitment is being conducted primarily via social media. At 6-12 weeks postpartum, participants are administered perinatal anxiety screening and randomized to: (a) screening only; (b) screening plus individualized feedback on their anxiety scores; or (c) screening plus individualized feedback, and personalized referrals for treatment options that best suit their needs and preferences. At 6-8 months postpartum, all participants complete a follow-up questionnaire to assess the impact of condition on: symptoms of anxiety and depression, sleeping difficulties, mental health treatment seeking behaviours, and engagement in mental health treatment.

Hypotheses: Compared with participants who are administered screening alone, those who receive screening with feedback, or screening with feedback and referrals will later in the postpartum: (a) obtain lower scores on measures of anxiety, depression, and sleep difficulties; (b) be more likely to report mental health treatment seeking behaviours; and (c) be more likely to have accessed treatment for their mental health concerns. Similarly, participants who are administered screening plus feedback and referrals will have better outcomes compared with those receiving screening and feedback only.

Impact: Findings from this study will yield the first data regarding the effectiveness of perinatal anxiety screening in improving mental health outcomes and will provide much needed evidence to support universal screening for perinatal anxiety.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #1 | Poster #8 Natalie South, Medical Student, Royal College of Surgeons Ireland Supervisors: Emily Schaeffer & Kishore Mulpuri, Evidence to Innovation

Assessing the Impact of COVID-19 on Health Resource Utilisation by Paediatric Patients with Cerebral Palsy Natalie South, Sophia Provenzano, Emily Schaeffer, Stacey Miller, Maria Juricic, Kishore Mulpuri

Background: Cerebral Palsy (CP) is the most common cause of motor impairment or disability in children. The prevalence of CP is 1 out of every 400 individuals in Canada. Management of CP requires medical and surgical attention as well as the continuous support of various healthcare professionals, including rehabilitation therapists and occupational therapists. Prior to the start of the COVID-19 pandemic, the BC Children’s Hospital Orthopaedic Clinic Cerebral Palsy team conducted a study on the accessibility of care for patients with CP and how it varies over the Gross Motor Function Classification System (GMFCS) levels.

COVID-19 has caused major delays in all healthcare settings, decreasing access to healthcare services for patients with long term illnesses like CP. The purpose of this study is to develop and administer a follow-up survey to understand how access and utilisation of healthcare services has been impacted by the COVID-19 pandemic and to determine whether changes to service delivery are required to accommodate the needs of patients and families.

Objectives: In this prospective cross sectional study we will be assessing the impact of Covid-19 on the health services utilised by paediatric patients with cerebral palsy and comparing them to the results from 2019, prior to the pandemic.

Methods: - Adapt the original survey used in 2019 to collect data on how access to care has changed throughout the pandemic for patients with CP. - Reach out to all patients involved in the 2019 study by email.

- Contact and survey patients with CP who attend the orthopaedic clinic at BC Children’s.

- Evaluate the type and frequency of healthcare services used by children with CP over the course of the pandemic.

Anticipated Results: It is anticipated that during the pandemic there has been a decrease in the frequency of in-person healthcare visits, specifically rehabilitation services.

Implications: The overall goal of the study is to identify gaps in care of patients with CP. It will allow identification of service areas of need, and of how resource delivery may need to be adjusted to accommodate patient needs in the event of future pandemics and the evolving balance of virtual and in-person care.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #2: Virtual CLINICAL & POPULATION HEALTH Moderator: Meingold Chan Participants: Ibreez Asaria Laura Cunningham Gia Da Roza Mary Daniel Kyle Hui Jayne Owston Deirdre Reynolds Erica Zeng

Watch Virtually: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 10:00 - 11:30 am www.bcchr.ca/posterday

Session #2 | Poster #9 Ibreez Asaria, Undergraduate Student, McMaster University Supervisor: Manish Sadarangani, Healthy Starts

Evaluating the Safety and Effectiveness of Capsular Group B Meningococcal Vaccines In Children

Ibreez Asaria, Mahin Delara, Rachael Chow, Suzanna Liu, Julie Bettinger, Nicole Basta, Manish Sadarangani Background: Meningitis is a serious illness characterized by the inflammation of the membranes surrounding the brain and spinal cord, often due to infection. The most life-threatening form of meningitis is referred to as invasive meningococcal disease (IMD), which is most commonly caused by the gram-negative bacteria Neisseria meningitidis capsular group B within Canada. Given it’s severity, the World Health Organization (WHO) has called for the creation of an evidence-based policy on immunization strategies pertaining to Meningococcal B (MenB) vaccines. There are two licensed vaccines used for different ages, with a 4-component MenB vaccine (4CMenB) used for those aged 2 months to 25 years; and a factor H binding protein based MenB vaccine (MenB-fHbp) used for those aged 10-25 years.

Study Purpose: This study will provide data regarding the immunogenicity, efficacy, effectiveness, and safety of both licensed MenB vaccines. This data will be used to establish the optimal protection from both MenB vaccines across the age spectrum by contributing to national immunization policy-making discussions.

Objective: To evaluate the effectiveness, efficacy, immunogenicity, and safety of both the 4CMenB and MenB-fHbp vaccines for immunized infants, children, adolescents, and young adults 25 years old or younger.

Methodology: A systematic review and meta-analysis of using literature from MEDLINE (OVID), EMBASE (OVID), CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL). Including grey literature, published papers on or before January 2021 were searched. These papers were only included if they were human-only original studies including observational studies and prospective/retrospective cohort designs among others, and reported at least one of the four desired data outcomes in participants. Participants were identified as having received ​​ at least 1 dose of MenB vaccines, with age limited to infants, children, adolescents, and young adults 25 years old or younger.

Future Direction: This study is currently in the data extraction and review phase in which studies separate for infants and children or adolescents are being reviewed in REDCap. An analysis of subgroups or subsets including type of MenB vaccine administered, sex, and age will soon be conducted along with a sensitivity analysis for different study designs.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #2 | Poster #10 Laura Cunningham, Undergraduate Student, University of British Columbia Supervisor: KS Joseph, Healthy Starts

Congratulations to Laura on receiving a BC Children’s Hospital Research Institute Summer Studentship

A Systems Approach for Enhancing Perinatal Care Regionalization Laura Cunningham, KS Joseph

Background: The Term Breech Trial, a large state-of-the-art randomized trial carried out in 2000, showed that a planned cesarean delivery (rather than planned vaginal delivery) for breech presentation at term gestation significantly reduces perinatal mortality and serious neonatal morbidity. However, a small fraction of breech deliveries continue to occur by the planned vaginal route in Canada (patient preference, controversies regarding optimal mode of delivery, unplanned delivery, etc).

Objective: To assess the safety of singleton breech deliveries at term gestation by province/territory, tier of obstetric service, and hospital in Canada (excluding Quebec).

Methods: The study included all singleton, term (≥37 weeks), breech deliveries in Canada (excluding Quebec) from 2013 to 2019. The primary outcome was composite serious neonatal morbidity or neonatal mortality (SNMM) and included birth injury, seizures, assisted ventilation and neonatal death. Analyses included comparisons of rates by province, tier of obstetric service, and hospital, and were carried out using SAS software. Ethics approval was obtained from the BC Children’s and Women’s Hospital Research Ethics Board.

Results: The study population included 45,228 singleton breech live births and 435 SNMM cases (10 per 1000 live births).

Alberta, Ontario, and Newfoundland and Labrador had the highest SNMM rates, while British Columbia, Manitoba, and Nova Scotia had the lowest rates. Additionally, BC, Ontario, and New Brunswick had the highest rates of cesarean delivery, while Manitoba, Saskatchewan, and Alberta had the lowest rates. Tier 2 hospitals had the lowest rate of SNMM at approximately 9 per 1000 live births. Some hospitals had significantly higher rates than others. In British Columbia, two hospitals, namely, the Royal Columbian Hospital and the Women’s Hospital of British Columbia, carried out the majority of the breech deliveries. BC Women’s Hospital had a lower rate of cesarean delivery and half the SNMM rate compared with the Royal Columbia Hospital (7 per 1,000 and 15 per 1000 live births, respectively).

Conclusion: This study provides information on the safety of breech delivery at term gestation by province and hospital in Canada. Hospitals should continuously assess their performance with regard to breech delivery at term gestation and take steps to improve outcomes.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #2 | Poster #11 Gia Da Roza, Undergraduate Student, University of British Columbia Supervisor: Janis Dionne, Evidence to Innovation

Congratulations to Gia on receiving a UBC Faculty of Medicine Summer Studentship

Cost Savings Analysis of a Clinical Pathway for Diagnostic Testing in Pediatric Hypertension Gia Da Roza, Marisa Catapang, Linda Ding, Janis Dionne

Background: Pediatric hypertension has an estimated prevalence of 4% worldwide. Diagnostic testing to identify causes of secondary hypertension, which are common in children, is highly variable, resulting in unnecessary testing and possible missed diagnoses. The 2017 American Academy of Pediatrics (AAP) guideline provides recommendations for diagnostic testing based largely on expert opinion and limited literature. A locally developed BCCH clinical pathway (BCCH-CP) balances these recommendations with local data and context. The objective of this study is to compare the historical costs of diagnostic testing with the potential costs of applying the AAP or BCCH-CP. Methods: A retrospective database (2000-2015) for hypertensive outpatients aged 1-18 years referred to BCCH was used to determine the number and types of historical tests performed. Cost per test was based on the BC MSP payment schedule for insured patients. Potential guideline and pathway costs were estimated according to their respective recommendations, along with database-derived demographic factors and test results. The AAP recommends a chemistry panel, urinalysis, and lipid profile, with HbA1c, liver transaminases, and lipid panel for overweight/obese patients, as well as renal ultrasounds for patients <6 years old or those with abnormal urinalysis or renal function. The BCCH-CP recommends renal ultrasounds for all, with fasting lipid panels for overweight/obese patients. Costs for each diagnostic approach were quantified as a mean cost per patient with a 95% confidence interval and compared using a paired T-test.

Results: A total of 154 patients were included in this study (median age 13 years (IQR 8.45), 66.9% male, 58.4% overweight/obese). Mean cost per patient of historical diagnostic testing was $349.67 (95%CI=295.86-403.49).

Mean testing costs based on the AAP and BCCH-CP were significantly lower at $91.43 (95%CI=84.99-97.87) and $99.13 (95%CI=97.46-100.81) per patient, respectively (p<0.001 for both as compared to historical).

Conclusions: These results support the implementation of standardized clinical pathways in pediatric hypertension.

Compared to the AAP guideline, our proposed hypertension pathway would result in a comparable cost reduction for the healthcare system and fewer diagnostic testing requirements.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #2 | Poster #12 Mary Daniel, Undergraduate Student, University of British Columbia Supervisor: Wendy Robinson, Healthy Starts

Congratulations to Mary on receiving a UBC Faculty of Medicine Summer Studentship

Characterizing X chromosome DNA methylation in the placenta Mary Daniel, Icíar Fernández Boyano, Wendy Robinson

Background: Preeclampsia (PE), a maternal hypertension disorder, is amongst the greatest causes of preterm birth, fetal growth restriction and maternal death. Placental samples from cases with early-onset preeclampsia (EOPE) have been found to be differentially methylated in the autosomes when compared to normotensive preterm births (nPTB).

Sex differences have also been reported in the incidence of PE, with EOPE favoring females. We hypothesised that differential methylation would also be observed on the X chromosome between cases affected by EOPE and nPTB. Aims:

- To preprocess DNA methylation microarray data (Illumina 450K) by completing various quality checks.

- To complete exploratory data analysis using PCA to identify the main drivers of DNAme variation in our discovery and validation cohorts on the autosomes and the X chromosome separately.

- To investigate any X-linked CpG sites that are differentially methylated in early-onset preeclampsia (EOPE), stratifying the analysis in XX and XY placentae.

Methods: A discovery cohort (n=270, 48% XX, 52% XY) and validation cohort (n=93, 47% XX, 53% XY) of placental chorionic villi samples measured using the Illumina 450K Array were collected from the Gene Expression Omnibus (GEO), a public database repository.

Autosomal and X-linked DNA methylation was investigated using principal component analysis (PCA).

Linear models were run separately in XX and XY placentae to find CpG sites on the X chromosome that are differentially methylated between EOPE and gestational age matched controls.

Results: PCA on the placental X chromosome revealed that sex was significantly associated to PC1 (p=5.92e-53), indicating that placental sex is the main driver of variation in the X-linked methylation data.

In the differential methylation analysis, 2 CpG sites were found to be differentially methylated (FDR<0.05 and |Δβ|>0.1) between EOPE and nPTB cases in XY placentae in the discovery cohort, while none were found in XX placentae at these same thresholds. Less stringent thresholds (FDR<0.05 and |Δβ|>0.05) yielded the same results. The 2 differentially methylated CpG sites were not replicated in the validation cohort using a nominal p-value of <0.05 and a change in methylation in the same direction.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #2 | Poster #13 Kyle Hui, Undergraduate Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

Congratulations to Kyle on receiving a BC Mental Health & Substance Use Services Research Summer Studentship

Functional Brain Networks Underlying Deficiencies in Impulse Inhibition in Schizophrenia Kyle H. Hui, Linda V. Chen, Maiya Rasheed, Todd S. Woodward

Research Objectives: Schizophrenia is a psychiatric disorder characterized by positive, negative, and cognitive symptoms (e.g., delusions, abnormal motor behaviours). Impulsive behaviours have been associated with aggression in schizophrenia and is related to a large degree of psychiatric hospitalizations. However, the neural basis underlying these behaviours are not well understood. This study aims to examine the functional brain networks underlying the two visual task experiments in healthy controls and schizophrenia patients to elucidate the commonly activated functional brain networks and their association with abnormal motor symptoms.

Methods: The functional brain networks and hemodynamic response shapes were extracted from functional magnetic resonance imaging (fMRI) scans, taken while performing the visual tasks, using Constrained Principal Component Analysis for fMRI (fMRI-CPCA).

Results: Group differences were observed in the response network, a commonly activated network when a motor response is elicited, demonstrated by hyperactivity for schizophrenia patients in the probabilistic reasoning task followed by reduced suppression in both tasks.

Conclusions: Hyperactivity and reduced suppression in the response network is concurrent with previous literature indicating this response may be related to deficiencies in impulse inhibition. The well documented presence of excess dopamine in schizophrenia leading to greater activation of the substantia nigra leads to inhibition of the globus pallidus, which ultimately reduces the inhibition of the thalamus. This leads to a greater motor output which may provide a biological basis for this deficiency in inhibiting movement. Future investigations should determine the relationship between the overactivation of the response network with reported abnormal motor symptoms and investigate the differential activation of the thalamus and related structures with respect to the activation of the response network.

Precise spatial localization of these functional brain networks may yield a stronger framework in which to produce improved treatment options for schizophrenia patients.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #2 | Poster #14 Jayne Owston, Undergraduate Student, University of Toronto Supervisor: Stuart Turvey, Healthy Starts

Impacts and the Resulting Burdens of the COVID-19 Pandemic on Employment Changes within Canadian Families with Young Children: Data from the CHILD Cohort Study Jayne Owston, Conrado De Guzman, Alex Dempsey, Darlene Dai, Kate Del Bel, CHILD Cohort Study Investigators, Stuart Turvey

Background: The COVID-19 pandemic has brought about unfamiliar changes such as skyrocketing unemployment rates and the widespread adoption of working remotely. This crisis has exemplified greater issues of this pandemic which have impacted much more than just travel plans and concerts. The necessary adaptation by families during this unprecedented time has provided an opportunity to study how employment changes have altered components of daily life such as stress, spousal work, family dynamics, etc. Through this investigation, we can elucidate the key relationship between employment changes and transition to everyday life which allows further understanding of COVID-19’s burdens.

Objective: Through the use of a prospective survey, we aim to understand the relationship between the COVID-19 pandemic and modification in employment status amongst the CHILD cohort study participants at the Vancouver site.

Moreover, this project seeks to investigate the impact that these resulting employment changes have had on various aspects of daily life.

Methods: The COVID-19 Add-on project for the Vancouver CHILD study site consists of 364 households with 592 parent participants. One questionnaire was given to each adult participant involved in the project from January to April 2021.

Questions were proposed to each participating parent in the household covering topics ranging from the changes to habitual routines, family relationships, stress levels, and financial burdens related to the COVID-19 pandemic.

Results: Data analysis is ongoing at the time of abstract submission.

Conclusion: The results from this study will provide additional insights into how Vancouver families with young children were impacted by the COVID-19 pandemic. Ultimately, this knowledge will inform public policy on how best to support families through unprecedented global change.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #2 | Poster #15 Deirdre Reynolds, Undergraduate Student, University of British Columbia Supervisor: Paula Mahon, Brain, Behaviour & Development

Lived Experiences of Adolescents Living With Primary Complex Pain Paula Mahon, Deirdre Reynolds

Purpose: Primary Complex Pain (PCP), a relatively new diagnosis, that characterizes pain that is not a secondary response to an underlying primary condition such as trauma or cancer. This feasibility study evaluated the lived experience of adolescents with a diagnosis of PCP. Methods: We used a qualitative methodology, interpretative description to guide our study. Fifteen adolescents (N=15), living with PCP were interviewed.

Results: All participants reported struggling with diagnostic uncertainty, depression and anxiety. Adding to their distress was the fact that our participants perceived that health care professionals did not believe them when they described their pain and its intensity, this included medical professionals. The COVID-19 pandemic added to their isolation, plus lack of access to medical professionals and treatment, but it did make their lives more comparable to the lives of their non-PCP peers.

Conclusions: Participants believe there is a lack of knowledge about PCP as a diagnosis and thus there are limited resources and a lack sympathy and understanding for these adolescents.

Implications and Contribution: Adolescents with a Primary Complex Pain diagnosis experience diagnostic uncertainty and negative psychological effects. Increased training and awareness for healthcare practitioners regarding PCP as a diagnosis in adolescents would improve the experiences of these adolescents’ seeking treatment.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #2 | Poster #16 Erica Zeng, Undergraduate Student, University of Western Ontario Supervisor: Todd Woodward, Brain, Behaviour & Development

fMRI study of functional brain networks in the working memory task in healthy control & schizophrenia patients Erica Zeng, Nicole Sanford, Todd Woodward

Research Objective: As the dorsolateral pre frontal cortex (pFC) has been implicated in working memory impairment, it is important to understand the characteristics of the functional brain networks in the pFC elicited during tasks that evaluates working memory function.

Methods: The study participants included 26 healthy controls and 28 patients with schizophrenia. The modified Sternberg Working Memory task was administered in which for each participant, a string of 4 or 6 upper case consonants was displayed for 4 seconds, followed by a delay of 0 or 4 seconds, and then the display of a single probe letter for 2 seconds. The data was processed using Constrained Principal Component Analysis for fMRI (fMRI-CPCA) to extract a set of eight networks. The four functional networks containing activity in the pFC were further examined through the following steps: (1) the brain network activity for each task condition averaged over participants was plotted, (2) time points and HDR parameter of interest values were computed separately for each task condition, (3) a standard SPSS analysis was used to evaluate the effects of cognitive load and delay conditions on HDR response shapes.

Results: Four spatially and temporally distinct networks with pre-frontal cortex activation emerged and were classified as (1) maintaining, (2) auditory attention for response, (3) one-handed response, and (4) initiation. Classifications were aided by the computation of HDR parameters, which can be used to examine how activity in the identified brain networks correlates with phenotypes such as demographics, personality, and cognitive performance.

Watch Virtually: Thursday, July 28 | 10:00 - 11:30 am | www.bcchr.ca/posterday

Session #3: In-Person CLINICAL & POPULATION HEALTH Moderator: Mia McLean Participants: Maria Caray Aanisah Golam Zoe Kortje Christina Lam Abigail Netanya Tan Ngan Niki Shahraki Meaghan Smith Kaitlyn Treleaven Justin Yap

Watch In-Person: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 10:00 - 11:30 am Chieng Family Atrium, BC Children’s Hospital Research Institute

Session #3 | Poster #17 Maria Caray, Undergraduate Student, University of British Columbia Supervisor: Jorinde Polderman

Congratulations to Maria on receiving a BioTalent Canada Award

Anesthetic Management of the Pediatric Patient with Diabetes: A Retrospective Chart Review Maria Caray, Jorinde Polderman, Nicholas West, Andrew Poznikoff, Simon Whyte

Background: Anesthesiologists play an essential role in managing pain and stress on the body during surgery, which requires monitoring metabolic functions including blood glucose levels. This is especially important in pediatric patients with type 1 diabetes mellitus (DM1), who are prone to deranged glycemic control and thus require close observation to maintain blood glucose between 4-10 mmol/L. Previously, perioperative hyperglycemia has been associated with complications such as delayed healing and wound infections. Despite a growing prevalence of DM1 in Canadian pediatric patients, perioperative management has not been widely studied, and is based on clinical judgement.

Objectives: We aim to describe the glycemic control of the pediatric patient with DM1 undergoing surgery and to establish adherence to existing perioperative management guidelines.

Methods: A retrospective chart review was conducted of all procedures performed between January/2012-July/2015 in patients≤18 years diagnosed with type 1 or type 2 diabetes mellitus. Incidence of perioperative hyperglycemia (IPH), adherence to hourly intraoperative glucose checks, fasting times and effects of anesthetic medications were evaluated.

Results: A total of 74 charts have been reviewed: 37 females, median (range) age 15.5 (6-18) years, 58/74 (78%) diagnosed with DM1. IPH occurred in 43/58 (74%) DM1 patients. Hourly glucose checks were performed in 0/1 (0%) neurosurgery, 2/5 (40%) orthopedic and 0/3 (0%) spine procedures. There was no difference between mean fasting times of solids or liquids between DM1 patients with an IPH versus those with no IPH (p=0.23 and p=0.92, respectively). DM1 patients who received either dexamethasone (n=10) or dexmedetomidine (n=13) exhibited a decrease in postoperative blood glucose (0.13 mmol/L and 2.07 mmol/L, respectively). There was no difference in postoperative blood glucose between DM1 patients who did or did not receive dexamethasone (p=0.66) or dexmedetomidine (p=0.07).

Conclusions: Results suggest that DM1 patients often experience an IPH and management could be improved. Lack of adherence to hospital guidelines presents an opportunity to implement systems to establish hourly intraoperative blood glucose checks. Future directions include completing data collection and analysis for the following 4-year period, which may then be used to guide future prospective interventional research.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #3 | Poster #18 Aanisah Golam, Undergraduate Student, University of British Columbia Supervisor: Prakash Krishnan

Congratulations to Aanisah on receiving a Biotalent Canada Award

Anesthetic techniques for the management of neonatal inguinal hernia repairs: A retrospective audit Aanisah Golam, Halle Golding, Wendy Song, Andrew Poznikoff, Robert Baird, Prakash Krishnan

Purpose: Inguinal hernia repairs (IHR) are common surgical procedures performed in neonates, traditionally done under general anesthesia (GA) with an endotracheal tube (ETT). Previously, a technique of caudal anesthesia with sedation for neonatal laparoscopic IHR was shown to be viable, potentially minimizing complications associated with intubation in high risk neonates. This study investigates the efficacy of caudal blocks with sedation for neonatal laparoscopic IHR compared to three other combinations of anesthetic and surgical techniques in regard to operating room (OR) utilization.

Methods: A total of 338 patients undergoing IHR procedures between July 2016 and July 2021 were identified as eligible and included in analysis. Data collection included a range of OR related time points, description of anesthetic techniques, surgical details and postoperative outcomes. Caudal anesthesia with spontaneous ventilation was determined by use of nasal prongs or facemasks, while use of an ETT or laryngeal mask airway indicated GA, with either technique incorporated into open or MIS IHRs. As such, four groups were identified: GA for MIS IHR (GA MIS), GA for open IHR (GA Open), caudal block with sedation for MIS IHR (Caudal MIS), and caudal block with sedation for open IHR (Caudal Open).

Results: The anesthetic success rates were 100% for Caudal MIS (n=32) and 95.3% for Caudal Open (n=121). OR utilization was determined by anesthetic preparation time, procedure time and post-procedure time; the three times combined are calculated as total OR time. Comparing mean times between the four groups showed significance for only post-procedure time (p<0.0001) with Caudal Open having the shortest average time (7 ± 4). Caudal MIS was found to not be different from the other three groups for total OR time, as well as when including time spent in the postoperative anesthetic care unit (PACU).

Conclusion: In conclusion, caudal anesthesia with sedation avoiding airway instrumentation for neonatal MIS IHRs is not significantly different to standard methods regarding OR utilization times. Performing MIS IHRs under caudal anesthesia with sedation may confer long term advantage vis-à-vis surgical outcomes and perioperative anesthesia-related morbidity without compromising OR efficiency.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #3 | Poster #19 Zoe Kortje, Undergraduate Student, Queen’s University Supervisor: Donna Lang, Brain, Behaviour & Development

Congratulations to Zoe on receiving a BC Children’s Hospital Research Institute Brain, Behaviour & Development Summer Studentship

Assessing Cerebrovascular Burden in Post-COVID-19 Patients: A Quantitative Rating Scale Zoe Kortje, Ava Grier, Donna Lang

Background: The viral agent in COVID-19 is known as SARS-Cov-2, which binds to the angiotensin-converting enzyme 2 (ACE2) receptor. This receptor is found in neurons and glial cells, activated by viral particles hypothesized to spread to the CNS through the olfactory bulb. Neurological complications in post-COVID-19 syndrome emerge during the latent stage of the disease, where infectious particles remain in the CNS to potentially trigger symptoms such as anosmia, ageusia and headache. There is a strong link between neurovascular dysfunction and neurocognition, prompting analysis of the neurovasculature in post-COVID-19 research patients. The physiology of retinal vessels is similar to the cerebral vessels because they originate from the same tissue during development. The disruption of the blood-brain barrier and blood-retina barrier also occur simultaneously. There are many deficits of retinal vasculature associated with a decline in neurocognition, prompting the need for a quantitative rating system that can describe the comprehensive impact of all vascular markers at once.

Methods: As a pilot project of the COVID-19 NeuroOutcomes study, we aim to use retinal Fundus imaging to find the cerebrovascular deficits associated with post-COVID-19 syndrome. We completed a systematic literature review of retinal vascular markers and their connection to brain health. This information was used to construct a cerebrovascular burden rating scale that will be used to quantify our analysis of these images.

Results: The developed quantitative rating scale is comprised of 22 isolated vascular markers and scored out of 80. Each marker is analyzed using a different scale and semi-automated software. The score generated by this scale will be a result of the collective efforts of ophthalmology, bioengineering and research assistants on our team.

Implications: This rating scale will be used to obtain an average cerebrovascular burden score from our control and experimental groups. These will be compared to each other, as well as to the MRI and neurocognitive test results obtained by the CONOS study. This data will go towards characterizing potential retinal biomarkers for neurological complications in post-COVID-19 syndrome. Our research team plans to use this scale to quantify images from other study groups, including patients with schizophrenia and Alzheimer’s disease. It will also be made available for use by other research teams.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #3 | Poster #20 Christina Lam, Undergraduate Student, Simon Fraser University Supervisor: Ali Eslami, Brain, Behaviour & Development

Congratulations to Christina on receiving a BC Children’s Hospital Research Institute Summer Studentship

Responsiveness of children and adolescents to psychiatric crisis stabilisation by Indigeneity and family structure Christina Lam, Ali Eslami

Indigenous identity and family structure are both closely linked to mental health outcomes among youth. There is also a disproportionate number of Indigenous youths in government care or alternative family arrangements in Canada.

Thus, it is particularly relevant to explore how Indigenous identity and family structure interact in the context of child and adolescent emergency psychiatric care.

The present study explores whether the responsiveness to psychiatric crisis stabilisation differs among Indigenous and non-Indigenous patients with various family structures. Length of stay in a psychiatric stabilisation unit in British Columbia, Canada, is used as a proxy for responsiveness to stabilisation.

We predict the following: first, that length of stay will be longer overall for Indigenous patients; second, that length of stay will be longer overall for patients having a less intact family; and third, that given any family structure, the Indigenous group will have a longer length of stay compared to the non-Indigenous group with a similar family structure.

A retrospective chart review is being conducted with data registry records (n = 910) of admissions to the psychiatric stabilisation unit from July 2016 to present. Each patient’s first admission will be retained for analysis, and subsequent admissions will be discarded. A linear regression model, controlling for age and gender, will be conducted for each of the three study hypotheses.

Whether the results of the present study support our hypotheses or not, our findings will further our understanding of psychiatric crisis stabilisation among children and adolescents. This may inform both future studies in the field as well as care practices in the clinical setting.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #3 | Poster #21 Abigail Netanya Tan Ngan, Undergraduate Student, University of British Columbia Supervisor: Catherine Biggs, Healthy Starts

The Molecular and Phenotypic Landscape of Severe Combined Immune Deficiency in British Columbia Abigail Netanya Tan Ngan, Kyla Hildebrand, Stuart Turvey, Catherine Biggs

Background: Severe Combined Immunodeficiency (SCID) is an inborn error of immunity that severely hinders the development and function of an affected individual’s T cells. Consequently, those affected are predisposed to recurrent, severe, and opportunistic infections from an early age. Early diagnosis through newborn screening is essential to prevent life-threatening infections and ensure the best outcomes. Newborn screening for SCID is offered throughout the United States and in most of Canada, and is anticipated to be introduced in BC in the future. The purpose of this project was to create a systematic method for monitoring cases of SCID identified through newborn screening, and to create clinical and educational documents on SCID for providers and families.

Methods and Results: A REDCap database was created as a quality improvement initiative to monitor the clinical features, molecular and phenotypic diagnoses, and outcomes of children evaluated for SCID through the BC newborn screening program. A chart review was performed to identify the clinical features, genetic etiologies, laboratory evaluation, and treatments for SCID. With this information, we created the demographics, clinical data, and SCID newborn screen case questions and instruments for the REDCap database. Next, a SCID clinical assessment form and IPAC inpatient guidance document were made for medical professionals who will be working with these immunodeficient patients. Finally, educational handouts, such as an information sheet about SCID, home and hospital isolation guidelines for children with SCID, and an information sheet on how to safely feed a child with immunodeficiency, were created.

These documents are dedicated to supporting newly admitted patients who are undergoing evaluation for SCID. Significance: With the REDCap database, educational handouts for families, and clinical guidelines for medical professionals, this project will assist in facilitating the smooth and efficient integration of the newborn screening program for infants diagnosed with SCID in British Columbia. This public health service will ultimately assist medical professionals in diagnosing SCID among infants at an early age while also supporting families in ensuring the best outcome for their child.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #3 | Poster #22 Niki Shahraki, Undergraduate Student, University of British Columbia Supervisor: Kourosh Afshar, Evidence to Innovation

Non-Opioid Non-NSAID (NONN) Analgesia for Acute Renal Colic: A Systematic Review Kourosh Afshar, Maryam Noparast, Hameed Hamlaw, Niki Shahraki

Background: Renal colic is an acute pain caused by the obstruction of the urinary flow due to stone(s), resulting in ureteric smooth muscle spasm and inflammation. Symptomatic urolithiasis is among the most common emergency condition affecting 12% of the population and making 1% of ER visits and hospital admissions. The incidence of renal colic has been increasing globally due to changes in diet and lifestyle. Non-NSAID non-opioids (NONN), a class of analgesics, may relieve renal colic pain through their effect on the smooth muscle of the renal pelvis and ureters.

Primary Objectives: 1) To determine the change in pain score within 30-60 minutes of drug administration, measured by

validated pain scales.

2) To determine the proportion of patients with at least one major adverse event such as GI bleed or renal insufficiency.

Search Method: A search for randomized control trials on Cochrane Library, MEDLINE, and Embase published up to June 30th, 2022 will be performed. There will be no restrictions applied to language or publication status.

Data Collection: Two independent reviewers will screen titles and abstracts obtained from the electronic search for eligibility and irrelevant studies will be removed. A full text review will be carried where all excluded articles and reason for exclusion will be recorded. Studies that investigate NONN vs placebo, NSAID or another NONN with a different dose or route of administration will be selected and their population, interventions, comparators, and outcomes will be recorded and summarized into a table.

Expected Results: NONN agents are as effective and safe as other analgesic agents for renal colic in adults.

Significance: NSAIDS are used as a common course of treatment for renal colic but can increase the risk of gastrointestinal or renal dysfunction. NONN medication can be used to target renal colic pain in populations who have contraindications to NSAIDS.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #3 | Poster #23 Meaghan Smith, Undergraduate Student, McGill University Supervisor: Tamara Vanderwal, Brain, Behaviour & Development

Congratulations to Meaghan on receiving a BC Children’s Hospital Research Institute Summer Studentship

Graph-based properties of functional connectivity gradients in resting state and movie-fMRI Meaghan Smith, Ahmad Samara, Jeffrey Eilbott, Hallee Shearer, Will Clarke, Tamara Vanderwal

Functional connectivity (FC) analyses in fMRI assess correlations in blood-oxygen -level-dependent signal of different brain areas over time. Researchers have shown that dimensionality reduction (i.e., gradients analysis) of FC data reveals a functional hierarchy that is conserved across species. Until now, gradient studies have largely relied on data acquired during task-free rest. Movie-watching is another useful fMRI acquisition state that is thought to improve ecological validity by driving whole-brain dynamic processing. The current project investigates spatial relationships of brain regions within gradient space during movie-watching for the first time. Our main hypothesis is that movie data will better exemplify gradient geometry relative to rest.

FC matrices (1000 x 1000 brain regions) were created using rest and movie data (Human Connectome Project, N = 95, 59 females, mean age 29.5 +/- 3.3). The BrainSpace toolbox was used to perform diffusion embedding on the matrices, yielding a set of movie and rest gradients. Scores of the top 2 gradients were plotted as standard scatter plots, and graph-based analyses were conducted in this “gradient space.” The distance from the centroid was calculated for each data point, as was the distance to its nearest neighbour. A k-means clustering algorithm in MATLAB was run iteratively (k2-10), partitioning the data into k clusters. Silhouette values at each k were computed to reflect stability of the grouping, where values closer to 1 indicate that the data aggregates more naturally into k clusters.

We found that the mean point-to-centroid distance was shorter in movie than rest, and that in movie, more points were similarly distant from the centroid. The range of distances between nearest neighbours was also narrower in movie.

Finally, for all but one k-value, the mean silhouette coefficient was closer to 1 in rest. We suggest that the smoother point distribution and less stable clustering in movie means that the hierarchical gradient organisation of FC is better exemplified during complex processing states than during rest.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #3 | Poster #24 Kaitlyn Treleaven, Undergraduate Student, McMaster University Supervisor: Stephanie Glegg, Evidence to Innovation

Implementing KidsAction Coaching using the Theoretical Domains Framework and Behaviour Change Wheel

Kaitlyn Treleaven, Lauren Ho, Amanda Field, Mojgan Gitimoghaddam, Jean-Paul Collet, Lise Olsen, William McKellin, Tara Nault, Tyrone Joe-Mayes, Stephanie Glegg Introduction: Physical activity is foundational for children’s mental and physical health. Children with neurodevelopmental disabilities (NDD) have limited opportunities to participate in physical activity programs that address their physical, social, and emotional needs. KidsAction Coaching (KAC) is an evidenced-based approach that offers individualized, goal-directed coaching, while supporting home-based practice, social interaction, an Indigenous cultural lens, and ongoing evaluation to optimize health outcomes for children with NDD and their families. Implementation Plans (IPs) are co-created with partner organizations to guide the development of implementation strategies and their enactment.

Objectives: This project aims to: (1) identify barriers and enablers of KAC implementation at urban and rural physical activity program sites across Canada; and (2) customize and enact IPs to target these factors.

Methods: The implementation process was guided by the National Implementation Research Network framework.

Data on barriers and enablers of implementation gathered from interviews with partner organization leads were coded to the Theoretical Domains Framework’s 14 domains. To create the IPs, implementation strategies were then mapped to these barriers and enablers using the Behaviour Change Wheel and strategies and resources tailored in partnership with implementing sites.

Results: The IPs targeted Education, Training, and Environmental Restructuring domains of the Behaviour Change Wheel primarily, as well as Enablement, Incentivization, Modelling, Recognition, and Persuasion. Tailoring for sites included delivery format (e.g., online vs. in-person training, print vs. online resources), refining language and activities to be culturally appropriate and inclusive, and sport-specific adaptions (e.g., adapted skiing).

Conclusion: This comprehensive, theory-driven implementation planning process with each site ensures that the core components of KAC are implemented in response to the unique barriers and enablers, and in a way that aligns with the sites’ existing practices, preferences, and needs.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #3 | Poster #25 Justin Yap, Undergraduate Student, University of British Columbia Supervisor: Meera Rayar, Evidence to Innovation

Current state analysis of best practices and patient education in pediatric allogeneic hematopoietic stem cell transplant (HSCT) Justin Yap, Meera Rayar, Lisa Jacques

Background: Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment used for patients with hematology or cancer diagnoses. Preparation, transplantation, and post-discharge follow up can be complex and involve prolonged hospitalizations, periods of isolation and uncertainty. This process typically lasts for months and can put a strain on the patient and their families.

Objective: Through a QI project, we aim to identify the major themes for best practices and identify gaps in BCCH’s HSCT care pathway and patient education.

Methods: We conducted a current state analysis. To begin, we performed a literature search to identify best-practice and themes related to patient/caregiver lived-experiences of undergoing a HSCT. A grey literature search was used to identify patient educational resources. Qualitative interviews were conducted with key health care provider stakeholders to gain insight on the care pathway, clarity of roles and identify gaps. Information gathered from above mentioned searches were used to formulate an interview guide. Responses from these interviews will be analyzed, categorized into major themes, and used to construct a process map. Areas within the map will be further discussed among stakeholders to formulate changes.

Preliminary Results/Direction of Study: A total of 16 articles were identified as relevant from our literature search.

Only a few papers outline themes for best practices including effective flow of information among the health care team and standardized treatment procedures. Most articles identified common themes from HSCT patients and caregivers’ perspectives such as feelings of uncertainty, isolation, role conflict, education, communication, and lack of psychosocial support. Stakeholder interviews are ongoing, but we hope the information they provide will aid our goal of implementing changes to improve the HSCT process for patients and families.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #4: In-Person BASIC SCIENCE Moderator: Martin Prusinkiewicz Participants: Fatemeh (Shakiba) Baharvand Samantha Coleborn Nataly El-Bittar Jasleen Grewal Nicole Katz Parsa Khanbadr Emily Mei Yi Kon Colette Newby Kenzie Wrightson Conghao (Tony) Zhang

Watch In-Person: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 10:00 - 11:40 am Chieng Family Atrium, BC Children’s Hospital Research Institute

Session #4 | Poster #26 Fatemeh (Shakiba) Baharvand, Undergraduate Student, University of Tehran Supervisor: Gregor Reid, Childhood Diseases

Characterization of Precursor B Cells Pre-leukemic and Leukemic Cells by RNA Sequencing Fatemeh (Shakiba) Baharvand, Ali Farrokhi, Tanmaya Atre, Gregor Reid

Background: B precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. It is hypothesized that the leukemia-initiating genetic mutations occur in utero, followed by an event that promotes the pre-leukemic cell clone’s expansion, eventually leads to leukemia’s emergence. However, the exact mechanism of disease development and transformation of preleukemic cells into leukemic cells is not completely understood.

Aim: This project aims to identify the specific markers for pre-leukemic and leukemic cells to explain the transformation process of preleukemic cells into leukemic cells.

Methods: Emu-ret mice carrying an RFP/RET fusion gene under the transcriptional control of the IgH enhancer develop B lineage leukemias were used. RNA sequencing was performed on pre-leukemic and leukemic samples isolated from Emu-ret mice. The “DESeq2” package in R was used to explore the differentially expressed genes (DEGs). Data filtered based on the adjusted p-value (P < 0.05). 324 differentially expressed genes were obtained (54 downregulated genes and 270 upregulated genes in leukemic samples compared to pre-leukemic samples). Then “clusterProfiler” package in R was used to perform Gene Set Enrichment Analysis (GSEA) on all differentially expressed genes, using the Gene Ontology (GO) terms. Enriched pathways were filtered based on the adjusted p-value (P < 0.05).

Results: The top 3 most significantly enriched pathways for upregulated genes are “negative regulation of actin filament depolymerization,” “negative regulation of protein-containing complex disassembly,” and “negative regulation of supramolecular fiber organization.” Enriched pathways for downregulated genes are “cell activation” and “leukocyte activation.” The significantly downregulated genes in these pathways include Bik, Thy1, Cplx2, Bst1, Vpreb1, Tmem98, Cdkn2a, and Llgl1. Bst1 is a stromal cell gene that facilitates pre-B-cell growth. Thy1, also known as CD90, is widely used as a marker for hematopoietic stem cells. Also, Vpreb1 is expressed at the early stages of B cell development.

It is reported that Cdkn2a deletion occurs frequently in B-ALL patients.

Conclusions & Future Directions: The findings identify potential markers to study more and find the relation between their expression and transformation of pre-leukemic cells to leukemic cells. Results will be compared to the Proteomics pathway analysis to understand leukemic cell development better.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #27 Samantha Coleborn, Undergraduate Student, University of Victoria Supervisor: Clare Beasley, Brain, Behaviour & Development

Congratulations to Samantha on receiving a BC Children’s Hospital Research Institute Brain, Behaviour & Development Summer Studentship

Antipsychotics Effect on Sirtuin Protein Levels as a Possible Mediator of Metabolic Syndrome Clare Beasley, Li Shao, Samantha Coleborn

Background: Schizophrenia is a devastating chronic psychiatric disease that effects 1% of the global population.

This disorder is typically treated with second generation antipsychotics (SGAs), which are also prescribed for other psychiatric disorders such as bipolar disorder.

Metabolic disorders are common side effects of SGAs. Metabolic Syndrome (MetS) is a collection of health disorders, including abdominal obesity and dyslipidemia, that increase an individual’s chances of cardiovascular disease. MetS is diagnosed in over 50% of adult individuals with schizophrenia treated with specific SGAs. Sirtuin 1 (SIRT1) is a member of the sirtuin family of class III histone deacetylase, which are proteins involved in a number of essential physiological processes including metabolism, inflammation, lipid homeostasis, and insulin secretion. Prior studies have implicated SIRT1 in the development of MetS. However, the relationship between SGAs and sirtuins remains unknown. We hypothesize that SGAs alter SIRT levels and that this mechanism may be involved in the increased risk of metabolic disorder in individuals taking SGAs. Objective: To compare SIRT1 expression in the cortex of rats given the SGA, clozapine, the first-generation antipsychotic (FGA), haloperidol, or saline.

Methods: Levels of SIRT1 were determined by Western blotting in the cortex of rats given SGAs (n=10), FGAs (n=10), or saline (n=10).

Results: Results are currently being analyzed.

Implications/Significance: While individuals prescribed SGAs are dependent on these medications for their wellbeing and functioning, metabolic side effects of SGAs reduce individual’s quality of life and lead to further stigmatization and medication non-compliance.

As such, it is essential to understand the mechanisms underlying side effects of SGAs in order to improve medications currently available and develop new ones for the future.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #28 Nataly El-Bittar, Undergraduate Student, University of British Columbia Supervisor: Chris Carlsten

Congratulations to Nataly on receiving a UBC Faculty of Medicine Summer Studentship, Florence & George Heighway Endowment Fund

Effects of wood smoke exposure on human airway epithelial cells Nataly El-Bittar, Ryan D. Huff, Carley Schwartz, Christopher F. Rider, Chris Carlsten

Introduction: Exposure to wildfire smoke in western Canada has been an increasing problem over the last decade.

Vancouver, British Columbia, has historically experienced low levels of air pollution as measured by the level of ambient fine particulate matter (PM2.5). Over three years from 2016 to 2018, the average annual PM2.5 levels were 8.2 mg/m3; however, due to periods of increased forest fire activity in the lower mainland region, daily averages have been observed well above 100 mg/m3. There is also accumulating evidence to suggest that exposure to the resultant wood smoke (WS) is harmful to health, with associated increases in heart attacks, asthma exacerbations and even death. Research has shown that traffic-related air pollution exposures increase oxidative stress and inflammation of airway epithelial cells.

However, the effects of live aerosol WS exposure on human lung cells is underexplored.

Hypothesis: We hypothesize that exposure to high levels of WS will elevate oxidative stress levels and increase airway epithelial cell death likely through increasing inflammation.

Methods: Immortalized human lung epithelial cells (BEAS-2B) were exposed to fresh woodsmoke aerosol generated from untreated dried cedar that was combusted in a quartz fire tube. WS was delivered to cell cultures using a Cultex live aerosol delivery system. Particle counts and gases (NO, NO2, NOx, CO, CO2) were measured in real-time, with cells being exposed to ~1000 µg/m3 for one hour. Oxidative stress and cytotoxicity were measured 24 hours post-exposure using fluorescent lipid peroxidation, MTT and Calcein AM assays.

Results and Conclusions: Significantly increased cytotoxicity and oxidative stress were observed in BEAS2B cells 24 hours post-exposure compared to filtered air controls. These harmful effects on cells that line the lungs demonstrate how WS may be deleterious to human lung heath. Unfortunately, the infiltration of wildfire smoke plumes into cities and communities throughout Western Canada will continue to increase as global temperatures continue to rise and prime more intense fire seasons. This concerning trend underlies the importance of understanding the impact of these exposures on human respiratory health.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #29 Jasleen Grewal, Undergraduate Student, Queen’s University Supervisor: Jonathan Bush, Childhood Diseases

Congratulations to Jasleen on receiving a BC Children’s Hospital Research Institute Childhood Diseases Summer Studentship

Immunohistochemical Assessment of Methylation Status in Ewing Sarcoma Jasleen Grewal, Veronica Chow, Suzanne Vercauteren, Jonathan Bush

Background: Ewing sarcoma (EWS) is a classic small blue round cell tumor that typically grows in bone or soft tissue surrounding bone. EWS is the second most common bone malignancy in children and accounts for approximately 2% of all childhood cancer diagnoses. EWS is a highly aggressive tumor characterized by early metastatic spread and is associated with a disease-defining gene fusion between EWSR1 and several partners. The fusion transcript is hypothesized to be at the center of potential epigenetic regulation. It is postulated that the transcript may be regulated by methylation profiles, indicating that some tumors with a similar fusion transcript could behave differently based on their methylation profile and the fusion transcript may play a role in chromatin remodeling. Substantial epigenetic heterogeneity has been found within EWS tumors, particularly in patients with metastatic disease. DNA methylation differences between tumors have identified a continuous disease spectrum underlying EWS. Objective: The purpose of the project is to explore the methylation status of common histones using clinically available antibodies and provide an immunohistochemical signature for EWS using markers of closed or open chromatin (H3K4, H3K9, H3K27 methylation and acetylation, respectively) as well as a marker of chromatin condensation and a marker of instability (Histone H3 Serine 10 phosphorylation). The second objective is to determine if there is a marker of chromatin structure that can provide prognostic information such as disease response to therapy or risk of recurrence or metastasis.

Methods: Clinical and radiologic information was obtained for patients with Ewing sarcoma where formalin-fixed, paraffin-embedded tissue from primary biopsies was available. Two tissue microarrays (TMAs) were created using tumor samples from 45 EWS patients. The TMAs will be stained with antibodies to examine the methylation status of Histone H3 at H3K4, H3K9, and H3K27, their respective acetylation status, and Histone H3-S19phos.

Significance: Identifying methylation patterns that can be both disease-specific and prognostic using immunohistochemistry (IHC) provides a cost-effective method that is deployable throughout many pathology laboratories. Studies exploring histone methylation by IHC are currently absent from the literature.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #30 Nicole Katz, Undergraduate Student, University of British Columbia Supervisor: Angela Devlin, Healthy Starts

Congratulations to Nicole on receiving a NSERC Undergraduate Student Research Award

The Role Riboflavin in Cardiometabolic Health Nicole Katz, Rosie Papp, Angela Devlin

Background: We previously reported that ~40% of women of child-bearing age in Vancouver have biochemical riboflavin deficiency (EGRaC >1.4). Riboflavin is a water-soluble vitamin that functions as the enzymatic cofactors flavin adenine dinucleotide (FAD) or flavin adenine mononucleotide (FMN) in multiple redox reactions and energy metabolism. For example, fatty acid beta-oxidation, acetyl-CoA and coezyme Q synthesis, and the electon transport chain require riboflavin. Furthermore, riboflavin supplementation has been shown to lower blood pressure in adults with hypertension. However, little is known about the role of riboflavin in regulating blood pressure and other cardiometabolic parameters.

Objective: To determine the role of dietary riboflavin in cardiometabolic health.

Methods: Male and female Nos3+/+ and Nos3-/- (C57BL/6J) mice were fed a control diet (6mg riboflavin/kg diet) or a riboflavin deficient diet (1 mg riboflavin/kg diet) from weaning for 8 weeks (n=8-10 mice/sex/diet/genotype).

Nos3-/- mice have no endothelial nitric oxide synthase, an enzyme that uses FAD to produce nitric oxide. Ear-notch DNA was used to genotype Nos3 by PCR. Blood pressure is measured at 4 and 8 weeks by a tail cuff (CODA); body composition is measured at 8 weeks by EcoMRI; and body weight and non-fasting blood glucose measured weekly.

The liver, pancreas, and gonadal and inguinal fat pads were collected at the end of the 8-week feeding period.

Results: Studies are ongoing and not all data have been collected; preliminary data are presented. Mice fed the riboflavin deficient diet had lower serum riboflavin concentrations than mice fed the control diet. Riboflavin deficient female Nos3+/+ (n=10) and Nos3-/- (n=5) mice had lower body weight (p<0.01) and smaller gonadal fat pads (p=0.01) compared to control female Nos3+/+ (n=5) and Nos3-/- (n=4) mice. Riboflavin-deficient Nos3+/+ female mice had larger pancreas than control Nos3+/+ mice. Whereas, riboflavin-deficient Nos3-/- mice had smaller pancreas compared to control Nos3-/- mice mice. No differences were observed in male mice. Experiments are ongoing to investigate the effect of riboflavin on a- and b-cell mass in female mice using immunohistochemistry.

Significance: This research provides insight on the sex-specifric role that riboflavin plays in overall metabolism.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #31 Parsa Khanbadr, Undergraduate Student, University of British Columbia Supervisor: Christopher Maxwell, Childhood Diseases

Congratulations to Parsa on receiving a BC Children’s Hospital Research Institute Summer Studentship

Validating an Ex Vivo Model of Alveologenesis in Mouse Mammary Epithelial Organoids Parsa Khanbadr, Ryan Ghorayeb, Christopher Maxwell

Background: The mammary gland undergoes changes in a cyclical fashion. During pregnancy, the mammary gland becomes primed to produce and secrete milk in a process called alveologenesis, which generates alveolar cells.

These alveolar cells are binucleated and arise due to failed cytokinesis. Additionally, alveolar cells produce lipids during pregnancy in response to lactogenic hormones, such as prolactin. There is also an upregulation of the beta casein (Csn2) and whey acidic protein (Wap) transcripts during alveologenesis, two proteins found in milk. To represent this process of alveologenesis accurately ex vivo, 3D cell models, called organoids, can be used. Culturing cells in 2D is predominantly used in research settings to perform experiments, however this method limits how phenotypes can be represented.

Organoids have been able to partially overcome this limitation as they offer an alternative way of replicating animal and human characteristics in the lab. Culturing cells in 3D encourages the multi-directional proliferation and differentiation of cells that occurs in vivo. Similar to 2D cultures, organoids are easily manipulable and offer more efficient means of obtaining data compared to in vivo experiments with animals.

Hypothesis: I hypothesize that culturing primary mouse mammary epithelial cells in 3D and adding lactogenic stimuli will allow us to represent in vivo characteristics of alveologenesis accurately ex vivo.

Methods and Results: Mammary epithelial cells were dissociated from a virgin BLG Cre BRCA122-24f/f; Trp53+/- mouse and transduced with lenti-EGFP. They were next sorted using fluorescence-activated cell sorting and then grown in 3D culture for 10 days. At day 10, organoids were either cultured in the same medium for 4 days, or exposed to prolactin for 4 days.

Organoids grown in lactogenic stimuli are larger, develop binucleated cells and lipid droplets, and upregulate Csn2 and Wap. Significance: This study will allow us to perform future experiments with organoids that have mutations in breast cancer early onset 1 (BRCA1) to understand the potential role that this gene plays in alveologenesis.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #32 Emily Mei Yi Kon, Undergraduate Student, University of British Columbia Supervisors: Genelle Healey & Kevan Jacobson, Childhood Diseases

Congratulations to Emily on receiving a Canadian Association of Gastroenterology Summer Studentship

The impact of fermentable fibre on disease outcomes in a mouse model of ulcerative colitis Emily Kon, Genelle Healey, Kevan Jacobson

Background: In ulcerative colitis (UC), a key feature is a defective colonic mucus layer. Muc2-/- mice are suited to model UC as they lack intestinal mucus. In Muc2-/- mice, luminal bacteria translocate from the gut lumen resulting in spontaneous colitis by 12-16 weeks of age. Additionally, wildtype mice fed fermentable fibre-free (FF-free) diet display a thinner mucus layer, increased susceptibility to bacterial infections, and microbiome shift from fibre-utilizing to mucus-degrading bacteria.

Aim: To determine the effect of fermentable fibre on disease outcomes in a UC mouse model by observing whether feeding newly weaned Muc2-/- mice FF-free versus Chow or inulin-enriched (IN) diet leads to more rapid development of spontaneous colitis and total bacteria concentrations alterations.

Methods: Newly weaned Muc2-/- (KO) or +/+ (WT) mice (3-4 weeks old) were fed one of three diets: 1) normal chow (Chow; 14.7% fibre mix), 2) FF-free (10% cellulose – poorly fermented), 3) IN (same nutritional content as FF-free, with 10% inulin instead of cellulose). Disease activity was monitored daily. At day 10, Muc2 KO mice fed FF-free diet developed severe colitis requiring euthanization. Mice colonic tissue were collected for histopathological scoring.

Stool was collected to determine total bacteria concentration.

Results: FF-free-fed Muc2 WT and KO mice had shorter colons compared to IN-fed mice (p<0.05 and p<0.0001, respectively). Muc2 KO FF-free-fed mice had higher disease activity scores (p<0.0001) compared to IN and Chowfed Muc2 KO mice as well as FF-free-fed Muc2 WT mice (p<0.0001). Histopathological scores were higher in FF-free versus Chow (p<0.0001) and Muc2 KO IN-fed mice and FF-free-fed Muc2 WT mice (p<0.0001). IN-fed Muc2 WT mice had significantly higher total bacteria concentrations compared to Muc2 WT Chow (p<0.05) and FF-free-fed mice (p<0.0001) as well as Muc2 KO IN-fed mice (p<0.0001). However, there were no significant differences in total bacteria concentrations between Muc2 KO mice irrespective of diet.

Conclusion: Within 10 days (5-6 weeks old) of weaning, spontaneous colitis is observed in FF-free-fed Muc2 KO mice.

Chow or IN-fed mice displayed minimal to no signs of colitis, respectively. These findings will help future studies in UC patients to determine whether fibre-rich diets improve disease outcomes.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #33 Colette Newby, Undergraduate Student, University of British Columbia Supervisor: Angela Devlin, Healthy Starts

Congratulations to Colette on receiving a Canucks for Kids Fund Childhood Diabetes Laboratories Summer Studentship

Characterizing Vascular Damage at Type 1 Diabetes Diagnosis Colette A. Newby, Taylor A. Ricci, Angela M. Devlin

Background: Type 1 diabetes (T1D) is an autoimmune disease typically diagnosed in childhood and is characterized by the destruction of pancreatic beta cells and a loss of insulin production. Cardiovascular disease is a major complication of T1D; individuals with T1D have a 10-fold higher age-relative risk of cardiovascular disease compared to those without T1D. Traditionally considered a long-term complication manifesting in adulthood, our research has found that children who have been diagnosed with T1D for less than two years already have indicators of vascular damage, including blood pressure abnormalities and greater arterial stiffness. However, it is unclear when the vascular damage starts and what factors trigger the damage.

Objective: To characterize the chronology and pathophysiology of vascular damage in a mouse model of T1D. Methods: Mice heterozygous for a variant in the insulin 2 gene (Ins2+/Akita) were weaned on to a control diet and studied when blood glucose reaches >16.6 mmol/L (age 4 weeks in males; age 6 weeks in females) to represent the time of diabetes onset; and after 4 weeks of uncontrolled hyperglycemia (age 8 weeks in males; age 10 weeks in females) to represent the time of diabetes diagnosis. Blood pressure was measured by a non-invasive tail cuff (CODA). Body composition was assessed by echoMRI. Genotyping of the Akita allele was conducted on ear notch genomic DNA by real-time PCR. Preliminary Results: We have established a breeding colony of male Ins2+/Akita mice bred with female Ins2+/+ mice on a C56BL/6J background. I have optimized DNA extraction from ear notches and the Akita allele genotyping. We monitor the body weight and blood glucose of the mice on a regular basis. To date, data on blood pressure and body composition have been collected from n=2 female Ins2+/Akita mice and n=1 female Ins2+/+mouse. The studies are ongoing and we are continuing to the breed the mice and monitor the offspring blood glucose, blood pressure, and body composition. We collect tissue at the different time points including serum, aorta for scRNAseq, kidney, and visceral (gonadal fat pads) and subcutaneous (inguinal fat pads) adipose tissue.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #34 Kenzie Wrightson, Undergraduate Student, University of British Columbia Supervisors: Yi-Chun Chen & Bruce Verchere, Childhood Diseases

Congratulations to Kenzie on receiving a Canucks for Kids Fund Childhood Diabetes Laboratories Summer Studentship

Role of carboxypeptidase E in pancreatic beta cells during the development of diabetes Kenzie Wrightson, Yi-Chun Chen, Bruce Verchere

Introduction: Carboxypeptidase E (CPE) is an enzyme that facilitates the conversion of prohormones into mature hormones, like insulin, by cleaving basic C-terminal amino acids. In humans, CPE mutations have been identified and carriers of these mutations have elevated plasma proinsulin and develop severe obesity and hyperglycemia. Similarly, Cpe whole-body knockout mice and Cpe mutant mice become obese and have elevated glucose levels.

Objective: We aim to determine the roles of CPE in beta cells during the development of an experimentally induced form of diabetes in mice.

Methods: Ten-week-old βCpeKO and Wt mice were treated with multiple low dose streptozotocin (MLD-STZ) or saline (35 mg/kg body weight, daily for 5 days) to induce diabetes. Ten days after the last treatment, mouse pancreata were collected to examine beta cell function and identity markers, such as insulin, glucose transporter 2 (Glut2), and aldehyde dehydrogenase 1 family member A3 (Aldh1a3), via immunofluorescence staining and semi-quantitative image analysis.

In addition, islet cells from beta cell specific CPE KO (βCpeKO; Cpeflox/flox x Ins1Cre/+) and littermate wildtype (Wt; Cpeflox/flox x Ins+/+) mice were treated with high glucose (25mM) media to induce insulin secretory stress. Transcript levels of key glycolysis elements, mitochondrial biogenesis regulators, beta cell functional markers, and cell proliferation markers were analyzed.

Results: After multiple low dose streptozotocin treatment, βCpeKO mice had accelerated development of hyperglycemia, and showed reduced insulin and Glut2 levels in beta cells. Upon high glucose challenge, islet cells from βCpeKO mice showed reduced MafA and elevated Aldh1a3 transcript levels.

Conclusion: These findings suggest that Cpe and proper insulin processing are critical in maintaining beta cell function during increased secretory stress. Additional studies are needed to fully elucidate the role of CPE in the development of diabetes and the knowledge obtained will aid the discovery of new therapeutic targets to preserve beta cell function prior to the onset of diabetes

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #4 | Poster #35 Conghao (Tony) Zhang, Undergraduate Student, University of British Columbia Supervisor: Bruce Vallance, Childhood Diseases

Congratulations to Tony on receiving a BC Children’s Hospital Research Institute Summer Studentship

Effects of inulin on Muc2-deficient in vitro model Conghao (Tony) Zhang, Vivian Han, Genelle Healey, Bruce Vallance

Background: The gastrointestinal tract is lined by the gut epithelium which contains a plethora of distinct cell types.

Among these, goblet cells (GCs) are the sole producers of mucus, which acts as the physical barrier against pathogens supported by a mucin 2 (Muc2) protein backbone. It is known that diets deficient in dietary fibre can lead to mucus and epithelial defects; for susceptible individuals, they may lead to pathogenesis of inflammatory bowel diseases. Inulin, a commercially available prebiotic dietary fibre, has been shown to alleviate inflammation and promote epithelial barrier integrity in face of damage in vitro in traditional cell culture. Previous research by our lab has shown that Muc2-deficient mice fed with inulin presented fuller goblet cells than the same untreated mice.

Aims: We aim to investigate if inulin co-culture could induce changes in tight junctions, epithelial morphology, and goblet cell differentiation in 3D organoid models, a model which better represents the in vivo environment. We hypothesise that inulin co-culture will positively change expression of tight junction proteins and induce goblet cell maturation.

Methods: Murine distal colon epithelial stem cells (Muc2+/+ or Muc2-/-) were harvested and grown into organoids for two experiments: monolayers grown under air-liquid interface (ALI) system to investigate GC differentiation or polarityreversed apical-out organoids investigate changes in tight junction. Inulin was resuspended into the growth medium at 2.5% or 5% and co-cultured for 2 weeks, or 3 days, respectively. Samples were collected for western blotting or immunofluorescent staining.

Results: In the ALI system, Muc2-/- goblet cells were able to produce but not secrete glycosylated protein. However, basally supplemented inulin led to severe morphological defects and decreased epithelial viability. Through the apicalout organoid system, tight junction protein occludin expression increased in Muc2-/- after inulin supplementation, suggesting that inulin could induce higher production of tight junction proteins as a protective effect on epithelial integrity.

Conclusions: With Muc2-deficiency, inulin supplied at a low concentration may have a beneficial effect on the affected gut. It may be useful to extend this model to human patient organoids to better test whether inulin could have a significant protective effect therein.

Watch In-Person: Thursday, July 28 | 10:00 - 11:40 am | Chieng Family Atrium, BCCHR

Session #5: In-Person CLINICAL & POPULATION HEALTH Moderator: Irina Simin Participants: Evelyn Armour Aysha Ayub Vicky Cao Ella Chan Sanya Grover Lindy Moxham Bachviet Nguyen Maiya Rasheed Kendrew Wong

Watch In-Person: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 10:00 - 11:30 am Chieng Family Atrium, BC Children’s Hospital Research Institute

Session #5 | Poster #36 Evelyn Armour, Master’s Student, University of British Columbia Supervisor: Ruth Grunau, Brain, Behaviour & Development

Early exposure to sedation and analgesia is related to lower brain signaling efficiency and executive functions in children born very preterm at age 8 years Evelyn E. Armour, Mia A. McLean, Anne Synnes, Steven P. Miller, Alexander Weber, Ruth E. Grunau

Introduction: Infants born very preterm (<33 weeks gestational age) are exposed to frequent invasive procedures (~10/day) inducing pain and stress, at a time of rapid brain development. Neonatal pain/stress is associated with changes in brain microstructure and functional cortical activity in children born very preterm at school-age. Few studies have considered the role of sedation and analgesia in long term outcomes. Brain signaling efficiency has been measured by the Hurst Exponent (HE) in resting state fMRI signals. The extent to which neonatal pain/stress may contribute to altered brain signaling efficiency and thus executive functions (EFs) in children born very preterm is unknown.

Objectives: To examine whether in children born very preterm: 1) Neonatal pain/stress, sedation, analgesia, and clinical factors are associated with HE across brain networks at school-age; 2) HE in brain networks are related to executive functions.

Methods: In a prospective longitudinal cohort study, very preterm children were seen at age 8-years for MRI including resting state fMRI (rs-fMRI; TR=3s, 120 volumes) and parents completed the Behavior Rating Inventory of Executive Functions (BRIEF). Of 97 children with rs-fMRI, 64 scans passed quality check (fMRIPrep); we identified 23 robust independent networks from which HE was calculated using Welch’s method. Higher HE values indicate greater signal efficiency. Neonatal chart review included number of invasive procedures (pain/stress), clinical factors (eg. infection) and dosage of morphine and midazolam.

Results: Partial least squares correlation showed that greater morphine and midazolam exposure were related to lower HE in cerebellar, white matter, default mode network (DMN), frontal, executive control (EC), and lateral-visual networks (lambda = 6700.69, tau = .87, p <.001). Lower HE in lateral-visual, parietal, precuneus, lateral-frontal, sensory, DMN, EC, and frontal-temporal-parietal networks was associated with poorer EFs, specifically working memory and shifting (lambda = 28959.41, tau = .98, p <.001).

Conclusion: Early exposure to sedation and analgesia above and beyond neonatal pain/stress is associated with poorer brain signaling efficiency at rest in grey and white matter networks including frontal, DMN, EC, and lateral-visual networks. In turn, lower HE in these and other networks was related to executive functions critical for academic and social success in children born very preterm.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #5 | Poster #37 Aysha Ayub, Medical Student, University of British Columbia

Supervisors: Jonathan Rayment & Catherine Biggs, Childhood Diseases & Healthy Starts

Congratulations to Aysha on receiving a UBC Faculty of Medicine Summer Studentship, Florence E. Heighway Summer Research Award

Impact of early life serum immunoglobulin G on pulmonary outcomes in children with cystic fibrosis Aysha Ayub, Jeffrey Bone, Catherine Biggs, Jonathan Rayment

Background: Cystic fibrosis (CF) is caused by variants in the CFTR gene. This causes buildup of thick mucus in the lungs, making patients susceptible to chronic pulmonary bacterial infection. Antibody-mediated immunity protects against bacterial infections. The main antibody in the lower respiratory tract is immunoglobulin G (IgG). IgG levels vary in early life with a physiologic nadir in infancy. In CF, pulmonary exacerbations (PEx) result in flare ups of bacteria which may require antibiotics and hospital admissions. Even in early life, PEx can lead to lung damage. It is unclear whether factors, such as low IgG, predict severity and frequency of PEx in early life.

Objective: Assess if there is an association between serum IgG levels and clinically relevant pulmonary outcomes in CF patients in the first three years of life.

Hypothesis: Patients with low IgG may be more susceptible to adverse pulmonary outcomes.

Methods: This was a retrospective, quality improvement chart review of children with CF (born on or after January 1, 2012) at BC Children’s Hospital (BCCH). Deidentified demographic data, weight/height, serum IgG, hospital admissions for PEx, microbiology cultures, and antibiotic use were collected. Explanatory variables were mean, first and lowest IgG levels in the first three years of age. Outcome variables were the total number of courses of antibiotics, number of hospital admissions, age at first course of antibiotics, and mean weight z-score. Outcome variables were compared between groups using appropriate statistical tests.

Preliminary Results: Seventy-five CF patients (53.3% male, 73.3% pancreatic insufficient) were identified. The median age (IQR) at diagnosis was 22.5 (18.2) days. The mean serum IgG (g/L) ± SD was 5.47 ± 2.14. Per patient, the median number of IgG measurements was 2 (n=44), the median number of hospital admissions was 1 (n=20), and the median number of microbiology cultures was 19.5 (n=70). Analysis of the association between outcome variables and explanatory variables is ongoing.

Implications: If low IgG levels are associated with increased frequency of PEx, then more urgent immunology review and potential intervention may be needed. If no association is found, then the routine collection of IgG at BCCH will be reconsidered.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #5 | Poster #38 Vicky Cao, Medical Student, University of British Columbia Supervisor: Anita Datta, Brain, Behaviour & Development

Congratulations to Vicky on receiving a BC Children’s Hospital Research Institute Brain, Behaviour & Development Summer Studentship

Infantile Spasms and Trisomy 21: Unfavorable Outcomes with First-line Vigabatrin Therapy Vicky Cao, Peter K.H. Wong, Anita N. Datta

Introduction: Among children with infantile spasms (ISs), those with trisomy 21 (T21) and those with normal development at onset and no identifiable etiology (previously referred to as “idiopathic”) are expected to have relatively favorable outcomes. The study objective is to determine if differences exist in treatment response, relapse, and subsequent epilepsy between these two groups when vigabatrin is used as first-line treatment.

Methods: In this retrospective study, patients were classified into the following groups and clinical features were compared: T21 (n = 24) and IS with normal development at onset and no identified etiology (n = 40; control group).

Results: There was no significant difference in the age of IS onset, sex distribution, or treatment lag between the groups.

The T21 compared to the control group required a higher mean number of anti-seizure therapies (3.6 vs. 1.9, p < 0.001), had more relapses [10 (42%) vs. 4 (10%), p < 0.005)], and had higher risk of subsequent epilepsy [11 (46%) vs. 8 (20%), p < 0.003]. Relapses were often delayed in the T21 group, with a mean of 8 months after IS cessation.

Conclusion: Our results differ from most studies using steroids as first-line treatment where the groups were shown to have similar treatment response and T21 patients had a low risk of relapse and subsequent epilepsy. Therefore, our results suggest that vigabatrin as first-line treatment in T21 with IS may be less favorable than steroids.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #5 | Poster #39 Ella Chan, Medical Student, University of British Columbia Supervisor: Tom Blydt-Hansen, Childhood Diseases

Congratulations to Ella on receiving a BC Children’s Hospital Research Institute Childhood Diseases Summer Studentship

Bye Bye Biopsies? Implications to the clinical use of CXCL10 in pediatric kidney transplant monitoring Ella Chan, Jeffrey Bone, Amy Thachil, Kevin Vytlingam, Tom Blydt-Hansen

Background: Urinary CXCL10 is biomarker for kidney transplant rejection. Measuring rejection through CXCL10 reduces risks, minimizes invasive procedures and may be more sensitive to rejection relative to kidney biopsies. However, guidelines for scheduling and applications of this test are underdeveloped. Understanding that CXCL10 is not exclusive to rejection is key to its clinical application, as increases are also associated with urinary tract infections, BK viremia, and EBV. Objectives: This study aimed to estimate possible cut-points for CXCL10/Creatinine and determine if significant differences between CXLC10 occur in groups with different Banff scores for inflammation (i) and tubulitis (t). We also hypothesized CXCL10 trends may provide more insight than individual results.

Methods: Patients who underwent kidney transplantation and CXCL10 testing were selected from the HOPE-SOT database. Biopsies were grouped according to grade and linked to CXCL10 tests. ROC curves compared each group to “no rejection” to determine cut-points. A repeated measures ANOVA was performed to compare groups. Events were coded and Banff scores compared by clinical situation as “first positive” (FP), “persistently positive” (PP) and “trend to positive” (TP).

Results: Samples were from patients (n=72) aged 10.65±5.61 years at transplant, 61% male sex and 2.20±2.80 years post-transplant. Biopsies were grouped into no rejection (n=36), sub-i inflammation (i0t>=1; i5-9%) (n=5), i1t1 (n=10), i1t>=2 and i>=2t1 (n=14), and i>=2t>=2 (n=7). ROC analysis reinforced the clinical cut-points of 6 and 12 for “low” and “high”, respectively (i>=2 t>=2 ROC AUC = 0.75, 95% CI = 0.58-0.92). The repeated measures ANOVA analysis found a significant difference between the CXCL10/Creatinine values in the subgroups (p=0.021), with increasing CXCl10/Creatinine as acuity scores increase above i1t1. Pairwise analysis comparing i>=2t>=2 (Mean CXCL10/ Creatinine=2.68±0.82) i0t0 (Mean CXCL10/Creatinine=1.20 ± 1.09) had a p-value of 0.002. This analysis showed an insensitivity to i1t1-grade of rejection, as previously reported. Event-coding identified 18 instances of FPs, five PPs and four TPs. Analysis into the differences between these events is ongoing.

Significance: This work demonstrated that CXCL10/Creatinine levels are sensitive to minor changes in both i and t.

Future analysis of serial versus single tests will help inform clinical pathways for CXCL10 testing.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #5 | Poster #40 Sanya Grover, Medical Student, University of British Columbia Supervisor: Christine Loock, Brain, Behaviour & Development

Congratulations to Sanya on receiving a BC Children’s Hospital Research Institute Brain, Behaviour & Development Summer Studentship

Multi-Partner Approach to Place Based Rights Literacy and Action to address Equity, Diversity, and Inclusion

Sanya Grover, Lauren Bondi, Catherine Binda, Sabrina Gill, Amy Beevor-Potts, Will Lau, Alysha McFadden, Damian Duffy, Christine Loock Background: The United Nations’ Convention on the Rights of the Child (UNCRC) outlines the rights of children and youth to develop their greatest potential. Child and youth rights literacy (CYRL) has been identified as a priority by the Downtown Eastside (DTES) community and BC Children’s Hospital Youth Advisory Committee (YAC). Between September 2020 and November 2021, a survey was piloted in partnership with DTES children and youth at RayCam Cooperative Centre to explore their views on the UNCRC. A total of 18 youth, 16 caregivers, and 11 staff members completed the survey. A lack of knowledge of the UNCRC was found within the inner-city neighborhood.

Objectives: 1) Adapt a survey developed by the DTES community to the YAC context; 2) Identify knowledge of and access to rights as outlined by the UNCRC among YAC members.

Methods: Dialogues between the research team and YAC members were held to discuss content and formatting of the UNCRC survey. The survey was adapted to the YAC context and completed by YAC members on Qualtrics from May 2022July 2022. Demographic information and survey results were analysed using descriptive statistics.

Results: In total, 12 YAC members completed the survey, including 11 youth and 1 staff member. The mean age of the youth participants was 22.3 (n=11, min=14, max=29). Prior to participating in the study, 9/12 (75%) of participants did not know or only sort of knew that the UNCRC existed. Overall, 9/12 (75%) participants felt that all or most of their rights were being protected. Participants reported that children and youth of ages 0-10 and 11-14 have the most access to article 31 (rest, play, culture and arts), while 15–24-year-olds have the most access to article 12 (respect for children’s views). Participants reported that children and youth have the least access to article 28 and 29 (education), article 12 (respect for children’s views), and article 23 (support for children with disabilities).

Conclusion: A lack of knowledge of the UNCRC was found, indicating a need for future dialogue and knowledge sharing in the community. These results will inform communities experiencing vulnerabilities on gaps in access and empower advocacy around child rights.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #5 | Poster #41 Lindy Moxham, Medical Student, University of British Columbia Supervisor: James Chen

Congratulations to Lindy on receiving a UBC Faculty of Medicine Summer Studentship

Bubble-Blowing as a Method for Distraction During Pediatric IV Insertion: a Randomized Control Trial for Effectiveness Lindy Moxham, Matthias Görges, Yoelit Lipinsky, Andrew Poznikoff, James Chen

Background: Maximizing patient comfort during the perioperative period is important to improve both patient experience and outcomes. Preoperative stress has been linked to increased pain, use of analgesics, and incidence of postoperative delirium. Methods for reducing perioperative anxiety include pharmacologic methods, distraction methods and parental presence during induction of anesthesia. BC Children’s Hospital uses a combination of all three methods, and used bubble-blowing as a distraction technique until it was identified as a potential infection control issue and eliminated. Some anesthesiologists believe that the current distraction method of video watching is not as effective, particularly in the youngest children.

Objectives: 1. To determine if bubble blowing is a more effective method of reducing pain during IV insertion than video watching, as measured by the Face Legs Activity Cry Consolability (FLACC) scale.

2. To compare child anxiety before and after IV insertion, as measured by the modified Yale Preoperative Anxiety Scale - Short Form (mYPAS-SF).

3. To quantify the rate of distress-free IV starts for both methods.

Methods: The trial is a randomized, controlled, superiority trial involving 120 two- to five-year-old children having IVs inserted in the medical imaging department. Participants will be randomized into two groups: a bubble-blowing group or an iPad video group. IV insertion will take place after the topical anesthetic placed on the child’s hands has had adequate time to take effect. All children will have a baseline mYPAS-SF taken as soon as consent is given and immediately before the IV insertion procedure. A FLACC score will be recorded at the removal of the topical anesthetic, at the moment of skin penetration by the stylet, and once the procedure is complete, either when the occlusive IV dressing has been applied, or after the initial IV insertion attempt has been abandoned.

Analysis: Differences in FLACC scores between the two groups will be determined via a T-test or Wilcoxon rank sum test. Additionally, a linear regression model, controlling for age, sex, and baseline FLACC score, will be used to confirm superiority of the bubble-blowing technique.

Future: Participant recruitment will begin later this summer.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #5 | Poster #42 Bachviet Nguyen, Medical Student, University of British Columbia Supervisor: Quynh Doan, Evidence to Innovation

Congratulations to Bachviet on receiving a BC Children’s Hospital Research Institute Evidence to Innovation Summer Studentship

Language barriers and research at the Children and Women’s hospital (C&W): A current state analysis Bachviet Nguyen, Jennifer Claydon, Britt Udall, Quynh Doan

Background: Research is critical to advance knowledge and improve clinical care delivery for patients and families.

Without sufficient provisions to enable informed consent for research participants experiencing language barriers, they may be disproportionately excluded from participating and benefiting from research. A lack of diversity and inclusion in participants cannot result in equitable research that is generalizable to the population.

Objectives: To improve the quality of research conducted at C&W, we are taking a quality assessment approach to evaluate the current status of 2nd language provisions for non-English proficient participants. We will estimate the proportion of studies that specifically exclude based on language proficiency and among those that do not, describe what 2nd language provisions are implemented to facilitate proper informed consent procedures for participants without English proficiency.

Methods: We accessed the list of studies submitted for research ethics review at C&W from 2017 to 2021. We excluded retrospective studies (no direct engagement with participants) or studies where this information could not be gathered.

Results: Our current state analysis found that among 1670 studies, 878 required interactions with research participants for informed consent processes. 144/878 (16.4%) excluded participants if unable to reliably complete informed consent in English. Among the remaining 734 studies, 6/734 (0.8%) provided translated informed consent documents in at least 1 other language than English and used research-dedicated interpreters for the informed consent process, 50/734 (6.8%) provided translated informed consent documents in at least 1 other language than English and used clinical interpreters, 221/734 (30.1%) planned to use clinical interpreters but had no translated documents, and 16/734 (2.2%) mentioned ad-hoc use of individuals (staff or relatives) who spoke the required language. Finally, 441/ 734 (60.1%) studies did not mention any provisions for language barriers despite not explicitly excluding based on language proficiency.

Significance: While 293/878 (33.4%) of studies engaging participants prospectively have at least partial provisions to facilitate the informed consent procedure for participants without English proficiency, standardization of language provision requirements and institutional support for translation and professional interpretation is necessary to facilitate diverse, inclusive and equitable access to research participation from a language perspective.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #5 | Poster #43 Maiya Rasheed, Master’s Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

Congratulations to Maiya on receiving a NSERC Undergraduate Student Research Award

Predicting variance in behaviour and cognition from task-based fMRI derived functional brain networks Maiya Rasheed, Todd Woodward

Research Objectives: Schizophrenia is a psychiatric disorder that is characterized by positive symptoms such as delusions and hallucinations and negative symptoms such as poverty of speech or flat affect, as well as other symptoms affecting cognition (for example, impaired memory, attention, or executive function). It is a complex disorder and no single cause has been identified. The Cognitive Neuroscience of Schizophrenia Lab has developed a classification framework of twelve task-activated functional brain networks that can be used to identify brain networks that occur in both healthy individuals and schizophrenia patients when attempting a task. In this analysis, the relationship between the hemodynamic responses associated with these brain networks and measures of behaviour (including symptom ratings) and cognition is investigated.

Methods: Two datasets were included in this study; Functional Brain Networks Underlying Probabilistic Reasoning and Delusions in Schizophrenia and Functional Brain Networks Involved in Fluid Intelligence (in prep). Constrained principal component analysis was used with task-based fMRI networks as the G-matrices (predictor variables) and demographics, task performance, symptoms, and cognitive measures as the Z-matrices (criterion variables).

Results: There was a positive association between activity in the visual attention network’s hemodynamic response peak to end slope (r=-0.70) and delusions (r=-0.41) and hallucinations (r=-0.37). There was also an inverse relationship between activity in the auditory attention network in the end timebins of the hemodynamic response and delusions as well as poorer cognitive performance on neuropsychological tests.

Conclusions: Lack of suppressive activity during the peak to end slope of the response in the visual attention network was related to increased delusions and other positive symptoms of schizophrenia such as hallucinations, while increased suppressive activity in the auditory attention network correlated with delusions and decreased cognitive performance.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #5 | Poster #44 Kendrew Wong, Medical Student, University of British Columbia Supervisor: Sylvia Cheng, Childhood Diseases

Congratulations to Kendrew on receiving a BC Children’s Hospital Research Institute Summer Studentship

A retrospective study of pediatric patients treated with proton radiation therapy in Canada Kendrew Wong, Derek Tsang, Craig Erker, Akshdeep Sandhu, Beth Brooks, Dina McConnell, Andrea Lo, Sylvia Cheng

Introduction: Proton beam therapy (PBT) is likely associated with a lower burden of late effects of therapy compared to conventional photon therapy given its ability to limit radiation to normal tissues via its steep dose gradient and its absence of an exit dose. However, PBT is unavailable in Canada. Canadian patients with indications for PBT require out-of-country referral to the US. Currently, there is no published information on proton utilization patterns for Canadian pediatric oncology patients.

Purpose: Our study sought to describe the Canadian pediatric population being referred for PBT and describe outcomes using this treatment modality, including survival and late effects.

Methods: Data was extracted from medical records for pediatric patients treated in British Columbia (BC) and the Maritimes, and the Pediatric Oncology Group of Ontario Networked Information System (POGONIS) database for patients treated in Ontario (ON). Data from remaining provinces are being similarly acquired. Children were eligible if they were diagnosed with cancer at ≤20 years old between 2001-2021 and received PBT with curative intent. Demographics, diagnosis, treatment details, and outcomes were collected in REDCap. Fisher’s exact test or Kruskal-Wallis rank sum test was used to compare PBT details. The Kaplan-Meier method was used to estimate overall survival.

Results: 147 children (56% males) were eligible. The mean age of diagnosis was 7.5 years, with 77 children (52%) from BC. 93 children (63%) had central nervous system (CNS) tumours, with medulloblastoma (19%) being the most common.

Most referrals to Seattle (97.8%) were from BC, while all referrals to Florida and Cincinnati were from ON. PBT variables, such as radiation doses administered and locations targeted, were not statistically significant across different proton facilities for the most common cancers among our cohort, such as medulloblastoma (p>0.9). 5-year overall survival was 79.6%, which is higher than the reference population in the CYP-C database for Canadian children with CNS or solid tumours.

Conclusion: We described Canadian children receiving proton radiation in BC, the Maritimes, and ON, with the most common being medulloblastoma. Overall survival seems to be compatible with population-based data. Future directions include reviewing radiation toxicity data and examining barriers to access.

Watch In-Person: Thursday, July 28 | 10:00 - 11:30 am | Chieng Family Atrium, BCCHR

Session #6: Virtual CLINICAL & POPULATION HEALTH + BASIC SCIENCE Moderator: Emily Schaeffer Participants: Myriam Beaulieu Karen Johal Rebecca Lim Caroline McCamus Ariel Qi Fidan Sadig Tim Song Andrew Wilk Bernice Wong

Watch Virtually: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 1:30 - 3:00 pm www.bcchr.ca/posterday

Session #6 | Poster #45 Myriam Beaulieu, Undergraduate Student, McGill University Supervisor: James Lim, Childhood Diseases

Congratulations to Myriam on receiving a BC Children’s Hospital Research Institute Summer Studentship

Role of α6 Integrin Isoforms in Breast Cancer Cell Metastasis Myriam Beaulieu, Ling Li, James Lim

While most pediatric tumours can be treatable to achieve excellent rates of survival, the prognosis for children with metastatic solid tumours remains dismal. Metastasis is the phenomenon of tumour cells dislodging from the original tumour mass, invading surrounding tissues, entering the blood circulatory system, and ultimately disseminating to distant tissues. At the cellular level, α6 (CD49f) integrin subunit expression has been positively correlated with cancer cell invasion-ability. α6β1 or α6β4 integrins are formed when α6 dimerize with β1 or β4 and enable binding to laminin in the extracellular matrix surrounding the cancer cells, an important step in the process of invasion. Interestingly, the cytoplasmic tail of α6 can be alternatively spliced at the post-transcriptional level, giving rise to divergent isoforms (α6A and α6B). Apart from the isoform respective regulation of stem cell responses to biochemical stimuli and/or biophysical cues, previous research demonstrated that a higher expression ratio of α6B over α6A facilitates breast cancer cell tumorigenesis while higher ratio of α6A expression over α6B supported T cell and macrophage migration.

This project aims to explore expression of total β1 and β4 integrins in MDA-MB-231 α4-chimeric rescue cell lines in order to understand the roles of α6 cytoplasmic tails for each splice variant. Aggressive triple negative breast cancer cell lines were used to express chimeric α4-α6 integrin construct with either α6A or α6B cytoplasmic tail. The expression of both isoforms in MDA-MB-231 cells were confirmed using antibodies targeting α6 cytoplasmic tail sequences. Furthermore, it is expected that the loss of α6 will abolish β4 expression in MDA-MB-231 cells because α6 is the only known partner for the β4 integrin subunit. However, it is also expected that β4 expression will be restored with α6A chimeric construct expression as this α6 isoform supports integrin-ECM interactions (such as α6β4/laminin) in cellular migration. Given the ongoing challenges of clinical management for pediatric oncology patients with metastatic diseases, such fundamental tumour cell biological knowledge is needed towards building a future for improved care and treatment of children diagnosed with malignancies.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #6 | Poster #46 Karen Johal, Undergraduate Student, University of British Columbia Supervisor: Ali Eslami, Brain, Behaviour & Development

Parent versus patient understanding of suicidal crisis: Is a difference in understanding a cause for concern?

Ali Eslami, Karen Johal, Simya Surani, Rawda Tomoum

Introduction: Suicidality is a pressing concern among youth and has increased drastically over the years. Children and adolescents with suicidal ideations largely benefit from support, whether that be emotional or physical. However, there are many barriers that prevent parents from being able to provide effective support. For instance, a discrepancy in their knowledge of their child’s crisis and its causes. Frequently, especially among minority ethnic groups, older individuals lack understanding and knowledge on mental health, such as what it is and how it impacts their child. Therefore, research evaluating parent and patient understanding can be valuable to improve treatment by enhancing support.

Objective: To explore whether differences in initial understanding of the suicidal crisis between the patient and their family is associated with the length of the patient’s stay under psychiatric care.

Methods: We will perform a secondary analysis of a REDCap data registry which has been collecting information about patients admitted to the Child and Adolescent Psychiatry Emergency Unit (CAPE) for short term stabilization of a psychiatric crisis.

Expected Results: We anticipate the outcomes of our project to show that a lack of common understanding between the patient and their family on the cause of the crisis will result in a longer stay under psychiatric care.

Implications: The results of this project can contribute to and allow adjustments in treatment plans to better support patients at risk of suicidality. It can encourage efforts to provide counselling and/or education to patients and their families regarding ways to optimize treatment. Nonetheless, there is little research exploring influences of familial initial understanding and influences on treatment length; therefore, this research can encourage and open the door to exploring this topic further.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #6 | Poster #47 Rebecca Lim, Medical Student, University of British Columbia Supervisor: Clare Beasley, Brain, Behaviour & Development

Congratulations to Rebecca on receiving a UBC Faculty of Medicine Summer Studentship

Effect of clozapine on brain complement C5b9 protein levels Rebecca Lim, Clare Beasley

Schizophrenia is usually treated with second generation antipsychotic medications but around one-third of people living with schizophrenia don’t respond to these antipsychotics. Clozapine is the only antipsychotic medication that has been proven to be effective in people who are resistant to other treatments for schizophrenia. However, clozapine has several side effects that negatively impact health which limit its use, including an increased risk of agranulocytosis, which is a potentially fatal drop in neutrophils, myocarditis, fever, and weight gain. The cause of these adverse effects is unknown, but they may be due to clozapine’s effects on the immune system.

Complement proteins are crucial to the body’s innate ability to defend against pathogens and respond to tissue damage.

There are three ways that the complement cascade can be activated, and the endpoint of all three is the formation of a complex called C5b9, also known as the membrane attack complex. This complex is formed from several complement proteins and can bind to pathogens and kill them. However, too much complement protein can result in the membrane attack complex attacking the body’s own tissue, which can drive immune and inflammatory diseases. If clozapine increases levels of the membrane attack complex, this could be why it has such adverse effects.

Previous research from our lab has shown that rats that were given clozapine had increased markers of immune activation, including C-reactive protein and complement C9, in their blood compared to rats that were given saline.

Using the same rodent model, Western blotting was used to determine whether clozapine has a similar effect on immune activation in the brain by comparing levels of the membrane attack complex C5b9 in rats given clozapine, the first-generation antipsychotic haloperidol, or saline.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #6 | Poster #48 Caroline McCamus, Medical Student, Royal College of Surgeons Ireland Supervisor: Mahmoud Pouladi, Childhood Diseases

Leukodystrophy-linked mutant claudin-11 sensitizes cells to endoplasmic reticulum stress-induced death Caroline McCamus, Mahmoud Pouladi

Introduction/Background: The endoplasmic reticulum (ER) is the main site for intracellular calcium storage, as well as protein synthesis and folding. ER stress-induced cell death is a cellular process that is triggered under a variety of conditions in response to disturb protein folding in the ER. There are several diseases associated with ER-stress induced cell death, including Pelizaeus-Merzbacher disease (PMD), a rare, progressive, hypomyelinating condition associated with damage and degeneration of oligodendrocytes in the central nervous system. Patients with PMD show symptoms such as muscular trunk rigidity, spasticity of extremities, nystagmus and strabismus. The mechanisms by which ER-stress-induced cell death leads to disease is still unclear. Stoploss mutations in CLDN11, the gene encoding the tight junction protein claudin-11, have recently been identified as a novel cause of PMD. How mutant claudin-11 causes PMD is unclear. In this project, we sought to test the hypothesis that the PMD-linked stoploss mutations induce ER stress as a result of mutant claudin-11 misfolding, sensitizing to ER stress-induced cell death.

Methods: HEK293 cells with stable expression of wildtype (WT) or mutant (MT) claudin-11 were assessed by Western blot to examine the impact of the stoploss mutations on claudin-11 expression. The Claudin-11 HEK293 cells were also evaluated using assays of cell viability and death at baseline and following treatment with the ER stress induced Thapsigargin (Tg).

Results: Western blot analyses showed that the stoploss mutation causes a shift in MT claudin-11 to a higher molecular weight species and appears to decrease its steady-state levels. Treatment with the ER stressor Tg (3 and 6µM) for 24-48 hours resulted in lower cell viability and higher cell death in MT claudin-11 HEK293 cells compared with WT. Conclusions: Our results indicate that MT claudin-11 sensitizes cells to ER stress-induced cell death, and suggest that ER stress may contribute to CLDN11-induced leukodystrophy. More broadly, ectopic expression of transgenes in immortalized cells can allow the impact of different mutations to be further examined. This can help clarify the impact that specific mutations have on ER function and how ER stress can lead to cell death in cells harbouring mutant proteins.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #6 | Poster #49 Ariel Qi, Recent Graduate, University of British Columbia

Supervisor: S. Evelyn Stewart, Brain, Behaviour & Development

Congratulations to Ariel on receiving a BC Mental Health & Substance Use Services Research Summer Studentship

COVID-19 Era Psychiatric Illness among Canadians: Exploring Intersectionality of Vulnerability Factors

Ariel (Ruo Chen) Qi, John R. Best, Anna MacLellan, Boyee Lin, Cynthia Lu, Zainab Naqqash, S. Evelyn Stewart Background: During the COVID-19 pandemic, Canadians faced unprecedented life challenges. The Personal Impacts of COVID-19 study (PICS) examined predictors for clinically-relevant mental health (MH) outcomes following the first Canadian pandemic wave. PICS identified socioeconomic disadvantage, LGBTQ2S+ status, and lifetime medical diagnoses as predictors for poor MH outcomes. Given the complexities in MH determinants, there remains a need to investigate COVID-era MH outcomes among Canadians through an intersectionality lens, that is, how social identities combine to create unique vulnerability profiles.

Aims:

1) Examine pandemic-era MH outcomes of Canadians, in relation to 2-way identity intersections across ethnicity, gender, LGBTQ2S+ status, education level and poverty.

2) Identify the intersecting identities most vulnerable to poor MH outcomes.

Methods: We analyzed baseline online survey data from 1559 Canadians (age range: 8 to 70+ y), obtained from targeted multi-source recruitment. MH outcome was defined as presence or absence of probable depression, generalized anxiety disorder, obsessive-compulsive disorder and/or pandemic-era suicide attempt. Statistical analyses utilized multivariable logistic regression models, whereby the MH variable was regressed on identity variables and covariates. Ten categorical variables were created to encode for each of the identity intersections. Ten models were constructed to separately examine each intersection. A significance threshold of p<0.005 was utilized to account for multiple testing.

Results and Significance: We found that LGBTQ2S+ Canadians in poverty (Odds Ratio/OR=5.02; p=8.04e-07) experience greater risk for poor MH outcome than those with LGBTQ2S+ (OR=2.07; p=0.00464) or poverty status (OR=2.23; p=1.09e-08) alone. Further, LGBTQ2S+ Canadians with limited education (OR=4.19; p=0.000127) experience greater risk than those with LGBTQ2S+ (OR=1.80; p=0.015468) or limited education status (OR=1.39; p=0.016130) alone. Additionally, those in poverty and with limited education (OR=3.39; p=6.48e-13) experience increased risk compared to poverty (OR=2.07; p=1.26e-05) or limited education status (OR=1.37; p=0.057719) alone. Our results highlight the importance for clinicians and policymakers to consider the intersectionality of vulnerable identities, particularly those involving LGBTQ2S+, poverty and limited education status.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #6 | Poster #50 Fidan Sadig, Undergraduate Student, University of British Columbia Supervisor: Wendy Robinson, Healthy Starts

microRNA Expression In Healthy Human Placenta Fidan Sadig, Nikita, Telkar, Wendy P. Robinson

microRNA are small non-coding RNA molecules that play a role in gene modification. The ones expressed in the placenta - a vital organ developed during pregnancy to facilitate nutrient, oxygen, and waste exchange - can serve as biomarkers to warn about preeclampsia and hypertension, or indicate an optimal progression. However, there is a lack of data on microRNA profiles of healthy pregnancies to serve as a reference point for comparisons to monitor the changes. The aim of my project was to expand the microRNA transcriptome by analyzing their expression in 30 healthy human placenta samples across stages of pregnancy and to compare the results with publicly available data. 17 microRNAs were found to be differentially expressed across all three trimesters. Pathway analysis showed the IL-3 and PRC2 as the top hits.

The variation in expression observed was significantly influenced by trimester, but not by sex. There were 386, 398, 44 differentially expressed microRNA when compared between trimester 2 and 1, trimester 3 and 1, and trimester 3 and 2 respectively. When compared to a public dataset, only one microRNA - hsa-miR-370-3p - showed a similar pattern of expression across trimesters. Furthermore, the variable contributing the most towards expression in the public dataset was a technical one - batch effect. This lack of reproducibility majorly exists due to no standardized method being proposed yet for placental processing and analysis. According to recent research, microRNAs expressed in the placenta also pass into the mother’s blood, and therefore, a simple blood test from the mother can give information about the microRNA levels to access the pregnancy with a non-invasive method. My project adds to the knowledge of microRNA expression in the healthy placenta, with the ultimate goal to be able to detect changes specifically in early pregnancy to ensure healthy progression for both fetus and mother.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #6 | Poster #51 Tim Song, Recent Graduate, Amherst College

Supervisor: Evelyn Stewart, Brain, Behaviour & Development

Improving health outcomes and access to care using digital pediatric mental health services during COVID-19: A systematic review Tim Song, Anna MacLellan, S. Evelyn Stewart

Background: The COVID-19 pandemic has accelerated the implementation of digital mental health services, adapting remotely to address subsequent elevated anxiety and stress levels and remove barriers in accessing care in-person.

While literature broadly suggests success in the implementation of remote healthcare, little is known about remote pediatric psychiatry health outcomes and barriers to care. A particularly vulnerable population due to pandemic-derived developmental challenges, assessing digital mental health service efficacy in children reveals strengths and weaknesses of aspects to strengthen and remaining unreached vulnerable populations. This systematic review of qualitative studies examines the scope of digital mental health services to recognize which populations remain vulnerable to equitably address mental health as a public health crisis and assess feasibility of transitioning digital interventions for postpandemic implementation.

Aim: To identify effectiveness of digital mental healthcare interventions on improving health outcomes and access to care in children during the COVID-19 pandemic.

Methods: PubMed, MEDLINE, and PsycInfo were searched using appropriate search terms to identify English peer-reviewed literature on digital pediatric (population below age 18) mental healthcare during the COVID-19 pandemic (March 2020 - current). Two reviewers conducted initial abstract and title screenings using Covidence, then selected papers for eligibility based on inclusion criteria with discrepancies resolved by a third reviewer. Data such as basic study information, subject demographic data, and study findings (health and delivery outcomes, access to healthcare) were extracted and recorded on a standardized form for inclusion in the final systematic review.

Future Directions: We hypothesize that while digital pediatric mental healthcare broadly improves health outcomes and access to care, its impact is limited on underserved communities including rural, low-income, or non-white children.

Currently in the title and abstract screening stage, this study hopes to determine strengths and limitations of digital mental health services to pursue equitable access to mental healthcare.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #6 | Poster #52 Andrew Wilk, Undergraduate Student, University of Southern California Supervisor: Dan Goldowitz, Brain, Behaviour & Development

The role of genetics in a choline intervention for fetal alcohol spectrum disorder (FASD) in a mouse model Andrew Wilk, Fannia Xu, Cheryl Tan, Samuel Mok, Yasaman Hariri, Jennifer Thomas, Daniel Goldowitz, Kristin Hamre

Background: FASD is the most widespread preventable developmental disability globally, affecting approximately 1-5% of newborns. FASD is caused by fetal ethanol exposure. One result of fetal ethanol exposure is elevated levels of apoptosis in the developing neural tube, and this phenotype is believed to be a significant contributor to the development of FASD. Symptoms of the disorder vary greatly in type and severity, ranging from cognitive or behavioural problems to physical abnormalities affecting organ development and facial features.

Different strains of mice exhibit different susceptibilities to ethanol’s teratogenic effects. Two such strains are C57BL/6(B) and DBA/2J(D) and their resulting BXD recombinant inbred strains, derived from cross breeding the B and D strains.

There is currently no cure for FASD, but early intervention methods are being examined. The nutrient choline has been shown to ameliorate some of ethanol’s teratogenic effects. However, whether choline protects ethanol-induced cell death in the neural tube is unknown.

Purpose: This project employs BXD mouse embryos and three different dose strengths of choline to determine if choline ameliorates ethanol-induced cell death in the neural tube. Furthermore, it tests if choline is equally effective at decreasing levels of ethanol-induced apoptosis in different regions of the neural tube (forebrain and brainstem) and across various BXD genetic strains.

Methods: Pregnant dams at E9.0 are treated with either ethanol or a maltose-dextrin sugar control, and either 0, 100, or 250 mg/kg of choline. 7 hours later, the BXD embryos are extracted, embedded, sectioned, and then stained using a TUNEL assay, so that apoptotic cells (TUNEL+) can be distinguished microscopically. TUNEL+ cells within a region of interest are then counted and the number is divided by the total area of the region to give TUNEL+/mm2.

Preliminary Results: Choline partially protects ethanol-induced cell death in the neural tube. However, its efficacy is not equal in different regions of the neural tube or across different strains of BXD mouse embryos. In other words, the results suggest that choline has region- and strain-specific effects.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #6 | Poster #53 Bernice Wong, Undergraduate Student, University of British Columbia Supervisor: Bruce Vallance, Childhood Diseases

Developing an ex vivo assay to examine composition and functional changes in individual gut microbiome from stool Bernice Wong, Christine McCulloch, Catherine Chan, Ho Pan Sham, Roger Dyer, David Levy-Booth, Bruce Vallance

Within our gastrointestinal tract live millions of microbes that actively interact with our body. The microbiota aids in digestion, protects us from infection, and helps maintain a healthy balance within the intestinal environment.

The microbiota can interact with our body by producing short-chain fatty acids (SCFAs) through bacterial fermentation of indigestible carbohydrates, including inulin and starch, and oligosaccharides, present on mucin. Much research on the most abundant SCFAs, such as acetic, propionic, and butyric acid, shows they are important for the host’s health.

Currently, there are limited methods to investigate an individual’s gut microbiota in a clinical setting. Thus, we sought to establish an ex vivo assay to provide insight into the direct impact of varying substrates on individual gut microbiome and its functionality by analyzing concentrations of SCFAs. In this ex vivo assay, stool samples from human and mice (C57BL/6 mice) were inoculated into varying concentration of Brain Heart Infusion (BHI) broth. Inulin, starch, and mucin were added to the stool cultures to examine their influence on the gut microbiota and SCFA concentrations after 24 hours of incubation. These cultures were incubated in anaerobic conditions to mimic the native oxygen environment in the gut. The microbiome composition was analyzed using 16S sequencing, while SCFA concentrations were determined by gas chromatography-tandem mass spectrometry (GC-MS/MS).

We established that concentrations of 25% BHI or lower are optimal growth media conditions. We observed a shift in bacterial taxonomic distribution after 24 hours of incubation. Testing the impact of inulin, starch, and mucin individually, we found distinctive SCFA concentrations in both human and mice stool after the incubation period. Hence, our assay shows its potential in detecting the composition and functional differences of individual gut microbiota under the presence of differing substrates. In the future, this ex vivo incubation assay may be utilized as a drug testing platform or method of determining the impact of diverse diets on individual gut microbiota composition and SCFA concentrations for clinical use.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #7: Virtual CLINICAL & POPULATION HEALTH Moderator: Martin Prusinkiewicz Participants: Ishmam Bhuiyan Lauren Ho Tina Nguyen Leora Pearl-Dowler Sarra Pirmohamed Rameen Siddiqui Shambo Basu Thakur Ted Zhou

Watch Virtually: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 1:30 - 3:00 pm www.bcchr.ca/posterday

Session #7 | Poster #54 Ishmam Bhuiyan, Medical Student, University of British Columbia Supervisor: Gang Wang

Congratulations to Ishmam on receiving a UBC Faculty of Medicine Summer Studentship

Predictive Biomarkers of Successful Immunotherapy for Renal Cell Carcinom Ishmam Bhuiyan, Spencer Martin, Gang Wang

Renal cell carcinoma (RCC), the most common form of cancer that affects the kidneys, is an immunogenic and angiogenic malignancy, which, in its advanced stages, is treated primarily using immunotherapeutic agents and/or tyrosine kinase inhibitors (TKIs). RCC has several histological subtypes, such as clear cell RCC, chromophobe RCC, and papillary RCC, adding complexity to the treatment of this disease.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block the inhibition of anti-tumour immunity and have demonstrated that they are effective tools in the treatment of advanced RCC. Although ICIs that block that block CTLA-4, PD-1, and PD-L1 have improved efficacy over previous treatments for RCC, resistance to immunotherapy is becoming a significant challenge. Only a subset of patients with metastatic RCC are responsive to these drugs. In order to improve the provision of treatment to RCC patients, researchers have explored whether various biomarkers can be used to predict successful response to immunotherapy.

In this poster, we aim to review biomarkers that are predictive of successful immunotherapy in RCC. For example, we discuss the role of tumour mutation burden in predicting immune resistance and identify mutations that distinguish RCC from other tumour types. We also aim to describe the extent to which tumour intrinsic markers of immune resistance, such as PD-L1, can be used to predict response to ICIs. Relevant features of tumour microenvironments, ecosystems consisting of immune and infiltrative cells that help determine the progression of disease, that are associated with positive responses to immunotherapy are also discussed.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #7 | Poster #55 Lauren Ho, Undergraduate Student, McMaster University Supervisor: Jean-Paul Collet, Brain, Behaviour & Development

Congratulations to Lauren on receiving a BC Children’s Hospital Research Institute Summer Studentship

Assessing the measurement properties of the Child Comprehensive Assessment scale Lauren Ho, Amanda Field, Kaitlyn, Treleaven, Mojgan Gitimoghaddam, Lise Olsen, Stephanie Glegg, Tara Nault, Tyrone Joe-Mayes, William McKellin, Jean-Paul Collet

Background: For children with neurodevelopmental disabilities (NDD), physical activity offers many benefits including motor skill development, improved executive function, social growth, behavioural regulation, mental wellness, and self-confidence.

KidsAction Coaching is an evidence-based program aimed at enhancing physical activity interventions to improve children’s development. A key feature of KidsAction Coaching is the evaluation of multiple dimensions of child performance over time. This evaluation is challenging due to the time-consuming and costly nature of existing standardized scales. To overcome this issue, the Child Comprehensive Assessment (CCA) scale, that assesses dimensions of child development such as behaviour, mental wellness, sleep, and social and cognitive skills, was developed. The CCA scale requires less time to complete and is available free of charge; however, its psychometric properties have yet to be assessed.

Objective: This project is aimed at (i) assessing the reliability of the CCA scale; and (ii) assessing the validity of the CCA scale by comparing CCA scores to those obtained from the Behaviour Assessment System for Children, version 3 (BASC-3) scale, a standardized scale that assesses cognition as well as emotional and behavioural atypicalities in children.

Methods: Between 30 and 40 families with a child with NDD will be recruited to participate in the study. Families with a child enrolled in the FUNdamentals program at SpecialOlympics BC will be contacted via e-mail. Families will confirm their interest, via e-mail response, and provide verbal consent to the research coordinator, via telephone. Following their consent, families will receive a REDCap survey comprised of CCA and BASC-3.

- Validity will be assessed by comparing the CCA and BASC-3 scale scores.

- Reliability will be assessed by inviting families to repeat the CCA survey on REDCap five days later.

Next Steps: This study is currently in the process of recruiting families. After survey data has been collected, statistical analysis will assess the reliability and validity of the CCA scale.

Implications: If the CCA scale is proven to be reliable and valid, it will allow for more frequent evaluation of children’s behavioural, mental, cognitive, and social development during physical activity programming or other clinical situations.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #7 | Poster #56 Tina Nguyen, Undergraduate Student, University of British Columbia Supervisor: Kelly Sandhu

Integrating Research into Clinical Practice: Developing an Educational Video for Healthcare Professionals in Pediatrics Tina Nguyen, Kelly Sandhu

Background: Delivering quality clinical research in hospital institutions is dependent on the engagement of healthcare professionals. However, a major issue faced by Pediatric Academic Health Care Centers is a lack of integration and awareness of research in clinical care. From a scoping review, the main barriers we aim to address that contribute to this disconnect are pediatric nurses’ concerns about overburdening families and their negative attitudes towards pediatric research. Negative views include beliefs that there are no incentives to participate, children should not be research participants, and that research is not included in a staff’s role. Because of these views, a patient’s care team may not see research as a part of their care journey and not share opportunities with the patient. Therefore, patients may miss an opportunity to be involved, and the research team may miss patients to recruit.

Nurses with negative views often feel they are protecting patients, but families often feel differently about research opportunities. From a patient’s perspective, many studies challenge the view of research being a burden. Motivations to take part in research include altruism, hope that the child medically benefits from the research treatment, the opportunity to advance and contribute to medical knowledge, and the desire to learn more about the child’s illness.

There is a clear contrast between nurses’ and families’ attitudes towards research that needs to be bridged.

Objective: To foster a more positive attitude towards clinical research by creating and delivering a short educational video that challenges nurses’ misconceptions, advocate for families’ rights to participate in research opportunities, and increase awareness for researchers to involve nurses in studies.

Methods: Seven healthcare professionals split into two groups: clinical staff with (n=4) and without (n=3) a research dedicated role and two families with research experience participated in a semi-structured interview through Zoom to determine the theme of the video.

Significance: The educational video developed will be shared across pediatric health care centers in Canada, used in staff orientation at BC Children’s Hospital, and entered in the Institute of Human Development, Child and Youth Health video competition.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #7 | Poster #57 Leora Pearl-Dowler, Medical Student, University of British Columbia Supervisor: Tim Oberlander, Brain, Behaviour & Development

Congratulations to Leora on receiving a BC Children’s Hospital Research Institute Brain, Behaviour & Development Summer Studentship

Patient engagement in the development and dissemination of a developmentally-informed, home-based research platform Leora Pearl-Dowler, Katelynn Boerner, Liisa Holsti, Harold Siden, Marie-Noelle Wharton, Tim F. Oberlander

Background: Community-based data collection tools create an opportunity to collect ecologically valid, real-world data and increase accessibility to research participation by underrepresented populations, especially in the context of the COVID-19 pandemic.

Objective: The Living Lab at Home (LLAH) project aims to address barriers to research participation for children and youth across the developmental spectrum by bringing data collection into their own homes.

Methods: The LLAH kit includes 3 modalities of data collection that can be used by multiple researchers to answer a variety of questions: 1) smartphone-reported Ecological Momentary Assessment, including self-report on symptoms, affect, and social context, 2) physical activity monitoring via accelerometer, and 3) saliva collection to measure stress biomarkers cortisol and alpha-amylase. Through engagement activities with parents/youth and investigators/ collaborators (Phase 1; N=24 families), feedback has been gathered regarding perceived barriers and opportunities to ensure that methods of data collection are ethical, feasible, and aligned with patient and family values. Incorporating this feedback, a pilot project is underway (Phase 2) to determine the feasibility and acceptability of use of these methods in children/youth with Cerebral Palsy, Autism Spectrum Disorder, Complex Pain, and Severe Neurologic Impairment (N=10/group). After the 14-day data collection period, feedback will be collected to understand perceived barriers, facilitators, and suggested changes.

Results: Qualitative analysis of Phase 1 interviews identified three key themes based on family feedback about the LLAH concept: 1) flexibility and customization, 2) reciprocity, and 3) opportunity and accessibility. The information gathered will be used to shape recommendations for future research using the LLAH kit and inform adaptations that may be needed to make data collection successful for youth with varying levels of impairment.

Conclusion: The LLAH project will make it possible to investigate the real-world experiences of children and youth outside of a laboratory setting, broadening the scope of research questions that can be addressed and reducing inequities in our research and health care system. Furthermore, this patient-centered approach will encourage children and families to take an active role in research by shaping data collection and dissemination methods, including finding useful ways for patients to interact with their own data.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #7 | Poster #58 Sarra Pirmohamed, Undergraduate Student, Simon Fraser University Supervisor: Ian Pike, Evidence to Innovation

Developing a Case Study for Injury Prevention – Vision Zero Surrey Sarra Pirmohamed, Kate Turcotte, Shazya Karmali, Ian Pike

Background: Injuries are the leading cause of death for people aged 1-44 in BC. Most injuries are preventable, and by taking steps to address causes and contributors, injury rates can be significantly decreased. With approximately 87,000 people injured in a motor vehicle incident each year in BC, road safety plays a large role in injury prevention. Developing case studies for injury prevention provides support for the creation of new legislature, policies, prevention programs, and more.

Methods: Vision Zero is a global initiative that was selected for this case study, with the principle that traffic collisions are not accidents, but are predictable and preventable. To develop the case for injury prevention, the City of Surrey’s Vision Zero Safe Mobility Plan was analyzed to evaluate the effectiveness of specific road safety interventions being implemented over the course of 2019-2023. The Vision Zero Surrey update, among other resources, was consulted to further evaluate the progress of the initiative.

Results: Following the launch of the Vision Zero Surrey initiative in 2019, a decrease in collisions resulting in death or serious injury was recorded, including those involving vulnerable road users (i.e., pedestrians, cyclists, and motorcyclists).

In the past three years alone, there has been a 22% decrease in the rate of these types of collisions. The content for the case study for Vision Zero Surrey was completed, to be added to the collection of case studies as part of the British Columbia Casebook for Injury Prevention.

Conclusion: Vision Zero Surrey has shown measurable steps and successes to realize this vision, and is actively contributing to injury prevention in British Columbia. Once added to the Casebook, this case study will be reviewed by policy makers, senior decision makers, and others to support programming and fund allocation addressing injury prevention.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #7 | Poster #59 Rameen Siddiqui, Recent Graduate, University of British Columbia Supervisor: Ali Eslami, Brain, Behaviour & Development

Congratulations to Rameen on receiving a UBC Faculty of Medicine Summer Studentship

Prevalence and Nature of ADHD Diagnoses Among First-Generation Immigrant Adolescents Visiting CAPE – A Retrospective Cohort Study Rameen Siddiqui, Ali Eslami

Background: Almost every aspect of attention-deficit hyperactivity disorder (ADHD) has been the subject of extensive research, and the diagnostic criteria seem quite straightforward. However, cross-cultural studies have indicated significant differences in the way ADHD symptoms are rated between countries, as well as significant variation in the way children from different cultures are interpreted as having ADHD symptoms. Previous research findings suggest that migrant youth are less likely to access mental health services due to barriers such as stigma, socioeconomic hardships, or language struggles in the host country.

Many studies describe what they refer to as the “immigrant paradox” or the “healthy immigrant effect” in which there is scientific agreement that the prevalence of mental health disorders is lower in immigrant children compared to their native counterparts. A recent 2022 study in BC looked at the prevalence of mental health disorders among immigrant children and is also consistent with this finding for ADHD, however, all studies propose that future research needs to determine why this difference is observed.

Objectives: This study will examine how the prevalence of ADHD diagnoses and associated risk factors differ between Canadian-born and first-generation immigrant adolescents admitted to BC Children’s Hospital’s Child and Adolescent Psychiatry Emergency (CAPE) unit for an acute crisis. We aim to understand if differences in the rate of ADHD diagnoses reflect any barriers to care or cultural biases that first-generation immigrant families may encounter.

Methods: A retrospective chart review will be performed to assess how ADHD diagnoses among both groups correlate with comorbidities, patient psychosocial history, family psychiatric history, and other patient demographics. Data on admission and discharge diagnoses will also be analyzed to provide insight into the frequency of change in diagnosis, including novel ADHD diagnosis, between both adolescent groups.

Expected Results: By analyzing patient data received at CAPE, we can begin to describe the extent to which sociocultural factors impact ADHD diagnosis among Canadian-born and first-generation immigrant children. Expected outcomes include the generation of descriptive and comparative analyses for both populations receiving an ADHD diagnosis at this hospital and understanding the underlying factors behind ADHD diagnoses received in Canada.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #7 | Poster #60 Shambo Basu Thakur, Undergraduate Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

fMRI-CPCA to study the contribution of hyperintensity of functional networks to the blurring of ego boundaries as a characteristic of schizophrenia Shambo Basu Thakur, Crystal Han, Todd S. Woodward

Research Objective: An important aspect of schizophrenia symptomatology is alienation, which can lead to blurring of ego boundaries, or symptoms such as hallucinations and Schneiderian delusions. Our hypothesis was that cognitive processes involved in thought generation contribute to this. Examination of the cognitive operations contributing to thought generation and speech perception can be enhanced using fMRI because the neural regions involved in these cognitive operations are relatively well established. Measurement of functional network activation thus should provide evidence germane to alienation theories. It is important to point out here that there are two main theories to explain the phenomenon of alienation - a top-down process of degradation of thought signals and a bottom-up process of addition of perception to internal attributes.

Method: We collected fMRI data from 15 participants - 10 healthy controls and 5 schizophrenic patients during a task that involved two separate experimental conditions: ● In the silent verbal thought generation condition, participants were required to mentally generate a simple definition of a word. ● In the speech perception condition, participants listened to a simple definition of a word with the word and corresponding object visually presented on the screen.

Extensive pilot testing was carried out to ensure that the nouns included in the experiment evoked consistent definitions, and that when presented with definitions only, the intended target word was produced. fMRI-CPCA, on the basis of these images, generated predictor weights later used to estimate the haemodynamic response associated with each network.

Results: A 6-component solution was proposed from the scree plot and each component was classified after comparing them to existing artefacts. The components and their HDR plots were then analysed independently: ● Components 2 (NDMN) , 5 (NDMN)1, and 6 (TDMN) showed greater activation for speech perception than thought generation. ● Components 1 (EXT) and 4 (TDMN)2 showed greater activation for thought generation than speech perception. ● Component 3 (INT) showed no significant difference between either conditions or groups.

Conclusion: The study found evidence for hyperintensity of functional networks during silent thought generation in schizophrenia however, its contribution to blurring of ego as a characteristic of schizophrenia is yet to be ascertained.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #7 | Poster #61 Ted Zhou, Undergraduate Student, McMaster University Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Congratulations to Ted on receiving a BC Children’s Hospital Research Institute Summer Studentship

Sleep as a Treatment-Emergent Adverse Event in Randomized Controlled Trials Investigating Amphetamines Ted Zhou, Scout McWilliams, Dean Elbe, Sylvia Stockler, Osman S. Ipsiroglu

Introduction: Stimulants are first-line pharmacological interventions for ADHD; however, they can cause sleep disturbances (SD). We previously investigated interventional ADHD randomized controlled trials (RCTs) and sleep as an outcome measure. The majority of identified amphetamine-based stimulant studies reported SD as treatmentemergent adverse events (TEAEs) and were excluded. We conducted a secondary analysis with the goals: (1) identify the incidence rates of sleep-related TEAEs in treatment and placebo/control groups, and (2) evaluate medication timing, administration, and titration schedules.

Methods: Search strategy and used databases for included and excluded studies has been published in 2022 (DOI: 10.1016/j.smrv.2022.10161). Inclusion criteria: (1) study design: RCT; (2) diagnosis: ADHD, (3) Intervention: amphetamine-based stimulant(s), (4) reported sleep-related TEAEs. Results: 33 RCTs reported sleep-related TEAEs: 11/33 were performed in an adult population (n=2029), 22/33 in pediatric populations (n=3917). No adult RCT and only one pediatric RCT specified a validated side effect rating tool. 3/33 studies specified an employed terminology system for TEAE reporting. Three major TEAEs categories were reported: insomnia/ initial insomnia (nadult=11, npediatric=22), fatigue (nadult=5, npediatric=3), and somnolence (nadult=0, npediatric=3). One pediatric study reported early morning awakenings. For adult-TEAEs, incidence rates of insomnia/initial insomnia ranged from 5%-37% vs. 1%-13% and for fatigue from 1%-7.6% vs. 3.7%-12% in the treatment vs. placebo groups; non-restorative sleep/somnolence was not reported. For pediatric-TEAEs, incidence rates of insomnia/initial insomnia ranged from 4.3%-35% vs. 0%-19%, for fatigue 0%-4.3% vs. 2.6%-3.7%, and for somnolence 3.1%-4.7% vs. 3.7%-28.1% in the treatment vs. placebo groups; non-restorative sleep was not reported.

Conclusion: The incidence rates of sleep-related TEAEs are higher in treatment groups than placebo/control groups.

There is a lack of validated sleep-related side effect assessment tools used, and specifying adverse event reporting criteria and/or coding systems was infrequent. Further, the number of participants in amphetamine studies reporting sleep-related TEAEs was 2.8 times higher than in studies reporting sleep as a primary/secondary outcome. Our findings show that sleep is a critical issue that must be monitored, highlighting the need for standardization of sleep-related assessments and inclusion of sleep as an obligatory outcome measure.

Watch Virtually: Thursday, July 28 | 1:30 - 3:00 pm | www.bcchr.ca/posterday

Session #8: In-Person CLINICAL & POPULATION HEALTH + BASIC SCIENCE Moderator: Katelynn Boerner Participants: Madeline Elder Laveniya Kugathasan Davy Lau Ying Jie Li Samantha Pang Benjamin Shaw Leo Xu Jennifer Yi Annie Zhou

Watch In-Person: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 1:30 - 3:00 pm Chieng Family Atrium, BC Children’s Hospital Research Institute

Session #8 | Poster #62 Madeline Elder, Medical Student, University of British Columbia Supervisor: Mandeep Tamber, Evidence to Innovation

Congratulations to Madeline on receiving a UBC Faculty of Medicine Summer Studentship

Management of Post-Hemorrhagic Ventricular Dilation: When to Intervene Madeline W. Elder, Isabella Watson, Mandeep S. Tamber

Background: Post hemorrhagic ventricular dilatation (PHVD) is the dilation of the ventricular system that develops as a complication of intraventricular hemorrhage (IVH) of prematurity, occurring in over 30% of children born preterm.

In some children, the ventricular dilation progresses to symptomatic post hemorrhagic hydrocephalus (PHH), which is associated with neurocognitive impairment. Historically, surgical intervention to temporize PHVD and prevent PHH was pursued only when children showed clinical signs of elevated intracranial pressure, associated with a grossly dilated ventricular system. However, recent research has suggested that earlier intervention before the onset of symptoms may decrease the need for permanent cerebrospinal fluid (CSF) diversion and improve neurodevelopmental outcomes.

Inspired by these findings, BCCH implemented an early approach protocol to PHVD in 2019. This early intervention approach uses frequent ultrasound imaging to intervene when ventricle size reaches a predefined threshold, instead of waiting for symptoms to develop.

Aim: The goal of this quality improvement project is to determine whether the management of children with PHVD based on ventricular size instead of clinical symptoms results in improved outcomes, such as a reduced need for permanent CSF diversion and improved neurocognitive development. This project also examines the complication profile and resource demands of this more intensive approach.

Methods: A retrospective chart review was conducted of patients at BCCH who sustained grade 3-4 IVH resulting in PHVD and requiring intervention between 2018 and 2022.

Results: 15 eligible patients were identified. Of these, 8 had been treated with a late approach, and 7 with the early approach. Of the 8 late approach patients, 7 required a permanent CSF shunt. In contrast, only 3 of the 7 early approach patients required such a shunt. Complication rates were similar between groups. In terms of resource use, ultrasound use was more frequent in the early intervention group.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #8 | Poster #63 Laveniya Kugathasan, Medical Student, University of British Columbia Supervisor: Zöe Brown, Evidence to Innovation

Congratulations to Laveniya on receiving a UBC Faculty of Medicine Summer Studentship

Does non-invasive microcirculation monitoring using near-infrared spectroscopy during scoliosis correction surgery help inform blood transfusion? – Results of a prospective observational study Laveniya Kugathasan, Roan Raina, Nicholas West, Matthias Görges, Zoë Brown

Background: Anesthesiologists play a critical role in ensuring perioperative patient safety, including deciding if blood transfusion during surgery is needed. Blood transfusion can be required during scoliosis surgery, which is associated with significant blood loss. At BCCHR, no transfusion guideline exists and thus decision depends on the individual anesthesiologist’s clinical judgment. Near-infrared spectroscopy (NIRS) can be used to measure capillary and venous oxygenation. The goal of this study was to explore the utility of NIRS as a guide in deciding the need for blood transfusion.

Objective: To explore the temporal characteristics of cerebral oxygenation (ScO2) and muscle oxygenation (SmO2) in response to intraoperative blood loss and blood transfusion and to determine ScO2/SmO2 thresholds associated with clinically-determined blood transfusions.

Methods: A prospective, observational, single-blinded pilot study in children undergoing single-stage scoliosis correction surgery was completed (N=48). NIRS sensors were placed on the forehead to measure ScO2 and on the forearm for SmO2.

Anesthesiologists were blinded to NIRS values. ScO2/SmO2, mean arterial pressure (MAP), and heart rate (HR) data were collected throughout the procedure. Values before and after intraoperative transfusions were compared. Absolute NIRS thresholds below 70 and 65 were explored for their ability to predict blood transfusion. Relative thresholds, against a baseline value from 30 min after the patient went prone, of -10 and -20 units were also considered as a personalized approach.

Results: Data from the 22/48 children who received 31 blood transfusions were analyzed: 10 females, median (interquartile range) age 16.4 (13.7-17.9) years, weight 50.7 (40.7-62.0) kg. ScO2, SmO2, and MAP increased with transfusions (p=.01, p=.02, p=.005 respectively), and HR did not decrease (p=.2). Absolute ScO2 values did not help predict transfusions (p=.25 and .30 respectively), and neither were relative ScO2 changes (p=.50 and .61 respectively).

Both suffered from high false negative detection rates.

Conclusion: We were unable to demonstrate associations of absolute and relative NIRS changes in predicting intraoperative blood transfusions, which would be needed to identify its feasibility for use as a transfusion success predictor. While NIRS may have some use in monitoring physiological changes during intraoperative interventions, further research is needed.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #8 | Poster #64 Davy Lau, Medical Student, University of British Columbia

Supervisors: Faizal Haji & Erika Henkelman, Evidence to Innovation

Congratulations to Davy on receiving a BC Children’s Hospital Research Institute Summer Studentship

Improving Assessment and Training in Craniosynostosis: The Role of Interactive 3D Models and Multimodal e-Learning

Davy Lau, Faizal Haji, Erika Henkelman, Douglas Courtemanche, Belinda Dundon, John Jacob, Mandeep Tamber, Saoussen Salhi, Ash Singhal, Isabella Watson Background: Craniosynostosis (CSO) refers to the premature fusion of a child’s suture lines, leading to distinct head shape differences. Early diagnosis is important, as CSO not treated with surgery can lead to increased intracranial pressure, and surgeries done early are generally less invasive. However, CSO can be confused with non-synostotic, non-surgical head shape differences, leading to incorrect diagnoses delaying treatment, or unnecessary referrals and parental anxiety.

Traditionally, the diagnosis of CSO is taught using didactic methods and during clinical encounters with infants presenting with an abnormal head shape. However, the relative rarity of CSO (1 in 2000-2500 births) limits the clinical exposure required to develop diagnostic accuracy. Creating an e-learning platform for physicians, with examples of CSO and non-CSO head shapes, can help address this educational gap. Specifically, interactive e-learning modules with 3D representations have been shown to be effective at teaching anatomical concepts.

Objectives: 1. Develop a customized, multimodal e-learning course augmented with interactive 3D virtual models for teaching postgraduate trainees how to clinically identify non-syndromic CSO and non-synostotic cranial asymmetry.

2. Develop and generate validity evidence for an instrument to assess a trainees’ CSO diagnostic accuracy.

3. Evaluate the efficacy of e-learning augmented with 3D virtual models versus e-learning utilizing 2D visualizations or didactic methods in improving postgraduate trainees’ CSO diagnostic accuracy.

Methods and Next Steps: First, we are examining the available literature on the components of effective medical education, how CSO is currently taught in medical training, and the use of interactive 3D representations in medical education. Concurrently, we are recruiting patients presenting with CSO and non-synostotic head shape differences, to have their pictures taken at the BCCH Digital Lab, to be converted into 3D interactive virtual models.

Next, the e-learning platform will be created with a multi-disciplinary team, combining the tenets of effective medical education with the 3D interactive virtual models. An identical platform will be created, but without the 3D models.

After creation of a tool to assess learners’ diagnostic accuracy, the two platforms will be disseminated to medical residents, to compare the efficacy of the platforms with and without 3D representations.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #8 | Poster #65 Ying Jie Li, Undergraduate Student, University of British Columbia Supervisor: Pascal Lavoie, Healthy Starts

Congratulations to Ying Jie on receiving a BC Children’s Hospital Research Institute Healthy Starts Summer Studentship

Characterizing neonatal CD4 T cells expressing mitochondrial biogenesis-related transcription factor, PGC-1α Ying Jie Li, Martin Prusinkiewicz, Christina Michalski, Claire Cheung, Bethany Poon, Pascal Lavoie

Compared to the adult immune system, the immune responses of neonates tend to be primed towards immunotolerance (Treg) and humoral/mucosal (Th2/Th22) rather than cellular helper (Th1/Th17) responses. This may prevent energetically costly proinflammatory responses during development. However, this could increase neonates’ susceptibility to infectious diseases which are not a concern to healthy immunocompetent adults.

These differing helper responses could partly be explained by the distinct nutrient and oxygen-limited environment in utero. Our preliminary data shows that the expression of cellular respiration-related genes differs between neonatal and adult CD4 T cells; and, the number and activity of mitochondria in adult CD4 T cells exceeds those in neonates. We aim to investigate whether neonatal CD4 T cells exhibit less cellular respiration than adult CD4 T cells and whether increased mitochondrial biogenesis in neonatal CD4 T cells will lead them to become more adult-like. We hypothesize that induced mitochondrial biogenesis in neonatal CD4 T cells will cause them to become more functionally similar to adult CD4 T cells.

Differing mitochondrial activity between neonates and adults was confirmed after Seahorse Extracellular Flux analysis experiments were performed on naïve CD4 T cells isolated from cord and adult blood. Neonatal CD4 T cells appeared to have less maximal mitochondrial respiration than adult CD4 T cells. Additionally, our preliminary results show reduced mRNA expression of a transcriptional co-activator responsible for mitochondrial biogenesis, PGC-1α, in neonatal CD4 T cells. We will determine whether this metabolic phenotype is reversible by overexpressing PGC-1α in neonatal CD4 T cells. PGC-1α was amplified and cloned in a pBK-CMV blue/white vector. Sequencing of successful transformants confirmed our insert. We are currently cloning PGC-1α in a pCCL lentivirus transfer vector.

Once we have generated a lentivirus vector which we will use to endogenously express PCG-1α in naïve neonatal CD4 T cells, we will characterize their mitochondrial and immunological function in comparison to adult CD4 T cells.

If alterations to the metabolism of neonatal T cells confer more adult-like immune function, immunometabolism could be an avenue for modulation of immune function in CD4 T cells to help protect infants from serious disease.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #8 | Poster #66 Samantha Pang, Undergraduate Student, University of British Columbia Supervisor: Christopher Badenhorst

Congratulations to Samantha on receiving a Biotalent Canada Award

Self-reported clinical practice and attitudes about cricoid pressure among pediatric anesthesiologists in Canada Samantha Pang, Christopher Badenhorst, Nicholas West, Andrew Poznikoff, Stephan Malherbe

Background: For patients undergoing general anesthesia, gastric regurgitation is a significant source of complications and morbidity. One technique to prevent gastric regurgitation is cricoid pressure (CP), though it is a controversial technique in today’s anesthesia practice.

Objective: This study aimed to characterize Canadian pediatric anesthesiologists’ views on the use of CP, their perception of its harms and benefits, and their opinion regarding relevant medico-legal and professional concerns.

Methods: The study survey was created in REDCap, and it was tested and approved by the Canadian Pediatric Anesthesia Society (CPAS) committee. CPAS members received the public survey link via the CPAS newsletter in the summer of 2020.

The survey link was open for three weeks, and responses were collected anonymously. Data was then downloaded and analyzed using Excel.

Results: There were 58 respondents, of which 8 were excluded due to incomplete responses. Overall, 38/50 (76%) respondents indicated that they would not use CP for pediatric patients with an increased risk of gastric regurgitation and 32/50 (64%) believed that clinicians should exercise individual judgment about the use of CP in routine practice.

Of those who did not routinely use CP, 27/38 (71%) believed there is a lack of research demonstrating the benefits of CP. However, 8/12 (67%) respondents who routinely use CP believed that, while the benefits of CP are uncertain, it carries a minimal risk of harm. Lastly, 31/50 (62%) respondents indicated that the medico-legal and professional consequences of omitting CP do not influence their practice more than their interpretation of the scientific evidence on the harms and/or benefits of CP. Implications/Future Aim: This study suggests that most Canadian pediatric anesthesiologists do not use CP for pediatric patients with an increased risk of gastric regurgitation though a majority believe its use is a matter of individual clinical judgment. These results can be compared to anesthesiologists working with adult populations and may contribute to airway management guidelines.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #8 | Poster #67 Benjamin Shaw, Undergraduate Student, University of Toronto Supervisor: Anamaria Richardson, Brain, Behaviour & Development

Congratulations to Benjamin on receiving funding from PHSA QI, MASES, and the CHILD-BRIGHT SPOR Fellowship

Exams Under Anesthesia (EUA): The Need for Optimized Healthcare in Children with Severe Behavioural Complexities Benjamin Shaw, Boxon Zhang, Anamaria Richardson

Introduction: Many children present with severe behavioural complexities due to varying conditions. This results in typically routine medical investigations (e.g. bloodwork) becoming difficult, necessitating Examinations Under Anesthesia (EUA). Difficulties in coordinating care between various providers results in fragmented service provision and inequitable care, resulting in preventable stress to healthcare workers, patients, and their families. Opportunities exist for optimizing co-ordination of EUA for children with behavioural complexity at BC Children’s Hospital.

Methods: Pediatric patients (age 2-18) with severe behavioural complexities undergoing procedures requiring anesthesia were identified through use of specific tags from the Operating Room (OR) slate during the months of March and April 2022 (n = 200). An in-depth retrospective chart (electronic and paper) review was conducted to collect demographics data, detailed patient specific data (eg. diagnoses, distance to hospital), and procedure specific data (eg. number of procedures, time for induction).

Results: Analysis identified that almost 70% of patients were male, and about 65% were aged 6-15. Almost a quarter lived >100km away from BCCHR, suggesting increased consequences for missed medical opportunities. Many have multiple diagnoses, most commonly autism spectrum disorder and global developmental delay. The types of procedures varied, though the majority were admitted for dental procedures, and many patients had more than one (“add ons”).

Time for induction was notably higher than the preferred average (up to 7% requiring more than 45 minutes). Half of patients had no recorded bloodwork within the last 12 months, and only a third were administered pre-sedation either at home or the hospital before care. Many opportunistic medical examinations were missed. This quantitative data excellently lays the foundation for why an approach to streamline EUA is needed.

Implications This quantitative review emphasized that children with severe behavioural complexities require additional coordination/effort from healthcare providers to reach an equitable standard of care. Future work under the scope of this issue takes on a qualitative perspective (e.g. interviews with physicians and families). Additionally, future research is working on addressing this issue rather than identifying it, such as through algorithms that clearly indicate which medical tests a patient with severe behavioural complexities need.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #8 | Poster #68 Leo Xu, Undergraduate Student, University of Toronto Supervisor: Stefan Taubert, Healthy Starts

Congratulations to Leo on receiving a NSERC Undergraduate Student Research Award

Investigation of the Role of Lipid Metabolism in the Skin-like Hypodermis of C. elegans During Starvation Leo Xu, Brendil Sabatino, Stefan Taubert

The starvation response is an adaptive response to stress induced by a lack of nutrients. In humans, it involves processes such as autophagy and insulin signalling, which is conserved in Caenorhabditis elegans. Adult C. elegans has a simple body plan, consisting of only 959 somatic cells, and has a wealth of tools available to study molecular stress responses making it a useful model organism for this response.

Transcriptomics has been used to understand the starvation response, which varies tissue-by-tissue and is poorly characterized at the tissue level. Our lab RNA sequenced cells from tissues to find tissue-specific transcriptional responses. Compared to the intestines, body wall muscle, and neurons, the hypodermis had the most differentially expressed genes in starvation (54, 175, 212, and 3387, respectively). Surprisingly, the main site of lipid metabolism, the intestine, had no significant transcriptional changes in lipid metabolism between fed and starved states, whereas there was a significant transcriptional change in lipid metabolism in the hypodermis.

Our lab’s previous work with lipid staining found increased hypodermal fat storage compared to wild type in mutant strains with a knockout in cyp-13A7, ace-3, or lbp-1. We theorize that these genes are involved in hypodermal fat metabolism. Starvation survival assays found that lbp-1 and cyp-13A7 had the most deleterious effect on worm starvation survival. Currently, we are investigating if the starvation sensitivity and fat storage defects are solely found in cyp-13A7, a cytochrome P450 ortholog, or if it is also found in other closely related cyp genes. In addition, we are investigating the localization and induction of these genes during starvation using GFP imaging of live worms.

Understanding the genes involved in the starvation response pathway and how they are regulated and misregulated can give insight into human diseases such as cancer and eating disorders.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #8 | Poster #69 Jennifer Yi, Medical Student, University of British Columbia Supervisor: Paul Yong, Healthy Starts

Congratulations to Jennifer on receiving a BC Children’s Hospital Research Institute Healthy Starts Summer Studentship

Interleukin 1-Beta and Nerve Growth Factor as potential biomarkers in endometriosis Jennifer Yi, Dwayne Tucker, Heather Noga, Paul Yong

Background: Endometriosis is a chronic inflammatory disease characterized by the presence of endometrium-like tissue outside the endometrium and myometrium. It affects over 1 million Canadian women of reproductive age, causing significant psychological and financial burdens to individuals and society. Endometriosis is characterized by chronic pain such as dysmenorrhea, dyspareunia, dyschezia, dysuria and pelvic pain. Endometriosis pain is proposed to be driven by neuroangiogenic and inflammatory processes. As part of a larger ongoing work examining prognostic tissue markers for endometriosis outcomes, this study will explore the relationship between Interleukin 1-Beta (IL-1 b) and Nerve Growth Factor (NGF), an inflammatory and neuroangiogenic marker respectively, with endometriosis severity.

Hypothesis: Higher IL-1 b and NGF are positively correlated with more symptomatic endometriosis.

Aim: To examine the association between higher IL-1 b and NGF immunohistochemistry scores and clinical presentation of endometriosis.

Methods: This study will utilize registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort (EPPIC) database at the BC Women’s Centre for Pelvic Pain and Endometriosis. The study will include women who first visited the centre between December 2013 and June 2018 with suspected or confirmed endometriosis. Tissue samples (n=134) were obtained from Endo-Onc biobank and immunohistochemically (IHC) stained for IL-1 b and NGF separately. The Histoscore for each slide was calculated for each biomarker with a set formula of the proportion of positive cells at each tier of staining intensity. Statistical analysis will be done on biomarker scores to measure correlations to the American Fertility Society (AFS) surgical staging, patient-reported pain severity and the EHP-30 questionnaire (quality-of-life).

Anticipated Results: We predict that higher Il-1 b and NGF scores will be associated with worse AFS staging, patientreported pain and quality of life within all three anatomical subtypes of endometriosis.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #8 | Poster #70 Annie Zhou, Undergraduate Student, University of British Columbia Supervisor: Ramon Klein Geltink, Childhood Diseases

Congratulations to Annie on receiving a BC Children’s Hospital Research Institute Summer Studentship

Determining the role of mTOR signaling in rare, devastating infantile-onset liver disease due to LARS1 deficiency Annie Zhou, Annette Patterson, Ramon Klein Geltink

Background: Leucyl-tRNA synthetase (LARS1) is an enzyme that senses intracellular levels of leucine. The catalytic activity of LARS ligates leucine to leucine-tRNA to translate leucine-containing proteins. Children with bi-allelic loss-of-function variants in the LARS1 gene present with devastating multisystemic disorders and failure to grow. Current attempts with therapeutic supplementation of leucine have not shown a benefit to children with this disorder and the unsuccessful management of LARS1 deficient patients has resulted in high mortality for this condition. Therefore, a better mechanistic understanding of the effects of LARS1 loss-of-function is needed. Recently, LARS1 was shown to impact protein translation through the mechanistic target of rapamycin (mTOR) pathway. This project aims to assess the effects of LARS1 loss-of-function in mouse fibroblasts on the mTOR nutrient-sensing signaling pathway, which will generate mechanistic insight into potential therapeutic targets in this devastating disease.

Methods: Mouse embryonic fibroblasts (MEFs) were transduced with retrovirus engineered to express LARS1 shRNA constructs and control construct with GFP. Knockdown efficiency was established via a western blot analysis of LARS1 protein levels. MEFs expressing differential levels of LARS1 were analyzed for changes in phosphorylation of targets of mTOR kinase complexes by western blotting using phospho-specific antibodies. To determine the effects of LARS1 knockdown on cell proliferation, which is strongly linked to mTOR activity, proliferation assays were performed by the generation of growth curves based on cell counts on four consecutive days after plating equal numbers of cells.

Preliminary Results: Strikingly, despite similar knockdown of LARS1 protein expression using 4 different shRNA constructs, not all MEF lines generated displayed similar signaling or growth perturbations. Our preliminary data suggests that LARS1 knockdown influences the phosphorylation levels of mTOR targets in 1 of 4 MEF cell lines. Growth curves showed reduced proliferation of different magnitude in all MEF lines with LARS1 knockdown when compared to control MEFs. Conclusions: mTOR signaling and cell proliferation can be impacted by a loss of LARS1 expression in mouse fibroblasts.

However, further research is required to elucidate the precise link between LARS1, mTOR signaling and cell proliferation to develop potential therapies that correct the effects of LARS1 loss-of-function.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9: In-Person BASIC SCIENCE Moderator: Ali Farrokhi Participants: Grace Bernard Tiffany Chang Ria Gill Torin Halvorson Henry Li Ava Momeni Samuel Salitra Claire Sie Valérie Sprockeels

Watch In-Person: Each presenter will have 5 minutes to discuss their poster and 5 minutes for questions from attendees.

Thursday, July 28, 2022 | 1:30 - 3:00 pm Chieng Family Atrium, BC Children’s Hospital Research Institute

Session #9 | Poster #71 Grace Bernard, Undergraduate Student, Dalhousie University Supervisor: Alexander G. Beristain, Healthy Starts

Congratulations to Grace on receiving a NSERC Undergraduate Student Research Award

​TNFα production kinetics following LPS challenge in myeloid cells Grace Bernard, Lauren E. St-Germain, Alexander G. Beristain

Background: The immune system during pregnancy exists in a fine balance where it is imperative that the immune cells allow for tolerance of the developing fetus while remaining active enough to fight infection by foreign pathogens. Within the uterus, many subtypes of immune cells exist, one of which being myeloid-derived macrophages that help control placental development and immunity. Lipopolysaccharide (LPS), an endotoxin derived from gram negative bacteria, is a commonly used inflammatory stimulant and resulting downstream LPS-driven inflammatory cascades likely underlie the development of pregnancy complications in both humans and mice. However, uterine macrophage kinetics in response to inflammatory challenges are still largely unknown.

Objectives: To determine the kinetics of tumor necrosis factor alpha (TNFα) production and secretion in myeloid cells following stimulus with LPS. Methods: RAW264.7 cells will be cultured and organized into two conditions; stimulated and unstimulated. All cells will be treated with Brefeldin A, a Golgi apparatus block, to ensure the proteins produced by the cells were retained.

Each condition will then be treated with culture media or media containing LPS and left to culture. The cells will then be collected and stained intracellularly at timepoints 0, 1, 2, 3, 4, 6, and 8 hours post stimulus at which point the intracellular levels of TNFα will be analyzed using flow cytometry.

Significance: Previous research from our lab shows that LPS challenge leads to an increase in peripheral pro-inflammatory cytokines in the peripheral blood of pregnant mice. To our surprise, and contrary to the role macrophages are thought to play in potentiating inflammatory responses in tissues, uterine macrophages showed a decrease in TNFα production 6 hours following LPS exposure in pregnant mice. This project will fill gaps in previous research which can then be used to further educate both healthcare professionals and the general public about inflammation and pregnancy.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9 | Poster #72 Tiffany Chang, Undergraduate Student, University of British Columbia Supervisor: Stefan Taubert, Healthy Starts

Congratulations to Tiffany on receiving a BC Children’s Hospital Research Institute Summer Studentship

The Role of Mediator Subunit MED15 in Lung Cancer Cell Stress Response Tiffany Chang, Jean Cheng, David Liang, Stefan Taubert

A healthy immune system naturally controls malignant disease. However, cancers are able to activate stress responses to continuously grow, resisting stresses such as immune responses. Inhibiting these hyperactive stress and inflammatory responses can render cancer cells susceptible to immune control, providing a therapeutic entry point to combating cancer. MED15, a subunit of the transcriptional coregulator, ‘Mediator’, is upregulated in numerous human cancers, and its high expression is associated with poor overall survival. Our lab’s previous work showed that it is required for many stress responses, including immune response, in the worm model Caenorhabditis elegans, but little is known about its role in mammalian cells. Notably, MED15 is a druggable protein, with two classes of small molecules that target MED15, so targeting stress and inflammatory responses through the MED15 entry point could represent a new strategy to treat cancers. Thus, we explored the role of MED15 in A549 human lung cancer cells by knocking down or knocking out MED15 using RNA interference and CRISPR prime editing, respectively. RNA-seq results showed decreased expression of pro-inflammatory markers in our two MED15 loss of function models. Downregulated genes include prostaglandinendoperoxide synthase-2 (PTGS2, encoding cyclooxygenase-2 [COX-2], an enzyme that catalyzes the formation of proinflammatory prostaglandins), and the chemokine ligands CXCL1, -2, -3 and -5. In my summer project, I validated these findings using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blots. Additionally, I treated A549 cells with optimized levels of signalling molecules tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), which stimulate the production of proinflammatory PTGS2 and CXCLs. I observed significant downregulation of PTGS2 after treatment in MED15 loss of function cells. These results help characterize the role of MED15 in mammalian cells and suggest that MED15 may be relevant for future cancer treatment strategies.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9 | Poster #73 Ria Gill, Undergraduate Student, University of British Columbia Supervisor: Ian Pike, Evidence to Innovation

Congratulations to Ria on receiving a BC Injury Research and Prevention Unit Summer Student Research Award

Developing Case Studies for Brain Injury Prevention Ria Gill, Shazya Karmali, Kate Turcotte, Ian Pike

Background: Traumatic brain injuries are a leading cause of death and disability. In 2019, there were approximately 16,000 traumatic brain injury related hospitalizations for children ranging from 0-17 years old. A concussion is a mild traumatic brain injury that occurs when there is a blow to the head or the body which causes the brain to move.

Given that concussions are not visible on X-rays, CT scans, or MRIs, it is important to be able to recognize and respond to concussions accordingly.

Objective: To develop case studies on successful brain injury prevention programs in order to support the case for investing in injury prevention Methods: Brain injury prevention programs were identified by the project team and online searching. Information about the programs was collected by reaching out to program coordinators. Information was organized and formatted for a case study.

Results: Two programs targeting brain injury prevention among the youth population were identified; Brain Waves and Smart Hockey. Brain Waves is a national program dedicated to preventing brain and spinal cord injury and delivers free, informative, and engaging neuroscience presentations for students in grades 4 to 6. Smart Hockey is a program that provides minor hockey leagues across Canada with information and tools to identify, prevent, and manage concussions with the overall goal of creating a concussion-safe environment to promote the safety of all players. Given that ice hockey is associated with one of the highest rates of concussion, Smart Hockey provides tools and resources to help educate coaches, trainers, players, and parents on how to manage concussion. Both of these programs are run by Parachute, which is a non-governmental agency focusing on injury prevention while at home, at play, and on the move.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9 | Poster #74 Torin Halvorson, MD/PhD Student, University of British Columbia Supervisor: Megan Levings, Childhood Diseases

Congratulations to Torin on receiving a BC Children’s Hospital Research Institute Summer Studentship

Insulin receptor engineering in regulatory T cells for enhanced immunosuppressive function in the pancreatic islet microenvironment Torin J.X. Halvorson, Karoliina Tuomela and Megan K. Levings

Type 1 diabetes (T1D) is a devastating autoimmune disease characterized by T cell-mediated destruction of insulin-producing beta-cells in the pancreatic islets. Regulatory T cells (Tregs), are a specialized T cell subset that promotes immune tolerance by suppressing autoreactive T cells and preventing autoimmunity. Treg-based immunotherapies, in which patient Tregs are expanded ex vivo prior to reinfusion, have shown promise in preclinical studies, and may represent a curative approach for T1D and other autoimmune conditions. Although the safety of Treg immunotherapy has been demonstrated in clinical trials, questions remain regarding its efficacy. Moreover, the process of ex vivo Treg expansion allows a unique opportunity to genetically engineer patient Tregs to enhance specificity and tailor their function to the pancreatic microenvironment. In particular, insulin, an abundant hormone in the pancreatic islets, has been shown to exert detrimental effects on Treg function in mice. Conversely, interleukin (IL)-2 is a critical growth factor for Tregs that may be limiting in the pancreatic microenvironment. As the expression patterns of the insulin receptor in human Tregs are unknown, we aimed to first characterize protein expression and downstream signalling of the insulin receptor by Western blotting in resting Tregs and post-activation, using conventional effector T cells for comparison. We also determined insulin concentrations in typical media used to culture Tregs and will use this information to evaluate the effects of insulin on Treg growth, function, and insulin receptor expression. Together, our preliminary data provide important insights into how a high-insulin microenvironment, such as within pancreatic islets, might influence Treg function. Additionally, these findings will serve as a strong foundation for understanding how insulin receptor signalling might be manipulated to enhance efficacy in the context of Treg immunotherapies. Specifically, we hypothesize that engineering the insulin receptor to deliver an IL-2-like signal to Tregs using a CRISPR-based gene knock-in could enhance Treg function in the islet microenvironment. Our approach would replace the cytosolic domain of the insulin receptor with that of the IL-2 receptor, converting a potentially detrimental insulin signal into one promoting Treg growth and survival, and ultimately leading to improved tolerogenic immunotherapies for T1D.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9 | Poster #75 Henry Li, Undergraduate Student, University of British Columbia Supervisor: Michael Steffen Kobor, Healthy Starts

Congratulations to Henry on receiving a NSERC Undergraduate Student Research Award

Exploring the role of histone SUMOylation in the DNA damage response Zi Han (Henry) Li, Hilary Brewis, Michael Steffen Kobor

Background: Many essential biological processes depend on chromatin remodeling for regulating DNA access, such as transcription, replication, and DNA repair. The basic packaging unit of chromatin is the nucleosome core, consisting of ~146 base pairs of DNA wrapped around a protein octamer constructed from two copies of each of the core histones: H2A, H2B, H3, and H4. Post-translational modifications are covalent biochemical alterations to proteins after biosynthesis. Histone post-translational modifications and histone variants regulate gene expression by remodeling chromatin structure. Small ubiquitin-like modifier (SUMO) protein is post-translational modification shown to be involved in the DNA damage response. SUMO can be reversibly linked to all histone proteins; however, it is unclear whether histone SUMOylation is correlated with DNA damage. Additionally, it is unknown the extent of which specific ligases involved in the SUMOylation pathway are involved with modifying histones.

Method: Using Saccharomyces cerevisiae (brewer’s yeast) as a model organism, SUMOylation of histones can be investigated through immunoprecipitation and western blotting. Yeast strains were transformed with plasmids containing HIS-tagged SUMO genes. Cells were grown in SC-LEU media to mid-log phase and whole cell extract was collected.

Immunoprecipitation (IP) was performed on the whole cell extract using Ni-NTA beads to isolate for his-tagged SUMO proteins. SUMOylation levels of H2A, H2B, H3, and H4 were then assessed through western blotting.

Results: Preliminary results showed that SUMOylation occurs on H3 and H4 histones, while H2A and H2B SUMOylation remains unclear. Additionally, current results showed a functional protocol in which SUMO modified histones can be isolated and analyzed.

Next Steps: Moving forward, hydroxy urea can be used to stimulate a DNA damage response in S. cerevisiae, allowing SUMOylation in DNA damage conditions to be measured. Other strains of yeast with knockout ligases involved in the SUMOylation pathway have also been created. These can be used to investigate which specific ligases play major roles in histone SUMOylation.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9 | Poster #76 Ava Momeni, Recent Graduate, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

Functional Brain Networks Underlying Selective Attention in Schizophrenia Ava Momeni, Nicole Sanford, Todd Woodward

Cognitive impairments are considered to be a core symptom in patients with schizophrenia, rather than a secondary outcome of the illness (American Psychiatric Association, 2013). Thus, it is important to study the various cognitive processes that are affected in patients with schizophrenia, as well as their neurological underpinnings, to subsequently work towards finding effective treatments for curing those impairments. In the following study, we employed the novel approach of multi-experiment fMRI-CPCA to examine the functional brain networks evoked during a set-switching Stroop task (i.e., a measure for selective attention) which we call Task Switch Inertia (TSI) in schizophrenia. We found four functional networks that were recruited during this task: Two-Handed Response (2-RESP), Focus on Visual Features (FVF), Default Mode Network (DMN), and Cognitive Evaluation (CE). Furthermore, we found that in patients with schizophrenia, there was a deficit in suppression of the 2-RESP, FVF, and DMN networks relative to healthy individuals. This aligns with the findings of a previous study that used a slightly different version of the TSI task and found that the activity of the Default Mode Network does not suppress in patients with schizophrenia relative to healthy controls (Woodward et al., 2016). Thus, on balance, patients with schizophrenia show impairments in suppression of activity in several functional brain networks, and this may underlie the cognitive impairments that they present within the domain of selective attention.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9 | Poster #77 Samuel Salitra, Undergraduate Student, University Of British Columbia

Supervisors: Mohammed Abdallah & Wyeth Wasserman, Evidence to Innovation

Congratulations to Samuel on receiving a NSERC Undergraduate Student Research Award

GraphTF: Integrating Transcription Factor Annotation into a Graphical Database Samuel Salitra, Mohammed Abdallah, Wyeth Wasserman

Understanding how transcription factors (TFs) regulate the human genome has been a dominant theme in biological research for decades. An enormous body of research has accumulated, sharing a focus on cell-specific transcription patterns and the mechanisms of gene regulation involved in inducing cellular differentiation. Researchers strive to understand gene regulation under the expectation that it will eventually allow therapeutic advances, such as cell therapies, to be realized.

Due to the breadth of literature available on DNA-binding TFs (DbTF), it is impractical for researchers to stay informed on all new findings across the research domain. As a result, potentially useful insights are becoming increasingly siloed. Concurrent to these advances in genomics, dramatic advances in machine learning have occurred that allow the inferential analysis of complex graphs. By synthesizing current knowledge about DbTFs into a knowledge graph, heterogeneous data will be seamlessly integrated into a format usable by graph-based machine learning to generate automated insights into how DbTFs influence tissue differentiation.

To facilitate this analysis, a data pipeline has been constructed to unify DbTF information. Titled GraphTF, it gathers DbTF annotations from popular protein databases and ontologies. This data is then imported into a common graph database according to a predefined schema. The GraphTF database can be queried remotely using Cypher (a popular declarative query language) to gain insights into DbTF interaction and generate testable hypotheses.

Upon project completion, a GraphTF database containing all available human DbTFs (~1500) will be made available for query and follow-up. A pairwise DbTF similarity score will also be included with the database. Data pipeline code and associated data will be made available on the Wasserman Lab Github to ensure reproducibility. Finally, an embedding, or vector representation, of the graph will be made available for machine or deep learning projects that aim to classify or learn DbTF functions and connections.

Going forward, the Wasserman Lab will transition GraphTF to a more robust DbTF analysis tool. This will be accomplished by incorporating it into machine learning processes that parse the current body of gene regulation research and automatically extract common trends and connections between DbTFs or studies.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9 | Poster #78 Claire Sie, Undergraduate Student, University of British Columbia Supervisor: Bruce Vallance, Childhood Diseases

Congratulations to Claire on receiving a Canadian Association of Gastroenterology Summer Studentship

Modeling bacterial gastroenteritis: Using enteroids to define how epithelial-intrinsic inflammasomes recognize and respond to invading Campylobacter jejuni Claire Sie, Qiaochu Liang, Bruce Vallance

Background: Campylobacter jejuni is the leading cause of food-borne bacterial gastroenteritis worldwide. In infected individuals, C. jejuni invasion of intestinal epithelial cells (IECs) is known to be characteristic in those that develop symptomatic disease. Despite its prevalence and public health significance, the mechanisms by which C. jejuni interacts with and invades the intestinal epithelium remain unknown. Relevant models are scarce, as most murine or avian models do not reflect disease outcomes in humans, while transformed cell lines cannot accurately recapitulate the complex epithelial structure and functionality. Recent advances in enteroid research show impressive in vitro potential to mimic in vivo microbe-IEC interactions. The development and application of a robust C. jejuni-enteroid infection model will aid in understanding the molecular details of how IECs respond to C. jejuni infection. Finally, IEC-intrinsic inflammasomes detect intracellular pathogens and have been shown to limit intracellular replication of Salmonella. However, the role of the inflammasome complex in fighting C. jejuni infections is poorly understood.

Aim: To optimize an in vitro 2D monolayer model of C. jejuni invasion using murine and human enteroids. Then, using this model, evaluate the role of intestinal inflammasomes in controlling C. jejuni invasion.

Methodology: IEC monolayers derived from murine and human enteroids were infected with C. jejuni strain 81-176, followed by treatment with gentamicin. Infected cells were assessed through immunofluorescence staining and CFU recovery of C. jejuni.

Results: C. jejuni 81-176 invaded confluent murine and human monolayers at similar levels across various multiplicities of infection. Additionally, microaerobic conditions promoted invasion over atmospheric oxygen conditions. Inflammasome deficiency did not alter the invasion rate of C. jejuni for Caspase 1/11–/– and Caspase 1/11+/+ monolayers.

Conclusions: Our data establishes that C. jejuni is capable of invading 2D monolayers derived from enteroids regardless of murine or human origins. Low-oxygen environments mimicking the intestinal lumen appear to provide advantages for C. jejuni to invade. In our model, caspase-1 and caspase-11 inflammasomes did not play a critical role in host defenses against C. jejuni invasion. However, this model can be easily adapted to assess the roles of alternate IEC defense mechanisms in limiting C. jejuni infection.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR

Session #9 | Poster #79 Valérie Sprockeels, Master’s Student, Université de Namur/University of British Columbia Supervisor: Bruce Verchere, Childhood Diseases

Congratulations to Valérie on receiving a Erasmus+

Evaluation of prohormone processing in diabetes Valérie Sprockeels, Yi-Chun Chen, Bruce Verchere

Pancreatic islets contain endocrine cell types responsible for producing numerous peptide hormones involved in blood glucose regulation. Each of these hormones is first synthesized as a prohormone that is processed by various enzymes to the mature form. Multiple research groups have shown that defects in prohormone processing are associated with islet malfunction and, in some cases, increased risk of diabetes. However, most studies were focused on investigating a particular hormone or prohormone processing enzyme and failed to evaluate overall prohormone processing efficiency in different islet endocrine cell types in (patho)physiological settings. We aim to create an antibody panel compatible with co-detection by indexing (CODEX), allowing for the in situ detection of up to 100 different target proteins involved in prohormone synthesis, processing and hormone secretion, to evaluate whether (and how) islet prohormone processing efficiency is disturbed in subjects with diabetes.

Watch In-Person: Thursday, July 28 | 1:30 - 3:00 pm | Chieng Family Atrium, BCCHR