THINK. LEARN. DISCOVER.
SPRING 2023
Exploring Pediatric Neuro-Oncology
Dr. Uri Tabori’s Research in treating Childhood Cancers
Neurorights will let your Mind Fly
The Intersection of Ethics, Law, and Neuroscience
Dr. Michael Chaiton on:
Youth Vaping and the Mental Health Crisis
MAGAZINE STAFF
EDITORS-IN-CHIEF:
Jason Lo Hog Tian
Stacey J. Butler
EXECUTIVE DIRECTORS:
Dorsa Derakhshan
Elizabeth Karvasarski
Iciar Iturmendi Sabater
Kyla Trkulja
SOCIAL MEDIA TEAM:
Elizabeth Karvasarski (Director)
Lizabeth Teshler
Mahbod Ebrahimi
DESIGN EDITORS:
Xinyi Li (Director)
Joshua Koentjoro
Anais Lupu
Vanessa Nguyen
Emily Tjan
Livia Nguyen
Stephen Nachtsheim
PHOTOGRAPHERS:
Dorsa Derakhshan (Director)
Niki Akbarian
JOURNALISTS & EDITORS:
Nikou Kelardashti
Niki Akbarian
Benjamin Traubici
Kristen Ashworth
Goldin Joghataie
Lindsey Thurston
Iciar Iturmendi Sabater
Syed Hussain Ather
Sipan Haikazian
Ali Golbabaei
Kyla Trkulja
Sena Gok
Mahbod Ebrahimi
Molly Zhang
Shu’ayb Simmons
Denise Sabac
Kateryna Maksyutynska
Jennifer Ma
Bahar Golbon
Akshat Pai
Nayaab Punjani
Copyright © 2023 by Institute of Medical Science, University of Toronto. All rights reserved. Reproduction without permission is prohibited.
The IMS Magazine is a student-run initiative. Any opinions expressed by the author(s) are in no way affiliated with the Institute of Medical Science or the University of Toronto.
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As we welcome the (hopefully) warmer weather of springtime, we are pleased to release our Spring 2023 issue of IMS Magazine focusing on Children’s Health. We also welcome all the new students who joined IMS during the Winter term, some of whom have decided to be a part of the IMS Magazine team!
In this issue, we highlight the work of Drs. Helen Dimaras, Cathy Barr, Uri Tabori, and Brian Ballios, who are conducting innovative research in a variety of areas in children’s health including neurodevelopmental disorders, paediatric oncology, genetics, and retinal diseases. We have several thought-provoking Viewpoint articles examining topics such as social media and youth mental health, the use of astrological signs, neurotechnology and neurorights, and attachment theory. This issue also includes an insightful book review on Antidepressed by Beverly Thompson and the validity of the “serotonin hypothesis” of depression, a travel bite describing one of our writers’ experience at a stem cell conference in Vancouver, and an article from our good friends at Raw Talk Podcast covering one of their episodes on burnout in healthcare.
As always, we would like to thank the new and returning members of the IMS Magazine team – we could not highlight the incredible work going on at IMS without you. We hope you enjoy reading this issue have a rejuvenating spring season. We look forward to working on our next issue coming in the summer!
Jason is a 4th year PhD student examining the mechanisms linking HIV stigma and health under the supervision of Dr. Sean Rourke.
@JasonLoTweets
Stacey Butler
Stacey is a 4th year PhD student under the supervision of Dr. Andrea Gershon evaluating the quality of care for patients with respiratory disease using a population-based approach.
@StaceyJButler
Spring is a season of change, a time of growth, and new beginnings. This season coincides nicely with the theme of the Spring 2023 issue of IMS Magazine which shines the spotlight on Children’s Health. At the University of Toronto, we are fortunate to have one of the world’s best children’s hospitals on our doorstep. Many IMS faculty and students are conducting ground-breaking research at the Hospital for Sick Children to address some of the most important issues affecting children and youth today.
This issue features several IMS faculty from SickKids who are dedicated to improving the health of children both within Canada and abroad. Dr. Helen Dimaras is taking a global health approach to remove barriers to diagnosing retinoblastoma using genetic testing. Dr. Cathy Barr is furthering our understanding of the role genetics plays in neurodevelopmental disorders such as autism spectrum disorder and attention-deficit/hyperactivity disorder. Dr. Uri Tabori is finding new ways to diagnose and treat brain tumours with novel and noninvasive methods. Dr. Brain Ballios is exploring how stem cell transplantation could be used to treat vision loss in children with inherited retinal diseases.
In this issue, we also hear from two student leaders in the IMS. Nairy Khodabakhshian is a PhD Candidate and the leader of the Peer-2-Peer Mentorship program at the IMS. Nairy is also assisting with the development of a new modular course which uses virtual reality to teach clinical research skills to new graduate students in the IMS. In the Diversity in Science section, PhD student Ali Golbabaei, the President of the IMS International Community, discusses some of the barriers affecting the international graduate student experience.
This issue also covers the 12th annual Ori Rotstein lecture in translational research which took place on November 2nd 2022. The keynote address was delivered by Dr. Yasmine Hurd, an internationally renowned neuroscientist who discussed the neurobiology of opioid addiction. This is a very important and timely topic given the rise in opiod-related deaths in recent years. Also in this issue, Dr. Michael Chaiton discusses the impact of public health policies on youth vaping and mental health and how we can leverage technology to better support the younger generation.
On behalf of the entire IMS community, I extend my sincere congratulations to the new faculty joining the IMS, members who have recently been promoted, and our recent graduates. I would also like to thank the Editors-in-Chief, Jason and Stacey, along with the editors, journalists, photographers, and design team producing another great issue of IMS Magazine. I hope you enjoy reading about how the IMS is contributing to incredible discoveries in children’s health.
Sincerely,
Dr. Mingyao Liu Director, Institute of Medical Science
sipanhaikazian
Niki Akbarian is a first-year MSc student under the supervision of Dr. Linda Mah and Dr. James Kennedy. Her research focuses on better understanding the association between personality traits and biomarkers of Alzheimer’s disease and the genetic basis of this association. Outside of academia, Niki enjoys photography, playing the piano, and watching sitcoms.
Kristen Ashworth is a first year MSc student working under the supervision of Dr. Brian Ballios at the Donald K. Johnson Eye Institute and Krembil Research Institute. Her thesis is focused on developing a retinal organoid model to evaluate stem cell therapies for USH2A- and CRB1-related inherited retinal diseases. Kristen loves cross country running, reading a good book, going to Marshalls, and doting on her two adorable golden retrievers.
Syed Hussain Ather is a first-year Ph.D. student working under John Griffiths at the Centre for Addiction and Mental Health (CAMH). He uses and develops computational modeling techniques to investigate the brain connectivity structures underlying neuropsychiatric disorders. He also likes cosplaying.
Ali Golbabaei is a PhD student under supervision of Dr. Paul Frankland at The Hospital for Sick Children. His research focuses on investigating the engagement of different brain circuits at long term memories. Outside of the lab, Ali enjoys traveling and exploring new places.
Sipan Haikazian is a first year MSc student researching the efficacy and safety of maintenance ketamine infusions for relapse prevention in patients with treatmentresistant bipolar depression, under the supervision of Dr. Joshua Rosenblat. Outside of research, Sipan enjoys playing the piano, exercising, and being around good company.
Iciar Iturmendi Sabater is a PhD student researching social processing and adaptation across neurodevelopmental conditions (autism, ADHD, learning disabilities, etc) under the supervision of Dr. Meng-Chuan Lai and Dr. Hsiang-Yuan Lin. Iciar likes reading, exploring new places, and spending time with family and friends.
Goldin Joghataie is a first year MSc student supervised by Dr. Carmela Tartaglia at the Krembil Brain Institute, Toronto Western Hospital. Her research focuses on neurodegeneration and concussion, specifically post concussion neuropsychiatric issues faced by ND patients who experience falls. Outside of academia she enjoys writing, skating, listening to music and reviewing movies.
Nikou Kelardashti is a first year MSc student under the supervision of Dr. Karen Davis. Her research focuses on the relationship between neural oscillations and pain-attention interaction. Outside of academia, Nikou enjoys reading poetry and classic literature, watching old movies, and going for long walks.
Lindsey Thurston is a PhD candidate studying sex/gender and sex steroid hormones in the brain. Specifically, she investigates biopsychosocial relationships in white matter microstructure using diffusion tensor imaging. Lindsey’s work with transgender and gender non-conforming populations bridges social and scientific disciplines by drawing on neurofeminist theory. Lindsey also enjoys photographing the CN tower and nature’s delights.
Kyla Trkulja is a second year MSc student at IMS studying under the supervision of Dr. Armand Keating, Dr. John Kuruvilla, and Dr. Rob Laister at Princess Margaret Hospital. Her work focuses on better understanding the mechanism of action of a novel cancer therapy for lymphoma so it can be better utilized in the clinic. Outside of academia, Kyla enjoys reading, writing, video games, and going for road trip adventures across the province.
Lizabeth Teshler is a first year MSc student at IMS supervised by Dr. Brian Feldman at The Hospital for Sick Children. Her research investigates physical joint health assessment in people with Hemophilia. Outside of research, Lizabeth loves biking, spending time outdoors and volunteering for various community initiatives.
The IMS Design Team is a group of second year MSc students in the Biomedical Communications (BMC) program. Turning scientific research into compelling and effective visualisations is their shared passion, and they are thrilled to contribute to the IMS Magazine.
Ben Traubici is a first year MSc student under the supervision of Dr. Brian Feldman at The Hospital for Sick Children. His work focuses on developing and testing a social participation measurement tool for patients with rheumatic conditions. Outside of academia, Ben enjoys hockey, travelling and running.
Elizabeth Karvasarski (Lead) is a PhD IMS at Mount Sinai Catheterization Laboratory under the supervision of Dr. Susanna Mak. Her research involves investigating right ventricular and pulmonary arterial interactions in patients with pulmonary hypertension and heart failure. Outside of research, Elizabeth practices martial arts and is a 4th degree black belt.
Mahbod Ebrahimi is a first-year MSc student investigating the association between immune gene expression and suicide risk in schizophrenia patients under the supervison of Dr. James Kennedy. Outside of research, Mahbod enjoys a good book, playing chess, and listening to Jazz music.
Retinoblastoma is the most common type of eye cancer diagnosed in infants and young children. The incidence of retinoblastoma is uniform across populations at one in 16,000 to 18,000 live births.1 This malignant cancer begins in the retina of the eye and is caused by mutations in a tumour suppressor gene called the retinoblastoma gene (RB1).1 Depending on the timing and location of the RB1 mutation, retinoblastomas can be either heritable or non-heritable. Children with heritable retinoblastoma can have tumours in one or both eyes and are at a higher risk of developing secondary cancer in the future.1 This makes genetic testing for RB1 mutations a valuable tool that is available for at-risk individuals in Canada and other high-income countries (HICs). However, many of the low- and middleincome countries (LMICs) lack this type of care. This is only one of the underlying reasons for the global disparity in survival outcomes of children with retinoblastoma.
Dr. Helen Dimaras—a Scientist and Director of Global Eye Health Research in the Department of Ophthalmology & Vision Sciences at The Hospital for Sick Children (SickKids)—focuses on delivering optimal care for retinoblastoma patients globally. Dr. Dimaras completed her Ph.D. in Molecular & Medical Genetics at the University of Toronto, where she investigated the genetics of retinoblastoma. It was during this time that she developed an interest in global health and the social determinants of health in retinoblastoma cases. Dr. Dimaras completed her
postdoctoral training at SickKids, through which she was able to become more involved in global health by working on a capacity-building project being developed at SickKids with collaborators at the University of Nairobi. As a result of her extensive research in the field, Dr. Dimaras is a pioneer and expert when it comes to looking at retinoblastoma through the lens of global health.
Although retinoblastoma is a curable disease in HICs, it remains a significant challenge in many LMICs with large populations and high birth rates.2 LMICs have more than 80% of global retinoblastoma cases; however, they have a poor prognosis due to the limited availability of healthcare services resulting in delayed diagnosis and treatment.2 Therefore, one of the key factors that can alleviate the health inequality seen in retinoblastoma cases is universal health care. “When there is a unified approach in health care, families can navigate it and feel confident in it,” Dr. Dimaras explains.
Dr. Dimaras was part of the Kenyan National Retinoblastoma Strategy (KNRbS), a remarkable initiative that was launched in 2008 to improve the quality of care and survival of retinoblastoma patients in Kenya. As Dr. Dimaras explains, designing and conducting global health research teaches you “how to overcome challenges by focusing on removing barriers and implementing solutions known to work.” As a result of the KNRbS’s success, other countries such
as Ethiopia and Ghana have initiated their national retinoblastoma strategies based on the lessons learned from the KNRbS.
One of the main features of Dr. Dimaras’s research is to utilize patient-oriented methods to conduct global health research on retinoblastoma. According to the Canadian Strategy for Patient-Oriented Research (SPOR), patient-oriented research involves including individuals with the lived experience of a health condition, their family members, and informal caregivers as partners in the research process.3 “Patients are experts by experience,” Dr. Dimaras says. “Lived experience is important and research should be driven by what the community wants [scientists] to do. This is a central tenet in global health, and it is now making its way to everyday research.”
Inspired by the community engagement methods of global health, Dr. Dimaras established the Canadian Retinoblastoma Patient Engagement Strategy. The overall goal of this strategy is to more efficiently address the needs of retinoblastoma patients through meaningful engagement and co-direction of research with patients. As a part of this strategy, the Canadian Retinoblastoma Research Advisory Board (CRRAB) was established in 2016 with three main aims and is co-led by Dr. Dimaras and a patient partner. The first aim of CRRAB is to identify a diverse population of individuals affected by retinoblastoma and have them join this community. The second aim is to share
research results with the community by hosting an annual retinoblastoma research symposium and organizing a lay language journal club called Cup of Tea. The Cup of Tea events allow patients to work with scientists and clinicians to produce lay summaries of research papers
for presentation at the event, thus sharing research with a wider community. Lastly, CRRAB aims to empower retinoblastoma patients and promote research that is created and led by the patients alongside researchers.
The success of the CRRAB program allowed Dr. Dimaras and her lab to conduct a priority-setting exercise. In this project, clinical and scientific experts, alongside individuals affected by retinoblastoma, were invited to determine and rank the top ten unanswered research questions in the field of retinoblastoma in Canada. The goal of this project was to encourage researchers, advocacy groups, and funding agencies to align their goals with the priorities identified. The highest priority challenge recognized by the participants in this study was regarding the improvement of early detection of retinoblastoma.4 This is noteworthy as it shows the importance of early cancer detection even in a HIC such as Canada, where the diagnosis of retinoblastoma happens much earlier compared to many LMICs. Although the Canadian Paediatric Society recommends eye examination of children when newborn to three months and at six to 12 months, the mean age at diagnosis for bilateral and unilateral retinoblastoma in Canada is 15 and 27 months, respectively.4 This suggests either inefficiency of guidelines in diagnosing retinoblastoma or poor adherence to them.
Notably, two of the other challenges identified in the priority-setting exercise were related to the psychosocial health of individuals affected by retinoblastoma.
“What retinoblastoma families have been telling us is that they are enjoying good survival because of the care they are receiving, but they feel that their psychosocial needs are unmet,” Dr. Dimaras explains. Guided by these identified challenges, Dr. Dimaras is currently working on a project to further understand the psychosocial experiences of retinoblastoma patients and their families in order to better cater to their unmet psychosocial needs.
Multidisciplinary scientists like Dr. Dimaras, who are highly dedicated to identifying and fulfilling the needs of their patients, provide a bright outlook for research, especially pediatric research. In particular, Dr. Dimaras highlights the importance of including more diverse populations in research and capacity building in the future. “We should support inquiry,” Dr. Dimaras says. “As we improve diversity and include different people in research, we are going to see more innovative and different research with maybe even different results.”
Neurodevelopmental disorders (NDDs) are heterogeneous conditions characterized by atypical development of the nervous system, which results in cognitive impairment and deficits in communication, behavior, and motor skills. 1 Intellectual disability, autism spectrum disorder (ASD), attentiondeficit/hyperactivity disorder (ADHD), neurodevelopmental motor disorders such as Tourette Syndrome, and specific learning disorders including reading disabilities are NDDs that affect 15-20% of children worldwide. 2 Comorbidity among NDDs is pronounced as they can co-occur with one another and/or with psychiatric disorders such as anxiety, depression, psychosis, and schizophrenia. 1 In addition, the clinical symptoms of NDDs overlap significantly, making their diagnosis and treatment challenging. Dr. Cathy Barr–a Senior Scientist at the Krembil Research Institute and the Neurosciences & Mental Health Program at the Hospital for Sick Children (SickKids)–investigates the genetics of NDDs and psychiatric disorders, which is one of the most effective approaches to understanding their underlying basis.
Dr. Barr completed her Ph.D. in molecular biology at the M.D. Anderson Cancer Center, University of Texas, and subsequently pursued her postdoctoral training at Yale University and SickKids. Although Dr.
Barr started her postdoctoral training at SickKids with a specific focus on the genetics of Tourette Syndrome, she then broadened her field of study as she witnessed the extent of overlap between the genetics and clinical symptoms of Tourette Syndrome and other NDDs, such as ADHD and reading disabilities. Currently, Dr. Barr and her research team are attempting to identify genes involved in childhood NDDs, their function, and mechanisms that alter their function.
Over the past few decades, more than 1,500 genetic risk alleles associated with NDDs have been identified, 3 most of which alter the expression of genes by influencing their splicing or transcription. Interestingly, some of the identified genes are known to be shared among various NDDs. For example, Dr. Barr and her research team demonstrated that several genes associated with reading disability are also related to the autism spectrum disorder. While these genes undergo more severe changes in autism compared to reading disabilities, in both disorders, they are suspected to interfere with the neural development of brain regions implicated in language functioning. Specifically, an imbalance between excitatory and inhibitory neurons enriched with affected genes is suggested to underlie the clinical manifestation of these disorders.
Another potential mechanism impacted by the genes involved in the pathology of reading disabilities and autism is neural migration. Neural migration is a critical process in the normal development of the nervous system that regulates the migration of cells into appropriate spatial positions relative to each other. 4 To understand how neural migration may differ in reading disabilities, Dr. Barr and her research team collected blood cells from children with reading disabilities and turned them into induced pluripotent stem cells and subsequently neural precursor cells. Thereafter, they examined how fast these neural cells could migrate in vitro. It was observed that neural cells from children with reading disabilities migrated faster and further than neural cells from their strong reader siblings. These deviations in neural migration can lead to the mislocalization of neural cells, resulting in improper development and functioning of brain circuits. 5 In her future research, Dr. Barr aims to complement these findings with neuroimaging data in order to compare the in vitro and in vivo behavior and migratory patterns of neural precursor cells. Further, it is of interest to understand how changes in the neural migration, in turn, impact the function and development of the brain in children with reading disabilities.
Senior Scientist at the Neurosciences & Mental Health Program, The Hospital for Sick Children
Senior Scientist at the Krembil Research Institute
Professor in the Departments of Psychiatry and Physiology and the Institute of Medical Sciences, University of Toronto
Moreover, recent international collaborations have made it possible to gain new insights into how specific variations in genes result in the pathology of NDDs. For instance, by using a Toronto-based sample, as well as the dataset from the GenLang consortium, an international network that facilitates large-scale genomic investigations, 6 Dr. Barr and her research team found that singlenucleotide polymorphisms, defined as the substitution of a single DNA building block, in the Dedicator of
Cytokinesis 7 (DOCK7) gene alter its splicing, yielding the production of an abnormal proportion of one DOCK7 protein variant over another. It is known that the DOCK7 protein is crucial for cortical neurogenesis and neural migration. 7 This explains how the substitution of a single nucleotide in the DOCK7 gene may impact neural migration and brain development in reading disabilities.
In addition, advances in genetic techniques also promise breakthroughs in the future. As Dr. Barr notes, “it took years of doing things that didn’t work out. We had no idea they weren’t going to work because the genetics are just so much more complex, and the tools that we used back then just wouldn’t work.” Genome engineering with CRISPR/Cas9, a novel method for genome editing that allows DNA break and permanent addition or deletion of genome sequences, 7 is an example of a newly developed method that can be a great asset to better understand the function of genetic risk alleles of NDDs and their mechanisms of action. Indeed, due to various complexities, the field of genetics is filled with tremendous obstacles for both trainees and principal investigators. However, as Dr. Barr states, “if you love it, you will figure it out.” The key in this field is to keep going and to learn from mistakes and challenges.
Despite all the valuable discoveries in the genetic studies of NDDs, it is still too early to translate this knowledge into clinical practice in order to change the therapeutic targets and the clinical care for these disorders. However, as Dr. Barr says, “just knowing that disorders like reading disabilities are familial, that they are inherited, that there is a neurobiological basis for them, that it’s not children’s fault, that they’re not dumb, and that 5% of other kids also have reading difficulties can be really helpful to families.” The truth is that there is a community of people, including geneticists and scientists, that would understand, support, and help children with NDDs to thrive in life.
Gokhale A, Moreno-De-Luca A, et al. Neurodevelopmental disorders: Mechanisms and boundary definitions from genomes, interactomes and Proteomes. Translational Psychiatry. 2013;3(12).
2. Francés L, Quintero J, Fernández A, et al. Current state of knowledge on the prevalence of neurodevelopmental disorders in childhood according to the DSM-5: A systematic review in accordance with the Prisma Criteria. Child and Adolescent Psychiatry and Mental Health. 2022;16(1).
3. Leblond CS, Le T-L, Malesys S, et al. Operative list of genes associated with autism and neurodevelopmental disorders based on Database Review. Molecular and Cellular Neuroscience. 2021;113:103623.
4. Rahimi-Balaei M, Bergen H, Kong J, Marzban H. Neuronal migration during development of the cerebellum. Frontiers in Cellular Neuroscience. 2018;12.
5. Pan, Y. H., Wu, N., & Yuan, X. B. (2019). Toward a Better Understanding of Neuronal Migration Deficits in Autism Spectrum Disorders. Frontiers in cell and developmental biology, 7, 205. https://doi. org/10.3389/fcell.2019.00205
6. Genlang Consortium [Internet]. GenLang. [cited 2023Jan24]. Available from: https://www.genlang.org/
7. Watabe-Uchida M, John KA, Janas JA, et al. The RAC activator dock7 regulates neuronal polarity through local phosphorylation of Stathmin/OP18. Neuron. 2006;51(6):727–39.
8. Ran, F., Hsu, P., Wright, J. et al. Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8, 2281–2308 (2013). https://doi. org/10.1038/nprot.2013.143
By Benjamin Traubici
Cancer is the second leading cause of death in children under the age of 15.1 The most common childhood cancer in this age group is leukemia, accounting for 28% of childhood cancers, followed by brain cancer and lymphoma, which account for 26% and 19% respectively.1 However, brain cancer is currently the leading cause of death and morbidity among all childhood cancers.2 The large-scale impact of childhood cancer means that improving clinical outcomes remains an important focus for many researchers and institutions, including Dr. Uri Tabori, a clinician-scientist focused on children with brain tumours.
Dr. Tabori completed his medical degree at the Hadassah School of Medicine in Jerusalem, Israel. He completed his pediatric residency in Israel at the Sorasky Medical Center (SMC), followed by his pediatric hematology and oncology fellowship at the Chaim Sheba Medical Center (CSMC). After working as a staff physician at the CSMC and the SMC, he completed his research and clinical fellowship at the Hospital for Sick Children (SickKids). Now, as a professor at University of Toronto’s Institute of Medical Science (IMS) and an oncologist at SickKids, he treats children with brain cancer and conducts cancer research, concentrating on neuro-oncology.
Dr. Tabori chose to pursue a specialty in pediatric oncology because at the time, he felt that this field was on the cusp of incredible advancements. He believed
that progress in molecular biology and genomic research would help provide important strides to improve clinical care for children with cancer. And he was right. What Dr. Tabori finds important about his work is that it begins from a clinical perspective, finds its way into molecular research, and then translates back to new therapies for children.
A major focus of Dr. Tabori’s research is on pediatric cancer predisposition, which refers to conditions in which there is an increased risk of developing cancer at a young age. His research found that many patients with childhood cancer have mutations in the mismatch repair and polymerase genes. These mutations cause dysfunctional DNA proofreading, or simply, the inability to repair mistakes in the DNA code, which lead to hypermutation in every cell in the body, significantly increasing the risk of developing cancers. After exploring the implications of these mutations, Dr. Tabori contemplated on how to help these patients. Since it is a rare condition, he and many other researchers formed an international consortium, called The International Replication Repair Deficiency Consortium (IRRDC),3 which now includes institutions in more than 50 countries. The IRRDC provides free molecular testing and counselling for patients around the world, including in low- and middle-income countries. The IRRDC also collects data in order to learn more about these mutations and create animal models to test new drugs
and treatments for patients.3 The IRRDC has already produced significant findings on the impact of these mutations, such as the fact that the mutational burden of cancers arising from these mismatch repair and polymerase deficiencies is 1000 times more than other childhood tumours.4 Even more importantly, they also discovered that these cancers with hypermutations are highly immunogenic, so they are responsive to immunotherapy.4 Thanks to his research as part of the IRRDC, physicians can find these deadly tumours early and offer innovative treatments beyond the standard cytotoxic chemotherapy and radiation therapy.
Dr. Tabori believes that translational research like this is an essential part of healthcare and a pivotal reason why he entered the field: “You take a condition, you think, you work in parallel, you do
clinical, molecular, and animal models, and you find therapy for these children.” This is the path he tries to take in his research, to identify clinical problems and use research to find treatments for patients.
Currently, the standard practice for treating children with brain cancer is surgery followed by radiation, and then chemotherapy. This course of action can be risky to the patient since radiation is damaging to the developing brain, so an important aspect of Dr. Tabori’s research is to analyze the effectiveness of immunotherapy, which uses the immune system to attack cancers. Dr. Tabori focuses on a specific type
Dr. Uri Tabori
MD, Professor in the Institute of Medical Science, and Medical Biophysics and Paediatrics Department at University of Toronto; Section head of Neurooncology in the Division of Haematology/ Oncology at The Hospital for Sick Children; Garron Family Chair in Childhood Cancer Research; Lead of International Replication Repair Deficiency Consortium (IRRDC)
Photo provided by Dr. Uri Tabori
of immunotherapy called immune checkpoint inhibition. An immune checkpoint is active when proteins on the surface of immune cells called T cells form a connection with partner proteins on tumour cells.5 This checkpoint sends a signal to the T cell that prevents it from attacking the cell; this is usually used in our bodies as a way for our immune systems to recognize our own healthy tissues and prevent it from attacking them, but cancer cells have learned to express these proteins as well to mask as normal tissues and “evade” destruction by T cells.
Immune checkpoint inhibitors block checkpoint proteins from binding with partner proteins, thus allowing T cells to attack tumour cells. Some checkpoint proteins that these inhibitors act against include CTLA-4, PD-1, and PD-L1.5 Dr. Tabori helps to conduct clinical trials utilizing immunotherapy, sometimes in conjunction with colleagues around the world, to understand its effects and hopefully utilize it more in clinical practice, preventing the deleterious side effects of radiation and chemotherapy.
Translational researchers like Dr. Tabori are always looking for ways to improve clinical practices, and in his case part of his work has focused on improving diagnostic procedures for brain tumours. Today, to reach a definitive diagnosis for a brain tumour you must perform surgery and do a biopsy to analyze tissue. However, Dr. Tabori is developing non-invasive “liquidbiopsy” diagnostic techniques that detect mutations in the cerebrospinal fluid (CSF) or blood of patients with brain tumours. Not only can these techniques detect brain tumours without invasive procedures, but they can also detect tumours when they recur before they can be detected on medical images.
As Dr. Tabori states, “The best way to treat cancer is to prevent it,” which has led to a highly interesting project that his lab is embarking on. He and the members of his lab are working with key scientists involved in mRNA vaccine formulations, including some at the biotechnology
company Moderna, to develop cancer vaccines. These would enable doctors to prevent cancers from forming in some children. Therefore, the challenge for his lab in the future is to create cancer preventative methods through conducting cutting edge research on both vaccine and immune-related interventions to improve upon cancer interception techniques.
The translational process of using research to find new therapies to treat disease and solve clinical problems is an essential part of healthcare advancement. Clinician scientists like Dr. Tabori work every day to bring the innovations of research into clinical practice. The products of Dr. Tabori’s research on childhood cancers will provide us a greater understanding of these conditions and open doors to new treatments that improve patient health and wellbeing. As he continues to push the boundaries of research and innovate for the benefit of his patients and patients all over the world, Dr. Tabori emphasizes that, “for us here at SickKids, the future is now.”
1. Seigel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2022. CA: A Cancer Journal for Clinicians. 2022 Jan; 72(1):7–33.
2. Cancer.gov. Cancer in Children and Adolescents [Internet]. NIH: National Cancer Institute. 2019 [updated 2021 November 4; cited 2023 Mar 7]. Available from https://www.cancer.gov/types/childhood-cancers/child-adolescent-cancers-fact-sheet
3. Replicationrepair.ca. Research. [Internet]. IRRDC. [cited 2023 Feb 16]. Available from https://replicationrepair.ca/team/.
4. Shlien A, Campbell BB, de Borja R, Alexandrov LB, Merico D, Wedge D, et al. Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers. Nature Genetics. 2015;47(3):257–62.
5. Cancer.gov. Immunotherapy to Treat Cancer [Internet]. NIH: National Cancer Institute. 2019 [updated 2019 September 24; cited 2023 Feb 16]. Available from https://www.cancer.gov/about-cancer/ treatment/types/immunotherapy.
...it begins from a clinical perspective, finds its way into molecular research, and then translates back to new therapies for children.
Inherited retinal diseases (IRDs) encompass a diverse group of blinding eye conditions that commonly present in childhood.1 Pediatric patients diagnosed with IRDs face a challenging lifelong outlook: progressive vision loss caused by photoreceptor degeneration, often from the periphery inward (as is the case with retinitis pigmentosa, the most common clinical IRD diagnosis).2 Often, the disease results in irreversible loss of vision and legal blindness.3
Variants in over 300 IRD-associated genes have been discovered. But, of the hundreds of IRD-causing mutations, an effective treatment for all but one IRD has yet to be found—Dr. Brian Ballios has a vision to change that. By developing a novel, pre-clinical, humanized model of disease, he believes the evaluation of stem cell transplantation therapies could be optimized, potentially changing the course in IRD treatment discovery.
Dr. Ballios is an ophthalmologist and clinician-scientist at the Donald K. Johnson Eye Institute at the Krembil Research Institute and Toronto Western Hospital. Before deciding on the field of ophthalmology, he pursued an MD/PhD here at the Institute of Medical Science, where he built on his undergraduate background in engineering to work on a bioengineered approach for the transplantation and delivery of stem cells in human retinal disease. After completing his training in ophthalmology, Dr. Ballios obtained sub-specialty training in rare
retinal genetic disorders at Harvard University. He has now returned to his home base in Toronto, where he continues to apply his academic and clinical expertise in rare retinal disease and stem cell biology as a clinician-scientist. The primary aim of his research program is to develop new stem cell-based therapies for IRDs. But, he’s doing it with a new approach—one that can hopefully address some previous challenges in treatment discovery.
Some fundamental stumbling blocks have impeded vision scientists from finding IRD cures in the past. Firstly, the vast molecular heterogeneity and phenotypic variability in these disorders make it inherently difficult to study, define, and elucidate a treatment for any particular IRD. “The patients that I see in clinic who have inherited retinal disorders—no two of them are alike,” Dr. Ballios explains. The second challenge is finding a treatment that benefits patients with advanced photoreceptor degeneration, where most of the retina’s light-sensitive cells have already been lost. In the case of these patients, treatment is likely to be more effective if it can replace cell function altogether rather than attempting to ‘fix’ a pre-existing population of diseased cells.
Stem cell engraftment is one approach that could be particularly beneficial for patients with advanced photoreceptor degeneration. Healthy cells from human donors are injected into a patient’s eye, replacing and repairing diseased photoreceptors. Dr. Ballios explains that
the important question then, is “how do donor or transplanted cells interact with IRD-mutated host tissue, and how can we enhance how those [healthy] cells interact with that tissue?”
Traditionally, mouse models have been used to try answering this question. However, some challenges with translatability arise, as animal models are limited in their ability to faithfully recapitulate the molecular and physiological intricacies of the human retina. “We’ve learned a lot from those [animal] experiments. But one thing we haven’t been able to really get at is how healthy human cells and diseased human cells interact.”
To fill this gap, Dr. Ballios and his team are developing a novel, humanized model of genetic disease in which stem cell transplantation can be tested preclinically. His lab uses pluripotent stem cells derived from patients with specific IRD-causing mutations and induces these cells to mature retinal tissue in vitro. The advantage of using these 3D retinal ‘organoids’ is that they closely reflect the human condition. To evaluate stem cell transplantation therapies, Dr. Ballios explains that healthy human stem cells can be added to the diseased organoid model, and cell survival and integration can then be monitored as the organoid matures. With downstream analysis of retinal development markers and by tracking morphological changes, Dr. Ballios hopes to gain new insight into donor-host cell
Assistant Professor, Department of Ophthalmology and Vision Sciences at the University of Toronto;Clinician-Scientist, Donald K. Johnson Eye
Institute; Associate Member, Institute of Medical Science
interactions and the rescue efficiency of healthy cells on diseased photoreceptors.
Children with IRDs have yet to accumulate the degeneration that comes with aging and thus typically retain a larger population of photoreceptors than the adults that Dr. Ballios sees in his clinic. Therefore, the necessary potency of a cell replacement therapy will differ between patients. A personalized approach is needed, and this requires experimenting with the proportion of healthy cells needed to be transplanted at varying stages of degeneration.
The end goal of the work in the Ballios Lab is to optimize stem cell engraftment therapies tailored to patients with specific types of IRDs and target these therapies for specific stages in disease progression. As Dr. Ballios points out, an effective treatment is “not just about identifying the right patient with the right disease, but also the right patient with the right disease, at the right time in their life.”
In the clinic, Dr. Ballios has seen first-hand the impact a cure can make on a patient with an IRD. He recounts a recent visit to his clinic by a pediatric patient with an IRD-causing mutation in the RPE65 gene. Fortunately, RPE65-related disease is the one IRD in which there is a Health Canada-approved gene therapy, known as Luxturna® (voretigene neparvovec-rzyl). Though it comes with a large price tag, Luxturna® is a one-time treatment that can stop adverse vision loss and restore visual function in patients with RPE65related IRD—a miracle drug for a patient otherwise progressing toward blindness. “Telling that young girl and her parents that there’s actually a gene therapy for that disorder, and there’s a treatment that can stabilize or regenerate her vision—that was incredible,” Dr. Ballios says.
Dr. Ballios emphasizes that perseverance is key to finding more cures and continuing to provide newfound hope for patients with IRDs. Just as much as he is inspired by the perseverance of his patients, he hopes he can pass that perseverance on to inspire others too particularly trainees,
who play a vital role in moving the field forward. “I hope I can help encourage graduate students to continue to follow their passions in research and medicine because many hands make light work. And we need that, we need more people,” Dr. Ballios reflects. “Research is not a straight line, and the path to cures is not a straight line. There’s discouragement along the way, there are successes and failures. But it’s important to stick with it,” he says. “That’s probably the most important lesson I’ve learned in the early part of my career.” Perseverance to do whatever it takes—a powerful fueling agent that drives his visions forward and empowers others to do the same.
To learn more about Dr. Ballios’ research, please visit www.ballioslab.com.
I knew in my junior year of high school that I wanted to be a biomedical illustrator. I knew that simply fine art or biological science would not be enough for me. Once I found out that this career existed, and I could mix my two interests, I immediately set my eyes on getting into a graduate program. I obtained a BFA in Studio Arts, where I focused on painting. I preferred working with oil on wooden panels, which allowed me to create glassy surfaces with high amounts of detail. The subject matter of my art in undergrad consisted of highly detailed, visceral, and often confrontational imagery. Now at BMC, I aim to create clear and accurate scientific visualizations with the same amount of care that I put into my paintings. I’m looking forward to learning more about visual storytelling and finding new ways to foster communication through art and science.
I’ve always had a deep interest in both the arts and sciences. I completed a Bachelor of Science in Biochemistry and entered the field of stem cell research post-graduation. My heart, however, longed for creativity. I eventually found it in the Biomedical Communications program. I hope to foster spaces of care and empathy within the field through the creation of accessible communication tools.
A love of art and of science have been two lifelong constants for me. Working as a biomedical communicator, I am grateful to be surrounded by the things I enjoy and share them with others. I completed my undergraduate degree in Honours Science, with a minor in Biology and a research focus in Astrobiology. Now at BMC I enjoy applying my passions, and have the opportunity to blend art and science in a way that makes the result even greater than the sum of their parts.
Throughout evolution, we’ve been used to hanging on to pieces of information from all senses that may be deemed important later for survival and daily life. For example, recalling that hidden beside a particular collection of trees is a stream of clean water, or a certain smell means that a food isn’t edible. In fact, every piece of information is relevant to us since it relates to a setting, an emotion, or people in our lives that characterize our daily experiences.
But embedded in today’s world is social media, in which we have a different type of existence—what I like to call the Mediabiome—also filled with social connections, locations, stimuli, information, aesthetics, and emotion which we either consciously compile, or randomly come across by browsing and scrolling.
These vastly different stimuli that come from our screens may have nothing to do with our tangible lives at work, home, or in our surroundings—they may also have no connection to our close circle of people. What’s most important is that we can reach a random irrelevant piece of stimuli just as easily as a relevant one, or perhaps, it might be even quicker to come across an irrelevant piece of information based on our random chances when scrolling.
Never in human history have we had so much information and so many connections to people so quickly at our disposal with such minimum effort (if any at all).
Think of closing your eyes when you’re bored and suddenly finding yourself in a pretty bakery with cute lo-fi themed music when you open them. Then you might get tired of this, close your eyes again, and find yourself in a dark alley full of loud rock music. This is the world of social media today, this is our Mediabiome, where the boundaries of place and time seem to vanish within a few seconds of typing.
I hypothesize that our brains over the years may indeed, through plasticity, start to realize that so much of our everyday stimuli coming from screens, if not all, are irrelevant to our tangible priorities. I wonder if our brains just go into this state of forgetting most of the stimuli they receive during the day since so much of it is irrelevant to our lives. Indeed, what’s the point of retention and memorization if all our questions or impulsive needs for entertainment are satiated within seconds with a quick transient search on the phone? Our brains may adapt to fit this setting of our Mediabiome, and in a way, we may be relying on an information base where recognition is more important than complete recall or storage.
Now you might say, well this proposed “Mediabiome brain” and forgetfulness may only be for random irrelevant content; the content one views can be catered and recommended based on personal taste thanks to algorithms. You’d be right. But even then, we face another issue of similar nature. This time it is not heaps of random information that can impact our brain, but
heaps of the same type of information. To use an analogy, it’s like having only one type of bacteria in our gut-microbiome, when we need a balance of many different bacteria to stay healthy. To add on, it may become worse when there’s only one or few dangerous types of bacteria in our gut microbiome, or only a few types of content in our Mediabiome that may negatively impact our mental health.
We might find ourselves roaming for hours in our slightest temptations for a new online setting. Because once you have a large bag of popcorn, you might be craving some sweet ice cream afterwards, and then some oily pizza, and then some more ice cream cake. Our stomachs, however, will soon warn us of the consequences of continuing this pattern and if not, surely, we’ll run out of supplies of ice cream, or run out of money to buy more.
With social media however, there’s no limit to storage and seemingly no cost to the variety of content available. Whatever type of information one is craving or is curious about, as long as they can think of it, is available online—there is, in other words, no boredom left in our world even if we waste our time with things we are not that satisfied with.
But would you randomly walk into an alley or a random setting without any preparation or a map, just because you felt like it? You might do that once and be just fine. But imagine teleporting into random streets and meeting strangers everyday.
If one does this, they may get lost, worried, or view things they weren’t prepared to see. Our lives online follow this analogy. Our mental health may end up having the need for some attention just as our stomachs would if we keep on eating buckets of ice cream. Think of how harmful this may be when our brains are still developing.
What is more is that all the stimuli, whether it’s important or not, come from the same medium—the virtual screen. That is our Mediabiome isn’t exclusive to only entertainment or the nontangible. From our work-related Excel datasheets to our current favorite TV show, music playlist, and text messages from loved ones—they are on the same screen! In place of thorough letter writing from just a few centuries ago, or hour-long telephone
calls that were common just a decade ago, now suddenly most of us resort to more frequent but choppy conversations through text message, sometimes between different time zones, that neither feel completely socially satisfying nor completely isolating. A hazy social existence between space and time.
Our emotions might feel a tad bit confused as well. Think about it, you open your Tik-Tok or Instagram reels and see a post about fraud that makes you angry, then you see a cute video of a puppy helping a small bird and smile, you scroll, and see another video of your favorite TV show’s most sentimental scene and you might even tear up. In a span of 40 seconds, you have now gone through an emotional rollercoaster but haven’t related to anything or anyone tangible.
Many say social media provides social opportunities for those who are lonely, and they’re right. But what if loneliness is becoming a new norm among some people since it may be a more (temporarily) efficient lifestyle? After all, this cycle will continually lead to more social isolation, depression, and feelings of dissociation.
Social media’s negative or positive impact may also have inequitable bias. For example, someone who lives in a neighborhood may already have close people they can meet up with and can take relaxing breaks form media to walk to their nearby park. On the other hand, a lonely immigrant college student, living on
a tight budget, knowing no one in a new country, living in a tiny studio apartment surrounded by nothing but concrete towers, already fixated on studying with mostly online classes is at far higher risk of social media’s negative impact. Social media, then, also brings into question topics of equity. Even though it gives easy and affordable access to those with lower economic standings, it also may pose just as many barriers if not dealt with properly.
Social media has been linked to increased risk for addiction, memory dysfunction, and social isolation in youth. If the evidence isn´t enough proof for action, must we wait for longitudinal studies to show us, when it might be too late, that we should take better care of our mental health and cognition in this new age of the virtual screen?
“ Never in human history have we had so much information and so many connections to people so quickly at our disposal with such minimum effort...”
The namesake of the modern physicians’ Hippocratic Oath has been attributed to this quotation, which may elicit surprise from steadfast scientists and critics of the newspaper horoscope. 1 Astrological medicine was once part of a physician’s university training, 2 but surely modern medicine doesn’t require a deep understanding of zodiac signs and the lunar cycle?
Astrology has observed connections between celestial and terrestrial events for millennia. This practice relied on planetary orbits around the sun, lunar cycles, and constellations to better understand human behaviour, and most importantly, humans’ interactions with the Earth. We can consider two streams of astrology: natural and judicial. 2
Natural astrology was based on astronomy, the science of the stars, where patterns of past events were used to predict future terrestrial events. For example, mapping the lunar cycle informed early human civilizations of the moon’s influence on the tide and led to the origin of the calendar. Tracking constellations provided the first tool for navigating the changing seasons as they rise in the night sky in a particular sequence with the Earth’s solar orbit. Constellations were used to predict annual flooding and optimal crop growth. Today, we see evidence of sophisticated astrological mapping in
the placement of ancient temples that align with certain celestial cycles. 3
On the other hand, judicial astrology applied more to individual health and personal matters. Judicial astrology was used in medicine for centuries and gives rise to the astrological signs we’re familiar with today. 2
The constellations: Aries, Taurus, Gemini, Cancer, Leo, Virgo, Libra, Scorpio, Sagittarius, Capricorn, Aquarius, and Pisces make up the Western zodiac signs. Most of us understand astrology as the constellation that appears in the sky on our birthday and the quizzical hold it has on our personality and behaviour. But this is only one part of the horoscope or astrological birth chart.
The birth chart maps the entire sky at the time of birth and astrologers believe the culmination of celestial placements creates individual identities and personalities. The three major elements that make up the birth chart are the sun, moon, and rising signs. The aptly named sun sign captures the point of the Earth’s rotation around the sun at the time of birth. The sun sign is commonly referenced when asked, “what’s your sign?” The moon sign refers to the position of the moon, and the rising sign to the constellation that was rising on the Eastern horizon at the time of birth. Birth charts differ from individual to individual based on the geographical location and the time of birth, right down to the minute.
The validity of astrologically influenced human behaviour has long been criticized. Reading a
A physician without knowledge of astrology has no right to call himself a physician
“ “
- Hippocrates
daily horoscope can be a fun gag or even thought-provoking, but these philosophical proclamations sway far from the sophisticated origins of natural astrology.
In fact, some scientific studies have falsified the relationship between astrological signs and specific human behaviour, reporting that astrology performs no better than chance. 5 Another study demonstrated that the belief in astrology can be influenced by confirmation bias, or the tendency to only seek out and interpret information that confirms a belief. 6 Still, astrological medicine may have predicted the biological correlations more recently demonstrated between birthdate and the risk of some diseases. 1
Modern astrology is considered a pseudoscience, but does this render it completely useless? For some, astrology still serves a purpose beyond the newspaper horoscope. In the US, the psychic services market, including astrology, was valued at $2.2 billion in 2021. 7 Astrological practices are part of the post-pandemic wellness movement, which prioritizes mind, body, soul, and spirit. 8 Astrology offers an opportunity for introspection, to explore spirituality, and to confront personal obstacles. 9 In this way, followers of astrology are not necessarily turning to the sky for answers to their problems, but rather
using the stars to develop a deeper understanding of the self and to attain a sense of non-religious spirituality. The application of modern astrology, thus, falls to the individual and their interpretations.
It is easy to pass judgement on the seemingly frivolous and unscientific pastime of astrology. However, our society is ripe with frivolous and unscientific ventures. Whether you turn to the stars to calm your anxieties or to learn of a change in season, there may be power in believing. Afterall, participating in spiritual practice has been correlated with better mental and physical health. 1 ⁰ So, what’s your sign?
1. Wolfson, E. Your Zodiac Sign, Your Health. The Atlantic. [Internet] 2013. Available from: https://www.theatlantic.com/health/archive/2013/11/your-zodiac-sign-your-health/281358/
2. Kassell, L, Hawkins, M, Ralley, R, Young, J, Edge, J, Martin-Portugues, JY, Kaoukji, N. (eds.), ‘Casebooks’, The casebooks of Simon Forman and Richard Napier, 1596-1634: a digital edition. Available from https://casebooks.lib.cam.ac.uk/astrological-medicine/early-modern-astrology.
3. History of Astrology. Wikipedia. [Internet]. 2022. Available from: https://en.wikipedia.org/wiki/History_of_astrology
4. Thomas, K. Sun, moon, rising signs: What they mean and how to find your big three. New York Post. [Internet]. 2022. Available from: https://nypost.com/article/sun-moon-rising-sign-meaning/
5. Hartmann, P, Reuter, M, Nyborg, H. The relationship between date of birth and individual differences in personality and general intelligence: A large-scale study. Personality and Individual Differences [Internet]. 2006; 40(7): https://doi.org/10.1016/j.paid.2005.11.017
6. Allum, N. What makes some people think astrology is scientific? Science Communication [Internet]. 2010; 33(3): https://doi. org/10.1177/1075547010389819
7. Psychic Services Industry in the US – Market Research Report. Industry Research Reports, United States. [Internet]. 2021. Available from: https://www.ibisworld.com/united-states/market-research-reports/psychic-services-industry/
8. Prinzi, M. ATH Opinion: Why Astrology and Witchcraft are Positive Wellness Practices. All things Hair. [Internet]. 2022. Available from: https://www.allthingshair.com/en-us/hairstyles-haircuts/ astrology-and-wellness/
9. Vennare, J. How Astrology Infiltrated the Wellness Industry. Medium. [Internet]. 2019. Available from: https://medium. com/@joevennare/how-astrology-infiltrated-the-wellness-industry-945348539a3b
10. Spirituality. Psychology Today [Internet]. 2009. Available from: https://www.psychologytoday.com/ca/basics/spirituality
If you pick up a novel written in the second half of the 20th century by a South American author, you are likely to find a character able to fly. One Hundred Years of Solitude 1 or The House of the Spirits 2 are prime examples of magical realism, a literature genre where real world accounts are tinted with a magical undercurrent of fantasy.
In The House of the Spirits, Isabell Allende narrates the story of a Chilean family throughout the 20th century. The family is faced with the repressive power of Augusto Pinochet’s military dictatorship. As if to make the series of tragical historical events more emotionally digestible, she endows her characters with the ability to read minds, move objects by will, and even fly.
Isabel Allende gave wings to her first characters during exile. 9/11 had become a date to remember for Chileans long before 2001. In 1973, a coup d’état led by the military on September 11th bombed the president’s palace in the capital, Santiago. The democratically elected president, Salvador Allende—Isabel Allende’s uncle—was killed. His socialist government was violently dismissed, and Augusto Pinochet raised to power. Chile remained under his military right-wing dictatorship until 1990, during which time Isabel Allende wrote her fears away.
Less than 25 years have passed since Chile’s return to democracy, yet the South American country is leading a pioneering effort in defending human rights, becoming the first nation to contemplate Neurorights in their constitution. Neurorights aim to provide a new international legal framework for the protection of brain activity underpinning our unique identity and decision-making abilities.
In October 2020, Chileans voted in favour of rewriting their constitution, which dated back to Pinochet’s era. Less than a year later, Chilean lawmakers approved a law protecting personal identity, privacy, and free will:
“Scientific and technological development will be at the service of people and will be carried out with respect for life and physical and mental integrity. The law will regulate the requirements, conditions and restrictions for its use in people, especially protecting brain activity, as well as the information coming from it.”3
I can’t help but think that unconsciously, Chile has pioneered the introduction of Neurorights to their new constitution in an effort to protect the creativity and independence of thought that inspired The House of the Spirits. That is, to watch over the magical realism that has facilitated healing during and after Pinochet’s dictatorship, giving value to individual stories.
The goal is that one day, Neurorights are not only present in independent countries’ constitutions, but also reach international human rights instruments, including the United Nation’s Universal Declaration of Human Rights (1948).
Through the integration of ethics, law, and neuroscience, Neurorights target four areas of concern that are not yet protected by existing medical and technological ethics guidelines—the Declaration of Helsinki (1964), the Belmont Report (1979), or the Asilomar Artificial Intelligence Statement of cautionary principles (2017). The concerns are privacy and consent, agency and identity, augmentation, and bias.4,5
Looking back on the past century of Chilean history, one can find examples of human rights that should be protected if history were to repeat itself in the Age of Neurotechnology.
An estimated minimum of 27,200 persons were tortured during Pinochet’s dictatorship, and a total of 38,000 imprisoned for political reasons. One wonders how the chronic state of fear that dominated the country then could have been reinforced if suspects had been traced through smart phone and computer activity-a fear felt in countries currently under war and political repression. Consider how torture strategies could be
enhanced by accessing one’s mental states through technological devices, violating one’s fundamental right to mental privacy.
Rafael Yuste, professor of Biology at Columbia University and co-founder of the Neurorights Foundation, has warned that in just about 20 years, everyone will have brain implants, ending the smart phone era by eliminating screens as the interface between the technological device and person.6 The link between them could be established directly. Without needing to type or dictate one’s questions to Siri, Siri would already know what we are thinking by reading our thoughts.
This takes us to the next concern: to what extent can neurotechnology blur our sense of self, agency, and identity?
About 12.8% of Chile’s population are Indigenous peoples (over 2 million). All suffered under Pinochet’s rule when it was forbidden to speak a native language other than Spanish, and Indigenous natural resources were sold to and exploited by big international corporations. Chile’s economy arguably grew at the expense of Indigenous peoples.7
Pinochet’s government aimed at erasing Indigenous identity. If in the future a repressive government had the power to control individual thoughts and feelings through neurotechnology, could cultural diversity and individual identities
disappear? The process could be sped up by controlling people’s thoughts at the press of a button through brain-computer interfaces, such as the brain implants Rafael Yuste is warning about.
In this Orwellian reality, enhancing neurotechnologies could further be used to benefit those in power, calling on Neurorights’ third concern: augmentation. Neurorights’ concern with augmentation argues that neurotechnology could exclusively benefit the rich if not regulated.
In 2019, Chileans took to the streets to protest the economic inequalities that have persisted in the country since Pinochet’s era, drawing international attention. Although in 2019 Chile was significantly wealthier than its neighbours, Argentina, Bolivia, and Peru, the difference between the richest 10% and poorest 10% of the population was the second highest in Latin America, only behind Mexico.8 Levels of economic inequality had remained intact for over a decade,8 leaving Chileans frustrated and thirsty for change.
I believe this frustration could be reinforced if neurotechnology was only accessible to the richest 10% of Chileans. Imagine the impact of OpenAI’s ChatGPT becoming a paid service,9 like Netflix; richer university applicants, for example, could gain advantaged access to write their motivation letters with the help of artificial intelligence.
The last concern of Neurorights, bias, precisely refers to the capacity of neurotechnologies of perpetuating and reinforcing inequalities. Neurorights will ensure bridges are laid between these extremes.
Yet from my perspective, Neurorights are not only essential to prevent the potential horrors if neurotechnology was leveraged by future repressive powers. Neurorights can also ensure future generations can use their voices to narrate their times from their own subjective perspective despite the rise of neurotechnology, perhaps resorting to magical realism like Isabel Allende did.
1. Allende, Isabel. The House of the Spirits. 1982. Vancouver: Penguin Random House.
2. García Márquez, Gabriel. One Hundred Years of Solitude. Vancouver: Penguin Random House, 1967.
3. Senado. Histórica aprobación: información cerebral estará protegida en la Constitución - Senado - República de Chile. Senado.
4. Yuste R, Goering S, Arcas BA y, et al. Four ethical priorities for neurotechnologies and AI. Nature. 2017 Nov;551(7679):159–63.
5. Ienca M. On Neurorights. Frontiers in Human Neuroscience. 2021; 15.
6. Ansede M. “Tener un sensor en la
7. El Mundo Indígena 2022: Chile - IWGIA - International Work Group for Indigenous Affairs.
8. OECD. 2019. Society at a glance 2019: OECD Social Indicators. OECD Publishing, Paris.
9. OpenAI. ChatGPT: Generative Pre-training Transformer. [Online software].
By Syed Hussain Ather
Are you “anxious”? “Secure”? “Avoidant”? Or perhaps, “none of these are accurate”? Across social media, these attachment styles have grown in popularity. People have found themselves defining and declaring into these neat categories, labeling, and providing them with a sense of identity and self as well as a connectedness to others. The “anxious” person may find themselves avoiding others in times of stress or being afraid or sensitive to rejection. Similarly, people with “avoidant” attachment styles may also avoid intimacy. Someone who’s “secure” doesn’t have these fears, and they, instead, appreciate their self-worth wholly independent of others. But are these broad, sweeping categories truly effective or even scientifically valid ways of looking at the ways we interact with others?
Since it was formulated in 1958, 1 attachment theory has grown from a single theory describing behaviors, habits, and tendencies that arise from children in their relational attachment to their caregivers. When the British psychologist John Bowlby formulated the theory, he sought to study how these early-life relationships of a growing child would set the basis for these tendencies with the rest of the world. Alongside American-Canadian psychologist Mary Ainsworth, Bowlby described three types of attachment styles between mothers and infants:
anxious, avoidant, and secure. As time went on, more categories were added with increasing complexity, including “anxious avoidant” and “disorganized.” These labels were meant to describe how, when observing the relationship between the child and their caregiver, the relational styles and ways in which the child would view their caregiver served as the basis for how the child would see other people in the world. It’s been shown that children with “secure” attachment styles had higher abilities to understand other people and their states of mind. 2 Some argue other cognitive and psychological capacities are rooted in these relationships too. Our capacity to empathize with one another, for example, could come from how close and secure our history of attachment is with parental figures from our upbringing. 3 Right off the bat, many of the initial studies came with limitations from the point of view of scientific inquiry. These studies have not been replicated to establish their credibility and reliability as thoroughly as needed.
In the 1980s, researchers expanded the use of attachment theory to relationships, 4 and, in turn, hopefully, attachment theory would expand to explain how individuals end up behind bars or unemployed. By the early 2000s, the field became known as “Modern Attachment Theory,” or “Contemporary Attachment
Theory,” and much of the work shifted from Bowlby’s original focus on infant-mother relations to romantic relations. Here came works like, “ Attached: The New Science of Adult Attachment and How It Can Help You Find and Keep Love ” by neuroscientist Amir Levine and psychologist Rachel Heller. And, with this, popularity took over scientific validity.
“Which style are you?” Everyone wanted to know. Those who were “anxious” would get mixed messages
..the relational styles and ways in which the child would view their caregiver served as the basis for how the child would see other people in the world.
from their caregivers. Sometimes they’d be met with positivity and other times they’d be pushed away. They would grow up worried that their relationships would end poorly. They had to be wary and cautious of sabotaging or worrying too much, lest they’d be met with the same fate as how their parents treated them. “Avoidants” feared intimacy and commitment and would lash out at people who would try to get close. And those who were “disorganized” would feel or believe they didn’t deserve love or closeness at all.
Despite there being scientific evidence that an individual’s attachment style with their caregivers doesn’t align with their attachment style with their romantic partners, 5,6 these categories have caught on with the public. Some raised their eyebrows. It’s been noted and questioned whether the categories of attachment theory line up with true ways of categorizing individuals and their personality traits or what the true mechanisms of attachment might be. 7 The styles themselves (including “secure” and “anxious”) were, more or less, made up to match and fit observation with some sort of neat set of categories. Other points of criticism have been raised, including how universal attachment style categories are when studies seem to be based on Western, middle-class perspectives of the world. 8
What hope is there for attachment theory? We should continue to explore how our upbringing and environment have given rise to patterns in thoughts, emotions, and behavior. The way one’s past shapes personality is key and central to many theories in psychology, neuroscience, and cognitive science. But attachment theory has strong limits that shouldn’t be crossed, otherwise, we’re doomed to anxiously wait for the approval of weak science.
1. Bowlby J. The nature of the child’s tie to his mother. In Influential Papers from the 1950s 2018 Nov 9 (pp. 222-273). Routledge.
2. Fonagy P, Redfern S, Charman T. The relationship between belief‐desire reasoning and a projective measure of attachment security (SAT). British Journal of Developmental Psychology. 1997 Mar;15(1):51-61.
3. Schmidsberger F, Löffler-Stastka H. Empathy is proprioceptive: the bodily fundament of empathy–a philosophical contribution to medical education. BMC Medical Education. 2018 Dec;18(1):1-6.
4. Hazan C, Shaver P. Romantic love conceptualized as an attachment process. In Interpersonal Development 2017 Nov 30 (pp. 283-296). Routledge.
5. Brennan KA, Clark CL, Shaver PR. Self-report measurement of adult attachment: An integrative overview.
6. Furman W, Simon VA, Shaffer L, et al. Adolescents’ working models and styles for relationships with parents, friends, and romantic partners. Child development. 2002 Jan;73(1):241-55.
7. Waters E, Beauchaine TP. Are there really patterns of attachment? Theoretical and empirical perspectives. Developmental Psychology. 2003 May;39(3):417-22.
8. Keller H. Universality claim of attachment theory: Children’s socioemotional development across cultures. Proceedings of the National Academy of Sciences. 2018 Nov 6;115(45):11414-9.
The styles themselves ... were , more or less, made up to match and fit observation with some sort of neat set of categories
“ “
Dr. Shannon Lange is an independent scientist with the Institute for Mental Health Policy Research at CAMH. She is also an assistant professor in the Department of Psychiatry. Her research involves the application of advanced statistical techniques in the understanding of suicidal thoughts and behaviours in relation to alcohol use.
Dr. Nicholas Neufeld is a psychiatrist (Early Psychosis Unit) and scientist (Kimel Family Translational Imaging-Genetics Laboratory) at CAMH. His research focuses on severe mental illness across the lifespan with an emphasis on brain imaging to obtain biomarkers of treatment trajectories and response.
Dr. Fa-Hsuan Lin is a professor in the Department of Medical Biophysics and IMS. Their research focuses on the development and application of human neuroimaging (MRI, EEG) and neuromodulation (TMS) methods and the translation of these cutting-edge tools to neuroscience studies and clinical applications.
Dr. Danielle Baribeau is a child and adolescent psychiatrist with a clinical focus in autism, neurogenetic disorders, and psychopharmacology. As a clinician scientist at the Bloorview Research Institute, she leads a research program focused on clinically translating genetic advances into improved mental health care in autism and neurodevelopmental disorders.
Dr. Aristotelis Kalyvas is a staff neurosurgeon (surgical neuro-oncology and skull base surgery) at Toronto Western Hospital and an assistant professor at the Department of Surgery. His research focus is on structural brain connectivity, brain mapping, and clinical research/surgical clinical trials on brain, skull base and pituitary tumors.
Dr. Ahmed Bayoumi is a general internist and clinician scientist. He is also a senior adjunct scientist at ICES. He has extensive experience in translating research to policy and has co-led large multi-method studies, His research interests include the delivery of health services to marginalized populations.
Dr. Lorne Zinman is an associate professor of medicine and an associate scientist at Sunnybrook Research Institute. His research focuses on the development of more reliable diagnostic and pharmacodynamic biomarkers in ALS to test the most promising therapeutics.
Dr. Siba Haykal is a surgeon-investigator at UHN and the Toronto General Hospital. Her clinical focus is on complex oncological reconstruction and microsurgical reconstruction of the breast, head and neck and extremity. Her research focuses on tissue-engineered techniques for tracheal reconstruction and the immunology of vascularized composite allotransplantation.
Dr. Sloane Freeman is a pediatrician at St. Michael’s Hospital and an assistant professor in the Department of Pediatrics at the Univerity of Toronto. She has expertise in the care of the medically complex child and child development. She is the lead for the REACH School Network, a program bringing health care to at-risk schools.
Dr. Rachel Vanderlaan is a cardiovascular surgeon at The Hospital for Sick Children. Her lab focuses on the role of mechanotransduction in pulmonary endothelial biology, with a special interest in pulmonary vein stenosis. In addition to laboratory work, she is the co-director of the PVS Network registry study.
Dr. Katharine Dunlop is a scientist at St. Michael’s Hospital and an assistant professor of psychiatry at the University of Toronto. Her research uses TMS, neuroimaging and multivariate methods to develop biomarkers of treatment response and suicide risk in depression.
Dr. Helen Dimaras is an associate professor and the Director of Global Health in the Department of Ophthalmology & Vision Sciences at the University of Toronto. Her research lies at the intersection of global health, cancer genetics and patient engagement.
Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) are rare, genetically distinct Connective Tissue Disorders (CTD). The primary contributor of morbidity and mortality is dilation of the aorta, the largest blood vessel in the body, leading to rupture and subsequent death if timely intervention is not administered. A few decades ago, the life expectancy of patients with these disorders was around 30-40 years. However, with the appropriate clinical management, driven by groundbreaking research, individuals with MFS and LDS can have life expectancies similar to that of the general population.
Nairy Khodabakhshian, a second-year PhD student in the Institute of Medical Science (IMS) program studies the cardiac response to exercise in pediatric patients with MFS and LDS. She works at the Hospital for Sick Children (SickKids) under the supervision of Dr. Luc Mertens. By studying differences in exercise responses in children with MFS and LDS compared to healthy volunteers, Nairy’s research hopes to better identify high-risk patients and reduce the risk of adverse aortic events.
Nairy’s journey into IMS has been a unique one. She graduated from the Biomedical Sciences program at Toronto Metropolitan University where she made her time count. Nairy worked in two labs over the course of her undergraduate studies, culminating in the completion of a fourth year wet-lab based thesis project.
This experience led her to appreciate the fundamentals of research methodology. Nairy also volunteered at SickKids and the affiliated Ronald McDonald House Charities throughout her undergraduate studies. After graduating, Nairy landed an administrative position in the cardiology unit at SickKids. Here, she received an opportunity to experience a side to science and medicine that was very different from wet-lab research. “Although this job was an administrative role, I got a lot of clinical exposure: learning about the patient journey from admission to discharge, observing the day-to-day flow of the clinical setting, and seeing how multidisciplinary teams manage high acuity patients.”
To Nairy, the world of pediatric cardiology was super interesting. “I would hear diagnoses and I would ask the nurses to explain the concepts to me during downtime, as well as look it up in my own time.” This experience had a strong influence on her chosen field of graduate study. “I made a pact to myself that if I was going to do a graduate project, it would 1) be in the field of pediatric cardiology and 2) be clinical research focused”. Nairy got to know several physicians and researchers at SickKids during her administrative role, including her future supervisor Dr. Luc Mertens. Being drawn towards the research he conducted, Nairy eventually applied to the IMS and secured a position in his lab as an MSc student. “Having a bit of a rapport with him from my time at SickKids propelled the student-supervisor
dynamic. He’s been incredibly supportive throughout my degree”.
While talking to Nairy, I got the sense that she has a very mature perspective about her research. Being surrounded by clinician-researchers in her lab, she gets to directly observe the transition of research from the bench to the bedside. “The Mertens lab is fortunate to have direct access to the Connective Tissue Disorders Clinic at SickKids, which is managed by my co-supervisor, Dr. Vitor Guerra. Through my interactions with clinicians, I always keep the question of ‘Is this clinically relevant?’ when I make decisions related to my research.” Although intimidating and challenging at times to be surrounded by clinician-researchers with a vast knowledge base, Nairy feels this allows her to excel in her research.
After 18 months into the MSc program, Nairy successfully completed her PhD transfer exam. The decision to transfer was a very calculated one. “If you asked me at the beginning of my Master’s whether I would ever do a PhD, I would have sworn ‘No’”, said Nairy looking back on her decision. Never say never though! Nairy had a fantastic opportunity to transition, as her program advisor committee members unanimously agreed that her project could obtain sufficient data to qualify for a PhD degree. But what made her decide to transfer? “There were many factors. I looked at my own career aspirations—I wanted to be a clinician-scientist myself. I didn’t want to give up the clinical exposure
or the research. I enjoyed everything about my research project, and really wanted to see my project through to the end. I asked other people who had obtained PhD degrees at different points in their careers. I learned about the pros and cons of each journey. Ultimately, I felt the best time for me to get the degree would be now.”
And what advice did she have for MSc students in IMS considering transferring into the PhD program? “It’s a massive commitment.” She stresses the importance of not doing a PhD degree just for the sake of doing it. “Think about your career aspirations, consider your own life and personal circumstances when deciding the best time to
do the degree. Ask the various PhD candidates and graduates for their advice.”
Apart from her research, Nairy is heavily involved in extracurriculars within the IMS. She joined the Institute of Medical Science Student Association (IMSAA), where she held executive roles for 2 years. Once she successfully transferred into the PhD program, she became the Program Lead of the Peer-2-Peer Mentorship program, aiming to assist incoming IMS students with navigating through various responsibilities during graduate school.
Furthermore, Nairy continues to spearhead a Clinical Research Skills course to be available to IMS students, where basic clinical skills is taught to graduate students in the early phases of their graduate work. The goal of this course is to enable the integration of graduate students into the clinical setting. Together with a team of IMS students and faculty, including one in the Biomedical Communications (BMC) program within the IMS, they are hoping to launch the course with a virtual reality (VR) component. “We didn’t want to task an already overburdened healthcare system with equipping our graduate students with clinical research skills, but we also knew that this course could not be taught in the traditional lecture format, so VR was a solution that addressed both those challenges. As a bonus, this project gets to be the MSc project of a BMC student.” Nairy has allowed me to share that their group is currently in the process of receiving
approval to formally offer the modular course to IMS students in Fall 2023.
One piece of advice for the incoming IMS student? “Be stubborn with your longterm goals, but flexible in your journey to them. If there’s anything I’ve learned from grad school, it is that things don’t always unravel as planned, but they always end up working out.”
Upon graduation, Nairy plans to continue her journey of becoming a clinicianscientist, perhaps within the field of pediatric cardiology. “That’s the ideal route for me. But as I learned, I am leaving the door open for other opportunities”. One thing is certain; the work during her PhD will not only help children with MFS and LDS, but will also help set up future generations of IMS graduate students for success.
Today it seems inconceivable that people once smoked cigarettes in restaurants, or in cars with children, and even on airplanes. The negative health effects related to cigarette smoking was known to researchers in the early 1900s but it was not officially recognized until a report was released from the United States Surgeon General in 1964. 1 Another 50 years went by before Canada implemented smoking bans. 2 Since then, smoking rates have been steadily declining in Canada. 3 However, a new public health concern has taken its place: vaping, or use of e-cigarettes. Vaping is particularly common among youth. Individuals between the ages of 15 to 24 have the highest rates of vaping in Canada. 3 Dr. Michael Chaiton, an Associate Professor in the Institute of Medical Sciences (IMS) is dedicated to answering two important questions; 1) why are youth in Canada vaping? and 2) what is the impact of new regulations on e-cigarettes and vaping products in Canada?
Dr. Chaiton uses a population-based approach to study vaping and the impact of health policies. His interest in public health policy and epidemiology began through his work with a nongovernmental organization (NGO) where he was working on a project related to the negotiation of the Framework Convention on Tobacco Control. Meeting epidemiologists in this role inspired him to pursue a Master’s and PhD in Epidemiology at
the University of Toronto. His graduate work sought to better understand the role of nicotine dependence in smoking cessation, as well as the relationship between smoking and depression in adolescents. During these graduate programs, he gained a better understanding of epidemiology and methods that can be used to study smoking-related behaviours at the population level. Dr. Chaiton is currently a scientist at the Centre for Addictions and Mental Health (CAMH) where he has been conducting large cohort studies and studying the impact of public policies on mental health and addictions.
Government regulations and public policies are unique interventions because they have the potential to impact health for the entire population. For example, Dr. Chaiton has studied the impact of Canada’s recent ban on the sale of menthol cigarettes, demonstrating improvements in smoking cessation rates. 4 Their study also projected the impact a menthol ban would have in the United States (US), finding that implementing the menthol ban in the US would be expected to lead to over a million people quitting smoking. This work has been cited by the US Food and Drug Administration (FDA) in support of new regulations on cigarette products.
Currently, his team is following a ‘vaping dependence cohort’ of ~3,300 Canadian youth to study the natural history of vaping and the impact of new
vaping regulations that have been put into place over the last few years. These regulations have limited the amount of nicotine in e-cigarettes, prohibited the sale of e-cigarette products to youth and restricted the sale of flavoured products. 5 There has been little research on the potential effects of these bans. This is particularly important because of the potential substitution of cigarettes and e-cigarettes, where even if these regulations may reduce vaping initiation and lead some people to quit vaping, the regulations may encourage others to switch to cigarettes instead. To help youth and young adults quit vaping, Dr. Chaiton’s team has been developing digital apps, websites and school-based programs. For example, the ‘Stop Vaping Challenge’ is a free app that encourages youth and young adults to quit vaping together with their friends. The app was co-designed by youth who were trying to, or had successfully quit vaping. The app helps users better understand the effects of their vaping dependence so that they can more easily quit and also provides local resources and support to quit vaping. To build upon this model, Dr. Chaiton is also developing the ‘Stop Cannabis Challenge’ which is aimed at youth and young adults who are starting to be concerned about their cannabis use.
Dr. Chaiton is also interested in improving youth mental health and understanding why there has been such a large increase in mental health
Associate Professor, Dalla Lana School of Public Health and the Institute of Medical Sciences, University of Toronto
Co-Director, Collaborative Specialization in Addiction Studies
conditions among this demographic over the past decade. This is especially important given that the COVID-19 pandemic has exacerbated the mental health crisis in Canada. He is currently using a randomized invitation trial to evaluate a digital platform called ‘Wellness Together, Canada’ (https:// www.wellnesstogether.ca/en-CA) which has features to track your mood and well-being and also provides mental health and substance use support from professionals.
Dr. Chaiton also recognizes the potential use of machine learning and artificial intelligence to study health at the population level. He is leveraging these novel techniques to identify predictors of behaviour change and use this information to guide interventions. His team is also committed to reaching populations that have been marginalized and highlight issues that have been otherwise ignored.
Since joining the IMS, Dr. Chaiton has had the opportunity to work with many talented graduate students. He advises current graduate students in the IMS to be resilient, stating that “the world of academics is 90% failure, doing a PhD or pursuing a career in academics is about being able to accept the failure and continue moving on”. Dr. Chaiton admits that he fell into his career by accident and that a little bit of luck in academia can go a long way.
1. Proctor RN. The history of the discovery of the cigarette–lung cancer link: evidentiary traditions, corporate denial, global toll: Table 1. Tob Control 2012; 21: 87–91.
2. Statistics Canada. Smoking ban legislation in Canadian provinces and municipal bylaws in selected cities, https://www150.statcan. gc.ca/n1/pub/82-003-x/2006008/article/smoking-tabac/t/4060721eng.htm (accessed 26 January 2023).
3. Canadian Public Health Association. Tobacco and Vaping Use in Canada: Moving Forward, https://www.cpha.ca/tobacco-and-vaping-use-canada-moving-forward.
4. Fong GT, Chung-Hall J, Meng G, et al. Impact of Canada’s menthol cigarette ban on quitting among menthol smokers: pooled analysis of pre–post evaluation from the ITC Project and the Ontario Menthol Ban Study and projections of impact in the USA. Tob Control 2022; tobaccocontrol-2021-057227.
5. Health Canada. Regulating tobacco and vaping products: Vaping products regulations, https://www.canada.ca/en/health-canada/ services/smoking-tobacco/vaping/product-safety-regulation.html (5 January 2023, accessed 28 February 2023).
Government regulations and public policies are unique interventions because they have the potential to impact health for the entire population
“ “
The Contribution of LncRNAs to Tip-Stalk Patterning in the Vascular Endothelium
Supervisor: Dr. Philip A. Marsden
Macrophage Migration Inhibitory Factor as a Critical Disease Driver and Novel Therapeutic Target in Spondyloarthritis
Supervisor: Dr. Nigil Haroon
Neuroimaging and Reward Processing in Major Depressive Disorder and Mild Traumatic Brain Injury
Supervisor: Dr. Sidney Kennedy
The Pathogenesis of CKD: Studies of FSTL1 and ACE2
Supervisor: Dr. James Scholey
Novel Ex-Vivo Strategies to Predict and Prevent Reactivation of Latent Human Cytomegalovirus in Lung Transplant Patients
Supervisor: Dr. Marcelo Cypel
Exploring Neural Stem Cell Activation in Endogenous Recovery Strategies for Neonatal Brain Injury
Supervisor: Dr. Cindi Morshead
Myocardial Structure and Function in Heart Failure with Preserved Ejection Fraction: Molecular Insights and Therapeutic Strategies Targeting Transforming Growth Factor Beta Signaling
Supervisors: Dr. Kim Connelly & Dr. Howard Leong-Poi
Development of a Cardiovascular Risk Prediction Model for Patients with Psoriasis and Psoriatic Arthritis
Supervisors: Dr. Dafna Gladman & Dr. Lihi Eder
Neuroimaging of the Dopaminergic System in Healthy Controls and Parkinson’s Disease with REM Sleep Behaviour Disorder
Supervisor: Dr. Antonio Strafella
By Kristen Ashworth
University of Toronto professors
James Till and Ernest McCulloch were studying the effects of radiation on the bone marrow when their experiments led to one of the greatest discoveries in recent medical science: stem cells. Fast forward to the present day, and an international network of stem cell scientists gather each year under their namesake. The annual Till & McCulloch Meetings (TMM), hosted by Canadian organization the Stem Cell Network, was held in-person in October 2022. As
a first-year master’s student one month into my stem-cell based thesis project, I had the fortunate opportunity to travel to Vancouver, British Columbia for six beautiful, rain-free days to soak up the groundbreaking science presented at TMM.
Kicking off the week, I attended a preconference workshop entitled “Surviving and Thriving in Grad School” (a felicitous theme for a new master’s student). The day consisted of a morning presentation and group activity on experimental design, and an afternoon panel on getting through the hills and valleys of grad school. The workshop set the stage for an inspiring week of learning. The following days encompassed a diverse array of keynote speakers, plenary sessions, poster talks, and meet-and-greet opportunities. My thesis work is specific to retinal stem cell biology, so it was exciting to be exposed to stem cell research happening outside the realm of vision science. Whether speakers discussed the impacts of the environment on muscle stem cells, the optimization of a bile duct organoid model, or the development of a novel regenerative fertility therapy, the topics were innovative and intriguing. A particular highlight was the opening keynote speaker, Dr. Catriona Jamieson, Professor of Medicine and Chief of Regenerative Medicine at the University of California San Diego. Dr. Jamieson discussed her groundbreaking research in developing an FDA-approved, selective therapeutic inhibitor that effectively
targets pre-cursor blood cancer stem cells. She also spoke of the next steps in her lab’s research portfolio: taking things to the next level (literally) by rocketing tumors into space to study the accelerated effects of aging on blood cancer development.
Although TMM was action-packed, I did have a few moments throughout the week to capitalize on the warm autumn weather and absorb the sights for which Vancouver is touted. At the end of each day, I walked to Coal Harbour downtown to marvel at the majestic triad of mountains, water, and cityscape that encircled my view and backdropped the perpetual landing of seaplanes closeby. Following the conclusion of the conference, a friend and I ventured to Capilano Bridge, where we experienced the natural beauty of a West Coast rainforest. Later, we walked the SeaWall in Stanley Park at golden hour. If you’ve never been to Vancouver, it’s a city to place at the top of your travel bucket list.
I am incredibly grateful for the opportunity to attend TMM this year. My takeaway from the experience was invaluable and potent: a surge of inspiration that would thrust me through the first few months of my own project on stem cell therapy discovery for those with blinding eye diseases.
Every graduate student goes through obstacles in graduate school, from exams, presentations, meetings, and grants, to many other things–as a whole, graduate students have a lot to catch up on in an otherwise short period. On top of every graduate student’s education challenges, international students face extra pressure due to immigration barriers and their limitations.
Starting a graduate program in a different country is an excellent opportunity to broaden our expertise internationally and grow personally by learning from a new culture. Indeed, lots of students transfer to new countries to experience academia and a different lifestyle. However, the life of an international student can be difficult. International students may encounter various challenges. These can include adapting to a new academic environment, handling cultural differences, overcoming the language barrier, managing financial problems, coping with homesickness and mental stress, and much more.
Personally, I think the biggest challenge international students have to overcome is the huge lifestyle change. Take housing, for example; whether it is your first time moving
between countries or not, your new environment won’t unfold itself. You may be exposed to an entirely new housing market, unfamiliar prices, neighbourhoods, and roommates. You may even need to rediscover a library to study, a grocery store to shop at, and a cafe to hang out with your new friends. Finding friends may not be easy either, as becoming familiar with a new culture will take time and effort. The language barrier can make this process harder. Although many international students have studied English before traveling abroad, they may not be comfortable using slang or regional dialect. Trying to understand a conversation may feel overwhelming and favour feelings of exclusion. I found help in appreciating that I was not alone. Regardless of where and when you start your international experience, meeting people who are or have been in the same situation always helps. Not only will you be able to take advantage of their experience, but also you can learn more about your journey as an international individual.
Another big challenge for international graduate students is adapting to the new academic system. Whether in a professional or research-based program, graduate school may differ from what students are used to in their native countries. Usually, international
students face much uncertainty. For example, many may not know how much engagement they should expect from their supervisor or may not be familiar with their program and exam requirements to confer. Although universities and colleges do their best to provide this information clearly, it usually helps if international students are in touch with an expert designated to explain all key information. This is especially essential as many international students arrive a few days late and miss the information sessions due to visa complications.
Speaking of visas, access to information is equally essential concerning visa-related matters. Immigration and visa procedures are substantive obstacles for international students that cause issues if appropriate resources are not provided. International students should always be conscious of their immigration documents and request extensions timely. If not followed carefully, international students can be denied entrance to Canada, stressing their studies significantly. Furthermore, long waiting times for visa applications can hinder international students from participating in conferences abroad as they may encounter visa troubles upon returning. What makes the process of visa applications frustrating is that there is yet another
government-issued document. Before applying for a visa extension, international students need to extend the validity of their study permit. Combining the waiting time for the study permit and visa extensions, international students face six months or more before leaving the country.
This list would be incomplete without talking about financial issues. As an international student, you must be wary of your expenditures. This is mainly because of high tuition rates and limited funding opportunities. Most Canadian institutes require significantly higher tuition for international students than their domestic peers, 1 which burdens students already struggling with living costs.
Furthermore, funding and loaning opportunities for international students are scarce. Most well-known funding applications, including the Natural Sciences and Engineering Research Council (NSERC), Canada Graduate Scholarships (CGS), and most Canadian Institutes of Health Research (CIHR) applications, require permanent residency status. Even opportunities like Ontario Graduate Scholarships (OGS) that allow for non-domestic applications have a minimum quota for international students. This also translates to financial aid programs
like Ontario Student Assistance Program (OSAP), which are not provided to international students. The high tuition costs and limited financial assistance not only impose a direct strain on the students but put them at a disadvantage in securing competitively funded positions.
The accumulation of the challenges above leads to an even more concerning issue; the emergence of a mental health crisis. Even a few of the mentioned matters can put tremendous stress on one’s mind. Still, it should also be appreciated that all of these coincide with a critical period of the student’s life. Many are starting to live by themselves for the first time. Others left most of their friends and family for graduate school. The students are vulnerable during this time, and international student life’s stressors can lead to substantial mental health issues like depression, anxiety, and panic attacks. Once again, I see human connections as a potent remedy. Support from others like your friends or your supervisor can help immensely. Another related issue with this case is that many students are unaware of the available counselling and therapy services suggesting these programs need to be better advertised, particularly to international students who are
less familiar with the Canadian healthcare system.
Overall, the life of an international student can be challenging, and there is much space for improving the situation. However, it wouldn’t be fair to ignore the steps that have been made to address these issues. International student centers, immigration seminars, proper health insurance coverage, and many other resources are examples of significant progress toward rendering the international experience more equitable and more appealing. One such step is made by initiating student groups with a focus on the international experience. In the past couple of years, I had the privilege to be a part of such a group, the IMS International Community. 2 We promote an international environment to support students in navigating their academic experiences. I hope the future holds more of these steps to improve the educational experience of international students.
References
1. Statistics Canada [Internet]. Canadian and international tuition fees by level of study (current dollars); 2022-09-07 [Cited: 2023-02-21]
Available from: https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=3710004501
2. IMS International Community [Internet]. 2022 [Cited: 2023-02-21] Available from: https://ims-international.ca/
On November 2nd, 2022, the Institute of Medical Science (IMS) held its 12th annual Ori Rotstein Lecture in Translational Research. The Ori Rotstein lecture series is an annual event established in 2011 to honor Dr. Ori Rotstein. Dr. Rotstein was the director of IMS from 2001 to 2011 and one of his many contributions was highlighting translational research as one of the main features of IMS. Throughout the years, the topics for these lecture series have ranged from basic science to clinical science and population health.
This was the first year after COVID-19 that this lecture was offered in person at the Li Ka Shing Knowledge Institute. The first half of the event consisted of an informative and very interesting keynote lecture delivered by Dr. Yasmine Hurd entitled “Translating the Neurobiology of Addiction for Novel Treatments of Opioid Use Disorder.” Dr. Hurd is an internationally renowned neuroscientist, the Ward-Coleman Chair of Translational Neuroscience, and the Director of the Addiction Institute at Mount Sinai Hospital. The keynote lecture was followed by an inspiring panel discussion with accomplished panelists of diverse backgrounds.
In her keynote lecture, Dr. Hurd first discussed the huge burden of the opioid
crisis and its roots in the over-prescription of opioids for chronic pain treatment. As Dr. Hurd explained, methadone has long been a conventional, substitution treatment for opioid use disorder (OUD). However, one of the major complications with substitution treatment is that it can lead to replacing one addiction with another. This signifies the need for new and more effective treatments for OUD as well as a better understanding of the neuroscience behind addiction. Upon examining the brain of heroin addicts, Dr. Hurd’s research team found dysregulation in their gene expression similar to what is seen in cancer patients. This has led them to try to repurpose and utilize the research in the cancer field for OUD treatment. Dr. Hurd also talked about the use of cannabidiol (CBD), one of 113 total cannabinoids in the cannabis plant, for OUD treatment. Their research has shown that CBD alleviates drug-seeking behavior associated with environmental cues while showing no addictive properties itself. Overall, Dr. Hurd’s research points towards a bright future for finding more effective treatments for OUD.
The second half of the event consisted of a thought-provoking panel discussion entitled “Highlighting Unique Journeys Through Research.” Dr. Rotstein moderated the panel discussion between Dr. Sarah Habibi (Ph.D., STEM content
creator), Dr. Neeru Gupta (MD, Ph.D., Temerty Faculty of Medicine), Dr. Gabriella Chan (JD, Ph.D., Temerty Faculty of Medicine), Dr. Aadil Ali (Ph.D., Traferox Technologies Inc.), and the keynote speaker Dr. Yasmine Hurd. The discussion revolved around the research journeys of the panelists and how they overcame different barriers throughout their journeys. Some of the advice from the panelists were being open to opportunities, creating a value system, remembering to focus on the process as much as the goal, dreaming big, and being persistent. They also emphasized that each person should find their unique path and not compare themselves to others.
Overall, the 12th annual Ori Rotstein lecture ended on a high note leaving the attendees excited about the future and passionate to embark upon their own unique journeys.
Raw Talk is a graduate student-run podcast at the University of Toronto about medical science, and the people who make it happen. We focus on the journeys, perspectives, and expertise of health researchers, professionals, students, patients, and community members at the University of Toronto and beyond.
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By Kyla Trkulja
Ihave a soft spot for science books. I love reading about scientific history and research in ways other than complicated, jargon-heavy journal articles, so when my Health & Pharmaceuticals class announced that one of our assignments was going to be a book review, I was thrilled that I would be able to dive into a new topic. We got a list of 25 books to choose from, but right away Antidepressed 1 stood out to me. The book was described as one that shares the real evidence surrounding antidepressant medications, mostly selective serotonin reuptake inhibitors (SSRIs) that are taken by millions of people every day around the world. As someone who knows dozens of people currently on SSRIs, I wanted to learn how they really work.
I was not prepared for what I was about to uncover, for one, the “serotonin hypothesis” of depression having no real scientific merit. For years we’ve been hearing that deficits in serotonin are what cause depression symptoms, which is why prescribing medications to increase serotonin in the brain seemed like a valid treatment for depression. This hypothesis originated in the 1960s due to the knowledge of serotonin’s important role in regulating mood, as well as the observation that many individuals with depression have deficits of this neurotransmitter. 2 However, this data is incredibly
inconsistent, and there is no credible scientific evidence to support this theory 1 – no scientific experiments or analyses, just observational speculations. In fact, some individuals with depression have too much serotonin in their brains, 3 indicating that if serotonin is playing a role, it’s not one that can be generalized as a treatment for millions of people.
The book described the formulation and acceptance of this hypothetical explanation as being orchestrated by the pharmaceutical industry to gain lifelong customers for their SSRI drugs. While I don’t doubt that Big Pharma played a role in this, I appreciated the other explanations for why this hypothesis spread like wildfire: we want a simple explanation with an easy fix. We as a society want to believe that there’s a generalizable biological process for depression that can be fixed by taking a pill once a day instead of reforming social and societal systems in place to better support people’s well-being. While the latter requires time, money, and structural changes to education, medicine, and social programmes, prescriptions can be written in the span of seconds and don’t require any additional effort on anyone else’s part.
This is a very dangerous way of approaching depression. Instead of meaningful change, millions of people are being prescribed medications
that work no better than placebo pills in 85% of people. 1 They create a chemical imbalance in the brain instead of fixing one, as increasing serotonin available for the brain to use shuts down the production of this key neurotransmitter, often making depression worse in the longterm. Even Dr. Candace Pert, the neuroscientist and pharmacologist whose work was key to the development of SSRIs wrote to the New York Times in 1997 saying she was “alarmed by the monster that Johns Hopkins neuroscientist Solomon Synder and I created when we discovered the simple binding assay for the drug receptors 25 years ago. The public is being misinformed about the precision of these SSRIs when the medical profession oversimplifies their action on the brain.” 4
“Oversimplified” is a great way to describe the knowledge shared with us about SSRIs. The association between serotonin and depression, the way these drugs act in the brain, and the effects they have biologically and clinically, are all oversimplified and vary so dramatically from person to person that it’s hard to know how someone will react to these medications. For many people, they often cause depression to
become worse before it gets better, and the increased risk of suicidality – especially in adolescents – has resulted in the FDA issuing a Black Box warning for SSRIs due to a potentially fatal side effect. 5
Antidepressed discusses a wide range of other issues regarding the widespread prescription of SSRIs, including personality changes, a lack of informed consent, dependence and withdrawal symptoms that prevent users from getting off the medication, and severe side effects. 1 “They should be called anti-sex drugs rather than antidepressants,” child psychiatrist Dr. Jon Jureidini explains, as “it’s more reliably predictable that they’re going to get rid of sexual function than it is that they’re going to get rid of depression.” 1
The risks of SSRIs are important to consider, especially since there are other treatment options that have more scientific evidence to support their efficacy without as many side effects, such as therapy, support systems, and even just time. 1 In fact, just family and friend support without help from antidepressants allows full recovery for 22% of people within one month, 67% of people within six months, and 85% of people within one year, making it “extremely difficult for any intervention to demonstrate a superior result to this.” 1 Antidepressed therefore allowed me to unlearn some of the myths and misconceptions surrounding SSRI use and made me question whether they are even needed for most people.
The book did miss the mark on one thing though – Thomson made it seem like antidepressants benefit no one, no one should use them unless they want their lives changed for the worse, and their entire market is a ploy by Big Pharma to bring in money. While I don’t doubt Pharma’s intentions, Thomson’s extreme stance was one-sided and didn’t consider the people SSRIs actually help. These mediations do work in people with severe depression, or those with a family history of it. 6 Some people also need them temporarily to go through a hard time and are able
to get off them with no problems, although I recognize that these cases may not be as common as I thought. If anything, these risks and unlikely benefits just emphasize the importance of informed consent so individuals with depression know all of the information about all of their available options, thus allowing them to make the right choice for themselves.
1. Thomson B. Antidepressed: A breakthrough examination of epidemic antidepressant harm and dependence. Long Island City, NY: Hatherleigh; 2021.
2. Albert PR, Benkelfat C, Descarries L. The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and Molecular Mechanisms. Philosophical Transactions of the Royal Society B: Biological Sciences. 2012;367(1601):2378–81. https://doi. org/10.1098/rstb.2012.0190
3. American Medical Association. American Medical Association Essential Guide to Depression. Pocket; 1998.
4. Pert CB. Letter to the Editor. TIME Magazine. 1997:8
5. Friedman RA. Antidepressants’ black-box warning — 10 years later. New England Journal of Medicine. 2014;371(18):1666–8. doi: 10.1056/NEJMp1408480
6. Naber D, Bullinger M. Should antidepressants be used in minor depression? Dialogues in Clinical Neuroscience. 2018;20(3):223228. https://doi.org/10.31887/dcns.2018.20.3/dnaber
‘Oversimplified’ is a great way to describe the knowledge shared with us about SSRIs.
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By Sena Gok, Junayd Hussain
Burnout, defined as an occupational syndrome by the World Health Organization in 2017, is a growing epidemic among all workforces, particularly in the healthcare field. Since it was first conceptualized in the 1970s, its impact on healthcare providers continues to be studied and advocated for, as a healthcare condition with significant consequences.1,2
The growing issue of burnout has plagued and tested the efficiency of healthcare systems globally, particularly since the beginning of the COVID-19 pandemic. With growing uncertainty of the individual and systemic issues leading to burnout among healthcare providers from all walks of life, we decided to review this issue alongside experts and providers in episode #101 of Raw Talk Podcast: The Many Faces of Burnout in Healthcare. 3,4
Burnout is characterized by emotional exhaustion, depersonalization, and reduced personal accomplishment. It can lead to losing passion for the role, feeling overwhelmed, and detachment from work – all of which negatively impacting patients, their families, and other healthcare team members.5 Dr. Amit Arya, a palliative care lead and Board Member of the Canadian Society of Palliative Care Physicians, says, “Burnout is the outcome of extensive stress on the job. In the last few years, research has shown that 38% of palliative care physicians have burnout due to the emotionally heavy work we do”. The current state of the healthcare system
in Ontario, with recurring staff shortages paralleled by underfunding and underresourcing of long-term care homes, has led to rationing of palliative care – often seen as a privilege rather than a human right, notes Dr. Arya.
Experts suggest that burnout among healthcare workers stems from systemic issues such as absenteeism, job insecurity, understaffing and the expectation for healthcare workers to perform outside their area of expertise. This can lead to feelings of being undervalued and segregated within the healthcare community, as well as conflicts and dissatisfaction with their roles. Emily Rowland, a registered nurse and a Ph.D. candidate at the Pediatric Rehabilitation Program at the University of Toronto, highlights the sources of burnout among healthcare providers, including advocating for better safety and equipment, trying to get people to take the virus seriously, and facing mistrust from the public and political system. For example, Bill 124, also known as the “Protecting a Sustainable Public Sector for Future Generations Act”, enacted in Ontario in 2019, has placed caps on public sector compensation, including that of nurses. This has spurred considerable opposition from the nursing body, who argue that the caps will negatively affect their ability to negotiate fair wages and working conditions.6
The impacts of burnout are widespread among healthcare providers and trainees, significantly altering the culture of
healthcare.7 According to Dr. Yezarni Wynn, a psychiatry resident at the University of Toronto, it has been difficult for residents with long hours and little time for self-care and relaxation. With the 80 hour-work weeks and fewer weekends, providers have sleep deprivation and develop further physical and mental health issues.8 In his words “Burnout is not just about feeling overworked, but also about the disproportionate expectations placed on healthcare professionals. For underrepresented minorities in medicine, burnout is an even more complex issue, as they may face additional stressors and factors that contribute to their burnout. These may include feeling underrepresented, imposter syndrome, a lack of safety in advocating for themselves, tokenism, and a lack of support and role models.” Recruiting a diverse population of healthcare professionals is one matter, but ensuring the consistent safety and support of a diverse healthcare workforce presents a distinct challenge within the healthcare system. Issues of discrimination and injustice, also providing support and resources for minority trainees, are key components of addressing this challenge and ensuring the well-being of all healthcare professionals.
The term “healthcare hero” was created at the beginning of the COVID-19 pandemic to show appreciation towards our frontline workers within the healthcare system. Nevertheless, this term needs to be revised
due to oversimplifying the struggles these individuals encounter daily. Furthermore, it falsely suggests that healthcare workers are invulnerable while failing to recognize that many face personal challenges and repercussions from the pandemic just like the rest.
According to healthcare providers, the “hero” label has not translated to any beneficial policies or sustainable support, as seen with the lack of paid sick days for many healthcare providers. It also glamorizes the field of medicine and healthcare, not acknowledging the challenges and difficulties that come with the profession.9
In medicine, there exists a culture of perseverance and the expectation that trainees should be able to “power through” difficult times. The culture of insisting on perseverance without disregarding burnout is deeply ingrained in the medical education system, which makes it challenging to disrupt. However, it is crucial to acknowledge the negative impact on trainees’ mental health and the effectiveness of future physicians. Thus, questioning the insistence on perseverance and considering the need to address the risk of burnout is necessary.10
Instead, much-needed attention must be paid to providing support and resources
for trainees to manage the stresses of medical training. Dr. Simone Bernstein, another psychiatry resident at Washington University, suggests that institutions should create opportunities for residents to take part in initiatives that promote wellness. This could be implementing an opt-out method, where institutions make accessible and confidential counselling services mandatory for residents during work hours, providing a way for everyone to understand and appreciate the importance of mental health in the healthcare profession. Additionally, supervisors and senior trainees should be mindful of the messages they send to junior trainees and make an effort to break the cycle of perpetuating this culture of perseverance.
The concept of “radical acceptance” is widely encouraged in healthcare as it involves acknowledging difficult circumstances and managing them. However, it should not be used to justify poor working conditions or blame individuals. Rather, a compassionate approach that addresses systemic issues contributing to burnout is necessary. This involves providing support and resources for trainees and fostering a culture of empathy within healthcare organizations. Shifting societal beliefs about success and performance in the field, and embracing a more holistic approach to resilience, may prove more effective in addressing burnout among healthcare workers than traditional resilience training. Prioritizing their wellbeing is crucial for healthcare workers
to deliver optimal care for their patients. It’s time for healthcare organizations to acknowledge that it is a systemic issue, take action and recognize the importance of supporting the well-being of its workforce.
We would like to acknowledge the efforts and ideas of the rest of the episode #101 team: Atefeh Mohammadi and Helen Yang were Show Hosts on the episode. Larkin Davenport Huyer held the position of Content Creator, Alex Jacob acted as the Audio Engineer, and Noor Al-Kaabi served as our Co-Executive Producer. To learn more about the impact of burnout among healthcare providers since the beginning of the COVID-19 pandemic, we invite you to listen to episode #101 of Raw Talk Podcast, titled “Many Faces of Burnout in Healthcare” (3). Also, check out our references for more information on the bolded topics and some interesting resources the team has compiled in the episode’s show notes on the Raw Talk Podcast website.
1. Burn-out an “occupational phenomenon”: International Classification of Diseases [Internet]. [cited 2022 Sep 27]. Available from: https://www.who.int/news/item/28-05-2019-burn-out-an-occupational-phenomenon-international-classification-of-diseases
2. Hillert A, Albrecht A, Voderholzer U. The Burnout Phenomenon: A Résumé After More Than 15,000 Scientific Publications. Front Psychiatry. 2020 Dec 9;11:519237.
3. #101 The Many Faces of Burnout in Healthcare [Internet]. [cited 2023 Jan 30]. Available from: http://www.rawtalkpodcast.com/ episode/101
4. Murthy VH. Confronting Health Worker Burnout and Well-Being. N Engl J Med. 2022 Aug 18;387(7):577–9.
5. De Hert S. Burnout in Healthcare Workers: Prevalence, Impact and Preventative Strategies. Local Reg Anesth. 2020 Oct 28;13:171–83.
6. About Bill 124 and Actions – Ontario Nurses’ Association [Internet]. [cited 2023 Jan 30]. Available from: https://www.ona.org/ about-bill-124/
7. Rodrigues H, Cobucci R, Oliveira A, Cabral JV, Medeiros L, Gurgel K, et al. Burnout syndrome among medical residents: A systematic review and meta-analysis. PloS One. 2018;13(11):e0206840.
8. Liu Y, Zhang Q, Jiang F, Zhong H, Huang L, Zhang Y, et al. Association between sleep disturbance and mental health of healthcare workers: A systematic review and meta-analysis. Front Psychiatry [Internet]. 2022 [cited 2023 Jan 30];13. Available from: https://www. frontiersin.org/articles/10.3389/fpsyt.2022.919176
9. Cox CL. “Healthcare Heroes”: problems with media focus on heroism from healthcare workers during the COVID-19 pandemic. J Med Ethics. 2020 Aug;46(8):510–3.
10. Veal CT. We Burn Out, We Break, We Die: Medical Schools Must Change Their Culture to Preserve Medical Student Mental Health. Acad Med J Assoc Am Med Coll. 2021 May 1;96(5):629–31.
