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CRITICAL REVIEW

CRITICAL REVIEW

Dear Reader,

As this year comes to a close, we must confront the need to change and grow. Change —as exciting as it can be— means we must bid farewell to the people and places we have grown to cherish. It is, however, essential for us to brave these changes to carry through the journey of life. As universities foster academic advancement, it is easy for us to be overwhelmed by the successes of others. We often forget to acknowledge our own success unless tangible gains are attached, whether that be a grade, scholarship, or job offer. Whether you are a student who has persevered through the academic year or a staff member who has persevered through the publication cycle, we applaud your unwavering efforts along the way. You have gained invaluable knowledge, grown in wisdom, and forged meaningful connections with peers and faculty. Your individual qualities make you incredible, regardless of any accolades you may or may not have received.

We take immense pride in our dedicated staff for embracing our vision to address critical social issues in healthcare. The cover art by Creative Directors Arim and Natalie, along with the table of contents by Aseel Abonawara, demand immediate action on the climate crisis to preserve our natural world and combat pollution. Katelyn Moore’s MeduGallery sheds light on the challenges elderly folk face as they age in place, while Jacqueline Chen, Florence Deng, and Dalraj Dhillon’s MeduAmplify examines the stigma and violence sex workers face in healthcare.

Through familiar article formats, our authors brave new territories of health and research. MedPulse features Audrey Dong and Aisling Zeng in their coverage of global healthcare and research news. In Pathoprofile, Olivia Kim and Rida Tauqir examine prion diseases, while David Gou and Matthew Olejarz present a Critical Review of α-GalCer in tumour suppression. Bhavana Soma and Zahra Alam tackle the use of psilocybin in mental healthcare in our Opinion Piece.

We welcome collaborations, new and old, with other organizations as well. It is our pleasure to feature abstracts from the International Women and Children’s Health Conference, covering important topics such as fetal alcohol spectrum disorder, childhood dyslipidemia, and early hospital discharge after birth. We are thrilled to have the McGill Science Undergraduate Research Journal joining us to deliver a Critical Review on perinatal mental health.

To Aisling, Arim, Carolyn, David, Diane, Eric, Gurleen, James, Ken, Leena, Natalie, Olivia, Shanzey, Suraj, and Yiming —thank you for your exceptional leadership and resilience. It was a great privilege to serve all of you and the McMaster community this past year. As we exit stage right, we welcome Natalie Chu and Suraj Bansal as the new Editors-in-Chief. We expect nothing less than greatness from them as they will continue to grow The Meducator beyond its limits.

Though we bid farewell, we will forever cherish the memories we have formed with you throughout this year. Thank you.

All the best,

Abstract

Prions refer to abnormal misfolded proteins which propagate rare, rapidly progressive, and inevitably fatal neurodegenerative infectious diseases affecting both humans and non-human mammals.1-3 The most common human prion disease is Creudtzfeldt-Jakob disease (CJD), aetiologically categorized as either (1) sporadic (sCJD), (2) acquired via infection (aCJD), (3) hereditary (hCJD), or (4) variant (vCJD).1,2 vCJD, in particular, is commonly known due to its contraction via consumption of beef infected with Bovine Spongiform Encephalopathy, also known as Mad Cow Disease: a similarly fatal prion disease affecting cows.2 Regardless of the causative mechanism, all CJDs are characterized by the rapid decline in cognitive function, myoclonus (involuntary twitching and/or jerking of muscles), akinetic mutism, and ultimately, death in all cases.1-3 As suggested by the aforementioned symptoms, CJD is considered a rapidly progressive dementia (RPD), alongside Alzheimer’s, Huntington’s, and Parkinson’s disease.4

Risk Factors

Although sCJD accounts for 85% of CJD cases, current literature has not identified concrete risk factors due to the stochastic misfolding of prions.2 However, age has been shown to influence sCJD, with an average age of onset of 60 years old.5 Numerous genetic factors have also been implicated in sCJD. Specifically, a heterozygous genotype at codon 129 of the PRNP gene, the prion protein gene, has displayed protective factors against the spontaneous prion misfolding in sCJD.6 Furthermore, a genomewide association study conducted by Jones et al. identified two loci that may increase risk of sCJD.7 These include risk variants located in, or nearby, STX6 and GAL3ST1.6 As for aCtJD, risk factors are virtually absent due to advances in clinical practices which mitigate risk of infection, such as the sanitization of neurosurgical instruments previously used on patients with CJD.2

Diagnosis

CJD is difficult to diagnose as it shares numerous symptoms with RPD. To provide a definitive diagnosis of CJD, a brain biopsy or autopsy must be performed so a pathologist can examine the brain tissue.8,9 Typical histopathological findings suggesting CJD doi: 10.35493/medu.43.4

AUTHORS:

OLIVIA KIM 1 & RIDA TAUQIR 2

1 Bachelor of Health Sciences (Honours), Class of 2026, McMaster University

2 Bachelor of Health Sciences (Honours), Class of 2024, McMaster University

ARTIST: MISHAL HOSSAIN 3

3 Bachelor of Health Sciences (Honours), Class of 2025, McMaster University include neuronal loss, spongiform degeneration, and astrogliosis.10 Due to this challenging nature of confirming diagnosis, medical professionals must rely on probable diagnostic criteria, which consists of a conjunction of laboratory testing and identification of clinical features. According to the Centers for Disease Control and Prevention, this diagnostic criteria includes a positive result on an electroencephalogram, a cerebral spinal fluid assay, or a magnetic resonance imaging brain scan. In addition to the aforementioned laboratory tests, identifying symptoms such as rapidly progressive cognitive impairment, myoclonus, and visual or cerebellar problems offer a more probable diagnosis of CJD.11

Mechanism

Part 1: Prion Proteins

CJD arises from the conversion of normal cellular prion proteins (PrPC) into a misfolded aggregated and pathogenic form called scrapie (PrPSc).12 PrPC are cell-surface glycoproteins, which are proposed to be involved in protection against apoptosis, transmembrane signalling, and synaptic formation.13 To complete the previously mentioned functions, PrPC are characterized by their highly α-helical structure, detergentsolubility, and susceptibility to protease digestion. On the other hand, PrPSc are conformationally altered isoforms, effectively adopting the opposite characteristics with a β-sheet structure, detergent-insolubility, and resistance to protease digestion.10,

Part 2: Transformation of PrPC to PrPSc

Represented by the different classifications of CJD, PrPSc can be acquired in several different ways, denoted by the four characterizations of CJD. Regardless of the categorization of CJD, the transformation process of the prion proteins remains consistent in which the PrPSc acts as a template for the conversion of PrPC, seeding the formation of an alternative self-replicating state with a different protein folding pattern.12,14 Although the exact molecular mechanism of the conversion of PrPC to PrPSc is unknown, a study using molecular-dynamics simulations by Chen et al. suggests large conformational changes of the C-terminal globular domain and other structural domains in response to harsh conditions of high temperatures and low pH.15 Ultimately, as the PrPSc conformation self-propagates, there is exponential accumulation of the misfolded isoform in the neurons of the central nervous system (CNS).12

Part 3: Degeneration of the CNS

The beginning stages of CJD appear to be associated with synaptic dysfunction. The human prion protein is enriched in the synapses of neuromuscular junctions and the CNS and thus, the conversion of PrPC to PrPSc results in the accumulation of PrPSc in synaptic structures.16 The toxicity of the accumulated PrPSc begins to induce the release of pro-inflammatory cytokines and reactive oxygen species by activated microglial cells, resulting in neuronal cell death by apoptosis.17 CJD is also characterized by spongiform degeneration in which small vacuoles occupy the gray matter of the brain, which is hypothesized to be caused by autophagic cell death.16 As the degree of neuronal cell death progresses, initial symptoms of slurred speech, dizziness, and vision problems rapidly become more severe with the complete loss of coordination and speech. Finally, patients enter a vegetative state in the final stages of CJD before their death.18 The fatal outcome of this disease can be attributed to extensive neuronal death by autophagy and apoptosis.

Treatment

Clinical studies investigating potential CJD treatments are hindered by its scarcity and rapid prognosis. duration of patient survival is 4.5 months following symptom onset, with 90% of patients surviving less than 1 year. there are no known treatments to impede or stop the destruction of neurons as a result of prion diseases. opt to alleviate symptoms and support patients and their families in coping with CJD.6 For example, opiates and anti-seizure medication may be prescribed to diminish pain and myoclonus, respectively.6 Other typically treated symptoms include urinary and bowel inconsistency, dysphagia, and blindness or vision loss. Eventually, once patients cannot move and/or speak, full-time care is administered to attend to their daily needs. patients may draw up an advance directive: a treatment plan detailing preferences in care for when that the patient enters a vegetative state and cannot communicate anymore. also worthy to acknowledge current exploration of potential CJD treatments. Notably, Mead et al. conducted the very first experimental treatment targeting human prion diseases in 2022, administering anti-PrPC monoclonal antibody (mAb) therapy to 6 CJD patients.20 Their findings suggest favorable concentrations of anti-PrPC mAbs in CSF and brain tissue, encouraging future exploration in this potentially groundbreaking CJD treatment.

REVIEWED BY: DR. ALBERT AGRO (MD, PHD)

Dr. Albert Agro is an assistant professor specializing in pathology and molecular medicine. He received his PhD in the Department of Medicine at McMaster University, and currently holds a position of chief medical officer of Cynapsus, a pharmaceutical company, as well as CEO of HNZ Strategic Holdings, Inc., a clinical consulting firm. He possesses a wide range of interests, particularly the pathology and treatment of Parkinson’s disease.

1. Iwasaki Y. Creutzfeldt-Jakob disease. Neup. 2016;37(2):174-88. Available from: doi:10.1111/ neup.12355.

2. Vacca VM. CJD: Understanding Creutzfeldt-Jakob disease. Nurse. 2016;46(3):36-42. Available from: doi:10.1097/01.NURSE.0000480598.84274.0f.

3. De Villemeur TB. Creutzfeldt-Jakob disease. Handb Clin Neurol. 2013;112:1191-3. Available from: doi:10.1016/B978-0-444-52910-7.00040-4.

4. Hermann P, Zerr I. Rapidly progressive dementias aetiologies, diagnosis and management. Nat Rev. 2022;18:363-76. Available from: doi:10.1038/s41582-022-00659-0.

5. Alzheimer’s Association. Creutzfeldt-Jakob Disease [Internet]. 2023. Available from: https:// www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/creutzfeldt-jakobdisease [cited 2023 Feb 22].

6. Jones E, Mead S. Genetic risk factors for Creutzfeldt-Jakob disease. Neurobiol Dis. 2020;142:104973. Available from: doi:10.1016/j.nbd.2020.104973.

7. Jones E, Hummerich H, Viré E, Uphill J, Dimitriadis A, Speedy H, et al. Genome-wide association study identifies risk variants for sporadic Creutzfeldt-Jakob disease in STX6 and GAL3ST1. Lancet Neurol. 2020;20:30273-8. Available from: doi:10.1016/s14744422(20)30273-8.

8. Tyler K. Creutzfeldt-Jakob disease. N Engl J Med. 2003;348(8):681-2. Available from: doi:10.1056/NEJMp020187.

9. Sitammagari KK, Masood W. Creutzfeldt Jakob disease. 1st ed. Treasure Island (FL): StatPearls Publishing; 2022

10. Budka H. Neuropathology of prion diseases. Br. Med. Bull. 2003;66(1):121-30. Available from: doi:10.1093/bmb/66.1.121

11. Centers for Disease Control and Prevention. CDC’s diagnostic criteria for Creutzfeldt-Jakob disease (CJD) [Internet]. 2018. Available from:https://www.cdc.gov/prions/cjd/diagnosticcriteria.html [cited 2023 Feb 22].

12. Atkinson CJ, Zhang K, Munn AL, Wiegmans A, Wei MQ. Prion protein scrapie and the normal cellular prion protein. Prion. 2016;10(1):63-82. Available from: doi:10.1080/19336896.20 15.1110293.

13. Westergard L, Christensen HM, Harris DA. The cellular prion protein (PrPC): Its physiological function and role in disease. Biochim Biophys Acta. 2007;1772(6):629-44. Available from: doi:10.1016/j.bbadis.2007.02.011.

14. Spagnolli G, Rigoli M, Inverardi GN, Codeseira YB, Biasini E, Requena JR. Modeling PrPSc generation through deformed templating. Front Bioeng Biotechnol. 2020;8:590501. Available from: doi:10.3389/fbioe.2020.590501.

15. Chen W, Van der Kamp MW, Daggett V. Structural and dynamic properties of the human prion protein. Biophys J. 2014;106(5):1152-63. Available from: doi:10.1016/j.bpj.2013.12.053.

16. Soto C, Satani N. The intricate mechanisms of neurodegeneration in prion disease. Trends Mol

SUPPORTING HEALTHY PREGNANCIES: UNDERSTANDING PREGNANT WOMEN AND NEW MOTHERS’ PERSPECTIVES REGARDS FETAL ALCOHOL

SPECTRUM DISORDER PREVENTION CAMPAIGNS TO INFORM EFFECTIVE AND NON-STIGMATIZING APPROACHES IN NORTHEASTERN ONTARIO

BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is a diagnostic term used to describe the lifelong impacts on fetal development from prenatal alcohol exposure. Alcohol use during pregnancy has been identified as a significant public health concern, as up to 15% of Canadian women report consuming alcohol during pregnancy. Current FASD prevention efforts have been criticized for their harmful and stigmatizing nature as emotional aspects (e.g., fear, guilt, and shock) have been relied on to discourage individuals from consuming alcohol during pregnancy. Consequently, pregnant individuals and new mothers may be reluctant to disclose information about their alcohol consumption, which may prevent them from receiving support. Therefore, improving current FASD prevention initiatives could help improve supports for pregnant individuals, new mothers, and individuals with FASD.

RESEARCH OBJECTIVES: The objectives of this study include:

(1) to explore pregnant and postpartum women’s attitudes about alcohol use during pregnancy, and their perspectives on existing FASD prevention campaigns; and (2) to generate recommendations for non-stigmatizing FASD prevention campaigns for Northeastern Ontario.

METHODS: Using a basic qualitative approach (Merriam & Tisdell, 2016), this study has employed small group and individual semi-structured interviews via Zoom. Participant recruitment was conducted utilizing social media platforms and through the assistance of community partnering agencies and local organizations. To date, 12 pregnant women and new mothers between the ages of 17 and 45 (Mage = 30, SD = 4.85) across the Sudbury and Manitoulin regions of Northeastern Ontario have participated in this study. Messaging and imagery from 10 existing prevention campaigns were employed to facilitate discussion. Data from this study are being analyzed using Bengtsson’s (2016) qualitative content analysis to generate salient themes from participants’ responses.

RESULTS: At the time of this submission, data analysis is ongoing. However, preliminary findings have revealed that participants have favourable attitudes towards abstaining from alcohol during pregnancy. Findings indicate that participants associate the effectiveness of FASD prevention efforts at preventing alcohol use during pregnancy with the strength of the campaign messaging, if the campaign has an emotive impact, and the overall relatability of the imagery used. For instance, campaigns with a strong message were perceived as being more effective at preventing alcohol use during pregnancy than those with a perceived weak message. Additionally, FASD prevention campaigns that evoked a strong emotional response were perceived as more effective at preventing alcohol use during pregnancy than FASD prevention campaigns that did not have an emotive impact. Preliminary findings revealed that the more relatable the campaign imagery is, the more effective the campaign is perceived to be at preventing alcohol use during pregnancy. Lastly, findings show that current FASD prevention initiatives are lacking and require enhanced accessibility and messages of support.

CONCLUSIONS: Although participants perceive these things as more effective, they can conflict with best practices for FASD prevention messaging, as evocative messages and imagery can reinforce stigma about FASD and alcohol consumption during pregnancy. In summary, the current study will contribute to the growing discourse on informing nonstigmatizing FASD prevention initiatives for Northeastern Ontario. Alcohol use during pregnancy is a growing concern among many Northern Ontario communities; therefore, it is crucial to acquire an understanding of pregnant women and new mothers’ attitudes about alcohol use during pregnancy to help inform non-stigmatizing FASD prevention efforts.

Community Clinician Management Patterns Of Childhood Dyslipidemia

BACKGROUND: Childhood dyslipidemia increases the risk of atherosclerosis in childhood and cardiovascular disease (CVD) in young adulthood. The atherosclerotic process begins in childhood. However, adverse health outcomes due to disease are rare in early life. Unmanaged lifelong atherosclerotic processes can result in myocardial infarction and stroke. Management of risk factors including childhood dyslipidemia can decrease the risk of CVD and adverse health outcomes in later life. At the time of the study, there were no Canadian paediatric guidelines for lipid screening. Children with abnormal lipid profiles may be overlooked. Despite childhood dyslipidemia identification, early intervention and management may not be initiated. Primary care physicians (PCP) are optimally positioned to educate and reinforce health behaviours that minimize the risk of CVD and promoting lifelong cardiovascular health.

OBJECTIVES: To describe clinician management patterns for childhood dyslipidemia in the community setting.

METHODS: A retrospective chart review was conducted for children 2 to 10 years of age with abnormal lipid profiles between 2008-2021. Participants were from the TARGet Kids! cohort, Canada’s largest primary care research network for children. Participants in the cohort had completed annual non-fasting blood samples and questionnaires. The primary study outcome was the proportion of physicians engaging in each management practice. R version 3.6.2 (R Foundation for Statistical Computing, Vienna, Austria) was used for statistical analysis.

RESULTS. Within the TARGet Kids! cohort, 790 children were identified with dyslipidemia. Among these children, 768 were seen by PCP at their next follow-up visit while 22 children had no follow-up visit. PCP rarely informed families about abnormal lipid profiles (n=11, 1.43%). All families notified about abnormal lipid profiles were informed at a follow-up visit (n=4, 36.4%), through a phone call (n=6, 54.5%), or through both methods (n=1, 9.1%). PCP frequently counselled on diet and eating habits (n=535, 95.0%), but less often on physical activity (n=160, 28.4%), sleep (n=108, 19.2%), and screen time (n=24, 4.3%). Family history of CVD, diabetes, high cholesterol, or hypertension was occasionally discussed (n=11, 2.0%). PCP repeated fasting lipid profiles uncommonly (n=23, 3.0%). Management plans for abnormal lipid profiles were infrequently documented (n=4, 0.5%), and all involved dietary counselling. Only 3 participants had a follow-up visit booked (n=3, 0.4%). Referrals were rarely made to dieticians and feeding clinics (n=6, 0.8%) and were not in response to abnormal lipid levels.

CONCLUSION. Childhood dyslipidemia is a risk factor for cardiovascular disease in later life. Our study showed that among children identified with dyslipidemia, PCP rarely identified and initiated early management for abnormal lipid profiles. Our results may inform the need for dissemination of paediatric lipid screening and management guidelines to support best clinical practice. There is no actual or potential conflict of interest in relation to the findings presented.

Early Hospital Discharge Following Uncomplicated Birth

KESHINI SRIARULNATHAN1, ANNE M. MALOTT RM PHD2

1Department of Science, McMaster University, 2Department of Family Medicine, McMaster University

BACKGROUND: The current rise of COVID-19 coronavirus has impacted the experiences of new parents in Canada with restrictions on hospital visitors and concerns of nosocomial infections. Early hospital discharge has the potential to reduce exposure, promote the transition to parenthood and breastfeeding duration, and reduce healthcare costs due to shorter hospital length of stay. However, little is known about the impact of early discharge on health outcomes for parturients, neonates, or the healthcare system.

AIM: This review examines existing literature on early postnatal discharge programs following uncomplicated vaginal births as relevant to the Canadian context to determine how it has impacted the clinical outcomes of parents and newborns, patient satisfaction, and the health system.

METHODS: A literature search of electronic databases: PubMed, Scopus, ScienceDirect, Web of Science, and CINAHL evaluated peer-reviewed, primary research published in English from 1976 through 2021. A total of 40 studies were yielded and content analysis identified the population, location, study design, methodology, and significant findings of each with attention to relevance to the Canadian context to determine the generalizability of the findings.

RESULTS: There is a dearth of well-designed studies that include consistent definitions of early discharge and uniform policies and practices for follow-up care for birthing people and their babies.

Conclusion: There is a need for further research exploring the health outcomes of Canadian birthing people and their neonates following early hospital discharge after uncomplicated births. There is also a need to examine the impact of early discharge on the healthcare system in the Canadian context that includes a clear definition of early discharge and specification of care provided in the community following discharge.

ARTIST: KATELYN MOORE

Bachelor of Kinesiology (Honours)

Class of 2023, McMaster University

With the risks that aging poses to health, elderly individuals often find themselves with a difficult choice to make: stay home or admit into a nursing home. With limited at-home resources available in today’s healthcare, several choose to move to long-term care homes to avoid risk of at-home dangers such as injuries and falls. Unfortunately, this transition often proves to be mentally challenging for many retired individuals. Between social disonnection, loss of familiar environments and memories, progression of disease/injury, and altering of financial autonomy, it is reasonable that elderly individuals often feel out of control of not only their health, but also their happiness when moving out of their homes.1

Progression of aging differs greatly between indviduals – there is no way of predicting how one person may develop with age in comparison to another – thus, elderly couples often face risk of separation due to differences in care needs. Along with moving between a familiar home to an unfamiliar care home environment, symptoms such as confusion and anxiety can be aggravated with separation from loved ones, making already-isolating cognitive disorders such as dementia even more challenging to manage.

In light of the COVID-19 pandemic, feeling out of place was particuarily easier for those making the transition from personal homes to nursing homes.2 With the isolation that quarantine demanded of communities, it was even more common for elderly individuals to be placed in vulnerable and confusing situations.2

Managing the phenomenon of aging is by no means an easy feat – when caring for an aging loved one, it’s hard to know what is the “right” decision when it comes to care homes and separation. Likewise, it’s difficult for elderly individuals to know when it is the right time to seek extra care outside of home. As such, the message of this piece is not one to bespeak a right and wrong answer, but rather highlight the importance of us to consider the needs of the people at the centre of the wake: our parents, our grandparents, relatives, siblings, friends, for it those people where home truly is.

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