Issue 32 by The Meducator

DECEMBER 2017 | ISSUE 32

EXPLORING ANOTHER PIECE OF THE PUZZLE SHORT-TERM C O M O R B I D M E N TA L H E AMEDICAL LT H C H A L L E N G ESERVICE S I N C H I L D R E N TRIPS ISORDER BWEI NT EHFAI CUITAI LS M O RS PDEI SCT R UR PU TMI VDE?

PHYSICIAN-ASSISTED WHY DO WE SLEEP DYING P T IHOANP PI NE NCA F L I F E CA R E A NNDE W HOAT S NWAHDEINA NW E NDDO ONâ&#x20AC;&#x2122;T?

SHINING LIGHT ON BIOMEDICINE: A FORERUNNER IN DNA DIAGNOSTICS R.BYRI NUGC FE UWA MNAAN,D DA IRREESCT I N T E RV I E W W I T H D R. L I,I NCA E AORRCOHFC H A I R I N NT H U EC LEEDI UC CAT A C I IDOSNRPERS OE AG RRA C HM I N A N ATO M Y

WWW.MEDUCATOR.ORG

table of

CONTENTS

M E D U CATO R | D E C E M B E R 2017

table of contents

DECEMBER 2017 | ISSUE 32

02 INTRODUCTION 03 MEDPULSE 05 MEDBULLETINS 07 PATHOPROFILE 09 ABSTRACTS 11 SPOTLIGHT 13 FORUMSPACE VIEWPOINTS 15 Health Perspectives on the Candian Legalization of Marijuana GLOBAL PERSPECTIVE 19 Conflicting Agendas in Care for Olympic Amateur Boxing: A Global Perspective OPINION 22 A Bioethical Critique of Short-Term Medical Service Trips 25 Q&A 27 INTERVIEW SPOTLIGHT 30 CONTRIBUTORS COV E R A RT I S T TO N Y C H E N T O C A R T I S T LA U R A N G U Y E N

Welcome to Issue 32 of The Meducator! As a continuously evolving discipline, the field of health sciences does not exist in isolation from other branches of knowledge. What lies at the heart of science is not simply the biological domain of molecules, cells, and tissues, but rather a series of intricate relationships modulated by a myriad of influences. This concept of interconnectivity is evident in our cover design by graphics member Tony Chen. The unfurling ribbons exemplify how scientific knowledge is intrinsically woven within the fabric of other disciplines. As you peruse this issue, we hope that you may consider how each article exists within an interdisciplinary framework of the health sciences. Issue 32 begins with our MedPulse piece, in which staff editors Kevin Chen and Parnika Godkhindi work in collaboration with graphics designer Suffia Malik to highlight health-related headlines worldwide. In Pathoprofile, Edward Cui, Eva Liu, and Sylvia Mohanraj elucidate the pathophysiology behind multiple sclerosis, providing an in-depth analysis of the mechanisms behind the autoimmune disease. We continue our longstanding partnership with the McMaster Health Forum through this issueâ&#x20AC;&#x2122;s Forumspace column. This piece acknowledges how communities of practice can be leveraged to address post-secondary mental health, while showcasing how policymaking factors impact innovations to improve health outcomes. With the launch of this issue, we introduce two new article formats, Spotlight and Q&A. Spotlight seeks to highlight a contentious health issue to provide readers with insight into the rapidly evolving field of healthcare. With graphics artist Michael Sun, Takhliq Amir discusses the raging opioid crisis in Canada, while James Yu examines the corresponding relationship between American football and chronic traumatic encephalopathy. In addition, Q&A provides a platform for readers to engage with our staff editors. In this publication, Jessica Chee and Daniel Diatlov answer thought-provoking questions to decipher the enigma behind the scientific concepts, sleep and speciation.

Sincerely,

M E D U CATO R

We would like to take this opportunity to thank all of our staff members for their unwavering creativity and commitment towards our journal during the 32nd publication cycle. Moreover, we would like to express our immense gratitude to Valerie Kim, Owen Luo, Cathy Lu, and Adrian Marcuzzi for their enthusiasm and dedication as team managers. Finally, we would like to thank you, the readers, for your continued support for The Meducator. We hope that Issue 32 will spur your curiosity and quest for scientific knowledge. Ask questions. Search for answers. Push the boundaries.

introduction

INTRODUCTION ISSUE 32

dear reader,

SABRINA LIN

D E C E M B E R 2017

SARAH GE

Bachelor of Health Sciences (Honours) Class of 2019

Radiation-Induced Brain Cancer August 2017 /// Canada Radiation-Induced Many adults that survive cancer in their childhood develop brain Cancer tumours, and research Brain conducted at the University of Toronto may help to explain why. TheAugust study found that radiation to the head and 2017 /// Canada spine, which is often used to treat leukemia or pediatric brain cancer, increases the risk of meningiomas. Meningiomas are the most common typeMany of tumour theincentral nervous develop brain adultsoriginating that survivefrom cancer their childhood system. Researchers compared scans of radiation-induced tumours, and research conducted at the University of Toronto may help to meningiomas. explain why. TheThey studydiscovered found that radiation to the head and meningiomas with typical that both which isand oftenwere used equally to treat leukemia looked the same spine, physically sporadicor inpediatric brain cancer, the risk of meningiomas. are the occurrence. However, theincreases radiation-induced meningiomasMeningiomas were most common type of tumour originating from the central nervous found to be more aggressive, as they contained a mutation of NF2. system. Researchers compared scans of radiation-induced NF2 is a gene whichmeningiomas encodes merlin, a tumour-suppressing with typical meningiomas. Theyprotein. discovered that both Scientists suggest that there are likely more oncogenic mutations looked the same physically and were equally sporadic in to be discovered. occurrence. However, the radiation-induced meningiomas were

Egg-regious Insecticide Contamination August 2017 /// Europe Insecticide Millions of eggsEgg-regious across 40 European countries have been destroyed after they wereContamination found to be contaminated with fipronil, an insecticide normally used to exterminate fleas, lice, and ticks. The European Union August 2017 /// Europe has banned this pesticide for use on animals intended for human consumption because it can have toxic effects on the kidneys, liver, and thyroidMillions if ingested in across large quantities. Furthermore, ingestion can of eggs 40 European countries have been destroyed lead to nausea, vomiting, abdominal pain, dizziness, and an epileptic after they were found to be contaminated with fipronil, insecticide normally used to exterminate lice, and ticks. The European seizures. This contamination was firstfleas, discovered on poultry farms Union in has banned pesticide useused on animals human the Netherlands, wherethis fipronil was for likely to treatintended red lice for found consumption because itthere can have effects on the kidneys, in egg-laying hens. Fortunately, havetoxic been no reports of harmliver, thyroid if ingested in large quantities. Furthermore, ingestion can due to this and multi-national scandal.

found to be more aggressive, as they contained a mutation of NF2. NF2 is a gene which encodes merlin, a tumour-suppressing protein. Scientists suggest that there are likely more oncogenic mutations to be discovered.

Awake for that Surgery Stay Awake Stay for that Surgery August 2017 /// United States August 2017 /// United States A brain aneurysm is a weakened region of a blood vessel that supplies

to the region brain. ‘Clipping’ is vessel a common therapeutic surgical A brain aneurysm isblood a weakened of a blood that supplies procedure thatis risks rupturing therapeutic the aneurysm,surgical potentially causing blood to the brain. ‘Clipping’ a common disability or death. research from the Saint Louis University procedure that risks rupturing theRecent aneurysm, potentially causing found that conscious sedation — keeping the patient awake during the disability or death. Recent research from the Saint Louis University surgery, rather than using general anaesthetic — mitigates these risks. found that conscious sedation — are keeping the patient during the the warning When patients conscious, they canawake better demonstrate surgery, rather thansigns usingof general — mitigates blocked anaesthetic blood flow, such as blurredthese visionrisks. or the inability to When patients are conscious, canconscious better demonstrate the warning make a fist.they Thus, sedation allows surgeons to monitor patients andsuch knowaswhen to readjust avoid ruptures. signs of blocked blood flow, blurred visionthe or clips the to inability to make a fist. Thus, conscious sedation allows surgeons to monitor patients and know when to readjust the clips to avoid ruptures.

lead to nausea, vomiting, abdominal pain, dizziness, and epileptic seizures. This contamination was first discovered on poultry farms in the Netherlands, where fipronil was likely used to treat red lice found in egg-laying hens. Fortunately, there have been no reports of harm due to this multi-national scandal.

New Virus Flight New Virus TakesTakes Flight July 2017 /// Brazil July 2017 /// Brazil In a stroke of luck, researchers at the University of São Paulo have

a new virus, avian in aPaulo migratory In a strokediscovered of luck, researchers at theparamyxovirus University of15, São havebird researchers were originally15, testing discoveredspecies. a new The virus, avian paramyxovirus in a migratory migratorybirds bird for Newcastle disease, which is harmless to humans but deadly to domesspecies. The researchers were originally testing migratory birds for tic poultry and wildfowl. Avian paramyxovirus 15 is a pathogen in the Newcastlesame disease, which is harmless to humans but deadly to domesfamily as Newcastle disease virus. Co-infection of the viruses tic poultrywas and discovered wildfowl. Avian paramyxovirussandpiper 15 is a pathogen in the in a white-rumped (Calidris fuscicollis). same family as Newcastleindicates diseasethat virus. of the harmless viruses to Experimentation this Co-infection new virus is similarly was discovered white-rumped (Calidris fuscicollis). humans.inAsaBrazil is the world’ssandpiper largest exporter of chicken products, this newindicates virus mounts for virus the industry. Experimentation thatconcern this new is similarly harmless to humans. As Brazil is the world’s largest exporter of chicken products, this new virus mounts concern for the industry.

Old Vaccine, New Protection? July 2017 /// New Zealand

CRISPR and Clearer August 2017 /// United States, South Korea, China CRISPR and Scientists from theClearer USA, South Korea, and China sucessfully used August 2017 /// United States, CRISPR-Cas9 gene editing to fix a mutation in the MYBPC3 gene in human embryos. mutation causes hypertrophic cardiomyopathy, a condition in SouthThis Korea, China which the heart muscle thickens, leading to heart failure and sudden death in seemingly healthy individuals. This major milestone in human genetic engineering a significant improvement efficiencyused and accuracy Scientists from marks the USA, South Korea, and China insucessfully over previous no evidence CRISPR-Cas9 geneattempts; editing to researchers fix a mutation found in the MYBPC3 geneof in off-target human genetic embryos. This mutation hypertrophic cardiomyopathy, a condition in mutations after thiscauses experiment. Furthermore, amongst 58 embryos, there which heart thickens,a leading to heart failure andgenetic sudden sequences death wasthe only onemuscle case where cell contained different than in seemingly individuals. This major milestone in human genetic the rest ofhealthy the embryo. engineering marks a significant improvement in efficiency and accuracy over previous attempts; researchers found no evidence of off-target genetic mutations after this experiment. Furthermore, amongst 58 embryos, there was only one case where a cell contained different genetic sequences than the rest of the embryo.

In a large-scale case-control study spanning 12 years, research-

Old Vaccine, Protection? ers in NewNew Zealand found that individuals given a discontinued version of the meningitis B vaccine (MeNZB) were less likely to July 2017 /// New Zealand

be diagnosed with gonorrhea, a common sexually transmitted disease. MeNZB is the first vaccine which protects against gonorrhea. this 12 study not establish a causal In a large-scale case-controlHowever, study spanning years,did researchrelationship; more research necessary before a ers in New Zealand found that individuals givenisa therefore discontinued vaccine gonorrhea can be version of thededicated meningitis B vaccineagainst (MeNZB) were less likely to made available to be diagnosedthe withpublic. gonorrhea, a common sexually transmitted disease. MeNZB is the first vaccine which protects against gonorrhea. However, this study did not establish a causal relationship; more research is therefore necessary before a dedicated vaccine against gonorrhea can be made available to the public.

MEDPULSE MEDPULSE

Writing // Kevin Chen, Parnika Godkhindi // Suffia Writing Art // Kevin Chen,Malik Parnika Godkhindi Art // Suffia Malik

Potential Ebola Potential Ebola Vaccines Bring Hope Vaccines Bring Hope October 2017 /// Liberia

October 2017 /// Liberia

Clinical trials have shown that two vaccines, rVSV-ZEBOV and ChAd3-EBO-Z, elicited a long-lasting immune response against Clinical trials have shown that two vaccines, rVSV-ZEBOV and Ebola. Within one month, most study participants developed ChAd3-EBO-Z, elicited a long-lasting immune response against antibodies that persisted for an entire year. Sustained vaccine Ebola.isWithin onebutmonth, most study participants durability important, researchers warn that the significancedeveloped antibodies persisted forisan entireInvestigators year. Sustained of this prolongedthat immune response unclear. could vaccine is important, but researchers warnEbola, that as thethe significance notdurability further study the vaccine’s efficacy against outbreak Liberia ended before response more clinical couldInvestigators begin. of thisinprolonged immune is trials unclear. could

not further study the vaccine’s efficacy against Ebola, as the outbreak in Liberia ended before more clinical trials could begin.

Close theClose Borders! the Borders! August 2017 /// Madagascar

August 2017 /// Madagascar

Every year between September and April, hundreds of cases of the plague are reported in Madagascar. In previous and years,April, mosthundreds cases Every year between September of cases of the were of the bubonic variety, which isinthe least severeInform of the years, most cases plague are reported Madagascar. previous plague and iswere transmitted flea bites. However, an alarmingly highsevere form of the of thebybubonic variety, which is the least death toll has been and noted this year, as by most been an alarmingly high plague is transmitted fleacases bites. have However, attributed to the disease’s most deadly and virulent form, the death toll has been noted this year, as most cases have been pneumonic plague. Pneumonic plague is transmitted from person to attributed to be thefatal disease’s and virulent form, the person via coughing and can within 24most hours deadly if left untreatpneumonic plague. Pneumonic is transmitted from person to ed. In the past, the plague was mostly confined toplague mountainous, rural person via coughing and can be fatal within major 24 hours if left untreatareas. However, the current outbreak has spread to several Malagasy cities the past, nearby country ofwas Seychelles. ed.and In the the plague mostly confined to mountainous, rural

areas. However, the current outbreak has spread to several major Malagasy cities and the nearby country of Seychelles.

MEDBULLETIN ALZHEIMER’S

DEVELOPMENT

SHE ILA YU

D ANIEL D IATLO V

An estimated 47 million people worldwide have dementia, with the majority of these cases being Alzheimer ’s Disease (AD). 1 AD is a neurodegenerative disease characterized by the deterioration of specific nerve cells, the formation of neuritic plaques, and the presence of neurofibrillary tangles. 2 Researchers have previously linked the characteristics of AD to severe declines in serotonergic neurons, but until recently, it was not clear whether these reductions were the cause or effect of the disease. 3

For years, researchers and physicians have been trying to extend the viability of babies that are born prematurely. Babies born under 37 weeks of gestation are considered premature and are at an increased risk for death and disability. 1 These risks increase exponentially the younger the age of the infant; the youngest possible age of viability is roughly 22 weeks. 1 Premature infants are usually placed on life support systems which allow for the maintenance of homeostatic stability. However, this increases their risk of infection, organ damage due to ventilation, and neurological defects. 2

M E D U CATO R

D E C E M B E R 2017

medbulletin

LOWER BRAIN SEROTONIN: A DRIVER OF COGNITIVE DECLINE

A study published in Neurobiology of Disease suggests that lower levels of serotonin transporters (SERT) may precede neurodegeneration. Led by Clifford Workman at the Johns Hopkins School of Medicine, the research team compared 28 participants with mild cognitive impairment (MCI) to 28 controls throughout a series of memory tests, MRI scans, and PET scans. Lower SERT levels were observed in the cortical, limbic, and peri-limbic regions of MCI patients compared to healthy controls. Results from the study reveal a strong correlation between SERT levels and scores on the memory test in participants with MCI, suggesting that serotonin is heavily implicated in the early stages of cognitive decline. 4

In recent decades, various researchers have been attempting to create artificial wombs in which a premature baby may continue to develop in a more stable and natural environment. The first successful attempt was in 1997 when Dr. Yoshinori Kuwabara of Juntendo University announced that a 17-week-old goat fetus survived for three weeks in an artificial womb. 3 The fetus was placed in a plastic container of warm amniotic-like fluid and supplied with nutrients through a tube inserted into its umbilical cord. 3

The conclusions from the study can be used to improve current methods of treatment for AD. Drugs such as cholinesterase inhibitors help to mask the symptoms of AD. However, they do not treat the underlying disease or slow its progression. 5 Methods to increase serotonin functioning in the brain provide a promising avenue to slow or stop the progression of AD along with other forms of dementia. 3 Studies are in progress to elucidate the mechanism of serotonin in the transition from MCI to dementia and to relate serotonin degeneration to other aspects of AD neuropathology. 4

Recently, in a paper published in June 2017, scientists used a technique called ex vivo uterine environment therapy to grow six premature lambs for one week in an artificial womb. 4 Five of the six lambs completed the week-long therapy with no significant physiological changes or defects. 4 The ex vivo uterine environment is essentially an amniotic fluid bath equipped with an artificial placenta that can sustain a developing preterm fetus. 4 It is important to note that the artificial womb is not intended to replace the human womb, but rather act as an alternative to current neonatal incubators. With refinement, this technology has the potential to be applied to human fetuses within the next decade, allowing for more successful outcomes in preterm fetuses. However, the ethics of such a therapy are questionable and have yet to be elucidated.

ARTIFICIAL WOMBS: A SOLUTION FOR PREMATURE BABIES?

WHO Dementia. WHO. Available from: http://www.who.int/mediacentre/factsheets/fs362/en. [Accessed Sep 16, 2017]. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical Diagnosis of Alzheimer’s Disease: Report of the NINCDS-ADRDA Work Group under the Auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984 Jul 1;34(7):939-939. Available from: https://www.ncbi.nlm.nih.gov/pubmed/6610841. [Accessed Oct 26, 2017]. Johns Hopkins Medicine. Brain Scan Study Adds to Evidence That Lower Brain Serotonin Levels are Linked to Dementia: Results suggest serotonin loss may be a key player in cognitive decline, not just a side-effect of Alzheimer’s disease. ScienceDaily. 2017 Aug 14. Available from: https://www.hopkinsmedicine.org/news/media/releases/brain_scan_study_adds_to_evidence_that_lower_brain_serotonin_levels_are_linked_to_dementia_. [Accessed Sep 16, 2017]. Smith GS, Barrett FS, Joo JH, Nassery N, Savonenko A, Sodums DJ, et al. Molecular imaging of serotonin degeneration in mild cognitive impairment. Neurobiology of Disease. 2017 Sep 1;105(Supplement C):33–41. Available from: http://www.sciencedirect.com/science/article/pii/S0969996117301109. [Accessed Oct 26, 2017].

2. 3. 4.

Petrini J, Dias T, McCormick M, Massolo M, Green N, Escobar G. Increased risk of adverse neurological development for late preterm infants. Journal of Pediatrics. 2008;154(2): 169-76. Available from: http:// www.jpeds.com/article/S0022-3476(08)00699-9/fulltext. [Accessed Oct 26, 2017]. Lista G, Maturana A, Moya FR. Achieving and maintaining lung volume in the preterm infant: from the first breath to the NICU. European Journal of Pediatrics. 2017;176(10):1287-1293. Available from: https:// link.springer.com/article/10.1007%2Fs00431-017-2984-y. [Accessed Oct 26, 2017]. Rosen C. Why not artificial wombs? The New Atlantis Journal of Technology and Society. 2003;3:67-76. Available from: http://www.jstor.org/stable/pdf/43152051.pdf?refreqid=excelsior:2ce0c4a146cc484 20420166b6267e165. [Accessed Oct 26, 2017]. Usuda H, Watanabe S, Miura Y, et al. Successful maintenance of key physiological parameters in preterm lambs treated with ex vivo uterine environment therapy for a period of 1 week. American Journal of Obstetrics and Gynecology. 2017;217(4):547e1-e13 Available from: http://www.ajog.org/article/S00029378(17)30675-0/fulltext. [Accessed Oct 26, 2017].

BACTERIA

CHOLESTEROL

AD A M WA D E - VAL L A N C E

K ELVIN N G

In September of 2016, Mo et al. published an article in Science entitled “Spatiotemporal Microbial Evolution on Antibiotic Landscapes”. 1 This landmark article describes a novel system for studying bacterial evolution. The findings elucidate the importance of antibiotic gradients in the emergence of antibiotic resistance in microbes and the many genetic pathways through which resistance can be achieved. 1

Familial Hypercholesterolemia (FH) is a genetic disorder that causes abnormally high levels of low-density lipoprotein cholesterol (LDL-C), a risk factor for early onset cardiovascular diseases such as stroke or heart attack. FH is often caused by dysfunctional LDL-C receptors, preventing effective removal of circulating LDL-C, but may also arise through other mutations. 1

PARALLELS IN SOCIETAL EVOLUTION BETWEEN MICROBES AND HUMANS

The authors observed a unique effect whereby many highlyresistant mutants were trapped behind the progressing bacterial front. By virtue of being first, lesser-resistant bacteria had colonized ahead of highly resistant mutants, physically excluding them from expansion. This led the authors to conclude that the evolution and expansion of a bacterial population is not necessarily driven by its most evolved members.

Clearly, FH requires aggressive cholesterol lowering therapy. Statins, which have traditionally been used to lower LDL-C levels, are often insufficient. In fact, Pijlman et al. found that only 21% of FH patients on statins reach target LDL-C goals set by doctors. 3 In cases where statins are inadequate, patients are forced to combine therapies or undergo invasive procedures. 4 A new class of drugs to enter the market, PCSK9 inhibitors, are much more powerful than statins. PCSK9 breaks down LDL-C receptors, preventing their ability to remove LDL-C from the blood. Thus, PCSK9 inhibitors prolong the lifespan of LDL-C receptors and allow for increased removal of LDL-C. Shown to lower LDL-C by 30-40%, PCSK9 inhibitors are very effective at treating FH patients. 5 PCSK9 inhibitors present an exciting opportunity to improve FH management, and with time may have a significant impact on the pharmaceutical industry at large due to their increased effectiveness compared to statins. Currently, however, PCSK9 inhibitors are not cost effective at the price of $503,000 per quality-adjusted-life-year gained. 6

Baym M, Lieberman TD, Kelsic ED, Chait R, Gross R, Yelin I, Kishony R. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 2016;353(6304): 1147-1151. Available from: http://science. sciencemag.org/content/353/6304/1147. [Accessed Oct 26, 2017].

Rader D, Cohen J, Hobbs H. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. Journal of Clinical Investigation. 2003;111(12):1795-1803. Available from: http://www.ncbi. nlm.nih.gov/pmc/articles/PMC161432/. [Accessed Sept 17, 2017]. Cuchel M, Bruckert E, Ginsberg H, Raal F, Santos R, Hegele R et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. European Heart Journal. 2014;35(32):2146-2157. Available from: http://eurheartj. oxfordjournals.org/content/early/2014/07/22/eurheartj.ehu274.[Accessed Sept 17, 2017].

5. 6.

Pijlman A, Huijgen R, Verhagen S, Imholz B, Liem A, Kastelein J et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in The Netherlands. Atherosclerosis. 2010;209(1):189-194. Available from: http://www.ncbi.nlm.nih. gov/pubmed/19818960. [Accessed Sept 17, 2017]. Raper A, Kolansky D, Cuchel M. Treatment of Familial Hypercholesterolemia: Is There a Need Beyond Statin Therapy?. Curr Atheroscler Rep. 2011;14(1):11-16. Available from: https://link.springer. com/article/10.1007%2Fs11883-011-0215-y. [Accessed Sept 17, 2017]. Steinberg D, Witztum J. Inhibition of PCSK9: A powerful weapon for achieving ideal LDL cholesterol levels. Proceedings of the National Academy of Sciences. 2009;106(24):9546-9547. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19506257. [Accessed Sept 17, 2017]. Kazi D, Moran A, Coxson P, Penko J, Ollendorf D, Pearson S et al. Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease. JAMA. 2016 ;316(7):743. Available from: http://jama.jamanetwork.com/ article.aspx?articleid=2544639. [Accessed Sept 17, 2017].

| D E C E M B E R 2017

M E D U CATO R

Human society faces a similar phenomenon. Capitalism has been espoused as “survival of the fittest ” for decades, yet this is a flawed truth. Fitness is surely required to survive in a capitalist society, but first-ness is also of great importance. High socioeconomic birth is accepted to predict success. Man, like microbe, is not governed purely by survival of the fittest.

1 in 500 people are heterozygous, having one allele for FH, while 1 in 1,000,000 people are homozygous, having two alleles. 2 Untreated, most homozygous FH patients develop cardiovascular disease by 20 and die by 30. Heterozygous FH is fortunately less severe, but still dramatically increases the risk of cardiovascular disease.

medbulletin

Among these findings was one particular observation: evolution is not simply survival of the fittest. 1 The paper studied bacterial evolution using a system in which bacteria were inoculated into a large agar plate full of growth media. However, to move beyond their starting location to access more growth media, the bacteria had to evolve antibiotic resistance. At each stage, the concentration of local antibiotic increased ten-fold. 1 One would imagine that only the most resistant bacteria would able to reach the front of the ever-expanding bacterial population and forge onwards into unexplored territory and greener pastures. However, this was not the case.

PCSK9 INHIBITORS FOR FAMILIAL HYPERCHOLESTEROLEMIA

Multiple Sclerosis AUTHORS: Edward Cui & Eva Liu ARTIST: Sylvia Mohanraj

Pathoprofile

INTRODUCTION Multiple sclerosis (MS) is a chronic, demyelinating, neurodegenerative disorder of the central nervous system (CNS). It is the most common cause of non-traumatic neurological damage among young adults, affecting approximately 0.24% of the North American population.1,2 Canada has the world’s highest rate of MS, with over 100,000 Canadians affected by the disease.3 Although there is evidence that suggests an autoimmune process initiates the disease and that demyelination results from myelin-targeted inflammation, the complex pathogenesis of MS remains poorly understood. There is currently no cure for MS.1

PATHOPHYSIOLOGY OVERVIEW There are several phenotypes of MS: primary and secondary progressive MS, which involve uninterrupted disease progression; relapsing-remitting MS (RRMS), which consists of intermittent periods of active inflammation; and progressive-relapsing MS (PRMS), which exhibits continuous progression with occasional relapse.1,4 One commonality linking all forms of MS is lymphocyte-mediated perivascular inflammation, occuring primarily in the white matter. The resulting diffused or randomly distributed demyelination and axonal loss lead to inflammatory lesions, otherwise known as demyelinating plaques. Depending on the location of the plaques, neurological symptoms vary. These symptoms include vision and hearing impairment, sensory and proprioceptive deficits, motor deficits, depression, pain, fatigue, and cognitive impairment.1,5,6 The CNS has the ability to partially counteract demyelination by mounting an anti-inflammatory response which may be partly responsible for the intermittent remission characteristic of RRMS and PRMS.5 It is unknown why a similar anti-inflammatory response is not seen in progressive forms of MS. While the exact mechanism that triggers MS remains elusive, epidemiological evidence has identified environmental factors, including exposure to the Epstein-Barr virus, to be a risk factor.7,8 In addition, variations in the human leukocyte antigen gene also influence likelihood of MS onset.9

Oligodendrocyte

AUTOIMMUNE DEMYELINATION The myelin sheath is a specialized lipid-rich organelle produced, maintained, and regenerated by a type of glia called the oligodendrocyte. Myelin sheaths surround neuronal axons for the dual purpose of insulation and enhanced transmission. Demyelination is the characteristic neuropathology of MS, and results from autoimmune destruction of the myelin sheaths.5,6 The current prevailing hypothesis states that CD4+ and CD8+ T lymphocytes initiate and propagate an autoimmune attack on oligodendrocytes.1 This process begins when T lymphocytes and B lymphocytes infiltrate the CNS. Once inside, they can be activated by myelin components presented by antigen presenting cells such as dendritic cells and microglia. Upon activation, a variety of potent pro-inflammatory cytokines with myelinotoxic effects are released, such as tumor necrosis factor-α (TNF-α).10 This complex inflammatory process results in myelin sheath destruction, which

induces localized astrogliosis (abnormal increases in astrocyte population and size). In progressive MS, demyelination is invariably associated with microglial activation. These CNS-specific immune cells express molecules that facilitate the production of reactive oxygen species (ROS), such as myeloperoxidase and NADPH oxidase. In turn, ROS act to accelerate oligodendrocyte injury.11 The primary result of demyelination is perturbed impulse conduction. In properly myelinated axons, action potentials leap between unmyelinated regions of the axon known as the nodes of Ranvier, resulting in fast saltatory conduction. In the absence of healthy myelin, action potential conduction becomes diffuse, slow, and weak.12 Additionally, demyelinated neurons become more excitable, generating abnormal impulses that produce symptoms of ataxia and tonic spasms characteristic of MS.10

AXON DEGENERATION

Saltatory Conduction

Healthy Myelin Sheath

T Cell

In addition to demyelination, white matter inflammation in MS also causes axon degeneration, which is mediated by several mechanisms including mitochondrial injury, hypoxia, and membrane ionic imbalance. Demyelination exposes the mitochondria within the axons to ROS, which can mutate mitochondrial DNA, decreasing their rate of energy production. This can manifest in axonal degradation through numerous pathways, such as reduced axonal oxygen consumption, termed histotoxic hypoxia; release of apoptosisinducing factors; and the activation of calpains, which can cause degradation of cytoskeletal proteins and axons.5 The mechanisms involved in axonal degeneration are complex, and more research is needed to develop effective therapeutic interventions to counter axonal damage occurring in MS.13

FUTURE RESEARCH Currently, researchers have not reached a consensus on the primary trigger for the autoimmune attack, nor have they completely delineated the mechanism behind anti-inflammatory CNS activities underlying disease remission.Moreover, since no reliable imaging or pathological characteristics exist to distinguish between early RRMS and progressive forms of the disease, further research is necessary to determine differences between the phenotypes via molecular analysis of cerebrospinal fluid samples from MS patients. Despite this gap, immunomodulatory treatments, such as the interferon beta protein, have proven to be effective in reducing the relapse rate of MS by inhibiting the activation of myelin reactive T cells. Future research priorities for MS treatment include elucidating neuroprotection mechanisms and exploring combination therapies.10

Inﬂammatory Cytokines (e.g. TNF-α)

ROS

Myeloperoxidase

Damaged Myelin Sheath Microglial Cell

REFERENCES 1.

3. 4.

Miljković D, Spasojević I. Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities. Antioxidants & Redox Signaling. 2013;19(18):2286-2334. Available from: https://www.ncbi.nlm.nih. gov/pmc/articles/PMC3869544/ [Accessed 8th Oct 2017]. Perez-Cerda F, Sanchez-Gomez MV, Matute C. The link of inflammation and neurodegeneration in progressive multiple sclerosis. Multiple Sclerosis and Demyelinating Disorders. 2016;1(1):9. Available from:https://msddjournal.biomedcentral.com/articles/10.1186/ s40893-016-0012-0 [Accessed 6th Oct 2017]. About MS — MS Society of Canada [Internet]. 2017 [cited 2017 Oct 27]. Available from: https://mssociety.ca/about-ms. Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nature Reviews Neurology. 2012;8(11):647-656. Available from: https://www.nature.com/ nrneurol/journal/v8/n11/full/nrneurol.2012.168.html [Accessed 6th Oct 2017]. Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. The Lancet Neurology. 2015;14(2):183193. Available from: http://www.thelancet.com/journals/laneur/arti-

cle/PIIS1474-4422(14)70256-X/fulltext [Accessed 6th Oct 2017]. Deber CM, Reynolds SJ. Central nervous system myelin: structure, function, and pathology. Clinical Biochemistry. 1991;24(2):113-134. Available from: http://www.sciencedirect.com/science/article/pii/00 099120919zt;jsessionid=0493064A2F28E4C0BD0F1B6D533A DC0A.f04t04 [Accessed 8th Oct 2017]. 7. Nielsen TR, Rostgaard K, Nielsen NM, Koch-Henriksen N, Haahr S, Sørensen PS, Hjalgrim H. Multiple Sclerosis After Infectious Mononucleosis. JAMA Neurology. 2007;64(1):72–75. Available from: https:// jamanetwork.com/journals/jamaneurology/fullarticle/793221 [Accessed 28th Oct 2017]. 8. Moutsianas L, Jostins L, Beecham AH, Dilthey AT, Xifara DK, Ban M, et al. Class II HLA interactions modulate genetic risk for multiple sclerosis. Nature Genetics. 2015;47(10):1107-1113. Available from: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC4874245/ [Accessed 28th Oct 2017]. 9. Goodin DS. Multiple sclerosis and related disorders. vol. 122. 1st ed. Edinburgh: Elsevier; 2014. 10. Fischer MT, Wimmer I, Hoftberger R, Gerlach S, Haider L, Zrzavy T, et 6.

al. Disease-specific molecular events in cortical multiple sclerosis lesions. Brain. 2013;136(Pt 6):1799-1815. Available from: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC3673462/ [Accessed 7th Oct 2017]. 11. Wang C, Paling D, Chen L, Hatton SN, Lagopoulos J, Aw ST, et al. Axonal conduction in multiple sclerosis: A combined magnetic resonance imaging and electrophysiological study of the medial longitudinal fasciculus. Multiple Sclerosis Journal. 2015;21(7):905915. Available from: http://journals.sagepub.com/doi/ pdf/10.1177/1352458514556301 [Accessed 8th Oct 2017]. 12. Heidker RM, Emerson MR, LeVine SM. Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis. Neural Regeneration Research. 2017;12(8):1262-1267. Available from: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC5607817/ [Accessed 7th Oct 2017].

ABSTRACTS THE LONG-TERM EFFICACY AND COGNITIVE EFFECTS OF ELECTROCONVULSIVE THERAPY IN INDIVIDUALS WITH DEPRESSION AND ANXIETY CHRISTINA PUCCINELLI1, HEATHER MCNEELY2 Department of Biology and Psychology, Neuroscience & Behaviour, McMaster University 2 Department of Clinical Neuropsychology Services, St. Joseph’s Healthcare Hamilton - West 5th Campus

abstracts

Electroconvulsive therapy (ECT) is a recognized intervention for treatmentresistant depression (TRD). However, uncertainty remains regarding the severity and duration of ECT-related cognitive impairments and whether psychiatric co-morbidities such as anxiety contribute to residual impairments. This study investigates the efficacy and cognitive outcomes of bilateral, brief-pulse ECT for TRD up to 6 months post-ECT. Additionally, it explores whether patients with co-morbid anxiety respond differently to ECT compared to individuals with only depression. Out of 118 outpatients receiving ECT, 17 (5-Depression; 12-Anxiety & Depression) fit the inclusion criteria. Assessment measures included: Beck Depression Inventory-II (BDI-II), Personality Assessment Inventory (PAI), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and Squire Subjective Memory Questionnaire (SSMQ). Assessments were performed at baseline, following the 4th ECT, 2-4 weeks post-ECT, and 6 months post-

ECT. BDI-II results indicated that bilateral, brief-pulse ECT is an effective acute treatment for TRD. In patients diagnosed with comorbid depression and anxiety, benefits are maintained up to 6 months post-ECT. Additionally, PAI anxiety levels decreased significantly with treatment of depression. The patients’ objective cognitive functioning measured by the RBANS was within the average range, and no significant cognitive changes were detected over time. The SSMQ results indicated that patients’ reported subjective memory impairment did not change significantly over time. Contrary to this, the subrgoup of patients with co-morbid depression and anxiety had significantly lower RBANS scores overall. However, the small sample size and medication differences provide substantial impetus for further investigation.

SEX DIFFERENCES IN STRESS ADAPTATION: NEUROPLASTICITY WITHIN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS

M E D U CATO R

D E C E M B E R 2017

AOI ICHIYAMA, XUE FAN WANG, SARA MATOVIC, WATARU INOUE Robarts Research Institute, Western University

The hypothalamic-pituitary-adrenal (HPA) axis is sexually dimorphic. However, little is known about sex differences in the HPA axis’ adaptation to chronic stress. Here, we studied sex-dependent neural plasticity mechanisms relevant to the habituation of the HPA axis to repeated stress. This habituation manifests as decreased excitability of HPA axis output neurons, which are neuroendocrine neurons that express corticotropin releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN). Mice were first subjected to 1 hour of daily restraint stress for 3 weeks, and were then challenged with the same stressor after either 1 day, 1 week, or 4 weeks of no-stress recovery periods. As controls, one group of mice received 1 hour of restraint without prior stress, and another control group received no stress. Using immunohistochemistry, we quantified the induction of the immediate early gene (IEG) c-Fos, a marker

of neuronal activation, in PVN-CRH neurons. We found that, in both sexes, 3 weeks of repeated stress decreased restraint-induced c-Fos expression in the PVN-CRH neurons. Furthermore, this habituation was fully reversed by 4 weeks without stress. However, females showed greater habituation and a slower recovery; significant attenuation persisted after 1 week without stress whereas males had fully recovered by that time. In summary, we found sex differences in the neural plasticity associated with the HPA axis habituation to and recovery from repeated stress. These findings should be further explored to elucidate the mechanistic causes for these differences in c-Fos expression. Acknowledgements: Supported by CIHR, NSERC and OMHF.

A RT I S T CA N DY N I U

MORPHOLOGICAL EFFECTS OF DEVELOPMENTAL ETHANOL EXPOSURE ON MEDIAL PREFRONTAL LAYER VI NEURONS IN JUVENILE MICE LAURA SPATAFORA, EMMA LOUTH, CHARLES SUTTON, CRAIG BAILEY Department of Biomedical Sciences, University of Guelph

the juvenile-equivalent age of postnatal day 15. Morphological measures analyzed included apical and basal dendritic matter, complexity, and cell body area. Compared to the controls, developmental ethanol exposure decreased the length and complexity of apical dendrites in male mice, but increased the length and complexity of basal dendrites in female mice. This demonstrates a sex difference in developmental ethanol-induced morphological alterations to mPFC layer VI neurons. These findings suggest that exposure to ethanol during development cause structural changes within the mPFC early in postnatal life, which may alter the trajectory of normal morphological refinements during mPFC maturation. Alterations to dendrite morphology may influence the function of the mPFC through changes to the location and type of afferent axonal inputs from other brain areas to layer VI pyramidal cell dendrites. Furthermore, these results provide a potential morphological mechanism underlying attention deficits associated with FASD.

ARELY CRUZ-SANCHEZ & MAITHE ARRUDA-CARVALHO Department of Cell & Systems Biology, University of Toronto Scarborough

objects; 2) they only expressed OR memory during the first 20 seconds of object exploration and required a long-term, 24-hour consolidation period; and 3) C57BLK/6J x 129S1/SvImJ mice are able to express TOR at postnatal day (PD) 32 but not at PD14, PD16 or PD23. These data suggest that TOR memory, which is known to depend on the medial prefrontal cortex (mPFC), features a late onset consistent with the delay in the maturation of the mPFC. Additionally, this indicates that behaviours such as TOR have a later onset than more survival-critical behaviours such as fear learning.

| D E C E M B E R 2017

Mental disorders with adolescent onset, such as schizophrenia, are theorized to be a consequence of the abnormal maturation of brain circuits implicated in learning and memory. To understand how developing brain circuits become pathological, it is important to investigate how these neural circuits mature to support behaviour. This study investigated the behavioural expression of object recognition (OR) and temporal order recognition (TOR) memory in C57BLK/6J x 129S1/SvImJ mice and identified the age at which they expressed TOR memory. We found that: 1) C57BLK/6J x 129S1/SvImJ mice had an innate preference toward select

M E D U CATO R

EXPRESSION OF OBJECT RECOGNITION MEMORY AND THE ONTOGENY OF TEMPORAL ORDER RECOGNITION MEMORY IN C57BLK/6J X 129S1/SVIMJ MICE

abstracts

The teratogenic effects of chronic prenatal alcohol exposure have been well documented and are classified as fetal alcohol spectrum disorders (FASD). Of the cognitive deficits associated with FASD, attention deficits are among the most prevalent and persistent, yet there is a limited understanding of the neural mechanisms underlying these deficits. It has been shown that pyramidal neurons in layer VI of the medial prefrontal cortex (mPFC) are critical for optimal attention. The morphological development of these neurons is driven by nicotinic acetylcholine receptors, which are vulnerable to dysregulation by developmental ethanol exposure in rodents. To date, studies of developmental ethanol exposure on mPFC neuronal morphology have been quite limited. In this study, a quantitative Sholl analysis of mPFC layer VI neuron morphology was performed on biocytin-filled neurons using Neurolucida software to produce three-dimensional neuron tracings. Mice of both sexes were exposed to either ethanol vapour or air during the human 2nd and 3rd trimester equivalents, and assessed for neuron morphology at

Shining a Light on the Opioid Crisis TAKHLIQ AMIR1 & JAMES YU 2 Bachelor of Health Sciences (Honours) Class of 2019, McMaster University Bachelor of Health Sciences (Honours) Class of 2020, McMaster University Correspondence: amirt@mcmaster.ca

1 2

spotlight

10.

M E D U CATO R

D E C E M B E R 2017

11.

12.

13.

14.

Rosenblum A, Marsch LA, Joseph H, Portenoy RK. Opioids and the treatment of chronic pain: controversies, current status, and future directions. Experimental and Clinical Psychopharmacology. 2008;16(5):405. [Accessed 20th October 2017]. Canadian Public Health Association. The Opioid Crisis in Canada. December 2016. Available from: https:// www.cpha.ca/sites/default/files/ uploads/policy/positionstatements/ opioid-positionstatement-e.pdf. [Accessed 20th October 2017]. Government of Canada. National report: Apparent opioid-related deaths in Canada (January 2016 to March 2017). 15 September 2017. Available from: https://www.canada.ca/ en/public-health/services/publications/healthy-living/apparent-opioidrelated-deaths-report-2016.html. [Accessed 20th October 2017]. Ubelacker S. Rising hospitalizations due to opioid crisis puts a burden on Canada’s health system: report. The Star. 14 September 2017. Available from: https://www.thestar.com/ news/canada/2017/09/14/risinghospitalizations-due-to-opioid-crisisputs-a-burden-on-canadas-healthsystem-report.html. [Accessed 20th October 2017]. Fischer B, Russell C, Murphy Y, Kurdyak P. Prescription opioids, abuse and public health in Canada: is fentanyl the new centre of the opioid crisis?. Pharmacoepidemiology and Drug Safety. 2015;24(12):1334-6. [Accessed 20th October 2017]. Robertson G, Howlett K. How a little-known patent sparked Canada’s opioid crisis. The Globe and Mail. 30 December 2016. Available from: https://beta.theglobeandmail.com/ news/investigations/oxycontin/ article33448409/?ref=http://www. theglobeandmail.com&. [Accessed 20th October 2017]. Center for Disease Control and Prevention. Fentanyl. 29 August 2017. Available from: https://www.cdc.gov/ drugoverdose/opioids/fentanyl.html. [Accessed 20th October 2017]. Dhalla IA, Mamdani MM, Gomes T, Juurlink DN. Clustering of opioid prescribing and opioid-related mortality among family physicians in Ontario. Canadian Family Physician. 2011;57(3):e92-6. [Accessed 20th October 2017]. Fischer B, Jones W, Urbanoski K, Skinner R, Rehm J. Correlations between prescription opioid analgesic dispensing levels and related mortality and morbidity in Ontario, Canada, 2005–2011. Drug and Alcohol Review. 2014;33(1):19-26. Gomes T, Mamdani MM, Paterson JM, Dhalla IA, Juurlink DN. Trends in high-dose opioid prescribing in Canada. Canadian Family Physician. 2014;60(9):826-32. Ballantyne JC, Shin NS. Efficacy of opioids for chronic pain: a review of the evidence. The Clinical Journal of Pain. 2008;24(6):469-78. [Accessed 20th October 2017]. Canadian Institute for Health Information. Opioid-Related Harms in Canada. September 2017. Available from: https://www.cihi.ca/sites/default/ files/document/opioid-harms-chartbook-en.pdf. [Accessed 20th October 2017]. Gomes T, Mamdani MM, Dhalla IA, Cornish S, Paterson JM, Juurlink DN. The burden of premature opioid-related mortality. Addiction. 2014;109(9):1482-8. [Accessed 20th October 2017]. Fischer B, Burnett C, Rehm J. Considerations towards a population health approach to reduce prescription opioid-related harms (with a primary focus on Canada). Drugs: Education, Prevention and Policy. 2015;22(1):60-5. [Accessed 20th October 2017].

Both natural and synthetic opioid drugs have been used as a popular therapy for chronic pain throughout history. However, their role as effective analgesics has been tainted by the potential for addiction, increased physical dependence, and often progressive reduction in drug efficacy.1 Currently, Canada is home to a raging opioid crisis with epidemic proportions of overdoses and related deaths as a result of prescription opioids (POs), as well as illegal and more potent synthetic opioids.2 In 2016, there were over 2500 opioidrelated deaths across Canada, and more than 3000 deaths are expected by the end of 2017.3,4,5 The rise in morbidity and mortality stemming from PO misuse has led Health Canada to declare this issue a major public health crisis. One of the most commonly used opioids, oxycodone, was patented and marketed in 1992 as OxyContin.6 As the cause of almost 50% of opioid-related poisoning deaths, OxyContin was delisted from most Canadian provinces’ public drug formularies in 2012.5 This attempt to delegitimize OxyContin only gave way to increased use of other POs, particularly fentanyl. This represents a much greater concern because fentanyl is an extremely potent synthetic opioid, approximately 50-100 times stronger than morphine.7 Alarmingly, Canadian fentanyl consumption rates are among the highest worldwide, and the number of deaths involving prescribed or illegal fentanyl between January and March 2017 was double that of the same period in 2016.3,5 This epidemic arises partly from Canada’s long history of over-prescribing practices. Dhalla, Gomes and Juurlink demonstrated that the top 20% of family physicians who prescribe opioids did so 55 times more often than the lowest 20%.8 Overprescribing practices may be positively associated with opioid-related mortality. Many studies have consistently suggested a correlation between PO availability and related morbidity and mortality in Canada.5,9 In particular, one study examining opioidrelated deaths between 2005 and 2011 reported significant correlations between PO dispensing and mortality due to oxycodone and fentanyl.9 Overprescription is further compounded by the fact that opioids have been marketed without an

upper dose threshold, despite limited evidence of their safety or effectiveness at high doses.1 In fact, increases in dosage for long-term treatment plans may lead to the development of tolerance over time, presenting an overarching concern for many individuals dependent on opioid therapy for chronic pain.11 Furthermore, a growing body of literature highlights the danger posed by morphine equivalent doses exceeding 200mg/day.10 The health repercussions are especially worrying for Ontario, given that this province has exhibited the highest annual rate of high-dose oxycodone and fentanyl dispensing between 2006 and 2011.10,11 A report recently released by the Canadian Institute for Health Information warns that the opioid crisis presents a significant burden on the healthcare system due to the rising number of Canadians seeking emergency care for overdoses.12 As high PO availability and demand continue unabated in Canada, evidence-based population interventions are needed to understand and address the primary determinants and consequences of PO misuse.1,5,13 Given that opioid dispensing rates in Canada are much higher than those in other high-income countries, there is room for substantive reductions in PO prescription and improvements in physician and patient education.8,14 Unless measures are taken to address this crisis, the widespread availability of dangerous opioids, including fentanyl, will continue to pose a significant public health concern. ■

A Pastime in Peril? JAMES YU1 & TAKHLIQ AMIR 2 Bachelor of Health Sciences (Honours) Class of 2020, McMaster University Bachelor of Health Sciences (Honours) Class of 2019, McMaster University Correspondence: yut20@mcmaster.ca

1 2

Mounting evidence has suggested a linkage between American football and chronic traumatic encephalopathy (CTE). Recently, a study examining the deaths of 111 National Football League (NFL) players found an overwhelming 110 CTE cases.1 CTE is a neurodegenerative disease associated with repeated blows to the head. Normally, tau proteins in the brain provide a scaffold for neurons, but repeated head trauma causes hyperphosphorylation of these proteins, which then aggregate to form neurofibrillary tangles (NFTs).2 NFTs can progressively spread throughout the brain over many years and disrupt function in critical regions, such as the hippocampus (responsible for memory and emotion), the amygdala (aggression), and the frontal cortex (cognition and executive functions). As a result, CTE symptoms include memory loss, aggression, and suicidal behavior.

Research on CTE is an increasingly popular field because of its social impact and widespread applicability. Results from previous studies that linked CTE and football have already facilitated a $1 billion settlement between the NFL and players who suffer from concussion-related diseases.5 However, a major difficulty facing future studies on CTE is that a definitive diagnosis can only occur through a post-mortem brain autopsy, highlighting the need for research on potential diagnostic tools. A reliable, in-vivo diagnostic method may come from a seven-year, $16 million study conducted by Boston University.5 The NFL was initially set to fund the study but later backed out amidst accusations that it attempted to direct funding to scientists with previous connections to the league.

| D E C E M B E R 2017

ARTIST MICHAEL SUN

Mez J, Daneshvar DH, Kiernan PT, Abdolmohammadi B, Alvarez VE, Huber BR, et al. Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA. 2017;318(4):360370. doi:10.1001/jama.2017.8334. [Accessed 20th October 2017]. 2. DeKosky ST, Blennow K, Ikonomovic MD, Gandy S. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nature Reviews Neurology. 2013;9(4):192-200. doi:10.1038/nrneurol.2013.36. [Accessed 20th October 2017]. Breedlove EL, Robinson M, Talavage TM, Morigaki KE, Yoruk U, O’Keefe K, et al. Biomechanical correlates of symptomatic and asymptomatic neurophysiological impairment in high school football. Journal of Biomechanics. 2012;45(7):12651272. doi:10.1016/j.jbiomech.2012.01.034. [Accessed 20th October 2017]. Alosco ML, Kasimis AB, Stamm JM, Chua AS, Baugh CM, Daneshvar DH, et al. Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes. Translational Psychiatry. 19 September 2017. doi:10.1038/tp.2017.197. [Accessed 20th October 2017]. Branch J. N.F.L. Tried to Influence Concussion Research, Congressional Study Finds. The New York Times. 23 May 2016. Available from: https:// www.nytimes.com/2016/05/24/ sports/football/nfl-tried-to-influenceconcussion-research-congressionalstudy-finds.html. [Accessed 20th October 2017]. Bazarian JJ, Zhu T, Zhong J, Janigro D, Rozen E, Roberts A, et al. Persistent, Long-term Cerebral White Matter Changes after SportsRelated Repetitive Head Impacts. Theoret H, editor. PLoS One [Internet]. 2014 Apr 16 [cited 2017 Nov 7];9(4):e94734. Available from: http://dx.plos.org/10.1371/journal. pone.0094734. [Accessed 20th October 2017]. Defense Health Agency. Defense and Veterans Brain Injury Center. Available from: http://dvbic.dcoe.mil/dodworldwide-numbers-tbi [Accessed 20th October 2017].

M E D U CATO R

Further research on CTE may have implications beyond the football field. Athletes in other injuryprone sports, such as hockey and wrestling, are at risk of developing CTE.6 20% of the two million American troops deployed to Iraq and Afghanistan are also affected by traumatic brain injuries.7 Additionally, tau proteins and NFTs are present in other neurodegenerative diseases, including Alzheimer’s disease. Accordingly, diagnostic tools and treatments developed for CTE may lead to breakthroughs for other diseases as well. ■

spotlight

Although CTE is well-known for its presence in high-profile NFL players, like the late Aaron Hernandez, a two-year study on high school football players suggests that CTE-associated pathology can be found in young, amateur athletes as well.3 Given that more than 1.1 million high school athletes play football in the United States, the impact of CTE may be more widespread than commonly assumed. Moreover, a recent study published in Nature suggests that playing football from a young age can result in more severe long-term symptoms of CTE.4 Specifically, the investiga-

tors noted that athletes who began playing before age 12, in comparison to those who started at or after this age, faced triple the odds of depression and more than double the odds of executive dysfunction, as characterized by poor impulse control, working memory, and cognitive flexibility. Nevertheless, studies providing evidence of the link between football and CTE have many limitations, including small sample sizes, and self-selected participants often with greater-than-average concern for their health. Moreover, these studies focus on the correlation, rather than the potential causal relationship, between football and CTE.4 Such considerations have prompted researchers to recognize the need for prospective, longitudinal studies in validating the causal link between football and CTE.

FORUMSPACE Leveraging Communities of Practice to Address PostSecondary Mental Health and Addictions Issues FANNY CHENG, PURU PANCHAL Bachelor of Health Sciences (Honours) Class of 2019, McMaster University

M E D U CATO R

| D E C E M B E R 2017

forumspace

INTRODUCTION

The progress made in recent years in promoting a greater awareness and acceptance of mental health and addictions issues has been accompanied by a concerning rise in mental illnesses among post-secondary students. In 2016, the Ontario University and College Health Association conducted a survey regarding the physical and mental well-being of over 25,000 post-secondary students. When asked about factors that affected their academic performance, 21.9% of respondents identified depression, 33.1% identified anxiety, and 42.9% identified stress.1 13.7% of students also reported that they had seriously considered suicide within the past year.1 The survey also identified alarming statistics of risky behaviours that accompanied substance use. Notably, about 12.1% of students reported driving under the influence of alcohol in the last month alone.1 By consulting various services and stakeholders, the McMaster Health Forum Fellows have identified several concerns regarding the delivery of mental health and addictions care at McMaster University. Several key informants have questioned whether mental health training programs operated by the university are guided by evidence. One such program is safeTALK, a threehour training program that teaches participants how to recognize persons with thoughts of suicide and connect them with suicide prevention resources. Other informants expressed concerns about funding shortages for initiatives like Arrive and Thrive, which aim to address detrimental coping mechanisms like substance abuse among students. Some informants have also questioned whether outsourcing mental healthcare to third parties like Aspiria would effectively and sustainably address the severe shortages in mental health care on campus, where only twelve counsellors are available for over 25,000 undergraduate students. Current evidence needs to be examined through a critical and evidence-informed lens to determine how health systems can be best leveraged to address these complex issues. This work necessitates a student-led organization with the structure of a community of practice.

DEFINING COMMUNITY OF PRACTICE A community of practice (CoP) provides a platform through which practitioners can collectively learn and share knowledge on a particular field.2 CoPs are defined by three characteristics:3

The McMaster Health Forum strives to be a leading hub for improving health outcomes at the regional and provincial levels in Canada. Through problem-solving and discussion, they harness information, convene stakeholders, and prepare action-oriented leaders to address pressing health issues creatively.

■ the domain, or the discussed field of interest, which distinguishes members from non-members; ■ the community, or the interactions through which knowledge is shared; and ■ the practice, or the requirement that members are active practitioners in the field. Though the term ‘community of practice’ itself may be unfamiliar to most students, CoPs have existed for centuries in various forms. They can be incredibly diverse in scope, location, and resource availability.3 Examples of CoPs can range anywhere from a group of surgeons who meet monthly to discuss novel techniques to an online forum of civil engineers working collaboratively to troubleshoot design problems.3 The most successful CoPs tend to have access to financial resources, existing professional networks, and opportunities for regular interactions between members.4 CoPs can be especially valuable in healthcare. Healthcare practitioners have long performed in silos without sufficient interdisciplinary collaboration beyond bedside care.5 For example, doctors and nurses rarely have professional interactions during mandated continuing education events. Unfortunately, this results in missed opportunities to improve best practices.5 CoPs seek to address this challenge by breaking down traditional performance silos and fostering collective decision making.6 This is especially relevant as Ontario’s healthcare system transitions to delivering care through interprofessional teams.7 An example of a CoP is Ontario’s Seniors Health Knowledge Network (SHKN), a platform that facilitates knowledge translation between healthcare providers, policymakers, and researchers.8 Since its launch in 2005, SHKN has become one of Ontario’s most effective CoPs. It has over 8,000 members who help develop healthcare innovations for seniors, use evidence to inform practices, and advocate for health system changes based on evolving demographics and needs.8 One recent initiative advocated for early detection of illnesses in elderly citizens receiving community care in order to prevent frailty-related injuries.9 Given the success of CoPs, as exemplified by SHKN, it would be beneficial to implement a similar initiative at the undergraduate level to address health challenges faced by postsecondary students.

ADAPTING CoPs TO EXAMINE STUDENT MENTAL HEALTH AND ADDICTION ISSUES Although CoPs are often comprised of practitioners, implementing such a platform within the student body can spark equally meaningful action for mental health and addictions issues. This year, the Forum Fellows recruited 25 undergraduate students to form a student-led Community of Action (CoA). Each participant brings unique perspectives based on their academic backgrounds and lived experiences. With members from the Faculty of Health Sciences, the Faculty of Science, the Faculty of Social Sciences, and the Arts and Science program, this CoA will tackle issues in an interdisciplinary and multifaceted manner.

panel discussions with experienced practitioners. By evaluating the current state of university policies for mental health and addictions, the CoA will provide McMaster University and its partners with an evidence-informed voice for issues affecting its students. Such a voice is critical to effectively address students’ mental health and addictions, especially in the face of campus legislative changes regarding tobacco and marijuana use and rising concerns from key stakeholders. Looking forward, it is hoped that the CoA will bring tangible improvements to the McMaster student experience. ■

4. 5. 6. 7. 8. 9.

American College Health Association. National College Health Assessment II: Ontario Canada Reference Group Executive Summary. American College Health Association. 2016. Hoadley C. What is a community of practice and how can we support it? In: Land S, Jonassen D. (eds.) Theoretical foundations of learning environments. 2nd ed. New York, USA: Routledge; 2012. p. 287-300. Wenger E. How we learn. Communities of practice. The social fabric of a learning organization. The Healthcare Forum Journal. 1996;39(4):20-26. Available from: https://www.ncbi.nlm.nih.gov/ pubmed/10158755 [Accessed 20th October 2017]. McKellar KA, Pitzul KB, Yi JY, Cole DC. Evaluating communities of practice and knowledge networks: a systematic scoping review of evaluation frameworks. EcoHealth. 2014;11(3):383-399. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25023411 [Accessed 20th October 2017]. Conway JB. Breaking down professional silos: the potential of integrated management. Radiology Management. 1997; 19(3):30-34. Available from: https://www.ncbi.nlm.nih.gov/pubmed/10168249 [Accessed 20th October 2017]. Ranmuthugala G, Plumb JJ, Cunningham FC, Georgiou A, Westbrook JI, Braithwaite J. How and why are communities of practice established in the healthcare sector? A systematic review of the literature. BMC Health Services Research. 2011;11:273. Available from: https://bmchealthservres.biomedcentral.com/articles/10.1186/1472-6963-11-273 [Accessed 20th October 2017]. Lavis JN. Ontario’s health system: Key insights for engaged citizens, professionals and policymakers. Hamilton: McMaster Health Forum;2016. Kothari A, Boyko JA, Conklin J, Stolee P, Sibbald SL. Communities of practice for supporting health systems change: A missed opportunity. Health Research Policy and Systems. 2015;13:33. Available from: https://health-policy-systems.biomedcentral.com/articles/10.1186/s12961-015-0023-x [Accessed 20th October 2017]. Centre for Studies in Aging & Health. Frailty: Overview [internet]. Belleville (ON): Seniors Health Knowledge Network; 2014 Mar [cited 2017 Oct 26]. Available from: http://seniorshealthknowledgenetwork. ca/node/1053. [Accessed 20th October 2017].

More discussions on current healthcare topics are available at http://www.mcmasterhealthforum.org/

| D E C E M B E R 2017

1. 2. 3.

ARTIST CATHY REN

M E D U CATO R

Through this CoA initiative, findings will be used to inform the scope of a winter capstone event, which may consist of student-led dialogues with regional health system stakeholders or public

forumspace

This year’s CoA will focus on developing students’ competencies in health evidence research and synthesis. From there, students will work in teams to closely examine current practices and policies on campus. This process will involve synthesizing evidence on specific problems, and exploring implementation considerations for potential solutions. Throughout the year, students will also network with field professionals through mentoring events and panel discussions on pressing issues. Additionally, our student team will publish written materials and videos that highlight new discoveries, policy changes, and pertinent questions in order to reach a broader audience through plain-language summaries of health evidence.

A RT I S T P E R I (P E I R U I) R E N

VIEWPOINTS Health Perspectives on the Legalization of Cannabis

PROS

DEVIN ROSHAN

Bachelor of Health Sciences (Honours) Class of 2019, McMaster University Correspondence: roshand@mcmaster.ca

Proponents of legalization argue that the influx of available cannabis could prevent opioid-related overdoses through the substitution effect, a behavioural economics theory postulating how the availability of one good can influence the use of other goods.4,5 For most of the present century, prescription opioid-related misuse has presented a unique public health epidemic in Canada, resulting in an alarming rise in morbidity and mortality. The province of Ontario has responded by removing OxyContin from its public health drug benefit formulary, yet a decrease in its availability has led prescription opioid users to begin using fentanyl as a substitute opioid. Subsequently, Canada is now one of the largest consumers of fentanyl in the world.6 It is argued that the prescribing behaviour of physicians has been the driver of the opioid epidemic.7 This suggests that physicians may need to be open to prescribing alternative antinociceptive treatments.

So what prevents physicians from prescribing cannabis for therapeutic purposes (CTP) as a substitute to opioids? In short, obtaining CTP in Canada is a tedious process. A study conducted by Belle-Isle and colleagues identified four barriers impeding Canada’s CTP program: accessibility, availability, affordability, and acceptability.4,13 Researchers determined that it is extremely difficult for Canadians with chronic pain to find a physician willing to support their application for CTP. The stigma and controversy surrounding CTP has been shown to strain patient-physician relationships, leaving patients with only opioids and thus further fueling the epidemic. Only 7% of patients access CTP from authorized dispenseries and the majority seek CTP from illegal sources due to the principal issue of unaffordability and compounded by strained patient-physician relationships.4,12 Despite the countless studies in support of cannabis as a safe and effective treatment for patients with chronic pain, the College of Physicians and Surgeons of Ontario refuses to endorse cannabis as a first-line antinociceptive therapy.13-15 Yet, a JAMA study reports that American states with medicinal cannabis laws have a 24.8% lower mean annual opioid overdose mortality rate compared to states without medicinal cannabis laws, providing compelling evidence in support of the harm-reduced substitution effect.16

| D E C E M B E R 2017

The current prohibition of cannabis in Canada has proven ineffective; public perception indicates that a revision of legislation is necessary. It is also clear that reevaluating restrictions on CTP and further legalization is required to ensure that patients suffering from chronic pain can receive adequate access. Canadian physicians, researchers, and policy makers need to step up to address the opioid epidemic. Further research on cannabis as a viable treatment alternative in Canada and continued exploration of the possible effects of legalization are needed to change physician-patient relationships and to clarify the controversy surrounding medicinal cannabis.

M E D U CATO R

The activation of cannabinoid receptors in the central and peripheral nervous systems has demonstrated antinociceptive properties.8 A study published in Neuropsychopharmacology suggests that medicinal cannabis provides effective pain relief in patients with HIV-associated intractable pain.9 In another recent study examining cannabis as a substitute for opioids, 97% of patients in the sample “strongly agreed” that they were able to effectively decrease the amount of opiates

they consumed when on cannabis.10 Furthermore, 81% “strongly agreed” that consuming cannabis alone was more effective at treating their condition than jointly using cannabis with opioids.10 Research on medicinal cannabis in Arizona — a state that legalized cannabis in 2010 — indicated that 75% of opioid-dependent users had experienced “a lot or almost complete relief ” from opioid dependency following the usage of cannabis.12

viewpoints

In recent years, the intricate issue of legalization and decriminalization of cannabis in Canada has engendered significant political and media scrutiny. In essence, decriminalization of cannabis would allow personal use of the substance without it being classified as a criminal offense, but — depending on the circumstance — it may still incur a legal fine. As is the case with alcohol and tobacco, legalization of cannabis would be regulated tightly.1 The past two decades of public opinion polls have unfolded a narrative that indicates increasing support for either decriminalization or legalization of cannabis.1,2 For instance, a public opinion poll featuring a randomized sample of 1473 Canadian voters determined that 53% favoured the legalization of cannabis. Comparatively, 34% of Canadians from this poll disagreed with legalization. When voters within this sample were asked how the government should handle cannabis, 68% of Canadians were in favour of reappraising cannabis legislation, of which 35% argued for legalizing with taxation while 33% supported decriminalizing possession of small amounts.3

CONS

ADAM WADE-VALLANCE

Bachelor of Health Sciences (Honours) Class of 2018, McMaster University Correspondence: wadevaa@mcmaster.ca 1.

Hajizadeh M. Legalizing and regulating marijuana in Canada: review of potential economic, social, and health impacts. International Journal of Health Policy and Management. 2016;5(8): 453. Available from: http://dx.doi. org/10.15171/IJHPM.2016.63 [Accessed 23rd Oct 2017].

Savas D. Public opinion and illicit drugs: Canadian attitudes towards decriminalizing the use of marijuana. P. Basham (éd.). Sensible solutions to the urban drug problem, Vancouver, The Fraser Institute. 2001. Available from: https://www.fraserinstitute.org/sites/ default/files/SensibleSolutionsSavas.pdf [Accessed 23rd Oct 2017].

Forum Research Inc.(2017). Support for marijuana legalization steady at more than half. [online] Available at: http://poll. forumresearch.com/data/011cc56c-fcc24aef-b005-f8f5c5ec0570Federal%20Marijuana%20News%20Release%20(2015%20 08%2020)%20Forum%20Research.pdf [Accessed 23rd Oct 2017].

M E D U CATO R

| D E C E M B E R 2017

viewpoints

Lucas P, Walsh Z, Crosby K, Callaway R, Belle‐Isle L, Kay R et al. Substituting cannabis for prescription drugs, alcohol and other substances among medical cannabis patients: the impact of contextual factors. Drug and Alcohol Review. 2016;35(3): 326-333. Available from: http://dx.doi.org/10.1111/dar.12323 [Accessed 23rd Oct 2017].

Lucas P. Rationale for cannabis-based interventions in the opioid overdose crisis. Harm Reduction Journal. 2017;14(1): 58. Available from: http://dx.doi.org/10.1186/s12954017-0183-9 [Accessed 23rd Oct 2017].

Fischer B, Russell C, Murphy Y, Kurdyak P. Prescription opioids, abuse and public health in Canada: is fentanyl the new centre of the opioid crisis?. Pharmacoepidemiology and Drug Safety. 2015;24(12): 1334-1336. Available from: http://dx.doi.org/10.1002/ pds.3901 [Accessed 23rd Oct 2017].

Barnett ML, Olenski AR, Jena AB. Opioidprescribing patterns of emergency physicians and risk of long-term use. New England Journal of Medicine. 2017;376(7): 663-673. Available from: http://dx.doi.org/10.1056/ NEJMsa1610524 [Accessed 23rd Oct 2017].

Calignano A, La Rana G, Giuffrida A, Piomelli D. Control of pain initiation by endogenous cannabinoids. Nature. 1998;394(6690): 277-281. Available from: http://dx.doi. org/10.1038/28393 [Accessed 23rd Oct 2017].

Ellis RJ, Toperoff W, Vaida F, Van Den Brande G, Gonzales J, Gouaux B, Bentley H, Atkinson JH. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34(3): 672-680. Available from: http://dx.doi.org/10.1080/02791072.201 5.1074766 [Accessed 23rd Oct 2017].

10.

Reiman A, Welty M, Solomon P. Cannabis as a substitute for opioid-based pain medication: patient self-report. Cannabis and Cannabinoid Research. 2017;2(1):160-6 Available from:http://dx.doi.org10.1089/ can.2017.0012 [Accessed 23rd Oct 2017].

11.

Troutt W, DiDonato M. Medical cannabis in Arizona: patient characteristics, perceptions, and impressions of medical cannabis legalization. Journal of Psychoactive Drugs. 2015;47(4): 259-266. Available from: http://dx.doi.org/ 10.1080/02791072.2015.1074766 [Accessed 23rd Oct 2017].

12.

Belle-Isle L, Walsh Z, Callaway R, Lucas P, Capler R, Kay R et al. Barriers to access for Canadians who use cannabis for therapeutic purposes. International Journal of Drug Policy. 2014;25(4): 691-699. Available from: https://doi.org/10.1016/j.drugpo.2014.02.009 [Accessed 23rd Oct 2017].

13.

Webb C, Webb S. Therapeutic benefits of cannabis: a patient survey. Hawai’i Journal of Medicine & Public Health. 2014;73(4): 109. Available from: https://www.ncbi.nlm. nih.gov/pmc/articles/PMC3998228/ [Accessed 23rd Oct 2017].

Marijuana use is increasing throughout Canada, seemingly in anticipation of its impending legalization by Justin Trudeau’s Liberal government.17 There are two ways to speculate about the health ramifications of this decision: firstly, by looking through a historical lens at the shift in public opinion on tobacco products in response to emerging scientific evidence, and secondly, by examining the alarming precedent set by marijuana decriminalization elsewhere in the world, such as in Colorado, USA.18 Beginning in the early 20th century, tobacco use and cigarette smoking exploded in Anti-smoking sentiment popularity.2 quickly emerged, but it was backed only by moral or religious arguments. Credible science lagged decades behind. Through unrestricted advertising, tobacco companies baselessly dubbed their products “healthy”. When concerns about tar and nicotine were raised, they were countered by “healthier” products with reduced tar and nicotine rather than real change. Corrupt researchers funded by tobacco companies published findings discrediting scientific evidence demonstrating smoking’s negative health effects. Even with the release of the Surgeon General’s report in 1964, which broadcasted the concrete link between smoking and cancer, public understanding of tobacco’s negative health effects remained inadequate well into the 1980s.18 However, this viewpoint is not about cigarettes. Marijuana is much “healthier” anyway, right? The answer: we don’t know. Smoking’s role in lung cancer became evident

only because its effect size was so enormous that global cancer rates skyrocketed. Yet, a decades-long time lag masked the insidious danger posed by tobacco, all the while smoking spread like wildfire.18 Let this disaster forewarn of the danger posed by incomplete scientific understanding and public complacency regarding the adverse health effects of recreational substances. So what are these adverse effects? Colorado was among the first American states to legalize marijuana, and much can be learned by observing its struggle with the resultant health impact, which has spanned human development from childhood to adolescence and adulthood.19 In the two years post-legalization, 14 children were admitted to the emergency department due to accidental ingestion of marijuana, compared to only 2 for accidental ingestion of alcohol. Before legalization, there had been zero admittances in a five-year period.20 Most of this phenomenon can be attributed to the accessibility of candied marijuana products, which are indistinguishable from un-drugged treats.20 Exacerbating this issue, the concentration of the active ingredient of marijuana, tetrahydrocannabinol (THC), is poorly regulated and can exceed recommended intoxication levels by up to 10-fold.4,5 THC concentrations in street marijuana have increased over recent decades.21 In adults, this increases overdose frequency, and delirium severity; in children, effects can be as serious as respiratory arrest.19 Therefore, marijuana legalization has created a novel health hazard ensnaring

our

youngest

and

most

vulnerable.

Approximately 9% of marijuana users become addicted. Prolonged heavy cannabis use has been associated with educational

In sum, history cautions us against drugs publicly believed to be harmless, or even medically beneficial, in discordance with scientific evidence. It is especially wise to be wary of medical claims made by dispensaries and drug users. Mistaken public views regarding tobacco smoking required almost a century to be dispelled in North America, and still remain in many parts of the world. Similarly, public opinion on cannabis products regards them as innocuous, or even “healthy” today. Meanwhile, adverse health effects of marijuana include addiction, cognitive deficits, educational underachievement, and mental health issues. And all that is only what we know of now. Imagine what we could discover with the whole Canadian public as our research subjects! ■

14.

Lucas P. Regulating compassion: An overview of Canada’s federal medical cannabis policy and practice. Harm Reduction Journal. 2008;5(1):5. Available from: https://doi. org/10.1186/1477-7517-5-5 [Accessed 23rd Oct 2017].

15.

Lucas P. Moral regulation and the presumption of guilt in Health Canada’s medical cannabis policy and practice. International Journal of Drug Policy. 2009 Jul 31;20(4):296-303. Available from: https:// doi.org/10.1186/1477-7517-5-5 [Accessed 23rd Oct 2017].

16.

Bachhuber M, Saloner B, Cunningham C, Barry C. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Internal Medicine. 2014;174(10): 1668-1673. Available from: https://doi.org/10.1001/ jamainternmed.2014.4005 [Accessed 23rd Oct 2017].

17.

Marijuana and Youth [Internet]. 2017 [cited October 18th 2017]. Available from: http:// www.ccdus.ca/Eng/topics/Marijuana/ Marijuana-and-Youth/Pages/default.aspx.

18.

The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General [Internet]. 2014 [cited October 18th 2017]. Available from: https://www.ncbi.nlm. nih.gov/books/NBK179276/.

19.

Monte AA, Zane RD, Heard KJ. The implications of marijuana legalization in Colorado. JAMA. 2015; 313(3): 241-242. Available from: https://jamanetwork-com. libaccess.lib.mcmaster.ca/journals/jama/ fullarticle/2022370. [Accessed October 12th 2017].

20.

Wang GS, Roosevelt G, Heard K. Pediatric marijuana exposures in a medical marijuana state. JAMA Pediatrics. 2013; 167(7): 630633. Available from: https://jamanetworkcom.libaccess.lib.mcmaster.ca/journals/ jamapediatrics/fullarticle/1691416 [Accessed October 13th 2017].

21.

Volkow ND, Swanson JM, Evins AE, DeLisi LE, Meier MH, Gonzalez R, Bloomfield MA, Curran HV, Baler R. Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: a review. JAMA Psychiatry. 2016; 73(3): 292-297. Available from: https://jamanetwork-com.libaccess. lib.mcmaster.ca/journals/jamapsychiatry/ fullarticle/2488041 Accessed October 12th 2017].

22.

Hayatbakhsh MR, Najman JM, Jamrozik K, Mamun AA, Alati R, Bor W. Cannabis and anxiety and depression in young adults: a large prospective study. Journal of the American Academy of Child & Adolescent Psychiatry. 2007 Mar 31;46(3):408-17. Available from: https://journals-scholarsportal-info.libaccess.lib.mcmaster.ca/details/08908567/ v46i0003/408_caaadiya.xml [Accessed October 14th 2017].

viewpoints

In adolescents, the problem is compounded. Ingestion becomes deliberate rather than accidental.The teenage mind is still developing, with key processes such as synaptic pruning and myelination only beginning to refine and cement neural circuitry. Marijuana impairs learning, memory, attention, and general neuropsychological function. These acute effects subside in adults only after prolonged abstinence, condemning regular users to a perpetually intellectually impaired state. Animal and human studies indicate that adolescents are more vulnerable to marijuana’s adverse effects, with a strong likelihood of permanent marijuana-induced impairment and progressive cognitive decline in early life (ages 13-38). The endocannabinoid system, an important regulator of neurodevelopment and a key candidate for perturbation by cannabis consumption, may drive this finding.21 Furthermore, there is evidence suggesting that adolescent cannabis use increases the risk for anxiety and depression in young adulthood.22 This is especially relevant given that Canadian youth are among the top users of marijuana in the developed world, consuming marijuana at over twice the rate of adults over 25.17

underachievement and impaired motivation. This is possibly due to THC’s capacity to interfere with reward-based learning via attenuation of endogenous dopamine synthesis and signalling. Importantly, marijuana is strongly linked to schizophrenia, with its usage accounting for 8-14% of all cases. Acute marijuana use can induce both positive and negative symptoms of schizophrenia; chronic marijuana use increases schizophrenia risk by 2-6 fold depending on its THC concentration.5 This effect is exacerbated in genetically susceptible individuals.21

EDITED BY VALERIE KIM & OWEN LUO

M E D U CATO R | D E C E M B E R 2017

global perspective

ARTIST CANDY NIU

GLOBAL PERSPECTIVE

Conflicting Agendas In Care For Olympic Amateur Boxing DION DIEP

Bachelor of Health Sciences (Honours) Class of 2017, McMaster University Correspondence: dion.diep@mail.utoronto.ca

INTRODUCTION Amateur boxing, also known as Olympic-style boxing, is governed by the International Boxing Association. Although authority is decentralized to national boxing organizations such as Boxing Canada, rules and safety standards remain consistent globally for amateur boxing. Amateur boxers compete in bouts typically comprising three three-minute rounds with intermittent one-minute breaks. Officials score the competing athletes after each round based on predetermined criteria, including the number of quality blows landed, the domination of bout, and the infringement of rules. Given that boxing is a contact sport, athlete health and safety are prioritized by all governing organizations.1 Boxers face a wide variety of health risks: strenuous movements, harsh training regimens, rapid dehydration, and repeated blows to the head and body.2 As such, the requirement of a ringside physician is mandated by all governing bodies. An interdisciplinary medical team may also be employed at larger boxing events.

MY ROLE IN THE COMMUNITY I had the privilege to be a member of the Boxing Ontario medical teams present at local and provincial tournaments throughout Ontario, the Boxing Canada medical teams present at the 2016 Rio Olympic Canadian Boxing Qualifiers, and the 2017 Canadian National Championships throughout Québec. In the latter two tournaments, my responsibilities included: contributing to clinical care for athletes; conducting an observational trial on the influence of headgear on risk for developing concussions; and informing athletes, coaches, and officials through presentations regarding weight-cutting, shoulder pain, and concussions.3

Ethical dilemmas arise during the care process because of conflicting agendas between care providers and athletes. Medical teams operate in the best interest of the athlete’s health. However, not all athletes share the same agenda, as some place priority on winning the bout over their own health. Many athletes train their entire lives to compete in a match at the national level. As such, one’s judgement may begin to blur when weighing a potential gold medal against possible long-term health consequences and the regret of failing to achieve one’s goals. This adds a layer of complexity to medical decisions, which determine the outcome of a bout. Should an athlete with a cut above his eye be disqualified from a local boxing bout? Would this judgement change for a gold medal bout? Medical decisions are always made considering the context of the event, giving rise to moral ambiguity.

MORAL AMBIGUITY IN PRACTICE While generalizing athlete perspectives on care should be minimized, it is important to recognize that psychosocial factors, such as the desire to win, may influence an athlete’s decision regarding their own health. The following are instances based on my experiences when conflicts between the athlete’s autonomy and their personal safety arose.

Cutting Weight Competitors are matched by weight classes to promote fairness. Unfortunately, athletes exploit the system by rapidly reducing their body weight before competitions through dehydration. As a result, they can compete in lower weight classes, gaining a competitive advantage over their opponent in terms of size, leverage, and strength.4 However, athletes endanger their health through severe and consistent dehydration.4

Musculoskeletal Injuries The physical demand of boxing places athletes at risk for various chronic and acute musculoskeletal injuries. This

| D E C E M B E R 2017

During the pre-bout medical examination, athletes typically present with low blood pressure due to reduced blood volume, as well as increased heart rate as a compensatory mechanism. I would confirm these findings by performing an orthostatic hypotension assessment, a highly specific test (94%) that would rule in hypovolemia.5 Judgements regarding disqualification can be difficult in pre-bout assessments if athletes are dehydrated. Dehydration presents with symptoms of, headache, muscle cramps, and/or dizziness, increasing the risks of injury.4 One study also reports an increased risk for brain damage after rapid dehydration.6

M E D U CATO R

Medical teams have a responsibility to ensure that athletes are safe by providing care before, during, and after a bout. To determine if athletes are physically fit to compete, the pre-bout medical examination reviews the medical history of the athlete and performs a focused physical examination. These examinations place more emphasis on common problems including skin lesions; deformities of the head, neck, teeth, ribcage, and hands; and potential concussions. Medical teams are also responsible for monitoring the physical integrity of athletes during the bout by looking for cuts, nosebleeds, abrasions, fractures, dislocations, or harm to the eyes, ears and brain. It is important that these injuries are noted as they may be further addressed in the post-bout medical examination. Throughout the care process, physicians have the authority to disqualify athletes from competition. This creates an imbalance

CONFLICTING AGENDAS

global perspective

As a member of the medical team for the boxing community, the purpose of this global perspective is to elaborate on my role, reflect on the barriers to care, and present future directions for improving care.

in power greater than the typical physician-patient relationship, requiring thoughtful navigation in consideration of the agendas of the stakeholders involved.

Jako P. Safety measures in amateur boxing. British Journal of Sports Medicine. 2002;36(6):394-395 [Accessed 25th July 2017].

Jordan B, Voy R, Stone J. Amateur Boxing Injuries at the US Olympic Training Center. The Physician and Sports Medicine. 1990;18(2):80-90 [Accessed 25th July 2017].

Diep D, Trinh K. Making Weight in Boxing: How to do it Better. Montreal: Boxing Canada; 2016. Available from: http://boxingcanada.org/wp-content/ uploads/2016/10/Making-Weight-inBoxing.pdf [Accessed 25th July 2017].

Franchini E, Brito C, Artioli G. Weight loss in combat sports: physiological, psychological and performance effects. Journal of the International Society of Sports Nutrition. 2012;9(1):52 [Accessed 25th July 2017].

McGee S. Is This Patient Hypovolemic? JAMA. 1999;281(11):1022.Accessed 25th July 2017].

Dickson J, Weavers H, Mitchell N, Winter E, Wilkinson I, Van Beek E et al. The Effects of Dehydration on Brain Volume - Preliminary Results. International Journal of Sports Medicine. 2005;26(6):481-485 [Accessed 25th July 2017].

global perspective global perspective

Consensus Statement on Concussion in Sport, 4th International Conference on Concussion in Sport, Held in Zurich, November 2012: Erratum. Clinical Journal of Sport Medicine. 2012;47(1)250-258. Available from: http://bjsm.bmj.com/ content/bjsports/47/5/259.full.pdf [Accessed 25th July 2017].

includes pain and loss of function in the head, neck, jaw, shoulder, elbow, wrist, and knuckles. Yet, many athletes underreport their symptoms in hopes of being cleared to compete. During the bout, medical staff must navigate through high-stress social pressures in addition to the already difficult task of distinguishing between low- and high-risk injuries. When the ringside physician is called by the officials to assess athletes during the bout, the physician has only seconds to decide whether to stop or continue the competition. Medical judgement can often be impaired by the atmosphere of the crowd and the boxer’s desire to continue competing.

Concussion Assessments Boxing Canada requires athletes to undergo pre- and post-bout medical assessment of concussions to detect measurable changes in neurocognitive status. I was responsible for conducting these assessments using the 3rd Edition of the Sport Concussion Assessment Tool (SCAT3).7 This role required me to navigate competing agendas. Specifically, my responsibility to gather accurate data during physicals was often at odds with the athlete’s tendency to underreport symptoms to avoid disqualification. Several negative consequences may arise as a result of underreporting. First, athletes place themselves in greater danger during the bout. Second, if inconsistencies are revealed upon comparison between the pre- and post-bout SCAT3 due to underreported pre-bout SCAT3, the likelihood of future suspension is increased.

FUTURE DIRECTIONS

M E D U CATO R | D E C E M B E R 2017 M E D U CATO R | D E C E M B E R 2015

Differences in expectations and a lack of trust between athletes and their medical teams create barriers to care. However, trust can be

21 21

built through transparent communication and continuity of care. These strategies help medical teams and athletes develop a mutual understanding of their respective agendas by providing an opportunity to negotiate and explore amendments. As physician-athlete interactions are often limited by time, medical teams provide additional support by clarifying questions and concerns. Care from familiar providers also facilitates accurate reporting of symptoms due to established rapport. While Boxing Canada has a team physician who provides consistent care for national team athletes, local club tournaments often contract different physicians based on availability. Recognizing barriers to athlete care and implementing changes in larger organizations is a logical step to provide essential information to athletes, coaches, and officials. As previously mentioned, my team and I worked with Boxing Canada to deliver presentations that provided information and management strategies on common health issues impacting athletes.1 More recently, we are working on projects to contribute to the limited concussion prevention literature, with the intention of improving athlete care. Overall, our goal is to disseminate this information to provincial organizations, followed by local boxing clubs, and ultimately the individual athletes and coaches.

ACKNOWLEDGEMENTS I would like to acknowledge all the ringside physicians, healthcare professionals, officials, organizing staff, coaches, and athletes that welcomed me to the world of boxing. Additional thanks goes to the BHSc Travel Bursary and the BHSc Summer Research Scholarship for minimizing financial constraints. ■

REVIEWED BY DR. SHIRDI NULLIAH Dr. Shirdi Nulliah is a primary care physician, serving as the Medical Director for Boxing Alberta. He is on the medical commission for Boxing Canada and was responsible for treating boxers in numerous events, including the 2016 Summer Olympic Games in Rio. EDITED BY MILENA CIOANA & JIM XIE

ARTIST BOB YANG

OPINION

Short Term Medical Service Trips: BENEFICIAL OR DISRUPTIVE?

NOOR HAMIDEH Bachelor of Health Sciences (Honours) Class of 2018, McMaster University Correspondence: hamiden@mcmaster.ca

ABSTRACT

opinion

This essay discusses the potential harms and benefits of shortterm medical service trips (MSTs), arguing that they should not be considered inherently ethical because they are a charitable act, and can have significant negative impacts on host communities (HCs) and low-income nations as a whole. This is done by evaluating the effects of MSTs through the lens of the four principles of biomedical ethics. While MSTs may empower HCs to make autonomous decisions about healthcare as a result of being less restricted by lack of resources and knowledge, the inherent power imbalance between volunteers and HC patients may undermine the autonomy of patients. Furthermore, while MSTs aim to improve the health of HCs, volunteers often lack the training to do so. MSTs are also not harmless, as their unregulated presence can disrupt local healthcare systems. Additionally, although MSTs often aim to address health inequities, they can result in HCs becoming dependant on outside intervention, further reinforcing global health injustice. Following a discussion of their drawbacks, the essay presents suggestions on how the ethics surrounding MSTs can be addressed.

D E C E M B E R 2017 | M E D U CATO R

INCREASING SELF-DETERMINATION?

It is argued that MSTs empower patients in low-income countries to become more autonomous through the exchange of information and the donation of goods and services. This purportedly allows patients to make informed decisions about their health — free of resource limitations.14 Additionally, students participating in MSTs claim that the response from HCs is overwhelmingly positive, suggesting that MSTs align with the wishes of the HCs.15 However, MSTs may also threaten the autonomy of HCs through improper communication and unfair collaboration. Because volunteers are unfamiliar with the language of their HC, obtaining informed consent from patients may be overlooked.16,17 On a broader scale, MSTs may undermine INTRODUCTION the autonomy of entire communities. Organizations executing MSTs often make decisions about the location and Short-term medical service trips (MSTs), sometimes re- duration of the trip, the nature of care being provided, and ferred to as “medical voluntourism,” involve students with the volunteers who attend the trip without consulting the minimal to no medical training travelling abroad to gain community. This subverts its capacity to self-govern.12 For healthcare experience and improve the health of the host example, when asked about medical brigades, the Honduras community (HC).1 MSTs are arranged by charities, for- Department of Health replied, “[W ]e (only) know about profit businesses, and universities.2–4 Over 250 million dol- those (teams) that apply for the permission but not for lars are spent annually on these trips,5 and approximately those that (do not and that) go only to small communities,” one third of medical graduates in the United States and suggesting that the interests of MSTs are not always aligned with those of HCs.12 Canada have completed an MST during their training.6,7 MSTs are often marketed to students as both charitable missions and experiential learning opportunities. They are primarily organized by high-income countries, with the destination often being a low or middle-income country.1 Due to the high disease burden in many low and middleincome nations, coupled with a small physician supply, these countries are perceived to be in need of medical aid.8 In turn, students believe that they are able to provide that aid through participating in MSTs.

countries reinforce barriers to global healthcare equity.13 This essay argues that MSTs deserve careful critique, as they have the potential to infringe on the autonomy of patients, cause undue harm, and promote global healthcare injustice.

Because MSTs are seen as charitable acts, their ethical implications are often left unexamined; a phenomenon known as “The Myth of Mere Charity”.9 However, many practices involved in MSTs directly oppose the principles of biomedical ethics, including autonomy (self-determination), beneficence (doing good), non-maleficence (avoiding harm), and justice (acting in fairness).10,11 Due to communication barriers and the inherent power imbalance between volunteers and patients, volunteers may compromise the autonomy of patients in HCs.10 Additionally, although volunteers intend to benefit patients, their lack of medical and cultural competence often leaves them incapable of doing so.10 Furthermore, the disruption to local healthcare systems by MSTs can harm the community.12 Finally, the short-term nature of many MSTs and the pressures they place on host

IMPROVING LOCAL CARE? A common argument given in support of MSTs is that they promote beneficence by improving the health of HC residents.9 However, due to the limited time, training, and cultural competency of volunteers, they are not likely to provide continuous care to patients nor substantially improve the long-term health of HC residents.10 MSTs usually last less than one month and are comprised of short, one-time patient visits.1 Additionally, volunteers often have little background knowledge in the healthcare challenges of the country they are visiting, thus limiting their ability to provide care to patients.6 For example, a Canadian medical student participating in an MST may be able to identify a patient with severe dehydration and know that she requires a saline drip; however, due to his inexperience in inserting needles into collapsed veins (which is not commonly encountered in Canada), he is unable to help the patient and must call a local nurse to insert the needle.18 Finally, in addition to lacking technical skills, volunteers are often unversed in the culture of their host country, and are thus unable to provide culturally-relevant care to patients.16,17 For example, an American student may suggest that a patient use condoms or oral contraception as a means of family planning, without understanding that the use of contracep-

tives, while commonplace in the USA, may carry strong negative connotations in the patient’s culture.17

Wallace LJ. Does Pre-Medical “Voluntourism” Improve the Health of Communities Abroad?. Journal of Global Health Perspectives. 2012 [Accessed 16th March 2017].

Dental and Medical Mission Trips for Volunteers | International Medical Relief [Internet]. International Medical Relief. Available from: http://www.internationalmedicalrelief.org/ [Accessed 16th March 2017].

Medical Internships Abroad - Gap Medics [Internet]. Gap Medics US. Available from: https://www.gapmedics.com/ [Accessed 16th March 2017].

International Opportunities | UCLA Volunteer Center [Internet]. Available from: http://volunteer.ucla. edu/international-opportunities [Accessed 1st April 2017].

Maki J, Qualls M, White B, Kleefield S, Crone R. Health impact assessment and short-term medical missions: a methods study to evaluate quality of care. BMC Health Services Research. 2008;8:121 [Accessed 1st April 2017].

Huish R. The Ethical Conundrum of International Health Electives in Medical Education. Journal of Global Citizenship & Equity Education. 2012;2(1). Available from: http://journals.sfu.ca/jgcee/index. php/jgcee/article/viewArticle/55/30 [Accessed 16th March 2017].

Association of American Medical Colleges. All Schools Reports - Medical School Graduation Questionnaire (GQ) - AAMC [Internet]. 2015. Available from: https://www.aamc.org/download/440552/ data/2015gqallschoolssummaryreport.pdf [Accessed 16th March 2017].

WHO | A Universal Truth: No Health Without a Workforce [Internet]. 2014; Available from: http://www. who.int/workforcealliance/knowledge/resources/ hrhreport2013/en/ [Accessed 16th March 2017].

DeCamp M. Ethical review of global short-term medical volunteerism. HEC Forum. 2011;23(2):91–103. [Accessed 16th March 2017].

10. Roberts M. A piece of my mind. Duffle bag medicine. JAMA. 2006;295(13):1491–2. [Accessed 16th March 2017]. 11. Beauchamp TL, Childress JF. Principles of Biomedical Ethics. OUP USA. 2013. 480 p. [Accessed 16th March 2017]. 12. McLennan S. Medical voluntourism in Honduras: “Helping” the poor? Progress in Development Studies. 2014;14(2):163–79. [Accessed 16th March 2017]. 13. Kumwenda B, Dowell J, Daniels K, Merrylees N. Medical electives in sub-Saharan Africa: a host perspective. Medical Education. 2015;49(6):623–33. [Accessed 16th March 2017]. 14. Green T, Green H, Scandlyn J, Kestler A. Perceptions of short-term medical volunteer work: a qualitative study in Guatemala. Global Health. 2009;5:4. [Accessed 16th March 2017]. 15. Holland T. First, Do No Harm: A Qualitative Research Documentary [Internet]. Vimeo. Vimeo; 2011. Available from: https://vimeo.com/22008886 [Accessed 19th March 2017]. 16. Pinto AD, Upshur REG. Global health ethics for students. Developing World Bioethics. 2009;9(1):1– 10. [Accessed 16th March 2017]. 17. Stone GS, Olson KR. The Ethics of Medical Volunteerism. Medical Clinics of North America. 2016;100(2):237–46. [Accessed 16th March 2017]. 18. Snyder J, Dharamsi S, Crooks VA. Fly-By medical care: Conceptualizing the global and local social responsibilities of medical tourists and physician voluntourists. Global Health. 2011;7:6. [Accessed 16th March 2017]. 19. Shah S, Wu T. The medical student global health experience: professionalism and ethical implications. Journal of Medical Ethics. 2008;34(5):375–8. [Accessed 16th March 2017]. 20. McCall D, Iltis AS. Health care voluntourism: addressing ethical concerns of undergraduate student participation in global health volunteer work. HEC Forum. 2014;26(4):285–97. [Accessed 16th March 2017]. 21. Petrosoniak A, McCarthy A, Varpio L. International health electives: thematic results of student and professional interviews. Medical Education. 2010;44(7):683–9. [Accessed 16th March 2017].

23. Sykes KJ. Short-term medical service trips: a systematic review of the evidence. American Journal of Public Health. 2014;104(7):e38–48. [Accessed 16th March 2017].

26. Crump JA, Sugarman J, Working Group on Ethics Guidelines for Global Health Training (WEIGHT). Ethics and best practice guidelines for training experiences in global health. American Journal of Tropical Medicine and Hygiene. 2010;83(6):1178–82. [Accessed 16th March 2017].

| D E C E M B E R 2017

Nicola Gailits holds an MSc in Global Health from McMaster University. She is currently a doctoral student at the Dalla Lana School of Public Health (University of Toronto), working on newcomer women’s mental health.

25. Perold H, Graham LA, Mavungu EM, Cronin K, Muchemwa L, Lough BJ. The colonial legacy of international voluntary service. Community Development Journal. 2013;48(2):179–96. [Accessed 16th March 2017].

M E D U CATO R

22. Montgomery LM. Short-Term Medical Missions: Enhancing or Eroding Health? Missiology. 1993;21(3):333–41. [Accessed 16th March 2017].

24. Angell M. The ethics of clinical research in the Third World. New England Journal of Medicine. 1997;337(12):847–9. [Accessed 16th March 2017].

REVIEWED BY NICOLA GAILITS

opinion

and resources to improve the condition of the HC’s healthcare system, helping bridge the gap between healthcare in high and low-income countries.14,23 In many cases, however, MSTs may support structures of AT THE VERY LEAST, social injustice by implying that low-income HARMLESS? communities are deserving of a lower quality While MSTs may not produce substantial of care.16,24 Care delivered by volunteers on long-term benefits in HCs, many argue that MSTs is often well below the standard of they are, at the very least, also unlikely to care in the volunteers’ own country.1 MSTs result in harm.19,20 Proponents claim that may also cause a dependency on foreign aid communities targeted by MSTs often suffer in HCs by disrupting and destabilizing the from insufficient healthcare resources, and existing healthcare system, resulting in the thus any effort to help these communities, perpetuation of health injustice.13,21,25 even if provided by untrained volunteers, is CONCLUSION likely to result in some positive net effect.19 However, MSTs can result in harm to communities by putting the health of patients at MSTs should not be considered inherently risk and disrupting the community’s health- ethical simply because they are charitable care system. During MSTs, volunteers are acts. Rather, they deserve careful ethical crisometimes pressured to carry out procedures tique, as they have the potential to infringe they are not trained to do.21 For example, a on the autonomy of patients, cause undue first-year medical student may be told to harm by promoting lower standards of care, suture an incision following surgery without and perpetuate global healthcare injustices supervision by a surgeon, despite not having — effects which directly oppose the prinsufficient training in this procedure, poten- ciples of biomedical ethics.11 tially resulting in infection or scarring.21 Additionally, residents of HCs may avoid local The manner in which many MSTs are curhealthcare providers in favour of volunteers, rently conducted is unethical, and provisions thereby disrupting the local healthcare should be put in place to counteract this. system and resulting in delayed care. Local Many suggestions have been put forward physicians in a Central-American HC have to increase the ethicality of medical service complained that some residents wait for the trips, including providing pre-departure free care and medication provided by MSTs training to volunteers on the culture and instead of seeking medical attention local- language of HCs; setting strict guidelines to ly.22 Volunteers may also take away training ensure that volunteers are not asked to peropportunities from local students, leading form tasks for which they are untrained; fosto a shortage of healthcare providers, thus tering fair partnerships with HCs to ensure that the trip is catered to their needs and weakening local healthcare systems.12,13 will not negatively disrupt their healthcare DECREASING system; collecting feedback from patients, HEALTH INEQUITIES? local healthcare workers, and community members; and working with HCs to address Proponents of MSTs argue that these trips and dismantle the systemic barriers to equipromote justice in healthcare by decreas- table healthcare access.26 ■ ing healthcare inequities and creating a cross-cultural network of information and resource exchange.9 Volunteers donate time

EDITED BY DEEKSHA KUNDAPUR AND KEVIN ZHAO

WHY DO WE SLEEP... AND WHAT HAPPENS IF WE DON’T? JESSICA CHEE1 , DANIEL DIATLOV 2 1

M E D U CATO R

D E C E M B E R 2017

q&a

9 25

Bachelor of Health Sciences (Honours), Class of 2020, McMaster University Bachelor of Science (Honours) Class of 2020, McMaster University

Sleep is a vital part of our routine and many of us can never seem to get enough of it. It is defined as a state of immobility with greatly reduced responsiveness that can be rapidly reversed.1 However, the reason we sleep has yet to be elucidated by the scientific community. One possible explanation, the synaptic homeostasis hypothesis, states that sleep plays a role in the regulation of synaptic weight, which is the strength of connection between two neurons in the brain.2 This hypothesis suggests that connection strength between neurons increases while we are awake and peaks right before we sleep. This is followed by a decrease in strength to a baseline level during sleep.2 The process can be thought of as a cycle of “heating up and cooling down” in the brain to maintain homeostasis, allowing the brain to save energy, prevent synaptic overload, facilitate learning, form new memories.2 Evidently, brain activity does not cease during sleep. In the 1950s and 60s, the regular cyclic alternation between rapid eye movement (REM) and non-REM (NREM) during sleep was discovered.3 REM sleep is associated with vivid dreaming, which indicates that the brain is highly active during sleep.3 However, it was also noted that during REM sleep, sensory inputs and motor outputs are “shut off ”.3 NREM sleep is characterized by a lack of dreams and a complete loss of consciousness, but some brain regions remain significantly active.3 These discoveries indicate that sleep is a “reorganization”, rather than a cessation, of neuronal activity.3 The cycle of NREM and REM sleep seems to be conserved in almost all mammals, suggesting that sleep may have a universally significant function.3 In addition, all mammals and even individual humans differ in the amount and nature of their sleep, which are dependent with genetics, environmental factors, and diet.1 Interestingly, some aquatic mammals, such as dolphins, have adapted a unique way of sleeping called unihemispheric sleep, in which they “shut off ”

only one hemisphere of their brain at a time.1 The study of sleep in multiple species further supports the theories that sleep saves energy, keeps species from being inactive at inopportune times, and differs qualitatively across individuals and species.1 So what happens if we don’t sleep? One study found that a night of sleep resulted in a 20% increase in motor speed without loss of accuracy.4 Furthermore, a significant positive correlation was noted between the amount of NREM sleep and cognitive performance the following day.4 Many studies show that sleep deprivation a negative impact on mood, cognitive performance, and motor function.5 Lack of sleep also results in daytime performance deficits, which lead to significant social, financial, and human costs.5 Accidents related to sleep deprivation have been estimated to have an annual economic impact of $43 billion to $56 billion.5 Notably, lack of sleep has been shown to have similar impairments to those induced by alcohol consumption at or above the legal limit.5 Overall, sleep deprivation has been linked with reduced cognitive performance, attention deficits, weaker immune responses, high blood pressure, and decline in normal human function.5 ■ 1. 2.

Siegel JM. Clues to the functions of mammalian sleep. Nature. 2005; 427: 12641271. Available from: doi: 10.1038/nature04285 [Accessed 22nd October 2017]. Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Medicine Reviews. 2006; 10(1016): 49-62. Available from: doi: 10.1016/j.smrv.2005.05.002 [Accessed 22nd October 2017]. Hobson JA. Sleep is of the brain, by the brain and for the brain. Nature. 2005; 427: 1254-1256. Available from: doi: 10.1038/nature04283 [Accessed 22nd October 2017]. Walker MP, Brakefield T, Morgan A, Hobson JA, Stickgold R. Practice with sleep makes perfecr: sleep-dependent motor skill learning. Cell Press. 2002; 35(1): 205-211. Available from: https://doi.org/10.1016/S0896-6273(02)00746-8 [Accessed 22nd October 2017]. Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Seminars In Neurology. 2005; 25(1): 117-129. Available from: http://depressiongenetics.med. upenn.edu/uep/assets/usercontent/documents/DurmerandDinges--NeurocognitiveConsequences--SEM.NEUROL.2005.pdf [Accessed 22nd October 2017].

ARTIST MATILDA KIM

HOW DO NEW SPECIES ARISE? ARTIST MATILDA KIM

DANIEL DIATLOV 1 , JESSICA CHEE 2

Bachelor of Science (Honours) Class of 2020, McMaster University 2 Bachelor of Health Sciences (Honours), Class of 2020, McMaster University 1

A modern definition of “species” focuses on a shared gene pool and reproductive ability.1 Based on this definition, in order to determine what mutations give rise to new species, we should consider what mutations cause reproductive isolation.

2. 3.

4. 5. 6. 7. 8.

De Queiroz K. Ernst Mayr and the modern concept of species. Proceedings of the National Academy of Sciences. 2005;102(suppl 1):6600-7. Available from: doi: 10.1073/ pnas.0502030102 [Accessed 14th October 2017]. Lande R. Genetic variation and phenotypic evolution during allopatric speciation. The American Naturalist. 1980;116(4):463-79. Available from: doi: 10.1086/283642 [Accessed 14th October 2017]. Dobzhansky T, Pavlovsky O. Spontaneous origin of an incipient species in the Drosophila paulistorum complex. Proceedings of the National Academy of Sciences. 1966;55(4):72733. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC224220/ [Accessed 14th October 2017]. Grant PR, Grant BR, Deutsch JC. Speciation and hybridization in island birds. Philosophical Transactions: Biological Sciences. 1996;765-72. Available from: https://www.ncbi.nlm.nih. gov/pmc/articles/PMC224220/ [Accessed 14th October 2017]. Gavrilets S, Li H, Vose MD. Patterns of parapatric speciation. Evolution. 2000;54(4):112634. Available from: http://www.tiem.utk.edu/~gavrila/PAPS/split.pdf [Accessed 14th October 2017]. Rocha LA, Bowen BW. Speciation in coral-reef fishes. Journal of Fish Biology. 2008;72(5):1101-21. Available from: doi: 10.1111/j.1095-8649.2007.01770.x [Accessed 14th October 2017]. Dieckmann U, Doebeli M. On the origin of species by sympatric speciation. Nature. 1999; 400:354-7. Available from: doi:10.1038/22521 [Accessed 14th October 2017]. Feder JL, Chilcote CA, Bush GL. Genetic differentiation between sympatric host races of the apple maggot fly Rhagoletis pomonella. Nature. 1988;336(6194):614. Available from: doi:10.1038/336061a0 [Accessed 14th October 2017]. Bokma F. Detection of “punctuated equilibrium” by Bayesian estimation of speciation and extinction rates, ancestral character states, and rates of anagenetic and cladogenetic evolution on a molecular phylogeny. Evolution. 2008;62(11):2718-26. Available from: 10.1111/j.1558-5646.2008.00492.x [Accessed 14th October 2017].

| D E C E M B E R 2017

Sympatric speciation is the most rare. It occurs when a new species evolves from an ancestral species in the same geographic population, usually resulting from polyploidy, a trait that describes organisms that inherit more than one homologous set of chromosomes.7 These polyploids will be

M E D U CATO R

Parapatric speciation is similar to allopatric speciation in that a geographic barrier separates a species, but interbreeding can still occasionally occur.5 While allopatric speciation results in two distinct geographic populations, parapatric speciation results in a continuous or discontinuous environmental gradient of hybrids, creating distinct species over time.5 Parapatric speciation usually occurs in marine environments due to the low probability of full geographic barriers. It is the primary mode of speciation in coral-reef fish. Although coral reef fish larvae do not disperse too far from their birthplaces and adults are predominantly sedentary, they can still be separated through the porous coral reefs. In addition, parapatric speciation can occur from the spatial and environmental heterogeneity of coral-reef habitats.6

Overall, the three modes of speciation discussed in this article can be summarized into two main events: anagenesis, which occurs when one species gradually accumulates enough genetic changes to become a new species, like in sympatric speciation, and cladogenesis, which occurs when gene pools split to result in two or more new species, like in allopatric and parapatric speciation.9 ■

q&a

There are three main modes of reproductive isolation that could lead to speciation: allopatric, parapatric, and sympatric speciation. Allopatric speciation occurs when a species splits into two geographically isolated populations in a way that prevents genetic exchange.2 First, a geographic barrier separates a species; this could be a result of continental movement, human activities, or formation of mountains, islands, and glaciers. Next, genotypic and phenotypic differences begin to arise due to mutations in the separate gene pools, divergence in selective pressures between the two populations, and genetic drift. These differences often gives rise to incipient species - species that may be infertile with each other but do not interbreed due to the geographic barrier.3 If this barrier were removed, the previously isolated populations could mate and produce low-fitness hybrids, which could become their own species or be eliminated from the population through mate choice discrimination. Over time, speciation progresses to completion. An example of allopatric speciation is the separation of Darwin’s finches in the Galápagos archipelago.4 The archipelago was colonized from continental South/Central America, in which a breeding population was established. Individual finches eventually colonized neighbouring islands to establish new breeding populations. Ultiamtely, eleven species of finches in the Galápagos arose from allopatric speciation.4

infertile with their parental species, consequently becoming reproductively isolated while remaining in the same geographic location.7 The apple maggot fly Rhagoletis pomonella may currently be undergoing sympatric speciation. The native host of this maggot is the hawthorn, but over the past 200 years, Rhagoletis pomonella have been found in domestic apples, Furthermore, significant allele frequency differences have been observed between hawthorn maggots and apple maggots.8

INTERVIEW SPOTLIGHT

YINGFU LI A FORERUNNER IN DNA DIAGNOSTICS ANGELA DONG1, SHEILA YU2 1 2

Bachelor of Health Sciences (Honours) Class of 2020, McMaster University Bachelor of Health Sciences (Honours) Class of 2019, McMaster University

DR. YINGFU LI IS A PROFESSOR OF BIOCHEMISTRY AND BIOMEDICAL SCIENCES AT MCMASTER UNIVERSITY, AN ASSOCIATE EDITOR OF THE JOURNAL OF MOLECULAR EVOLUTION, AND IS A CANADA RESEARCH CHAIR IN NUCLEIC ACIDS RESEARCH. HIS WORK EXPLORES DNAZYMES AS POTENTIAL THERAPEUTIC AGENTS AND PROTEIN BIOSENSORS. A LEADING RESEARCHER IN HEALTH AND BIO - INNOVATION, DR. LI FOSTERS CREATIVITY IN HIS STUDENTS, TEACHING BIOMEDICAL DISCOVERY AND COMMERCIALIZATION COURSES, AND PROVIDING MENTORSHIP TO THE YOUNG SCIENTISTS OF LI LAB.

CAN YOU TELL US A LITTLE ABOUT YOURSELF, YOUR LAB, AND HOW YOU GOT STARTED IN BIOCHEMISTRY? I came to [McMaster University] in October 1999. I was born and raised in China, where I did my Bachelor and Master of Science degrees. I worked in a couple of places there, but I knew that science at the time was much better outside [of China]. I wanted to receive the best training in science so I decided to apply to western universities and was fortunate to be admitted to Simon Fraser University in Vancouver. That’s where I started my PhD degree and did my training in the biochemistry of nucleic acids. I then took a research position at Yale University for two years before returning to Canada to establish my own group. Since then, I’ve been motivated to establish

a top research laboratory looking at interesting functions of nucleic acids. In the initial years, I looked at both DNA and RNA, but I found that there were not [too] many differences. [However], I realized that DNA can be easily produced through chemical ways. For the last few years, the lab has focused more on DNA molecules.

YOU’VE LEARNED MANY THINGS OVER THE YEARS. WHAT WOULD YOU SAY HAS BEEN THE MOST INSPIRATIONAL? There are many people who have had a huge influence on me. In middle school, I had this amazing mathematics teacher. I think she really got me interested in science, because she kept on telling me that I had a special talent for the subject. When I was in college, I had one [professor] who had a huge influence on me. I felt that learning science with him was fun. It was not about merely memorizing the chemical reactions or mechanisms. Particularly for chemistry — which I loved even when I was in college — I found it really fascinating that you could build complicated molecules using simple reactions, and that you could predict what would happen. Of course, when I came to North America, my PhD supervisor had an amazing influence on me as well. From him, I learned how to [justify] important scientific questions. He did not want me to just go after a question. He always asked, “Why are you doing this?”; he had to feel satisfied before he [proceeded with] anything. At Yale, I worked with a scientist named Ron Breaker and I learned different skills from him such as how to focus, how to write scientific stories, and [how to] treat science not as a profession, but as a passion with an engaging process.

DR. LI, YOU MENTIONED THAT YOU DO A LOT OF WORK ON NUCLEIC ACIDS. WHERE IS YOUR RESEARCH AT NOW AND WHERE DO YOU SEE YOUR RESEARCH HEADING IN THE FUTURE?

In the next three years, we really want to create an artificial DNA sequence for recognizing or targeting induced catalysis. This is on the fundamental side of my lab’s research. We then want to turn around to target certain applications. We have always known about bacterial and viral infections for humans and also for animals, [as well as] horrible diseases like cancer. If we can perform early diagnosis for any kind of human disease, we can prevent [the disease] and find better cures to treat patients, or prevent a larger outbreak. Our goal is to use the DNA molecules that we are creating and apply them to practical applications like the ones just described.

YOU MENTIONED THAT SOMETIMES THE DATA ISN’T ALWAYS WHAT YOU WANT IT TO BE. WHAT DRIVES OR MOTIVATES YOU TO CONTINUE DOING RESEARCH? Growing up, I was puzzled by the changing of nature. Seasonal changes, why insects can fly, why dogs can bark, things like that. I’m generally interested in finding out the reason behind this. When I was young, I was less patient and could get down quite easily. Like my grad students, in the beginning I came in [thinking], “Yes, I’m so excited, I’m going to change the world, I’m going to change the field,” but then I realized that [there are many] challenges. In science, we publish by the peer review process, so getting rejections is normal. Of course, now we get fewer rejections. [However], when you start and nobody knows you, your skills are not great, your data may not be outstanding, and your writing skills are limited, [you] face these kinds of challenges and get rejected by better scientists. After [these rejections], we have a couple of days of [down time], but then we return and objectively look at the comments to identify what we need to do and what we have learned from [this experience]. So

| D E C E M B E R 2017

I think every lab is unique. I wouldn’t necessarily see my lab as any more special than other labs. Obviously, as the head of the lab, I want to make sure that I am excited about the science we are doing. Also, I normally don’t think of myself as a scientist. I see myself as a decent human being working on something. [I believe that] in order to be a scientist, you have

In science, maybe 99% of the time, we don’t see the things we want to see. So then we have to figure out what we are seeing and what the data is trying to tell us. As scientists, we need to objectively look at the data and revise our hypothesis and try to make changes. I think my students are really receptive to that. We are not really looking for success, but rather trying to understand the class of molecules we are dealing with and trying to apply whatever we learned to challenging [realworld] problems. I think that lab culture is a big word and I don’t know if we are necessarily set up to achieve a certain type of lab culture. [However], I do encourage students to get involved in science and other events such as local conferences or departmental activities. I encourage [my students] to be creative and be a part of the community. I think that’s my favourite part about my lab. Essentially, we have a bunch of [creative] young people [working on a] project directed at understanding DNA molecules in artificial systems and applying the findings to practical applications.

M E D U CATO R

LI LAB HAS MANY INCREDIBLE ACCOMPLISHMENTS. WHAT IS IT ABOUT THE LI LAB MENTALITY OR PHILOSOPHY THAT YOU HOPE TO CULTIVATE TO ALLOW THIS SORT OF GROWTH? WHAT DO YOU DO AS A PRINCIPAL INVESTIGATOR?

On the science side, we make sure that we are doing creative science and not just copying [what is already] known. Often for me, publishing a paper is just a way of telling the story [of our] scientific discoveries. Although sometimes we do have a need to publish, [we are so excited] when we actually come to this stage [we know that] it’s time for us to get that piece out so other people can also get excited about it. I think that’s what my lab has: we have this strong interest in what we are doing. Each of [my lab members find] DNA and nucleic acids interesting, and actually want to work together to try making more discoveries about them. For me, I really just want to provide directional guidance and let my students be creative on their own. I try to be on the sideline and [support them by] telling them how excited I am.

interview spotlight

That’s an open question! In the ideal world, I want to continue to make fantastic discoveries about the capability of DNA beyond genetic rules. There are many things we don’t know and nature only provides us with a limited number of examples. This is why I decided to use artificial systems to create [DNA]; this will continue to be a big focus for us. Also, now that we know DNA can do amazing things, can we get it to do more? For example, can we get DNA molecules to see subtle differences between similar targets such as protein molecules? One of the things our lab has recently been working on is to see if a common protein from different bacterial species, with very small differences, can be identified using artificial evolutionary tricks which guide the DNA to recognize these differences. The reason we want to do this is because molecular recognition is very important. If we can find a simple way to generate the kind of DNA sequences that can fold into well-defined three-dimensional structures which detect subtle differences [between similar proteins], then we can turn these kinds of molecules into biomarkers. We can use [biomarkers] to track diseases and conditions, and potentially use them as therapeutic molecules. If the protein that we have is also a protein that bacteria has, then we can see the differences and design these sort of weapons which only attack bacterial targets, but don’t interact with human targets. We then know that it can be developed into a very effective therapeutic molecule.

to first be a great human being, and that’s what I’m trying to teach in my group.

each cycle when you publish a paper, you learn more and more. Now that I’ve published 170 papers, through all that cycling, I’ve really learned a lot. I’m an author. I’m [now] also a referee. I treat other people’s papers as if I were the author. [Conversely], when I write my own papers, I look at them as a referee. I want to make sure I understand both sides.

There are many, but maybe two [main] things for anyone who is willing to accept my advice. One, go with your heart — that’s very important. You can only succeed and enjoy life if you decide what you want to do with your life. Whether you want to be a farmer, scientist, medical doctor, astronaut, or anything that you think would be exciting, I think this is what separates our human race from animals — we are capable of achieving things if our minds are set on something.

The reason I have stayed persistent in working on projects, science, and challenges is because I honestly really love it. Everyday I go to my office, I feel quite excited because there are so many things waiting for me to do. Right now, I have about 10 manuscripts that I need to [complete]. There are so many exciting stories I want to tell!

My second [piece of ] advice is to dream. I think it’s very important not to get frustrated by the things at the moment. Really look way beyond at what you want to achieve and have that in mind. Think bigger, not necessarily about things you can never achieve, but rather about something that you really want to do that is beyond what you can reach at this point. This is something that will really keep you motivated and also happy. Being yourself is also very important. If you have something that you want to pursue, even if you are not successful every time, you’ll get back into it. If you’re forced into a situation or you feel that you need to do something, it will be a completely different outcome. Many of my friends are unhappy because they did not [follow their interests]. [Thus], I think it’s important to be yourself and go with your heart. Who knows what you can achieve? I have seen many talented scientists like that who have made huge discoveries because they are totally interested and driven in their field. If you decide to go down a road [you are interested in], you will really make a difference. No matter what, you can always reflect back, maybe when you’re in your 70s, and honestly say that, “I have done absolutely the best I can.”

M E D U CATO R

D E C E M B E R 2017

interview spotlight table of contents

[I feel] most happy about our work when we submit our paper to a journal and receive feedback. When our manuscripts get accepted right away, I know we’ve done something right because every manuscript is reviewed by several people. If everyone says this is a fantastic piece that needs to be published, then we know that we have done an amazing job in our research.

LI LAB IS NOTABLE FOR GIVING ITS MEMBERS RESOURCES. WHAT OTHER SOURCES OF RESEARCH, EDUCATION, OR MOTTOS DO YOU HOPE TO IMPLEMENT? [Sometimes], we talk about predictions for what might be the biggest discovery made in a specific field. We also go to scientific meetings and invite the experts in our field to give talks and answer our students’ questions about career development, skill development, or whatever they have in mind. We use these events to [expose] students and young scientists to all kinds of scenarios. We also have collaborations; my lab has accepted visiting scientists and I have also sent my students to other labs to learn techniques. Through these exchanges, students get to see the world outside of McMaster. Every couple of years, we do a lab retreat. In the last six years, we did three retreats at Blue Mountain where we talked about science and interesting ideas not related to lab work. I’m [also] pretty big on exercise. I run and play golf, and this also encourages my students to do the same thing — not spending all their time in the lab. I think our effective time [in the lab] is 7 or 8 hours maximum, so spending too much time working might frustrate us. We might be better off if our mind is not on science. Go for a run or do whatever you choose to do. That’s why I don’t normally look over the shoulders of my students to see what they are doing. It’s really trying to get them to engage in an activity that is important.

YOU HAVE A HUGE IMPACT ON MCMASTER IN TERMS OF RESEARCH AND EDUCATION. WHAT ADVICE WOULD YOU GIVE TO ASPIRING RESEARCHERS?

Missing: Tony Chen, Angela Dong, Laura Nguyen

EDITORS-IN-CHIEF Sabrina Lin Sarah Ge

GRAPHICS & DESIGN Creative Director Cathy Lu

EDITORIAL BOARD Managing Editors Owen Luo Valerie Kim

Graphic Designers Annisa Siu Michael Sun Bob Yang Peri Ren Candy Niu Suffia Malik Cathy Ren Sylvia Mohanraj Laura Nguyen Matilda Kim

Jim Xie Kelvin Ng Kevin Chen Kevin Zhao Milena Cioana Parnika Godkhindi Sheila Yu Shikha Patel Takhliq Amir

VIDEO TEAM Managing Video Editor Adrian Marcuzzi Video Producers Albert Zhao Arbaaz Patel Judy Chen Katherine Sliwowicz Khashayar Poorzargar

PRINTING Underground Media and Design

The Meducator, BHSc (Honours) Program Michael G. DeGroote Centre for Learning and Discovery Room 3308 Faculty of Health Sciences 1280 Main Street West Hamilton, Ontario L8N 3Z5

VISIT OUR WEBSITE FOR PAST ISSUES www.meducator.org

FOLLOW UPDATES ON FACEBOOK www.facebook.com/themeducator

INTERESTED IN WRITING FOR OUR NEXT ISSUE? Visit www.meducator.org/ submit-now

Bachelor of Health Sciences (Honours) Program

McMaster Student Union

McMaster Alumni Association

M E D U CATO R | D e c 2 0 1 4 | D E C E M B E R 2017

WE WOULD LIKE TO GIVE A THANK YOU TO OUR SPONSORS FOR THEIR GENEROUS SUPPORT

M E D U CATO R

Editors Adam WadeVallance Angela Dong Daniel Diatlov Deeksha Kundapur Devin Roshan Edward Cui Eva Liu James Yu Jessica Chee

ADDRESS

critical review contributors

STAFF

Undergraduate Student Initiatives Fund

INTERESTED IN WRITING FOR US? VISIT WWW.MEDUCATOR.ORG/SUBMIT-NOW