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Category Name Author Name

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REVIEWERS

EDITOR-IN-CHIEF

SEMRAN THAMER

SENIOR EDITORS APARNA ALANKAR MIKAELLA EVARISTO ZACHARY FRIEDRICH MARTINUS MEGALLA VIVEK TRIEDI

PRESIDENT KAREN LEE

ART DIRECTOR MICHELLE SHI

CREATIVE STAFFERS ARMANDO DI CICCO TARRA CHEN SORASICHA NITHIKASEM EMMA THEISEN SUSHANT THOMAS

VICE PRESIDENT

CLUB ADVISOR

NATASHA PANDIT SARAH MCGOUGH

TREASURER JASON YANG

COMMUNICATIONS

JAY GUPTA

MEDICAL DIALOGUE REVIEW Fall 2017 | Volume 12 Issue 1

ZAHIN AHMED ZAN AHMED SIMRAN BHARADWAJ DANIEL CHANG ADITI DESAI DEEPIKA DHAWAN MD FAHIM NICHOLAS FELL ABIGAIL GIRGIS MAANSI JAYADE ANNETTE KAMINAKA ANAIS KESSLER SHARUKH KHAN TAFAANI KHAN ANDREA OUYANG ASHMITHA MATHUKUMAR SARANYA RAMADURAI KRISTIN RIDDLE SARAH SEEDAT EDMUND SONG JANKI TAILOR SUKRITI THOMAS JORDAN WILCOX KEVIN WONG MICHELLE XU MICHAEL ZHOU NATALIE ZHU

MDR is a New York University (NYU) student publication. We publish bianually and accept articles, essays, literary pieces, reviews, art and photography relevant to healthcare.

Cover Art

EXPANDING THE MIND by Michelle Shi Watercolor Painting

The human mind is the most complex processing system that we know of. However, we still don't know much about how the human mind. This painting represents our continuous journey to always seek more than we know - using human thought to discover and challenge the world we live in.

Disclaimer: The contents of the journal, Medical Dialogue Review (MDR), represent perspectives of students, professionals, and patients on issues in healthcare. These ideas represent neither the opinions of the entire MDR membership nor the institution, New York University (NYU). Information presented is reviewed for accuracy but should not be used for medical diagnosis or as a substitute for medical advice. NYU is not responsible for its contents.


DEAR

Reader: In a period of uncertainty within the realms of public policy and healthcare, we have become more keen in recognizing the flaws in our healthcare system today. The current sociopolitical climate lends itself it to creating and stimulating dialogue between medicine and the humanities, as the diagnoses and presentations of these concerns must be clear and eloquent. It is through this endeavor that we strive to reach a greater audience and make advancements in tackling these issues, especially in light of the growing connections within the global community. In our Fall 2017 Issue, our contributors bring to attention some of these matters in the light of public policy, clinical practice, as well as biomedical research, covering topics that range from transgender related healthcare to the controversy surrounding the patenting of cDNA. Thus, it is with great pleasure that we share our ongoing dialogue of the conventionally segregated voices of medicine and the humanities in our twenty-third edition of the Medical Dialogue Review. Our contributors this semester have worked diligently on semester’s issue in an effort to present the myriad of voices from across the campus- bringing together diverse fields of study, cultures, and backgrounds. We would like to thank our remarkable creative and editorial staff, writers, artists, and peer-reviewers for their enthusiasm in striving for excellence in their work. This issue would not have been possible without their dedication and diligence. And we thank you, our readers, for your continued interest and support in this endeavor.

President

Karen Lee 3


...in this ISSUE CLINICAL PRACTICE Ease the Pain: Marijuana Rohan SHAH

and CTE

6 9

Decompartmentalizing the Scientist Erica NEBET

Attenuating the Aggression of the Biological Theory

14

How Luck Plays a Role in Influencing Medical Outcomes

19

Mikaella EVARISTO

Brendan HYSLOP

PUBLIC HEALTH & POLICY Maternal Health in India Loren KITA

23

Why Electronic Cigarettes are a Public Health Concern

28

Transgenderism: Addressing the Cry for Help

32

Supervised Injection Facilities

38

Ryan LAMRANI

Himari GUNASINGHE

Bailey HALL

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table of contents

BIOMEDICAL RESEARCH How We Can Use RNA Interference for Treating Ailments

42

Inconsistencies in Parkinson's Dopamine

46

How Does General Anesthesia Affect the Brain?

50

Patenting Life: To Whom Does the Human Genome Belong

54

Joanne CHUNG

Nadja ZAKULA-KOSTADINOVA

William SHIN

Mikaella EVARISTO

ARTISTS

Armando Di Ciccio P 19, Sushant Thomas P 6, 8, 28, Karen Lee P 17, 18, 36, 39, 30

Tarra Chen P 16, 23 Emma Theisen P 38

Sora Nithikasem

41, 48, 58, 59 P 9, 50

Michelle Shi P 11, 13, 32, 37, 41, 54, 55, 56

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Medical Dialogue Review Volume 12 | Issue 1

EASE THE PAIN: MARIJUANA AND CTE By ROHAN SHAH

"Every Type of Pain" by Sushant Thomas

"Stop killing each other man. Let's just smoke a blunt." ~ Tupac

Imagine you are sick with the common flu. Pop a Tylenol, maybe two, and get some sleep. In a few hours and certainly over the course of a few days , you’ll probably feel a lot better. Now imagine living a life in which your cold never ends, regardless of how many pills you take. This is the life of 29- year-old former National Football League player, Eugene Monroe. Eugene was diagnosed with a concussion in the first week of the 2015 NFL season after taking a hit to the head by defensive tackle, Demarcus Ware. After missing three consecutive games and later an entire season, he was cut by the Baltimore Ravens and subsequently retired. To this day, Monroe still feels the effects of the concussion he suffered in 2015. Although Monroe has not officially been diagnosed with Chronic Traumatic Encephalopathy (CTE), he has reported feeling some of the initial ef-

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fects of Traumatic Brain Injury (TBI) including memory loss, slight loss of facial recognition, daily headaches, and intense pain in his neck and back of his head. Eugene Monroe is one of 38 living former NFL players who has either been diagnosed with CTE or has reported symptoms consistent with CTE. A study published in July 2017 showed that the prognosis for individuals diagnosed with CTE is fatal by reporting that of 111 deceased former NFL players, 110 of them had CTE. Although the direct cause of CTE is unknown, it has been highly correlated with repetitive direct head trauma. The more pressing question lies in the effectiveness of current CTE treatment. While pharmaceutical drugs represent the most well known treatment plan to the neurodegenerative disease, there has been an increase in support for marijuana as an alter-


clinical practice rohan shah

-native treatment with fewer side effects. CTE is a type of traumatic brain injury that results from increased immunoexcitotoxicity. The molecular basis of increased immunoexcitotoxicity can best be explained by postulating that constant interruptions in the brain’s reparative and regenerative processes render the body’s corrective system futile. According to a 2011 study by Blaylock and Maroon, microglia in the peripheral nervous system (PNS) are activated immediately after traumatic brain injury and initiate an injury response mechanism. This innate inflammatory response couples reactive oxygen and nitrogen with cytokines and chemokines to provide temporary relief to the brain. Following this initial response, the brain undergoes a long-term and regeneration process. Under abnormal conditions, when a brain undergoes repetitive trauma before the reparative process concludes, immune mediators coupled with an increased release of excitatory intracellular glutamate trigger a cascade of neuronal damage. This damage includes dendritic retraction, synaptic injury, damage to microtubules, mitochondrial suppression and the over-production of tau (CTE in Contact Sports | PLOS One). While the damage happens mainly within the brain, an individual with CTE will experience physical and mental obstacles throughout the rest of his/her life. While no current treatment is effective in preventing fatality after incidence, marijuana as an alternative treatment has been proven to reduce pain significantly without side effects. The effects of marijuana are medically equivalent to a combination of different pharmaceutical drugs;therefore an ounce of marijuana can prove to be more effective and less hazardous than “100 pills a week”. Unfortunately, Tetrahydrocannabinol (THC) or marijuana has been associated with several injuries and accidents. In 2009, it was estimated that THC was a contributing factor in over 460,000 emergency room visits, an increase in alcohol use, and in a higher incidence of motor vehicle crash involvement (Effect of Marijuana Use on Outcomes in TBI). According to a study done by the Harbor-UCLA

Medical Center under Dr. David Plurad, a positive THC screen is associated with decreased mortality in adult patients sustaining any form of TBI. In a longitudinal 3-year study, Plurad showed how of 82 cases of TBI in individuals older than 15 with positive THC screens, the mortality rate decreased by 9.1% compared to those individuals with negative THC screens. The study measured the effects of Dexanabinol, a synthetic cannabinoid devoid of cannabimimetic effects. It was found that the synthetic analog inhibited the production of tumor necrosis factor alpha, a primary factor involved in neurotoxicity after TBI. This means that the drug prevented the over excitation of neurons and decreased neuronal cell death. The drug also reduced overall blood pressure over time and inter-cranial pressure, a symptom associated with CTE. Moreover, similar studies have reported that ingestion of THC increases appetite, reduces muscle spasms, alleviates inflammatory bowel disease, and reduces ocular pressure. In the last decade, CTE has been studied extensively and almost exclusively in contact sports in the United States. Since 1954, 153 confirmed cases of CTE have been reported. Of these cases, 45.1% are former boxers and 41.2% are former amateur and professional football players. The remaining 12.7% are made up of former NHL players, military personnel, wrestlers, and individuals who suddenly fell. The average age of general death in the United States is 76.2 years old; however, the majority of deaths of individuals with CTE occurred between the ages of 60 and 69. Although there is no direct evidence that CTE causes early death, there is a high correlation between CTE and certain side effects that may induce death. Of the 153 cases reported, there have been 111 deaths in the last decade. Seventy-eight of these deaths were from natural causes; however, these “natural causes” included respiratory failure, cardiac disease, dementia, and malignancy. Furthermore, 19 accidental deaths were reported from drug overdose and severe TBI injury and the remaining 14 deaths came as the result of suicide.

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Medical Dialogue Review Volume 12 | Issue 1 While THC use cannot prevent cardiac disease, dementia, and respiratory failure, it can provide significant pain relief that may reduce an individual’s dependence on pharmaceutical drugs and his/her depressive/fatal side effects. The systematic legalization of medical marijuana should be a testament to its increasing beneficial impacts on patients with injury and severe pain.

"Medical Rx" by Susant Thomas

REFERENCES Baskin, Ben. “How Cannabis Is Helping One Company Research Treatment of CTE.” SI.com, Sports Illustrated, 12 July 2016, www.si.com/nfl/2016/07/12/cannabis-cte-treatment-kannalife. “Chronic Traumatic Encephalopathy (CTE).” Alz.org, Alzheimer's Association, www.alz. org/dementia/chronic-traumatic-encephalopathy-cte-symptoms.asp. Maroon, Joseph C., et al. “Chronic Traumatic Encephalopathy in Contact Sports: A Systematic Review of All Reported Pathological Cases.” PLOS ONE 10. 6 (2015). Monroe, Eugene. “My Body Remembers.” The Players' Tribune, The Players’ Tribune, Inc., 3 Aug. 2017, www.theplayerstribune.com/eugene-monroe-nfl-opioids-cannabis-my-body-remembers/. Nguyen, Brian M, et al. “Effect of Marijuana Use on Outcomes in Traumatic Brain Injury.” The American Surgeon 80. 10 (2014): 979-983. Print. Ortiz, Aimee. “Learn the Symptoms in the Four Stages of CTE.” BostonGlobe.com, Boston Globe, 21 Sept. 2017, www.bostonglobe.com/metro/2017/09/21/symptoms-watch-forfour-stages-cte/Q1wniQOnQXH1bU8OibU3WJ/story.html. Rafferty, Scott. “Eugene Monroe on NFL, CTE and How Weed Changed His Life.” Rolling Stone, Rolling Stone, 25 Aug. 2017, www.rollingstone.com/sports/news/eugene-monroe-on-nfl-cte-and-how-weed-changedhis-life-w498611. Ward, Joe, et al. “111 N.F.L. Brains. All But One Had C.T.E.” The New York Times, The New York Times, 25 July 2017, www.nytimes.com/interactive/2017/07/25/sports/football/nflcte.html. “What Is CTE?” Concussion Legacy Foundation, 30 Aug. 2017, concussionfoundation.org/ CTE-resources/what-is-CTE.

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clinical practice erica nebet

Decompartmentalizing the Scientist By Erica Nebet

"How do Scientists Cope with Dissected Animals" by Sora Nithikasem Model organisms have always been used as a means to understand the varying functions of the body. For example, prior to technological developments in the scientific field, people observed those with specific ailments to determine the effects of a disease. Neuroscience

research, in particular, takes into account the connections between molecular abnormalities and the effects they have on one’s health and behavior. Thus, it becomes necessary to use animal models to survey the overall effects that a small change in the nervous system can

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Medical Dialogue Review Volume 12 | Issue 1 have. By as early as 200 C.E., Galen, a Greek physician, had carried out animal dissections on sheep in order to discern the cerebrum from the cerebellum.1 Similarly, around 1810, Charles Bell cut the two roots of the spinal cord separately in experimental animals and concluded that loss of ventral root function causes muscle paralysis, so he deduced that these nerves must carry information to the muscles.2 Without such experiments, we would not know the structure of the nervous system nor how neurons transduce information. Yet, the use of such animals tends to involve their sacrifice in order to examine their brains on a molecular level. To carry out such a procedure, scientists must find a way to distance themselves from the animals and view their actions solely as a mechanical procedure. This is where mental compartmentalization comes in to play, and although it is a helpful tactic, it may not be the healthiest option for a person in the long run. In order to cope with the use of other mammals in research, many scientists psychologically compartmentalize their emotional attachment to these animals as distinct from the actions that they are carrying out. Since mammals are evolutionarily quite closely related to humans, they tend to be favored in medical research, but this also makes it easier for people to empathize with them. At times, compartmentalizing is a subconscious act of the mind and body, used to prevent oneself from excessive mental and physical stress due to an occurrence that contradicts one’s beliefs; it allows one to resolve a personal emotional problem.3 However, when it comes to research, this is more of a voluntary process in which scientists actively convince themselves to detach from an act that tends to inflict stress on another living thing. For this reason, compartmentalizing is a beneficial practice. It allows one to efficiently and effectively complete the tasks at hand without dwelling on the situation and growing upset. Thereafter, one can go on with their day in a relatively easy manner. However, over-compartmentalizing can lead to emotional distress. Primarily, doing so poses the danger of one losing their ability

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to empathize with the subjects on which they are conducting experiments. If this becomes a reality, the organisms may be treated quite inhumanely, which should be avoided at all costs while conducting research. Additionally, this may produce a fragmented personality within an individual, which is indicative of mental illness. On a molecular level, the fragmentation of one’s identity may restrict neurons form firing together, which may limit the continuity of an identity produced from one’s experiences and memories.4 This is a common cause of identity and personality disorders. Still, when it comes to scientists who have the ability to choose to compartmentalize their work from the rest of their lives, they are able to protect themselves from hostile conditions and to allow for self-love and self-care. This, in turn, is essential for one to successfully complete such gruesome work. When it comes to animal research, behavioral tests are quite common, especially within neuroscience, and they most heavily rely on the use of mammals as model organisms. For studying ailments such as autism spectrum disorder (ASD), a common test to evaluate autism-like phenotypic behavior in mice is through the use of the Morris water maze. To do so, one could assemble two groups of mice: one wild-type (WT) and the other Timothy syndrome (TS2-neo) that suffer from a genetic mutation in the CaV1.2 calcium channel, which leads to cardiac arrhythmia and, in one particular mutation, behavioral effects similar to those found in autism spectrum disorder.5 The maze involves filling a pool with water to match the height of a platform, and then mixing white paint into the water so that the platform is no longer visible. The mice are placed in the pool at different points and use spacial-visual cues to learn the location of the platform. Upon reaching the platform, they are returned to their cages.6 After a few days, the platform is removed, and researchers have observed that the WT mice begin looking for a new platform location earlier than the TS2neo mice since preservative behavior is a hallmark of ASD.7 The reason this test works well is


clinical practice erica nebet because mice, although very good swimmers, hate swimming and want to get to the platform as soon as possible. The fact that they do not enjoy being in the pool is essential to the success of the experiment because the main data set comes from the amount of time it takes the mice to reach the platform. At the same time, however, this test leads to a decent amount of stress and discomfort on behalf of the mice. Nonetheless, this protocol has been approved by the Institutional Animal Care and Use Committee (IACUC), which ensures that animals are only used to provide advances in our knowledge of the nervous system, all necessary steps are taken to minimize pain and distress, and all possible alternatives are considered.8 Therefore, this behavioral test has been assessed and scrutinized, and the IACUC has concluded that one of the best ways to test for ASD-like phenotypes in mice is through the use of the Morris water maze. Still, watching these animals struggle as they paddle through the water is distressing, and many scientists want nothing more than to scoop them out and make sure they are safe. Nonetheless, doing so would impede the results of the experiment, so they distance themselves from these animals and refrain from intervening unless the mice are in serious danger. Similarly, medical students have also found it necessary to mentally separate a living organism from a body in their studies, especially when it comes to dissecting cadavers. They explain that it is almost essential that they detach themselves from any ‘human aspect’ of the body lying before them.9 Only then can they begin the dissection. Some describe this act as a mental and emotional overload, having difficulty describing in words the feeling associated with making that first cut. At the same time, it is important that they essentially push these feelings aside and stay focused to complete the task. They must also treat the body with care since this was once a living, breathing human who sacrificed themselves for someone else’s education.10 As the dissections continue, these students begin to learn about the people before them based on the evidence they find within

the bodies. The cadavers take the shape of real people, and while the students have to take that into consideration, they also have to keep themselves distant from such notions so that they can continue their work. This process is analogous to an emotional roller coaster for medical students as they try to cope with cutting open another’s lifeless body that used to belong to an individual with a whole life and personality. Nonetheless, in order to successfully complete such a task, these people have to reconcile the living and deceased portions of these bodies while keeping them separate within their minds. However, there have been instances during which organisms were clearly treated inhumanely during experimentation, such as during the Tuskegee Syphilis Experiment. This study was conducted on black males without their informed consent; they were never given enough facts to allow for proper consent, which is legally required in order to proceed with such clinical trials. Though they did agree to be examined and treated for syphilis, they were never actually provided with adequate treatment for the disease. In fact, once penicillin began to be used to treat syphilis, these subjects were not offered the treatment. The

"Brain" by Michelle Shi

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Medical Dialogue Review Volume 12 | Issue 1 advisory panel that examined the experiment deduced that they were also never given the option of quitting the study to go and seek better treatment.11 It is clear that these people were greatly mistreated, and it is hard to believe that the experimenters felt no remorse for their horrid actions. In order to do so, they must have compartmentalized their actions to an extent wherein they no longer felt any empathy for these subjects. This is a clear example of the danger of over-compartmentalizing. The experimenters completely disregarded the humanity of their subjects, which caused many people to suffer in the process. Therefore, while compartmentalization may be a helpful tactic for scientists conducting research on live organisms, detaching themselves too much from the organisms on which they are experimenting does not provide anyone with beneficial scientific insights since people begin to lose sight of why they are completing such work. Since certain manifestations of psychological compartmentalization can cause scientists to run into trouble, the most effective technique appears to be for them to remind themselves that what they are doing is intended to help others in the long run. Those who become involved with scientific research, whether in behavioral neuroscience labs or elsewhere, or enter medical school do so because they are truly interested in better understanding and developing cures for various disorders. Thus, they understand that this is something that simply has to be done for the greater good. Additionally, many scientists view such protocols, especially those that involve sacrificing the animal, as a mechanical matter that simply needs to be completed. They do not let themselves think too much about what that are doing, especially since scientists often need to carry out certain these procedures quite quickly, especially if they need to preserve fresh tissue.12 They essentially train themselves to consider these processes as a series of steps that have to be completed and refrain from contributing much sympathy to the process. This coincides with the practice of compartmentalization but to a lower extent, which keeps scientists away

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from the hazardous aspects of this practice and is, thus, enables the successful completion of an experiment. Overall, in order for research scientists to be able to effectively carry out protocols involving animal models, they should be able to separate their emotions and the empathy they feel for these creatures from their work while also finding a way to come to terms with the things they are doing. At the end of the day, it is important to remember that research scientists and doctors are good-natured, emotional people. They are doing what they do because they want to arrive at scientific advancements that can be used to treat or even cure people of various ailments. This would allow scientists, in particular, to move away from the social stigma that categorizes them within a box consisting of antisocial people who sit in a lab all day and inflict pain on innocent creatures. They are doing this work because they care and recognize how important it is as this research that will lead to significant, beneficial discoveries. Though compartmentalizing their actions makes it easier for researchers to carry out certain procedures, this practice can be dangerous when taken to too large an extent. Thus, what scientists truly need is a support system that lets them talk about what the actions they carry out with someone who understands the value of these experiments and can provide advice on how to cope with them since, in general, the vast majority of these scientists simply hope to learn something new that can aid the people in the world around them. This will allow for a decompartmentalization of scientists to erase the social stigma associated with always being in a lab doing experiments and will allow them to be validated as people who also have pure, raw human emotions.


clinical practice

"Emotion" by Michelle Shi

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Medical Dialogue Review Volume 12 | Issue 1

Attenuating the Aggresion of the

Biological Theory By MIKAELLA EVARISTO If there is anything that resembles the hues in the Pacific Ocean, the keys of a piano, or the individual hairs of hay in which the needle is lost, it is the answer to the question, “what is a person?” Answers to this seemingly undemanding inquiry lay in one’s vantage point: what do you see when you are asked the definition of a human being? For standardization, a biological perspective is one which lists the biochemical processes of which a person is composed, thereby labeling the person as “alive” or having “life.” Whether they know it or not, this biological standpoint is most likely one that physicians take. We label someone as “alive” if he or she is capable of universal biochemical processes: maintenance of homeostasis, multicellularity, the ability to grow and adapt to one’s environment, the ability to reproduce and response to stimuli.1 These big processes each have their micro pathways, which involve a collection of tiny mediators that have specialized jobs within the physical body. It has taken the lifetime of our world to study and further organize these processes so that we have a cohesive system for discovering the reasons that cause adversity upon the ill. It is this biochemical definition of a person that is ingrained within us, quite literally, whether we choose to verbally affirm this knowledge or not. And therefore, this makes it the only uncontested definition of a person on which we can agree: an objective truth that has been proven time and time again. In practicing medicine, it becomes an easier task to cure that which robs an individual of life from a biological perspective. It is this reduction that allows physicians who train for decades to be able to

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exactly pinpoint some dysfunctional feature in a body. Physicians look at the tiniest details: the effect of a virus on the immune system, the consequences of unregulated cell division, the influence of base pair mutations within one’s genetic code—a harmony of biochemical instruments that sometimes randomly strike the wrong chords, causing harm to the human body. Despite its truth, the biological definition is a completely reductionist point of view on the human being, one that doesn’t take into account the very defining feature of one’s individuality. People may then argue that the variation within the genetic code can be the seen as a factor which separates a person from another. This is another objective fact, but that still doesn’t illustrate the full picture of a person. We may have realized the human genome in 2003, and correspondingly the many functions of some of the individual genes, but that still does not encompass the complexity of the human being.6 For instance, imagine an alternative world filled with individuals that were created with our biochemical framework, but lack a subjective experience. We can conclude via the biological perspective that these creatures are alive and fundamentally identical amongst each other. In this strange case, the biological point of view may work in defining these creatures because there is nothing that sets them apart. However, we cannot apply this to a person, as there is a level of emotional and mental sophistication that we are still far from understanding.


clinical practice mikaella evaristo This is where other definitions of a person come into play. Many may be so inclined to answer by listing the abstractions of a person: a person is “alive” if they have a soul. Such a starting point can then unfold into a multitude of mini abstractions, wherein people are defined by the certain, sometimes elusive characteristics they have. However, these traits are already, to an extent, predetermined by the existing norm, which set the duality between notions of “good” and “bad.” One would praise Mother Teresa, but absolutely scorn a serial killer. This polar divide that is so integral in a person allows us to think about another dimension of which a human can be composed: the mind. In any case, in such a world, it is easy to definitively say that treatment for whatever ails these biologically identical beings would exist solely in “fixing” their faulty biochemical processes. In our world, neuroscience can tell us definite pathways that objectively elaborate on our motor responses from sensory stimuli that is the product of the electrical and chemical signal exchanges within the neural network (an example of this would be the pathway of pain). Neuroscience can also tell us about oxytocin, anandamide, or serotonin, neurotransmitters that play a key role in our feeling “better,” whatsoever that means. If curing someone were as simple as physically, strategically mending the faulty biochemically processes, then we would live in a world where mental illnesses do not have a hold over us. Since we do not live in such a world, more often than not, we become slaves to our mind. Though there may be some neurological correlate to a particular feeling of “sad” someone who is struggling with depression may feel, there is no explanation that fully reduces this experience of sadness to a biological identity. Thus, neuroscience cannot tell me exactly why the neural basis of a certain conscious experience I am having is the exact neural basis of that certain conscious experience2. These are highly provocative, insightful questions that lie behind the explanatory gap, a concept coined by philosopher Joseph Levine in 1983

that signifies the clear divide between one’s conscious. If defining a human being were similar to painting, we probably have, over the generations, created only the background despite the various, cataclysmic breakthroughs in medicine and research. We have painted varying shades of colors that have completely embraced the canvas that is a person. This is an important point to raise in the realm of medicine, where the biological theory seems to prevail. So often, many are told that Mind-Body Dualism, wherein the mind and body are two separate, distinct units, is a lazy theory. A previous Medical Dialogue Review article entitled “Rethinking the Mind and Body Problem” says that many “believe that the mind-body problem is the result of a lack of understanding of the brain, the mind, and the body”3. If we were to discount a theory based on the lack of knowledge supporting the claim, wouldn’t we be able to similarly conclude that materialism is equally lazy in that materialists believe the explanatory gap will be solved over time? The addendum “over time” suggests that there is no current knowledge to solve the explanatory gap at this present moment. “Rethinking the Mind and Body Problem” argues that there is a demand for “accurate objective knowledge” and that this “outweighs the romanticized constructs such as the mindbody problem” so that we as a people must “move forward to correct and rethink the errors of the past”3. I fervently disagree with this sentiment, as I do not think that past apparent elusive theories that try to define a person are “errors.” In looking at something as intricate as the human body, it is too easy to try to condense it to certain identities to be in control of the body. We are usually uncomfortable by the thought of vast ignorance on a topic, especially in medicine, where lives are at stake. For as long as this world exists, I do not doubt that science will continually progress in its desperate search for answers. Another article in a past MDR issue entitled “Psychoneuroimmunology: A Window into Mind-Body Medicine” states that “If

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Medical Dialogue Review Volume 12 | Issue 1 physicians were to aspire to improve standards in which their patients are to thrive and defeat their adversities, then they would need to build relationships, engage in conversation, and immerse themselves within various communities4. In this manner, a physician will heal beyond simply the alleviation of symptoms.” The author is proposing an outdated, 19th century perspective on approaching treatment. It is obvious that the pre-medical students are going to become physicians who will physically treat an illness, but another viable act during this long search for answers would be to exercise empathy. It is easy to discard this thought by fearing the potential practice of Eastern medicine. However, one doesn’t have to start prescribing acupuncture, cupping, meditating, and the like. This could be done simply by changing one’s mindset. Instead of looking at a patient as a platform on which to exercise medical prowess and knowledge, why not look at him or her as

Illustration by Tarra Chen

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a person that transcends just the biological? In addition, changing one’s mindset could also be done by simply acknowledging the story that is a sick patient. Columbia University’s Narrative Medicine Program calls this “narrative competence,” and firmly believes that the care of the sick should encompass the individual, differing voices of each patient. We can agree on the various mechanisms that allow us to be alive, but we should in no way reduce ourselves to them. It is nonsensical to identify a person as the sum of their internal processes, just as it is equally nonsensical to identify a bird on its ability to fly. A bird is an essential part of the ecosystem, and flying is a way it has adapted and evolved over time. People are more than cellular respiration, DNA replication, and feedback pathways. There is no set definition for a person because we are not finished building our blueprint; we aren’t finished with the intricate artwork of not only colors, but also dimensions.


clinical practice mikaella evaristo

REFERENCES 1. Ashraf, Muhammad Aqeel, and Maliha Sarfraz. “Biology and Evolution of Life Science.” Saudi Journal of Biological Sciences 23.1 (2016): S1–S5. PMC. Web. 15 Oct. 2017. 2. Block, Ned. Phenomenal and Access Consciousness. 2008 3. Kim, Junwoo. “Rethinking the Mind and Body Problem .” Medical Dialogue Review, 2012, pp. 36–38. 4. Akhand, Omar. “Psychoneuroimmunology: A Window into Mind-Body Medicine.” Medical Dialogue Review, 2012. 5. Nagel, Thomas. What Is It Like to Be a Bat? The Philosophical Review, Vol. 83, No. 4. (October 1974), pp. 435-450. 6. “Human Genome Project Completion: Frequently Asked Questions.” National Human Genome Research Institute (NHGRI),

Photo by Karen Lee

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Medical Dialogue Review Volume 12 | Issue 1

Photo by Karen Lee

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clinical practice brendan hyslop

CERTAIN

LUCK

By BRENDAN HYSLOP

"Luck" by Armando Di Ciccio The natural world we live in is defined by scientific laws. Phenomena are observed, deductions are made, and conclusions are drawn. Science sounds concrete and evident. It seems unfaltering and resolute. It acts certain; it can answer the formerly unanswerable. Given these algorithmic qualities, many view science as a portal to understanding and modulating their hitches. With the immense magnitude of information in circulation, it seems as though there is a piece or part that should offer some explanation, some remedy, for any type of difficulty or complication. However, the science of

medicine falls far outside these ranges. Medicine, like science, is defined by “laws,” according to Dr. Siddhartha Mukherjee, though these laws exist as oxymorons in being only “of uncertainty, imprecision, and incompleteness.”1 He describes medicine as the “reconciliation between knowledge (certain, perfect, fixed, concrete) and clinical wisdom (uncertain, fluid, imperfect, abstract).”1 Dr. Edward Gogel summarizes this less scientifically: “With luck we refine our findings over the clinical course of the work-up.”2 Luck. A very unscientific, non-absolute, unpredictable

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Medical Dialogue Review Volume 12 | Issue 1 thing. It is understandable why physicians and patients alike face difficulty in accepting this unpleasant reality: doctors do not know everything. Despite the huge volume of information, education, and training out there, there is a vast amount of unknown, and perhaps a vast amount of luck. Take the story of Lisa McCown, for instance, a waitress and mother from Burlington, New Jersey.3 In April of 2016, she had become sick with a simple case of the flu, but after a few days her health continued to deteriorate, breathing became harder, and she was flown to Temple University Hospital in Philadelphia, Pennsylvania.3 She was diagnosed with acute respiratory distress syndrome, which is characterized by the inflammation and hardening of the lungs.3 Doctors treated her with a ventilator carefully calibrated so it wouldn’t tear apart her fragile lung tissue, a RotoProne bed that manipulated her body position so her lungs would have more room to expand, and extracorporeal membrane oxygenation (ECMO) that respired for her outside her body.3 Nothing worked.3 Dr. Yaniv Dotan, one of the doctors treating McCown, said “I and most of the team didn’t believe she could survive this.”3 Given the dwindling odds, most of the care team met with McCown’s family and discussed the grim prognosis and the decision that had to be made regarding life support.3 They opted to continue fighting, and she was placed on ECMO for a second time.3 Several weeks later, she was taken off of it, having improved as sufficiently as she did surprisingly.3 At the end of August, she was finally healthy enough to go home.3 When asked about this astounding recovery, Dr. Dolan said “You know, it’s medicine. We can’t explain exactly the mechanisms.”3 However, McCown’s nephew Jayden, who had been bringing ladybugs to the hospital as good luck charms, had a different explanation: “Ladybugs are lucky and I think that made her health better.”3 Jayden’s insight towards McCown’s amazing return to health may be even more telling than Dr. Dolan’s. Dr. Dolan simply admitted the unknown quality that transcends all of

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medicine, while Jayden identified this quality as being luck. All the signs were pointing towards no recovery; all the science suggested McCown wasn’t going to survive. But the ladybugs, whose luck didn’t follow reason or rhyme, may have accurately represented why McCown healed. It’s not a traditional scientific answer by any means, but it makes sense. A team of clinicians with a massive amount of intellectual capital and access to millions of pages of knowledge had concluded, under all reasonable science, that McCown wasn’t going to make it. But she still did. And if medicine can’t explain this, then maybe luck is the next best option. However, curious recoveries aren’t the only area of medicine in which luck is concerned. There is a much larger, much scarier, much more personal aspect of care that luck finds itself inexorably intertwined with: the physician. A physician is shaped only minimally through education, mostly through experience. This is exactly the case for Dr. Atul Gawande. Eleanor Bratton was a young planner and daughter who moved to Boston, Massachusetts from her hometown in Hartford, Connecticut.4 She was admitted to the Brigham and Women’s Hospital emergency room (ER) at the direction of her internist after her presumed cellulitis, a minor and common skin infection, had not dramatically responded to the prescribed antibiotics from a day earlier.4 The emergency physician had agreed with the diagnosis and prepared to administer more drugs, but first called Dr. Gawande, the senior surgical resident in the ER, for a consult to make sure there was no surgical intervention needed.4 Dr. Gawande evaluated Bratton’s reddened leg, and agreed that it did superficially present as a cellulitis, though he had a burning, horrifying idea in the back of his mind.4 Dr. Gawande had seen another patient several weeks earlier, a fifty-eight-year old man, who was also diagnosed with a cellulitis. = Nothing seemed amiss about this diagnosis— all the symptoms matched—and he was sent home with antibiotics, much like in Bratton’s case.4 However, he returned the next day, with


clinical practice brendan hyslop a much worse infection, and not long after, entered shock.4 In the operating room, it was determined he did not have a common and benign cellulitis, but rather a much rarer, much more malicious ailment called necrotizing fasciitis.4 The rapidly-spreading, flesh-eating bacteria that causes the pathology had consumed much of the man’s internal left chest, and he died in the days following.4 Dr. Gawande reflected that “it was one of the most awful cases [he had] ever been involved in.”4 With this clinical horror story occupying the recent corners of his mind, Dr. Gawande contemplated that maybe, just maybe, Bratton too had this infection.4 He seemed to be ignoring the old medical school adage “if you hear hoofbeats in Texas, think horses not zebras,” going forward instead under the direction of his single earlier experience, and contacted his attending for further review.4 He ignored, quite luckily, the notion that “anecdotal experience, the material of traditional medical practice and teaching, is unrepresentative of the average case.”5 The attending consulted and agreed that a cellulitis was still the most likely diagnosis, but that necrotizing fasciitis couldn’t be disqualified, either.4 He, however, placed the odds of the latter being the case at “well under five percent.”4 Nevertheless, after an additional consult, Bratton chose to go forward with the biopsy, even if the odds were slim.4 To everyone’s astonishment, the sample came back positive as necrotizing fasciitis.4 The worst case scenario had become realized, and Dr. Gawande’s outlandish inkling vindicated. Over the next few days, the attending and another surgeon meticulously debrided the infected tissues from Bratton’s leg in an effort to prevent the need for total amputation.4 She was placed in a hyperbaric chamber, where atmospheric pressure is increased, in an experimental attempt to further oxygenate her tissues and promote wound healing.4 In the end, she was able to keep not just her life, but also her leg, all fundamentally due to Dr. Gawande’s clinical hunch.⁴ It seems reasonable to say, though, that his premonition was motivated by his recent, impactful experience with the patient

he lost to the same cruel ailment. Reasonable speculation can dictate that, had Dr. Gawande not previously seen a patient with necrotizing fasciitis, had another resident been the surgical consultant for the ER that day, had Bratton rejected the biopsy without the diligent medical advice she received, or had any other possible scenario occurred, her condition would not have been caught as quickly and critically as it was. In other words, she got lucky. The stars aligned, and luck was the reason she was seen by the physician who, based on his own circumstances, was the one who could diagnose her. Whether it be through cases of inexplicable recoveries or the intricacies surrounding marvelous diagnoses, luck finds itself spliced within every facet of medicine. “I don’t know” is something doctors are “reluctant to utter,” but medicine is a human enterprise and consequently faces all the fallibilities and limitations arising from such distinction.⁴ Dr. Gawande himself acknowledges, in the scientific wording that dominates his field, that “medicine’s ground state is uncertainty.”⁴ Among all the science, there is a lot of unknown. Dr. Kent Sepkowitz words this more directly: “All doctors believe in luck.”⁶ He admits that many hide from this uncertain reality, taking shelter in the “ordered rows of science,” but that “answers in medicine sometimes lie in luck.”⁶ He says that physicians, though reluctant to acknowledge it, understand this verity.⁶ It can be unnerving to think that something so abstract and arbitrary, unknown and unreliable, can hold so much power in such an analytical and scientific field. Luck by its very nature is unseeable and intangible, but its effects are often profound. It is why Lisa McCown regained her health and why Eleanor Bratton was diagnosed when she was. Medicine is uncertain. Doctors do not always have the answers or explanations patients are hoping for. But, perhaps the only certain thing among all this uncertainty, is that there will always be luck.

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REFERENCES 1. Mukherjee, Siddhartha. The Laws of Medicine. New York: Simon & Schuster, 2015. Print. 2. Terry, James S. and Edward L. Gogel. “Poems and Patients: The Balance of Interpretation.” Literature and Medicine, vol. 6, 1987, pp. 43-53. 3. Vitez, Michael. “The Art—and Sometimes Luck—of Medicine.” Medium. A Medium Corporation, 13 Oct. 2016. Web. 16 Oct. 2017. 4. Gawande, Atul. Complications. New York: Picador, 2002. Print. 5. Sepkowitz, Kent A. “Answers in Medicine Sometimes Lie in Luck.” The New York Times. The New York Times Company, 5 Mar. 2012. Web. 16 Oct. 2017. 6. Greenhalgh, Trisha. “Narrative based medicine in an evidence based world.” British Medical Journal, vol. 318, no. 7179, 1999, pp. 323-5.

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public health & policy loren kita

Maternal Health in India Loren Kita

Illustrated by Tarra Chen For a country to truly thrive, all the citizens must have equal access to health care and resources, specifically mothers and children, since these children comprise the new generation. India is a prime example of how the lack of health care and access to resources plays in a mother’s life. India, a country known for its industrial growth and economic expansion, still lacks in its medical support for mothers. Several barriers, affect the services women are provided including: availability of resources and accessibility to health facilities. However, the most prominent social barrier is sexism, due to the way it is engraved in India’s society, where women are constantly fighting for the right to their own bodies and to make their own choices. By understanding these limitations and recognizing the under-lining forms of sexism in-

volved, one can see the ways India can change in order to truly provide for the entire country. In recent years the mortality rate for mothers during pregnancy and delivery has been able to decrease significantly in first world countries. Yet, India remains lacking in this aspect in which this phenomenon of life or death during pregnancy is a pressing issue. According to ONE, “a woman’s lifetime risk of maternal death is 1 in 180 in developing countries, compared to 1 in 4900 in developed countries.” According to this statistic, India can be considered a developing country with its high maternal mortality rates. According to the World Health Organization, “of the 536,000 maternal deaths occurring globally each year, 136,000 take place in India” (Vora). These numbers are shockingly high, and show an urgent need for

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Medical Dialogue Review Volume 12 | Issue 1 improved maternal health care. This raises an important question of why? Why is this the case, even though this can be prevented? One must wonder why India, a prospering country, could not achieve this health-related inequity. While one can say healthcare has improved in India’s urban regions, there is a lack of maternal healthcare in India’s rural regions. However, the majority of India’s population lives in rural regions, and changes are still not being made, due to lack of education and myths surrounding medical treatments. In the rural regions, a majority of women suffer from traditional societal beliefs tying them down to the role of a mother, limiting their rights to own land, receive an education, and choose their own paths in life. Improving maternal health in these regions can be a step in the right direction to provide mothers with the rights they deserve. The government and society must work towards improving maternal health in order to allow their children to grow up, love, and one day give back to the country. Despite India’s extreme statistic on mother mortality, a majority of maternal deaths are preventable. The solution lies in the quality of care given to patients and furthermore if the women who need care can even access it. With preventive care, maternal mortality rates could decrease. According to the World Health Forum, “80% of these deaths could have been prevented by prenatal care, treatment of predisposing medical conditions, and rapid transport to a hospital” (Bhatia JC). If India could provide its mothers with better needed care, mothers could be saved. Care throughout pregnancy focuses primarily on preventive measures in hopes of improving birth outcomes, aiming to limit risk factors for mothers and their children. This preventive care could provide women with needed medical attention early in their trimesters by finding possible medical conditions which could affect the child and help mothers plan ways for transportation before delivery. This shows the importance of providing preventive and antenatal care to mothers throughout their entire pregnancies: such mea-

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sures can reduce the high maternal mortality rates throughout the world, and specifically in India. However, geographical and physical aspects such as time, distance, cost, and interference with work can prevent women from seeking the necessary treatment. Another apparent issue is the lack of transportation to and from these appointments. These challenges result in women seeking out less care, resulting in increased levels of child mortality and maternal deaths, which could be prevented. The World Health Organization believes women should have at least four preventive care assessments, however India fails to meet this guideline since Indian guidelines state women should only have three preventive care visits. This means insurance companies will likely not cover charges for more assessments and women may not seek out receiving more care. This limitation results in women not receiving the preventive care needed to help prevent unfavorable outcomes on pregnancy. This clearly shows the care mothers receive before delivery is limited. Lack of reproductive health can be seen widely throughout India in the lack of these assessments due to existing limitations. However, the way sexism affects mothers and daughters lives by limiting their rights to an education, to making choices, and to their own body is even more shocking. A woman’s level of education in terms of schooling is correlated to her rights to her own body, age of first marriage, and age at first pregnancy often because these young women do not have the right to make decisions. Fathers decide when their daughters will marry, while husbands decide when their wives will have children, as a result, women are deprived of their right to make choices. These young women lack the knowledge needed to make informed decisions about their health specifically with reproductive aspects. Statistics show “that 39 percent of the women were married at ages less than equal to sixteen years, 41.1 percent women got married between ages seventeen to twenty years, and 19.9 percent were married when their age was twenty years or more” (Pandey). This shows that a large percent of


public health & policy loren kita in India are married at a young age, resulting in many women having their first pregnancy also at a young age. Women who marry at a younger age are often considered to have less power in the house and never receive a full education, which is correlated to an increase in the number of births per mother. For example, in India, “the total fertility rates for these two groups are significantly different: 4.0 children for illiterate women compared to 2.2 children for women with a high school education or above” (Velkoff, Adlakha). One can argue this is due to the apparent patriarchy in society, which limits the education women have the right to receive. This emphasizes gender roles placed on women by society, especially the ideology that a woman’s role is to bear children. With this mindset, women are expected to have multiple children. Velkoff ’s article mentions the idea of increasing the use of contraception to reduce fertility rates, which is extremely important since “a low proportion of married 15-19-yearold women (13%) used contraceptives in 2006”(Guttmacher Institute). Data collected by the International Institute for Population Sciences discussed in Velkoff ’s article shows that contraception is used more often in urban regions than rural, and a huge difference exists between illiterate and educated women. For example, only one third of illiterate women reported using contraception. So to reduce fertility rates and therefore reduce mortality rates, the government should push to increase family planning and health education. The extent to which sexism is integrated into Indian culture goes as far as discriminating against daughters during gender reveal. For example, Indian mothers pregnant with boys are “…more likely to go to prenatal medical appointments, take iron supplements, deliver the baby in a healthcare facility (instead of the home) and receive tetanus shots than women pregnant with girls” (Doucleff). Specifically, in rural regions, if women are expecting a daughter instead of a son, families are less likely to find ways of transportation to health centers or hospitals for delivery. In India it is prohibited for doctors to reveal the gender of the baby. Yet,

doctors are often men who contribute to this gender preference and are willing to share the gender. Laws concerning a baby’s gender reveal should be more strictly enforced to protect innocent female newborns. Although, women may seek out this prenatal and preventive care, health facilities may not even have the resources to provide the support needed. Hospitals and health facilities must have access to labor rooms, enough beds, surgery drugs, anesthetics, electricity, technology, and staff. In poor regions throughout the country, access to space and these supplies is limited. For example, ranges of “533 persons per government hospital bed in Arunachal Pradesh to 5494 persons per government bed in Jharkhand” exist, showing the drastic differences between poor and rich districts (Balarajan). India is currently facing a shortage of doctors and nurses because many go abroad for their education and choose to work for foreign shores upon grduating. This lack of staff is even more drastic in rural regions, where the communities “only have 23.4% of the obstetricians and gynecologists they require” (Ghosh). On average there should be one obstetrics and gynecology doctor for every 1,000 mothers, however India with a population of over one billion, has approximately 1,000 specialists currently practicing in the country (Ghosh). Due to lack of facilities in rural regions, doctors choose to stay and practice in urban regions, where everything is easier to access. Thus, as India aims to provide universal health coverage and improve maternal health in all regions, this lack of resources and availability of health professionals proves to make this aim very difficult to achieve. Improving maternal health by providing women with needed preventive assessments, family planning, reproductive health education, and accessible resources will allow not only mothers of India, but the overall country to prosper. Such changes can empower women to take control of their lives and make better personal decisions concerning their health. However, convincing a patriarchal society and the government to improve these conditions

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Medical Dialogue Review Volume 12 | Issue 1 proves to be very difficult. By understanding the complexities of maternal health in the context of India, one can better understand the struggle to implement change.

REFERENCES 1. Balarajan, Yarlini, S. Selvaraj, and S. V. Subramanian. "Health Care and Equity in India." Lancet. U.S. National Library of Medicine, 05 Feb. 2011. Web. 10 May 2017. 2. Bhatia, J. C. "Light on Maternal Mortality in India." World Health Forum. U.S. National Library of Medicine, n.d. Web. 10 May 2017. 3. Biswas, Ranjita. Maternal Care in India Reveals Gaps Between Urban and Rural, Rich and Poor. N.p., n.d. Web. 10 May 2017. 4. "Dictionary: Search the Merriam-Webster Dictionary First. Here's Why..." Merriam-Webster. Merriam-Webster, n.d. Web. 10 May 2017. 5. Doucleff, Michaeleen. "In India, Discrimination Against Women Can Start In The Womb." NPR. NPR, 29 Mar. 2013. Web. 10 May 2017. 6. Ghosh, Abantika. "Paediatrics to Gynae, Where Are the Surgeons, Physicians?" The Indian Express. N.p., 20 Apr. 2015. Web. 10 May 2017. 7. Hanson, Jessica D. "Understanding Prenatal Health Care for American Indian Women in a Northern Plains Tribe." Journal of Transcultural Nursing : Official Journal of the Transcultural Nursing Society / Transcultural Nursing Society. U.S. National Library of Medicine, Jan. 2012. Web. 10 May 2017. 8. "The Issues Affecting Global Poverty: Maternal & Child Health." ONE. N.p., 16 Feb. 2017. Web. 10 May 2017. 9. "Late or No Prenatal Care." Child Trends. N.p., n.d. Web. 10 May 2017.

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10. Leone, Tiziana. "The Hidden Costs of Maternal Healthcare in India." Health and Social Care. N.p., 01 Mar. 2013. Web. 10 May 2017. 11. "Literacy Rate of India 2011." What You Want to KNOW and Need to KNOW. N.p., n.d. Web. 10 May 2017. 12. Namasivayam, Amrita, Donatus C. Osuorah, Rahman Syed, and Diddy Antai. "The Role of Gender Inequities in Women’s Access to Reproductive Health Care: A Population-level Study of Namibia, Kenya, Nepal, and India." International Journal of Women's Health. Dove Medical Press, 2012. Web. 10 May 2017. 13. Pandey, Anjali, and K. K. Singh. “Contraceptive Use before First Pregnancy by Women in India (2005-2006): Determinants and Differentials.” BMC Public Health, BioMed Central, 2015, www.ncbi.nlm.nih.gov/pmc/articles/ PMC4696327/. 14. "Pregnant Women Must Be Able to Access the Right Care at the Right Time, Says WHO." World Health Organization. World Health Organization, n.d. Web. 10 May 2017. 15. "Preventive Care Benefits for Women." HealthCare.gov. N.p., n.d. Web. 10 May 2017. 16. "Pregnant Women Must Be Able to Access the Right Care at the Right Time, Says WHO." World Health Organization. World Health Organization, n.d. Web. 10 May 2017. 17. "Preventive Care Benefits for Women." HealthCare.gov. N.p., n.d. Web. 10 May 2017. 18. "Standards." American Libraries 13.9 (1982): 603-04. Web.


public health & policy loren kita

19. “Sexual and Reproductive Health of Young Women in India.” Guttmacher Institute, 27 July 2016, www.guttmacher. org/fact-sheet/2015/sexual-and-reproductive-health-young-women-india. 20. "Support Smart Girls." Half the Sky: Turning Oppression Into Opportunity for Women Worldwide. N.p., n.d. Web. 10 May 2017. 21. UN Millennium Project | About the MDGs. N.p., n.d. Web. 10 May 2017. 22. User, Super. "The SDGs & MDGs." The Sustainable & Millennium Development Goals. N.p., n.d. Web. 10 May 2017. 23. Velkoff, Victoria A., and Arjun Adlakha. "Women’s Health in India." The British Medical Journal 1.4650 (1950): 422-23. Web.

30. Vora, Kranti S., Dileep V. Mavalankar, K.V. Ramani, Mudita Upadhyaya, Bharati Sharma, Sharad Iyengar, Vikram Gupta, and Kirti Iyengar. "Maternal Health Situation in India: A Case Study." Journal of Health, Population, and Nutrition. International Centre for Diarrhoeal Disease Research, Bangladesh, Apr. 2009. Web. 10 May 2017. 31. Vora, Kranti S., Dileep V. Mavalankar, K.V. Ramani, Mudita Upadhyaya, Bharati Sharma, Sharad Iyengar, Vikram Gupta, and Kirti Iyengar. "Maternal Health Situation in India: A Case Study." Journal of Health, Population, and Nutrition. International Centre for Diarrhoeal Disease Research, Bangladesh, Apr. 2009. Web. 10 May 2017.

24. "Standards." American Libraries 13.9 (1982): 603-04. Web. 25. “Sexual and Reproductive Health of Young Women in India.” Guttmacher Institute, 27 July 2016, www.guttmacher. org/fact-sheet/2015/sexual-and-reproductive-health-young-women-india. 26. "Support Smart Girls." Half the Sky: Turning Oppression Into Opportunity for Women Worldwide. N.p., n.d. Web. 10 May 2017. 27. UN Millennium Project | About the MDGs. N.p., n.d. Web. 10 May 2017. 28. User, Super. "The SDGs & MDGs." The Sustainable & Millennium Development Goals. N.p., n.d. Web. 10 May 2017. 29. Velkoff, Victoria A., and Arjun Adlakha. "Women’s Health in India." The British Medical Journal 1.4650 (1950): 422-23. Web.

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Medical Dialogue Review Volume 12 | Issue 1

Why Electronic Cigarettes Are a Public Health Concern Ryan Lamrani

"Duplicity" by Sushant Thomas

The combustible cigarette was popularized due to grandiose marketing strategies meant to hook customers for life. In fact, combustible cigarettes clients are unique in that the product that they consume is highly addictive, and deciding to quit is difficult although it is desired. It is well established that product advertising increases or maintains use1. In fact, cigarette companies realized early that there is a clear correlation between the amount of cigarettes sold and the amount of presented advertising. For instance, US-based multinational Philip Morris (Marlboro), which is the world’s biggest cigarette company, was the world’s ninth largest advertiser in 19962. The iconic Marlboro Man also known as the Marlboro Cowboy has proven effective in increasing the sales of cigarettes across the country. Philip Morris’ marketing team revolutionized advertising and how publicities are filmed; they managed to sell an emotion instead of a product. A recent study has observed an association between cig-

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arette marketing regulations and the number of smokers in the United States3. The broadcast ad ban of 1971 signed into law by President Nixon, which forbade cigarette companies to advertise their products on televisions and radios supports this finding since it resulted in fewer smokers3. Although the ban could not have been the only cause, it may have still been a significant factor. The billboard ad ban of 1999 is also associated with the decline of people smoking3. As for the youth, the percentage of combustible cigarette smokers amongst minors has been declining since 20114 while the percentage of electronic cigarette smokers has been increasing in the same time frame4, even tripling between 2011 and 2013⁵. While the marketing of combustible cigarettes is regulated, the marketing of electronic cigarettes is not, which might be the reason for the rapid increase in e-cigarette sale to minors. In fact, some of the electronic cigarette advertising in the United States today closely resembles the marketing strategies used by combustible cigarette company advertisers before the multitude of regulations restricted them6. For example, electronic cigarettes are sometimes distributed in places where minors tend to gather, which mirrors the techniques of combustible cigarette companies who used to distribute free packs of cigarettes to the youth during the big holidays. Consequently, if the marketing of electronic cigarettes is not regulated, it could increase initiation amongst minors and non-smokers⁷, matching the trends apparent before the times of combustible cigarettes regulation. It is indeed possible that the lack of bylaw would result in an increase of the pool of potential adult smokers⁸. It could potentially


public health & policy ryan lamrani bring a new group of people, who would not have initially been inclined to smoking combustible cigarettes in the first place to eventually switch their electronic cigarettes for combustible onesâ š. In fact, electronic cigarettes started as an alternative to combustible ones, allowing users to control the amount of nicotine they inhale over a period of time. However, given that minors are allowed to buy electronic cigarettes and their nicotine-charged flavorful cartridges, electronic cigarettes become a gateway tool for combustible productsâ ¸. Furthermore, teenagers are more influenced by cigarette advertising and marketing than adults. Indeed, 83.4% of children prefer popular brands cigarettes vs. 61.1% of adults10. Teenagers are also more likely to remember advertisements they saw displayed in the past two weeks than adults11. Also, teens are more likely to be influenced by marketing than by peer pressure12. The age at which an individual starts smoking also influences the length of time that individual will remain a user13. In fact, the earlier an individual starts smoking, the greater the risk of them becoming a regular smoker. For instance, 90% of adult smokers began as teenagers or younger, and two-thirds of that youth became regular, daily smokers before they reached the age of 1913. Thus, the key to reducing the health consequences that accompany nicotine use is to discourage young people from using nicotine products in the first place. While some argue that there should be no regulation to marketing electronic cigarettes to minors, as it is better for teenagers to experiment with electronic cigarettes instead of combustible ones, the latter is actually more detrimental to the body. Although it is true that combustible cigarettes are currently known to be more harmful than electronic cigarettes, the latter often become a gateway tool for combustible products. Furthermore, not much is known about the safety and health risks associated with smoking electronic cigarettes. In fact, some national public agencies have raised concerns regarding the health risks associated with electronic cigarettes14. Another myth argument would be that the

marketing of electronic cigarette might help combustible smokers transition to the less harmful option. Once again, while not much is known about the dangers of e-cigarettes, users have complete control over the amount of nicotine they inhale over time. Also, given that electronic cigarette smoking is not as tightly regulated as that of combustible cigarettes, smoking in public spaces is allowed, which lead to users often consuming more nicotine than they would have had they smoked combustible cigarettes. This increase in nicotine inhalation leads to users having a harder time quitting smoking. Actually, the Food and Drugs Administration (FDA) attests that there are some concerns about the health risks associated with electronic cigarette use14, while electronic cigarette smokers are associated with lower levels of depression, anxiety, and other mental health conditions than combustible cigarette smokers, these levels are still higher than those of non-smokers8; whether those mental conditions lead to smoking or vice-versa is still to be determined. From a physical health perspective, certain studies highlight that electronic cigarettes are potentially as carcinogenic as combustible cigarettes since the vapor smoke damages human epithelial cells, including the DNA contained in their nuclei15. Other researchers show that while smoking electronic cigarettes, also called ‘vaping’ reduces the risk of certain health risks associated with combustible cigarettes, electronic cigarettes introduce new ones related to memory and other mental disorders16, and lung infection, which is mainly due to the reduced immunity in lung cells that vaping causes17. Additionally, the FDA did not approve of electronic cigarettes as a safe or effective way of helping combustible cigarette smokers quit18. In fact, using electronic cigarettes make cessation even harder given the increased amount of nicotine consumed throughout the day. A study found that students who have used e-cigarettes by the time they start 9th grade are more likely to smoke combustible cigarettes,19 thus, making e-cigarettes a gateway to regular combustible cigarettes. It is thus necessary to

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Medical Dialogue Review Volume 12 | Issue 1 minimize the influence of e-cigarette marketing on teens, as to ensure the decrease of preventable deaths caused by smoking. Electronic cigarettes should not be marketed as freely as they are today given that they raised health

concerns. With a lack of regulations around the marketing of electronic cigarettes, the country is doomed to repeat the same mistakes it did in the past with combustible cigarettes, which we are still trying to fix today. "The Cool Thing to Do" by Sushant Thomas

REFERENCES 1. Lisa Henricksen, Comprehensive Tobacco Marketing Restrictions: Promotion, Packaging, Price and Place, 21 Tobacco Control 147, 149 (2012) 2. 2016, WPRO. “Smoking statistics.” World Health Organization. WHO Western Pacific Region, 20 Feb. 2016. 3. CDC. Trends in current cigarette smoking among high school students and adults, United States, 1965–2014. CDC, 30 Mar. 2016. 4. Tavernise, Sabrina. “Use of E-Cigarettes Rises Sharply Among Teenagers, Report Says.” Health. The New York Times, 21 Apr. 2015. 5. CDC. Trends Infographics. CDC, 14 Apr. 2016.

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public health & policy ryan lamrani

6. Durbin, Waxman, Harkin, Rockefeller & Members Of Congress: Report Shows E-cigarette Marketing Campaigns Lighting Up Among Young Users, U.S. Senator Dick Durbin (Apr.14, 2014) 7. Pallav Pokhrel et al., Receptivity to E-cigarette Marketing, Harm Perceptions, and E-cigarette Use, 39 Am. J. Health Behav. 121, 129 (2015) 8. McGovern J, Unger J, Leventhal A, et al. Teens with fewer mental health issues turn to e-cigarettes: Adolescents with moderate emotional health problems do not smoke, but they may vape, study finds." Journal of Psychiatric Research. 2015. 9. Leventhal A, Strong D, Kirkpatrick M, et al. Association With Electronic Cigarette Use With Initiation of Combustible Tobacco Product Smoking in Early Adolescence. The Journal of the American Medical Association. 2015. 10. Pollay, R, et al., “The Last Straw? Cigarette Advertising and Realized Market Shares Among Youths and Adults,” Journal of Marketing. 60(2):1-16, April 1996. 11. National telephone survey of 536 teens aged 12-17 conducted March 14-20, 2012 and 1,004 adults conducted March 14-20, 2012 by International Communications Research and has a margin of error of plus or minus 4.2 percentage points for the teen survey and 3.1 percentage points for the adult survey. 12. Evans, N, et al., “Influence of Tobacco Marketing and Exposure to Smokers on Adolescent Susceptibility to Smoking,” Journal of the National Cancer Institute, October 1995. 13. HHS, Preventing Tobacco Use Among Youth and Young Adults, A Report of the Surgeon General, 2012. 14. HHS, Youth and Tobacco: Preventing Tobacco Use among Young People: A Report of the Surgeon General, 1994 15. “Related consumer updates.” Food and Drug Administration. Office of the Commissioner, 10 Dec. 2015. Web. 16. Knapton, Sarah. “E-Cigarettes Are No Safer Than Smoking Tobacco, Scientists Warn.” The Telegraph. The Telegraph, 29 Dec. 2015. 17. J. Raloff. Vaping may threaten brain, immunity, and more. Science News. February 14, 2016. 18. J. Raloff. E-cigarettes proving to be a danger to teens. Science News. Vol. 188, July 11, 2015. 19. document. “E-cigarettes and lung health.” American Lung Association. American Lung Association, 2 June 2016. 20. Rigotti NA. e-Cigarette use and subsequent tobacco use by adolescents: new evidence about a potential risk of e-cigarettes. JAMA. 2015;314(7):673-674.

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Medical Dialogue Review Volume 12 | Issue 1

Transgenderism Addressing the Cry for Help By Himari Gunasinghe

"Equality" by Michelle Shi Transgenderism is not a new phenomenon. The fight for equal transgender rights has been a fight for basic civil rights and through great strife, much progress has been made and huge milestones have been achieved. In the 1960s, the transgender community was met with public disdain, with rioting occurring in affluent cities such as San Francisco and Los Angeles. Over the years, however, the transgender community has had its voice heard in the judicial and healthcare systems with the formation of LGBT support groups, and with strong historic LGBT figures such as Christine Jorgensen (first American to undergo a man-to-woman sex change) standing up for transgender rights. The transgender community cannot be refused

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jobs because of their orientation due to their inclusion in the Title VII of the Civil Rights Act, cannot be refused transgender-related health care by Medicare, and cannot be openly discriminated against. Scientific advancements have made many more safer treatment options available for transgenders, and sex-reassignment surgery is no longer as dangerous to attempt and difficult to have access to. Transgenders are also represented in the judicial system and even the White House, making the new decade the light at the end of the long dark tunnel for the transgender community. Support for the transgender community has risen strikingly over the years. A survey conducted in 2015 by the Human Rights


public health & policy himari gunasinghe Campaign showed that 66% of people knowing a transgender person expressed favorable feelings towards them, compared with 13% percent who did not. This is corroborated by the solidarity of the country towards the mass shooting in Orlando in 2016, that killed 49 people, most of whom were LGBT nightclub goers. Furthermore, Gay Pride Month is commemorated by most states and LGBT flags wave high and proud in the sky. The increase in social acceptance for transgender individuals is accompanied by milestones in the health services available to the LGBT community. In May 2014, the Department of Health and Human Services reversed a Medicare policy such that Medicare must cover the cost of sex reassignment surgery as part of treatment for transgender people. With the introduction of the Affordable Care Act, health insurance companies and clinics that accept federal funds cannot discriminately treat non-transgender people. As a result of the greater accessibility to transgender-related health care, the number of sex reassignment surgeries has risen by 20% from 2015 to 2016. Loren Schechter, a plastic surgeon based in Chicago stated that there was an “the number of transgender patients [she had] seen [had] grown exponentially.” Yet amidst this explosion in support and acceptance, the LGBT community, specifically the transsexual community faces a dark threat: suicide. A disturbing statistic reveals that 46% of trans men and 42% of trans women have attempted suicide. It is common opinion of many transgender advocates that this terrifying rate of suicide is due to “rejection, discrimination, violence, harassment, and the negative life circumstances that result from such treatment.” However, given the overwhelming uptrend in support for the LGBT cause in recent years, it is to be expected that overall, the rate of attempted suicide amongst transsexuals should decline, should discrimination and lack of acceptance be the main cause for transsexual suicide. This leads to the question; “what else could be contributing to the transgender suicide rate?”

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To assess the extent to which rejection by supportive figures and society contributes to the transgender suicide rate, it would be prudent to analyse suicide statistics in other minority groups that report social ostracization and rejection. The most comparable group to the transsexual group in terms of parental rejection is a subset of the LGBT community; those that identify as homosexual. A study done by the National Transgender Discrimination Survey (NTDS) states that 10-20% of adult LGB (lesbian, gay, bisexual) have attempted suicide at least once in their lives. 80% of LGB youth report isolation issues, and a comparable, but definitively lower percentage (57%) in the transsexual community reported that “Family chose not to speak/spend time with them.” Interestingly, although a higher percentage of lesbian, gay and bisexual populations report exclusion and isolation, the suicide rate among them is a half down to a quarter less than amongst transsexuals. This is a strong indicator that perhaps more than lack of social acceptance is the source of the suicide epidemic amongst this vulnerable population and more has to be done for them than fighting for bathroom rights. The first step in the amelioration. The notion that transgenderism is a psychiatric condition is one that is highly controversial. The DSM III declassified transgenderism from Gender Identity Disorder (GID) to the less stigmatized Gender Dysphoria (GD) currently in the DSM V, no longer considering it a ‘disorder.’ While these changes were intended to prevent society from thinking of transgender people as "mentally ill," psychiatric treatment may hold the key to increased suicide prevention amongst the transsexual community. The statistic of a 40% attempted suicide rate follows the trend for attempted suicide rate amongst mental illnesses. At least 40% of schizophrenic patients, who undergo episodes of lost identity, have attempted suicide at least once in their lives. Amongst the most severe illnesses, 30% of bulimia nervosa (BN) sufferers, who bear an unhealthy body image, have reported attempting suicide at least once. Yet it is perhaps the

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Medical Dialogue Review Volume 12 | Issue 1 identity disorder Body Dysmorphic Disorder (BDD) that may hold the key to the solution to reduce the transgender suicide rate. BDD is similar to GD in that sufferers do not identify with their current bodies in their natural form, and transformative surgery is a treatment option. BDD has a general attempted suicide rate of about 30% (28%); characteristic of identity disorders, yet what is more interesting is the statistic of only 25% of BDD patients undergoing transformational surgery being satisfied with the outcome. In a similar manner, it is a possibility that contributing to the transgender suicide rate is transition regret. Research from the US and Holland show that “a fifth of patients regret changing sex,” leading to the phenomenon of post-transitional regret not being as elusive as often depicted. Post-transitional transsexuals may report regret upto thirty years after their transition; a scope of time not often followed through in clinical trials. Given that many have undergone sexual abuse, deep trauma and terrible family circumstances early life, and given also that studies have shown that 62.7% of transgenders have at least one comorbid psychiatric illness11, psychiatric counseling is perhaps a great first treatment option for transsexuals. Any stress of a permanent transformative surgery should be left until all other treatments have been exhausted and an affirmative, informed choice has been made by the patient. Throughout the entire process, psychiatrists should remain vigilant and attentive to their transgender patients at the times when they are most vulnerable. External factors such as social rejection and poverty are blamed for the sky-rocketing transgender attempted suicide rate. However, it is more than likely that the associated extreme poverty is not the true cause of the transgender suicide epidemic; it might more than likely be a by-product of mental illness correlated with transgenderism. The McSilver Institute for Poverty Policy and Research at NYU states that the “rate of adults experiencing mental illness is highest among those with family income below the Federal poverty line.” With 59% of the transgender community reporting

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homelessness, it is likely that transgenderism may be a variant of an identity disorder, or at least comorbid with mental illness, in either case resulting in better psychiatric care being the best first course of action in transgender treatment. A suicide attempt rate of 40% in a community is a shriek for help. Improving social acceptance for the transgender community may have been effective in reducing suicidal effects in the past, but it is fast outliving its usefulness now. Help must be delivered to these people through another way; psychiatric care. Even if transgenderism IS a mental illness, mental illness is nothing to be stigmatized. The mentally ill are people like the rest of us and have rights; rights to have access to psychiatric, and if needed, surgical treatment that can finally alleviate the storms in their minds. All that is important is listening to the cry for help and finding a way to end the epidemic of suicide, leaving the stigma behind.


public health & policy himari gunasinghe

REFERENCES 1. “Milestones in the American Transgender Movement.” The New York Times, The New York Times, 18 May 2015, www.nytimes. com/interactive/2015/05/15/opinion/editorial-transgender-timeline.html.

“Body Dysmorphic Disorder: What You Don't Know About the Damaging Disease.” RealSelf. com, 1 July 2014, www.realself.com/blog/ body-dysmorphic-disorder-don-t-the-damaging-disease.

2. Campaign, Human Rights. “Survey Shows Striking Increase in Americans Who Know and Support Transgender People.” Human Rights Campaign, www.hrc.org/blog/surveyshows-striking-increase-in-americans-whoknow-and-support-transgende.

10. Sexuality, Walt Heyer within. “Regret Isn't Rare: The Dangerous Lie of Sex Change Surgery's Success.” Public Discourse, 16 June 2016, www. thepublicdiscourse.com/2016/06/17166/.

3. Surgeons, American Society of Plastic. “Gender Confirmation Surgeries Rise 20% in First Ever Report.” American Society of Plastic Surgeons, American Society of Plastic Surgeons, 22 May 2017, www.plasticsurgery.org/news/ press-releases/gender-confirmation-surgeries-rise-20-percent-in-first-ever-report. 4. “No, High Suicide Rates Do Not Demonstrate That Transgender People Are Mentally Ill.” ThinkProgress, thinkprogress.org/no-high-suicide-rates-do-not-demonstrate-that-transgender-people-are-mentally-ill-5074c09a5827/.

11. Gender Reassignment Surgery Protocol HealthNow New York https://www.bcbswny. com/content/dam/COMMON/Provider/Protocols/G/prov_prot_Gender_Reassignment. pdf 12. Mental Health and Poverty McSilver Institute http://mcsilver.nyu.edu/sites/default/files/reports/Mental_Health_and_Poverty_one-sheet. pdf17.

5. Suicidology LGBT Resource Sheet http://www. suicidology.org/Portals/14/docs/Resources/ LGBT%20Resources/LGBTresource-sheet.pdf 6. Williams Suicide Report Williams Institute https://williamsinstitute.law.ucla.edu/wp-content/uploads/AFSP-Williams-Suicide-Report-Final.pdf Accessed October 2017 7.

“Suicide .” Schizophrenia.com - Introductory Resources on Schizophrenia, schizophrenia. com/suicide.html.

8. Attia, MD Evelyn, and Ph.D. Deborah R. Glasofer. “Suicide Awareness: Not Just a Depression Problem.” The Huffington Post, TheHuffingtonPost.com, 17 Sept. 2014, www. huffingtonpost.com/evelyn-attia-md/eating-disorders-suicide_b_5798718.html. 9. Phillips, Katharine A. “Suicidality in Body Dysmorphic Disorder.” Primary Psychiatry, U.S. National Library of Medicine, Dec. 2007, www.ncbi.nlm.nih.gov/pmc/articles/ PMC2361388/.

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Photo by Karen Lee

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public health & policy

Photo by Michelle Shi

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Medical Dialogue Review Volume 12 | Issue 1

Supervised Injection Facilities (SIFs) By Bailey Hall

"SFI" by Emma Theisen Supervised Injection Facilities (SIFs) are legally sanctioned facilities in which individuals are able to intravenously inject pre-obtained drugs under direct medical supervision. The purpose of SIFs is to reduce the health and societal risks associated with injection drug use. Sterile injection equipment, treatment referrals, trained medical staff, and information regarding the risk of drug use is provided at SIFs, along with counseling and other services. SIFs have existed in various European countries since the 1980s and have proven to reduce incidents caused by high-risk intravenous injection, such as overdose. In October 2003, North America saw its first SIF with a SIF opening in Vancouver, Canada. Approximately one hundred SIFs are legally sanctioned throughout the world, but none currently exist

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within the United States. Providing drug users a safe facility to inject themselves with illegal lethalities is alien to many; much of the United States’ population is either unaware of or uneducated on SIFs. Stigmas surrounding the idea of SIFs are strong, yet advocates are committed to challenging such stigmas by properly informing both politicians and the public of the health and societal benefits of SIFs. A large-scale campaign is active in New York City: the campaign for Supervised Injection Facilities in New York City (SIFNYC). SIFNYC claims SIFs capable of improving the health and safety of communities by increasing public access to drug treatment services, which will decrease fatal overdoses and infections. In New York City, which has been his-


public health & policy bailey hall torically known as the epicenter of injection drug use, the homelessness rate is on the rise. A recent study by the Injection Drug Users Health Alliance (IDUHA) claims fifty percent of injection drug users inject themselves in a public setting. Additionally, the IDUHA claims homeless to be nine times more likely to inject publically than those who are stably housed. Public injectors are four times more likely than private injectors to reuse injection equipment, which increases the risk of disease. Human Immunodeficiency Virus (HIV) and Hepatitis C rates, among many others, are widespread amongst the population of injection drug users. But how can humanity accept the legal regulation of a crime as dangerous as intravenous drug injection? Whether because of medicine, politics, or morals, people are troubled by the government funding of drug injection, the rate of drug-dependents is undeniable. According to the World Health Organization (WHO), approximately thirteen million people intravenously inject themselves with illicit drugs. A worldwide drug epidemic exists and people are dying everyday because of it, all while people debate what can be done to inhibit the soaring rates. Many argue, such as those affiliated with SIFNYC, SIFs are not ideal due to their nature of allowing the injection of drugs; however, while the epidemic is being battled out, SIFs

act as powerful supervisors. Currently operating SIFs allow for more than one visit per day, closely monitoring each injection and standing by with Naloxone. “Naloxone is a medication designed to rapidly reverse opioid overdose. It is an opioid antagonist—meaning that it binds to opioid receptors and can reverse and block the effects of other opioids”. If an overdose occurs at a SIF, there is a higher probability the life of the drug user will be saved than if the drug user overdoses outside of a SIF. Emergency medical personnel carry naloxone, but often times too much time passes before a person who overdosed is reached by emergency medical personnel. With a drug epidemic sweeping the world, there are programs which attempt to eradicate the epidemic, such as the Act Against AIDS initiative. SIFs have proven to reduce the negative impacts on communities caused by injection drug users; there has been a notable decrease in drug-related deaths, substance abuse, and public criminal acts. An early evaluation of a SIF found, “the facility prevented 4 deaths per year and was associated with an increase in substance use disorder treatment, fewer episodes of public injection, and fewer discarded syringes”. Despite being a customarily taboo subject, should Supervised Injection Facilities exist within the United States?

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Medical Dialogue Review Volume 12 | Issue 1

REFERENCES 1. Supervised Injection Facilities. (n.d.). Retrieved October 01, 2017, from http://www.drugpolicy.org/ issues/supervised-injection-facilities 2. Beletsky, L., Davis, C. S., Anderson, E., & Burris, S. (2008, February). The Law (and Politics) of Safe Injection Facilities in the United States. Retrieved October 02, 2017, from https://www.ncbi.nlm.nih. gov/pmc/articles/PMC2376869/ 3. SIF NYC. (n.d.). Retrieved October 01, 2017, from http://sifnyc.org/ 4. The Case for SIFs. (n.d.). Retrieved October 04, 2017, from http://sifnyc.injectingadvice.com/index. php/library/ 5. The Case for SIFs. (n.d.). Retrieved October 04, 2017, from http://sifnyc.injectingadvice.com/index. php/library/ 6. The Case for SIFs. (n.d.). Retrieved October 04, 2017, from http://sifnyc.injectingadvice.com/index. php/library/ 7. People who inject drugs. (n.d.). Retrieved October 04, 2017, from http://www.who.int/hiv/topics/ idu/en/ 8. Abuse, N. I. (2016, September 26). Opioid Overdose Reversal with Naloxone (Narcan, Evzio). Retrieved October 02, 2017, from https://www.drugabuse.gov/related-topics/opioid-overdose-reversal-naloxone-narcan-evzio 9. Abuse, N. I. (n.d.). Naloxone for Opioid Overdose: Life-Saving Science. Retrieved October 10, 2017, from https://www.drugabuse.gov/publications/naloxone-opioid-overdose-life-saving-science/naloxone-opioid-overdose-life-saving-science 10. HIV/AIDS. (2017, March 16). Retrieved September 29, 2017, from https://www.cdc.gov/hiv/risk/idu. html 11. Frakt, P. A. (2017, April 05). JAMA Forum: Safe Injection Facilities Reduce Individual and Societal Harms. Retrieved October 10, 2017, from https://newsatjama.jama.com/2017/04/05/jama-forum-safe-injection-facilities-reduce-individual-and-societal-harms/

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Photo by Michelle Shi

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Medical Dialogue Review Volume 12 | Issue 1

Breakthroughs in RNAi Brings Many Possibilities for the Future By Joanne Chung

“RNA”by Armando Di Cicco

Medicine has come a long way since 1928 when Alexander Fleming first discovered the first true antibiotic, penicillin. The average life expectancy was 40 years, however over the last 90 years this number has nearly doubled because of the discovery of penicillin. Today, with the introduction to RNA Interference (RNAi), a new drug on its way, it’s interesting to note how much impact this drug will have on the world as we know of today. RNAi can be utilized as a revolutionary, biotechnological tool that will treat almost any disease imaginable – HIV, hepatitis B, Huntington’s, and many more. However, as with any groundbreaking research, a significant amount of time and money must be put into the project. Alnylam Pharmaceuticals Inc. and Sanofi Genzyme have done just that. On September 20th, 2017 they announced a positive clinical trial, APOLLO Phase 3 results. This breakthrough will pave the way for the future of RNA interference medi-

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cine that utilizes a reverse genetic approach to fight viral infections. However, with a world of possibilities, there is much room for error, and challenges will follow their ongoing research. To fully appreciate this biomedical technology, one must have a more complete understanding of what RNA is and how RNA interference works. Imagine a big castle (the nucleus) where the powerful book of DNA is locked inside. At the center of the castle is RNA acting like a scribe, copying the information and distributing the transcript into the realm, otherwise known as cytoplasm. This information, messenger RNA, is then handed to the ribosomes, which are organelles that read the mRNA in order to create proteins. In furthering the analogy above, one can think of ribosomes as construction workers who work with the mRNA to create a structure (protein). These proteins build up all kind of cells and the ribosomes must be careful to not copy any aberrant information. This is where RNAi comes into play; when double stranded RNA molecules are identified, an enzyme called dicer chops the identified RNA molecule up. These fragments of short double stranded RNA then float around in the cell, which is later picked up by RISC (RNA-induced silencing complex). RISC contains another important protein called the slicer, which splits this short double stranded RNA in half and uses a single strand to look for a matching mRNA target sequence (complementary RNA). Afterwards, the mRNA RISC slicer cuts the double stranded RNA up even more. Ribosomes recognize oddly shaped pieces of RNA is floating around, subsequently preventing the RNA from turning into a protein. Then RNAi is formed


biomedical research joanne chung through being transcribed by the genome and forming a hairpin structure. In essence, RNAi “describes a cellular mechanism that uses the gene’s own DNA sequence to turn it “off,” a process that researchers call silencing”1. Not much is known about RNAi and there’s still a long way to go before RNAi biotechnology will be prevalent and widespread in healthcare today. It took 30 years for RNAi to advance to this stage of development and understanding. RNAi was discovered accidentally when Rich Jorgensen and his colleagues wanted to deepen the color purple in petunias. They “introduced a pigment-producing gene under the control of a powerful promoter. Instead of the expected deep purple color, many of the flowers appeared variegated or even white”2. Originally thought of as a unique quirk of petunias, this “quirk” was found in many other plants and species. Reverse genetics was found successful in worms in 1998 when Andrew Fire and Craig Mello were able to degrade mRNA from a specific gene3. Expectations were high during the 20th century, but scientists kept hitting roadblocks in their research. Gene silencing was simple in worms and petunias, but more difficult in mammals which thus lead to a significant number of fatalities during the early stages of APOLLO. A revolutionary breakthrough was In Alnylam’s press release, John Maraganore, Ph.D., Chief Executive Officer of Alnylam, said “We are very proud to report the first ever positive Phase 3 results for an RNAi therapeutic, marking the potential arrival of an entirely new class of medicines. This moment is the culmination of a 15-year journey of tireless work by countless contributors who have overcome enormous scientific and business challenges to make RNAi therapeutics a reality”4. With this in mind, the APOLLO Phase 3 study of RNAi drug, patisiran, (ALN-TTR02) was developed to treat patients with hereditary transthyretin amyloidosis (ATTR) with polyneuropathy5. The APOLLO phase 3 trial is a randomized, double blind, placebo-controlled, study

whose purpose is to evaluate the efficacy and safety of patisiran in ATTR patients. This study was done at 44 sites in 19 countries around the world, where each patient was randomly assigned 2:1 ratios of patisiran to placebo. Patisiran is a RNAi investigational therapeutic drug, designed to target and silence TTR proteins before it’s made. The mutations of TTR gene can cause ATTR, a rare disease where amyloid (aggregates of misfolded proteins) builds up within the tissues of the body. These deposits damage the functions of organs and can affect almost any part of the body. Specifically, Alnylam’s patisiran investigated the body’s response to this medicine when administered into the body with intravenous fluid of a person who has familial amyloid polyneuropathy (FAP). This will essentially clear TTR amyloid deposits in the peripheral tissues and restore function to these tissues. The APOLLO phase 3 trials evaluated the efficacy (primary endpoint) and safety (secondary endpoint) by measuring the endpoint of modified neuropathy impairment score (mNIS+7) and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOLDN). The patisiran was administered through IV at 0.3 mg/kg once every three weeks for 18 months6. The endpoint measure of mNIS+7 were lower in patients who received patisiran. This number was favorable and an overall improvement as compared to the baseline. This included muscle strength, gait speed (how quickly a person can walk within a specified distance), modified body mass index (BMI), and nutritional status. The endpoint measure of Norfolk QOL-DN showed that the patisiran group experienced an improvement in the quality of life compared to the placebo group. Previously, Alnylam encountered problems with adverse effects and the safety of their investigational RNAi therapeutic. However, in APOLLO phase 3 trial both the patisiran and placebo groups had similar frequencies of serious adverse events (36.5% patisiran and 40.3% placebo) and deaths (4.7%

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Medical Dialogue Review Volume 12 | Issue 1 patisiran and 7.8% placebo). There were challenges facing the early APOLLO trials because ATTR amyloidosis is a rare disease; thus the diseases are hard to diagnosis since they are hidden among more common diseases. The patients were “uniformly distributed around the world, and that makes it a little more challenging to find a diagnosis type.” The safety profile results were encouraging with similar frequencies in adverse events and deaths. There were also fewer discontinuations from the patisirian treatment. Nearly all the patients who completed APOLLO have agreed to continue to the APOLLO-Open Label Extension study and continues to receive patisiran. With these positive results, Alnylam is expected to file a New Drug Application in late 2017 and commercialize patisiran in the first

half of 2018. “‘Nobody will put [RNAi therapies] back in the box, therapeutically,’ said Phil Sharp, a scientific co-founder of Alnylam and winner of his own RNA-related Nobel Prize. ‘They are now alive and out there, and more and more people will see them as answers to their problems. The next 10 years will be exponentially more impactful. But we won’t see this matured as a pharmaceutical approach for decades.’” This major achievement in drug therapy was only possible through the large amount of effort, dedication, money, and heartbreak that the team at Alnylam put in.

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biomedical research joanne chung

REFERENCES Adams, D., & Suhr, O. B. (2017, September 11). Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. Retrieved October 07, 2017, from https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC5594468/ Court, E. (2017, September 21). Alnylam shares surge 40% on drug results that may herald a new type of medicine. Retrieved October 07, 2017, from http://www. marketwatch.com/story/alnylamshares-surge-40-on-drug-resultsthat-may-herald-a-new-type-ofmedicine-2017-09-20 Gollob, J. (2017, September 18). APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis Full Text View. Retrieved October 07, 2017, from https://clinicaltrials. gov/ct2/show/NCT01960348 How RNAi Works - RNAi Biology | UMass Medical School. (2013, November 03). Retrieved October 07, 2017, from https://www. umassmed.edu/rti/biology/howrnai-works/ KeshavanSTAT, M. (2017, October 5). Experimental Drug That Mutes Defective Genes Raises New Hopes. Retrieved October 07, 2017, from https://www.scientificamerican.com/article/experimental-drug-that-mutes-defectivegenes-raises-new-hopes/ Lindenboom, C. R. (2017, September 20). Alnylam and Sanofi Report Positive Topline Results from APOLLO Phase 3 Study of Patisiran in Hereditary ATTR (hATTR) Amyloidosis Patients

with Polyneuropathy. Retrieved October 07, 2017, from http://investors.alnylam.com/releasedetail. cfm?ReleaseID=1041081 Nobel Assembly at Karolinska Institutet , Nobel Media. (2006, October 2). The 2006 Nobel Prize in Physiology or Medicine [Press release]. Retrieved October 7, 2017, from https://www.nobelprize.org/nobel_ prizes/medicine/laureates/2006/ press.html Philippidis, A. (2017, September 20). Alnylam, Sanofi RNAi Candidate Patisiran Aces Phase III Trial. Retrieved November 05, 2017, from https://www.genengnews.com/ gen-news-highlights/alnylam-sanofi-rnai-candidate-patisiran-aces-phase-iii-trial/81254951 Reuters, T. (2017, August 3). ALNY 2017 RNAi Roundtable: Patisiran, in development for the treatment of hereditary ATTR amyloidosis (Issue brief No. 77). Retrieved November 5, 2017, from Thomson Reuters Streetevents website: http:// www.alnylam.com/wp-content/up-

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Medical Dialogue Review Volume 12 | Issue 1

The Inconsistencies in

Parkinson’s Dopamine By Nadja Zakula-Kostadinova

The utilization of extensive studies of Parkinson’s Disease, a neurodegenerative disorder characterized by the gradual loss of motor function, has enabled the development of novel considerations of the disorder and its potential treatment. Parkinson’s Disease involves the loss and death of brain cells called neurons that produce dopamine, a neurotransmitter engaged in brain signaling to control coordination and movement.1 Since Parkinson’s is a progressive disorder, symptoms gradually worsen and the lack of dopamine causes difficulties in controlling voluntary movement and produces symptoms such as tremors of the extremities, bradykinesia (slowness of movement), limb rigidity, and a lack of balance.1 Individuals with Parkinson’s are typically diagnosed as middle-aged adults, though the disease may manifest itself earlier. Though there is no current cure for Parkinson’s, the knowledge of the chemicals involved in the progression of the condition enable the study of the pathways contributing to its development and could contribute to potential improvement. The neural transformation and symptoms apparent in Parkinson’s patients have led to reports that examine the complexity of the disorder. Parkinson’s effects on the normal cognitive function were also discussed, as well as how medical therapies can target these pathways to reverse or inhibit these disruptions. Parkinson’s Disease gradually disables individuals’ abilities to complete daily activities due to insufficient levels of the chemical dopamine. Dopamine normally acts as a messenger and mediator between two brain areas, the substantia nigra and the corpus striatum.1 When these areas are able to coordinate and communicate

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with each other, movements are controlled and voluntary. However, as Parkinson’s attacks the dopamine-producing cells in the substantia nigra, communication and movement become impaired. Previous studies in genetics indicate that cellular processes and stress lead to cell damage, though the specific mechanism of the cell deterioration in Parkinson’s is unknown and therefore idiopathic, having no known concrete cause aside from the assumption that genetic and environmental factors contribute.8 Despite the lack of a known cause of Parkinson’s, the awareness of its relation to dopamine synthesis introduces an opportunity to manipulate dopamine as a variable to observe the development of the disorder. A recent study highlighted that dopamine itself can cause a “toxic” signal transduction cascade that kills the neurons that produce it and that it is self-inhibitory.2 While dopamine controls movement (and its absence in Parkinson’s prevents this control), its oxidation also mediates its concentration and the symptoms of Parkinson’s. This oxidative stress was observed in the mitochondria which regularly oxidizes glucose for energy and if damaged, can release


biomedical research nadja zakula-kostadinova reactive oxygen that causes cellular death. In a particular study, fluorescent proteins noting whether oxidation has occurred was utilized along with a tag that sent it to the mitochondria.3 The protein was induced to only develop in dopamine-related cells and an increased amount of oxidative stress was observed in the neurons throughout regular intervals. The study was performed again on a mouse model with Parkinson’s which showed heightened oxidative stress.3 This emphasizes that the mitochondria and the state of Parkinson’s is connected and that the regular periods of stress in the mitochondria are caused by impulses that alter calcium levels as they propagate along neuron lengths. The sole notion of dopamine’s link to Parkinson’s permitted an extensive study of the contributing signaling pathways that decrease dopamine levels and can be inhibited to treat Parkinson’s progression. The oxidative stress caused by calcium and increased stress of Parkinson’s persuaded researchers to introduce a drug that blocks these fluctuations in calcium levels which reduces stress through additional stability and eases development of Parkinson’s. Signaling pathways are essential

to the determination of cellular function and how manipulating various portions of the pathway can induce their own cascade effect. A study performed by Northwestern Medicine and published on September 7, 2017, determined that interfering with the neural conduction in Parkinson’s will not only slow and prevent the degeneration of brain cells but also reverse its effects and improve neuron function.4 While the mouse models used were not identical to human counterparts, they illustrated the all-encompassing reach of motor control in terms of brain regions impacted. By losing brain cells, patients with Parkinson’s have extremely lessened brain plasticity, a phenomenon that allows the organ to compensate for parts that are damaged or inhibited. The oxidation of dopamine in the mitochondria and lysosome is key to understanding that dopamine is the ultimate mediator of this disorder.4 Parkinson’s development is not just exacerbated by its presence or absence but by its own mechanisms, essentially through self-destruction. The proposed mechanism of destruction sets the ground for studies that

"Parkinsons" by Emma Theisen

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Medical Dialogue Review Volume 12 | Issue 1 inhibit its attack and consequently inhibit the degenerative cycle. Though researchers treated dopamine neurons with antioxidants to lessen stress and inhibit oxidation, the differences between humans and mice and individual patients in general exemplifies the significance of holistic treatment and the use of genetic and diagnostic testing to screen people at risk and implement remedies before the extensive onset of Parkinson’s. Moreover, the investigation on dopamine’s contribution to Parkinson’s is not only valuable in assessing potential treatments, but also in evaluating the efficiency and safety of previous medications. Parkinson’s patients are often prescribed the medication Levadopa (L-Dopa), which is synthesized into dopamine to help control movement. However, the finding that increased dopamine can worsen Parkinson’s degeneration prompts a re-evaluation of L-Dopa and other medications that act as dopamine-replacers.5 A mice model was implemented to engineer mice that have lower amounts of a protein that package dopamine into vesicles to transport it out of cells and prevent excessive concentrations. Without this transport, the mice had higher levels of dopamine and of corresponding oxidative stress and Parkinson’s symptoms. Results of manipulating dopamine levels can be used to evaluate other medications for Parkinson’s such as dopamine agonists that mimic dopamine without actually increasing dopamine concentration directly.6 Additionally, a similar study used mice models to “re-create” lost brain cells through gene therapy by killing dopamine neurons with a toxin and introducing four specific genes which led to reprogramming and the correction of motor function.7 The variety of studies concerning Parkinson’s illustrates that what is known about the disease can be used to can be used to direct treatments that either lessen symptoms and more considerably reverse them and restore normal function. The investigation on dopamine’s contribution to Parkinson’s—despite the fact that its absence is what leads to Parkinson’s—emphasizes that all is harmful without moderation and that

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medicine has an additive nature. Contrasting results of different studies note that any significant manipulation of dopamine levels and normal cellular processes and regulation methods can increase the risk of Parkinson’s. Increased studies on Parkinson’s have lead to new and varied treatments and considerations of the interconnected mechanisms that can play a role in its onset or development. However the common ground that unifies these studies is the need for human studies and intense genetic screening and testing to discover predispositions and influencers of Parkinson’s. Dopamine serves as an example of a contributor to the disease that can be fluctuated in concentration, intensity, and presence to explore potential treatments. Research regarding neurodegenerative diseases such as Parkinson’s Disease encompasses the study of signaling cascades and an amplified focus on genetic mechanisms may one day lead to a surge of available treatments.


biomedical research nadja zakula-kostadinova

REFERENCES 1. Heyn PDSN. Parkinson’s Disease: 17 Early Signs, Symptoms & Treatment. MedicineNet. https://www. medicinenet.com/parkinsons_disease/article.htm. Accessed October 7, 2017. 2. Sanders L. Brain chemical lost in Parkinson’s may contribute to its own demise. Science News. https://www.sciencenews.org/ article/brain-chemical-lost-parkinsons-may-contribute-its-own-demise?mode=topic&context=69. Published September 20, 2017. Accessed October 7, 2017. 4. Beal MF. Faculty of 1000 evaluation for Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. F1000 Post-publication peer review of the biomedical literature. September 2013. 5. Rethinking Dopamine's Role in Parkinson's Disease. The DANA Foundation. http://www.dana.org/ News/Details.aspx?id=42783. Published February 12, 2008. Accessed October 7, 2017.

6.

Believe in Better. National Parkinson Foundation. http:// www.parkinson.org/understanding-parkinsons/treatment/Medications-for-Motor-Symptoms/Dopamine-Agonists. Accessed October 7, 2017. 7. Waghorn M. Brain cells killed by Parkinson's disease can be replaced says study. mirror. http://www. mirror.co.uk/lifestyle/health/ parkinsons-breakthrough-experiments-show-brain-10197226. Published April 10, 2017. Accessed October 7, 2017. 8. Lu S. How Chronic Stress is Harming Our DNA. American Psychological Association. October 2014. http:// www.apa.org/monitor/2014/10/ chronic-stress.aspx. Accessed November 3, 2017.

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Medical Dialogue Review Volume 12 | Issue 1

How Does General Anesthesia Affect the Brain? By William Shin

"How Does General Anesthesia Affect the Brain" by Sora Nithikasem

Anesthetics do not get the credit they deserve. In medical television dramas, operating room scenes are far too often focused solely on the surgeon. Very rarely are anesthesiologists and their roles in the operating room portrayed in these scenes. As a result, the general public does not understand the importance

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of anesthetics very well. The extent to which some understand the role of anesthetics is that they “put people to sleep”. Some may be complicit in thinking anesthetics simply “put people to sleep” and may not inquire any further about how exactly anesthetics accomplish this. As with any advancement in medicine,


biomedical research william shin it is crucial to understand how anesthetics induce a state of altered consciousness, more importantly, what they are doing to the human body. It is also important to understand how anesthetics affect the human body because there are an estimated 234.2 million major surgeries that are conducted worldwide every year.1 The first step to gaining a better understanding of anesthetics is to understand how the brain is affected once anesthesia is administered.

Anesthetic Targets

First and foremost, different types of anesthetics affect different parts of the body. For example, muscle relaxants and paralytics affect the peripheral nervous system (PNS), specifically at the neuromuscular junction, however, general anesthesia scarcely affects the PNS.2 Therefore, we will only look at how general anesthesia affects the brain in particular. However, before we think about how general anesthetics affect the brain we must first understand what anesthetics target in the body. These biochemical targets in the body can be classified into two major categories: target molecules that induce either inhibitory or excitatory responses. An example of an inhibitory response-inducing target is potassium channels while an example of excitatory response-inducing targets is serotonin receptors.3 Most of these aforementioned targets are located on the nerves, whether it be those in the CNS or the PNS. For example, targets for neurotransmitters serotonin receptors are located mostly on the postsynaptic portion of any neuron in the synaptic cleft. The synaptic cleft is the area where neurotransmitters get released and reabsorbed. The presynaptic region is the part of a neuron (downstream of the Soma, which is a neuron’s body) that holds and releases neurotransmitters which get released via exocytosis into the synaptic cleft. Some of these exocytosized vesicles then get reabsorbed by the postsynaptic portion of a neuron (upstream of the Soma) by the respective neurotransmitter targets. Some examples of anesthetics that mainly have an effect on inhibitory neurotransmissionare barbiturates, propofol

and benzodiazepines. An example of an anesthetic that mainly has an effect on excitatory neurotransmission is ketamine. Examples that have mixed effects are xenon and nitrous oxide.

Brain Levels Affected

The general consensus about anesthesia is that it achieves a state of decreased consciousness by decreasing brain function. However, this is not completely true. The brain controls everything that occurs in the body, from one’s metabolic processes to one’s heartbeat. Therefore, if general anesthetics were to heavily decrease brain activity during surgery, then all of these functions would diminish as well, which would be extremely detrimental to a person’s health. Instead of thinking of the brain as a simple organ, the brain’s activity should be dichotomized into two different entities: low frequency brain activity and high frequency brain activity. It is theorized that low frequency brain activity controls the maintenance tasks associated with survival such as metabolism and homeostasis. Examples of tasks that the body goes through to maintain homeostasis are breathing and pumping blood throughout the body. High frequency brain activity is thought to control activities relating more to higher-level functions, such as cognitive functions. Based on a study which looked at electro-corticography (ECoG) readings on human subjects anesthetized with propofol, a type of general anesthetic, high frequency brain activity decreases while low frequency activity is maintained.3 Now that we understand what activities are affected during general anesthesia, we can go into more specifics on which regions of the brain they affect. The degree to which the areas of the brain are affected can be categorized into three very general, categories: conscious/awake, light sedation, and profound sedation. Based on function magnetic resonance imaging (fMRI) studies which are studies that measure brain activity by detecting the amount of blood flow in the brain, it was observed that when individuals are awake and conscious, there is a clear connection between the default

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Medical Dialogue Review Volume 12 | Issue 1 mode network (DMN) and executive control network (ECN) of the brain.3

Fig 1. Shows the relationship between the level of brain activity in certain regions of the brain and the level of sedation that results from anesthetic induction. The thickness and intensity of the arrows are indicative of the level of activity that is occurring in that region.

The default mode network is the network in the brain that work together to function during periods of wakeful rest most commonly seen when individuals zone-out. The executive control network is a network in the brain that work together to control more higher-level

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cognitive processing such as problem-solving. During light sedation, higher order frequency activity in the brain decreases slightly as previously mentioned. Functional connectivity in the brain also decreases during states of light sedation. During states of profound sedation, cross modal interactions between higher order and lower order brain activity are severely decreased. As a result, conscious processing is complexly shut down. What remains is brain activity that controls homeostatic functions. Although thalamic activity is not affected during times of light sedation, it does, however, decrease during deep anesthesia. What is important to note is that although the level of sedation is inversely proportional to the amount of brain activity that can be seen in an fMRI, some areas of the brain are not very affected by anesthetic agents. For example, as can be observed in figure 1, the activity of sensory afferents remains relatively consistent from a state of full consciousness to a state of profound sedation. Sensory afferents are neurons that send sensory signals from the brain down the CNS and to other parts of the body. Shedding light on how anesthetics affect the brain and in what region is the first step in understanding the complex role of anesthetics in surgery. There are also different types of general anesthetics, different levels of sedation, and different types of anesthetics that are used for different procedures, not just major surgery. This first step is a mere introduction to anesthetics. With this first step, it is my hope that when readers now indulge in medical dramas and see the camera only focus on the surgeon they will now ask, “what about the anesthesiologist�?


biomedical research william shin

REFERENCES 1. Weiser, T.G. et al. An estimation of the global volume of surgery: a modeling strategy based on available. The Lancet. [Internet]. [cited 2017 Nov 12]; 372: 139-44. Available from: http://www.who. int/surgery/global_volume_surgery.pdf 2. Antkowiak, B. 2001. How do general anesthetic work? Naturwissenschaften [Internet]. [cited 2017 Oct 8]; 88: 201-213. Available from: https://www.ncbi.nlm.nih.gov/ pubmed/11482433

3. Bonhomme, V. et al. 2012. Neural correlates of consciousness during general anesthesia using functional magnetic resonance imaging (fMRI). Archives Italiennes de Biologie [Internet]. [cited 2017 Oct 7]; 150(2-3): 155-63. Available from: https://www.ncbi.nlm.nih. gov/pubmed/23165875 4. Alonso, L.M. et al. 2014. Dynamical criticality during induction of anesthesia in human ECoG recordings. Front Neural Circuits [Internet]. [cited 2017 Oct 8]; 8(20). Available from: https://www.ncbi.nlm.nih.gov/ pubmed/24723852

Photo by Karen Lee

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Medical Dialogue Review Volume 12 | Issue 1

Patenting Life: To Whom Does the Human Genome Belong? By Mikaella Evaristo

Illustration by Michelle Shi Intellectual property dates back to medieval Europe. During this time, artisans in a particular industry were granted authority by the government to control the regulation of their industries.1 They were able to control the items to be imported, marketed, and produced. Centuries later in the US in 1790, James Madison spoke out on the importance to give Congress the power to establish a patent regime to encourage creation and competition.1 The act that was then passed was based off of European common law and stated: To promote the Progress of Science and useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries." - U.S. Const. Art. I, Sec. 8 4

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A patent owner therefore has the right to decide who can or cannot use the patented invention during the time period in which it is protected.1 Thus, the invention cannot be commercially made, used, distributed, imported, or sold by others without the owner’s consent. With inventors’ racing to have their bottle caps or electric stop lights patented, it was only a matter of time before researchers started filing applications for patents on human genetic information, DNA. The start of the questions surrounding patenting organisms arose during the Diamond v. Chakrabarty case in 1980. Ananda Chakrabarty was a genetic engineer working for General Electric when he developed a bacterium from P. putida that was capable of


biomedical research Illustration by Michelle Shi

breaking down crude oil, and could thus be effectively used in oil spills.2 A patent was then filed by General Electric with Chakrabarty as the head inventor, but was rejected by the US Patent and Trademark Office on the grounds that “living things were not patentable matter,” which alluded to Section 101 Title 35 of the United States Code.2 In 1981, however, the patent was reviewed and was eventually granted because “the fact microorganisms are alive is without legal significance for purposes of patent law.”2 This began the controversy surrounding patenting “life” and the impression that ethics had no rightful presence in the American Patent Law.2 James Watson even saw patenting DNA as “outrageous” and “sheer lunacy.”2 He believed that if bits of sequences were patented, this would hinder scientific progress as parts of the genome would not be accessible to other researchers.2 Instead of working collaboratively to sequence the genome, people were sequestering bits and pieces of DNA. In 1992, Watson resigned as head of the genome project because he vehemently opposed the patents on genes that the NIH filed.2

mikaella evaristo Along with the growth of scientific research in 1991 came the growth of the patent applications being filed on expressed sequence tags (EST), fragments of cDNA derived from the body that served to identify the gene from which it came. In addition to causing more controversy, thus began an EST arms race.2 However, these ESTs failed to meet the criteria set forth by the US Patent Office, leading to the rejection of these patent applications.2 At the turn of the 21st century, molecular diagnostic company, Myriad Genetics, patented two genes that they found to be associated with breast and ovarian cancers, BRCA1 and BRCA2.3 Prior to the controversy that exploded in 2010, patenting genes was an established practice within genetic research.3 However, medical associations, doctors, patients, and university researchers, including NYU and Columbia, sued Myriad Genetics.3 The Supreme Court ruled that genes occur naturally in every human, and so their isolation does not count as an invention or creation, as their sequences already exist in nature.3 However, the Supreme Court also ruled that Myriad Genetics could patent the cDNA* that comes from the mRNA of the genes, another controversy that stirred the population’s thoughts.3 Proponents of patenting cDNA argue that these patents encourage investment in biotechnology and promote invention in genetic research. Companies and individuals can invest in patented cDNA, providing financial support for the development of useful gene therapies and drugs. Without these patents, some worry that companies would no longer have the resources and drive to continue viable biotechnological research. However, these patents hinder scientific research because of the need to license or pay for the patented cDNA, which could be extremely costly. The breast cancer diagnostic test alone ranged from $2500 to $4000.3 This capitalist mentality, however, calls into question the motivation of a human being, and the possibility of being inherently unmotivated to an extent. Thus, legal incentives are needed in order to drive innovation in the STEM field,

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Medical Dialogue Review Volume 12 | Issue 1 particularly the area concerning genomic data. Is invention dealing with human DNA truly invention? Does reverse transcribing mRNA to cDNA count as an innovation or merely a rearrangement of a preexisting molecule? Similar to translating a book into a different language, this does not change the plot, but merely the phrasing of certain sentences to better accommodate the new language. However, the Supreme Court decided that cDNA is patent eligible because it is not a product of nature, rather it is a “new� composition of matter.5 Many may think that this ruling is the product of reading too deep into the United States Code on inventions patentable, but others may complete agree. Nonetheless, biological patents are not like patenting the invention of a toaster or of an Amazon Kindle. These patents allowed for a progression in human sophistication by handing the common people creations to make life easier. Patents on cDNA allow an individual to have a right to building blocks within the human body. Those who are fervently against the patenting of cDNA argue that the act impedes scientific research, as it limits what scientists unaffiliated with the patent owner of the cDNA can do. The bigger bioethical argument, however, is that which says that patenting cDNA commodifies the human being.5 Many believe that the mere act of having rights to a sequence of DNA reduces human dignity. This is similar to the quasi-religious view where some believed that such patents suggest that life has no sacred property, and that it is nothing more than an arrangement of molecules to manipulate and later legally claim. Though there is definitely a question of bioethics in the patenting of cDNA, this argument implies that genetic identity in the form of cDNA determines personal identity to an extent. However, equating a human being to its components is a completely reductionist view on life, as this consequently insinuates that individuals are nothing more than their building blocks. Though this begs the question, to what extent does genetic identity determine personal identity and human dignity? Personal identity includes experience and

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Illustration by Michelle Shi


biomedical research mikaella evaristo nurture, rather than just genetic nature, and so it is safe to assume that the two are not the same. In this sense, patenting human cDNA does not reduce human dignity. It may threaten dignity in the sense that someone can have “control” of a DNA sequence, and could potentially customize an individual, which turns a person into a product or “means.” This then could put forward the notion that people are ends in themselves. However, having rights to a fragment of DNA simply means that one controls how, when, and why it is being used for a

limited period of time. This article serves to highlight the merging of science, law, and economics, and its obvious blur when dealing with patenting cDNA. Though at the moment cDNA is patent eligible, will other micro components of the human system also become patentable on the loophole that they would not be “naturally occurring?” Patenting any sequence of DNA is dangerous because of all its bioethical, economic, and social implications. Where does one draw the line?

*cDNA is DNA that is complementary to mRNA, the molecular messenger of the genetic code written in the language of DNA, which is “read” in the process of translation to produce proteins essential for function and survival (DNA to mRNA to protein). cDNA is created by reverse transcribing mRNA into DNA, which is then called Complementary DNA.

REFERENCES 1. “History and Sources of Intellectual Property Law.” History and Sources of Intellectual Property Law - LawShelf Educational Media, lawshelf.com/courseware/entry/history-and-sources-of-intellectual-property-law. 2. Kevles, Daniel. “The Gene Patenting Controversy: A Convergence of Law, Economic Interests, and Ethics.” Brooklyn Law Review, 2002. 3. Mears, Bill. “Court: Human Genes Cannot Be Patented - CNNPolitics.” CNN, Cable News Network, 13 June 2013, www.cnn.com/2013/06/13/politics/scotus-genes/index.html. 4. Counsel, Office of General. “Ethics Rules.” United States Patent and Trademark Office An Agency of the Department of Commerce, www.uspto.gov/learning-and-resources/ patent-and-trademark-practitioners/current-patent-practitioner/ethics-rules. 5. University, Santa Clara. “Ethics and Gene Patenting.” Markkula Center for Applied Ethics, www.scu.edu/ethics/focus-areas/bioethics/resources/ethics-and-gene-patenting/.

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Photo by Karen Lee

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Photo by Karen Lee

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Join the Dialogue.

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Fall 2017| Volume 12, Issue 1 | Medical Dialogue Review  
Fall 2017| Volume 12, Issue 1 | Medical Dialogue Review  
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