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“Beyond” by April Mueller Medical Dialogue Review FALL 2014 Volume | VOLUME 15 MEDICAL15 DIALOGUE REVIEW 1 MEDICAL DIALOGUE REVIEW Artwork by Chloe Chan The content of the Journal of Medical Dialogue Review represents perspectives of students, professionals, or patients on issues in healthcare. These ideas do not represent the opinions of Medical Dialogue or New York University. Information that is presented is reviewed for accuracy, but should not be used for medical diagnosis or as a substitute of medical advice. MDR is a New York University student publication. NYU is not responsible for its content. 2 MEDICAL DIALOGUE REVIEW Fall 2014 EDITOR-IN-CHIEF Grace Tartaglia In This Issue LAYOUT EDITOR Neha Srivatsa PRESIDENT 6 From Drug-High to SugarHigh: Recovering Drug Addicts Turn to Sugar By Kayana Jean-Philippe 9 Diptesh Tailor SENIOR EDITORS REVIEWERS By Diptesh Tailor The Threat of Misdiagnoses: Are There Forms of Dementia That Could Be So Similar That They Are Nearly Indistinguishable? By Julia Schneider Although Normal pressure Hydrocephalus (NPH) and Alzheimer’s Disease (AD) are two different types of dementia, their overlapping symptoms have led health care professionals to misdiagnose AD patients with NPH, and vise versa. Author Julia Schneider details the nature of both diseases to the molecular level, ultimately allowing her audience to understand why these misdiagnoses are so prevalent, and what health care professionals can do to distinguish between the two illnesses. 17 VICE PRESIDENT Manuela von Sneidern Vasiliki Gliagias Ardalan Khalafi Oasis in the Desert 14 Sehrash Shabbir Has the Medical Field Acknowledged Artists Make Better Doctors? By Nicole Marie D’Alessio Amy Lei Aqssa Mohammad Ayesha Shah Aiman Shaaban Arisheniah Sothilingam Bismah Akhter Chelsea Leonard Christina Octavia Martin Deshana Barua Gagarin Zhao Harsh Patel Harvinder Bassi Joseph Aryankalayil Jason Lin Joyce Chen Jessica Miller Jaewoo Shin Kartika Upadhyaya Leana Emma King Martinus Megalla Mona Hassanein Nihal Patel Natahsa Pandit Parth Patel Swan Cho Shawn Paustian Sophie Rosenmoss Tina Yu Yu Guan Yu Kong CLUB ADVISOR Nanci H Healy Volume 15 MEDICAL DIALOGUE REVIEW 3 19 Stem Cell Therapy – A Novel Treatment for Duchenne’s Muscular Dystrophy By Syed Rahman 22 Coconut Oil Unmasked 25 Controlling the Control Center of the Body By Chris Torres By Sally Buttar Sleep, once regarded as passive, has been assessed as an active phenomenon due to the discovery of a new neuron, the PZ GABA, which may lead to new methods of sleep inducement. The complex nature of this neuron stems from its need to activate after a ligand, clozapine-N-oxide (CNO), binds to G-protein coupled receptors and induces PZ neuron activity, releasing the GABA neurotransmitter and resulting in deep sleep for the affected individual. 28 From Degenration to Regeneration 34 Orthognathic Surgery 101 By Mark Robles-Long By William Pang In “Orthognathic Surgery 101,” author Will Pang describes the various ways that maxillofacial deformities can affect the health and physical appearance of the individual, and details how these irregularities can be fixed through orthognathic surgery. Despite its complexity and length, this procedure is often successful in increasing the quality of life in patients affected by skeletally related jaw discrepancies. 4 MEDICAL DIALOGUE REVIEW Fall 2014 42 NYU’s Police Stress and Health Program Gains Insight Into Stressors Police Officers Face By Rebecca Fabbro For the past eight years, researchers at the NYU Langone Medical Center have collaborated with Scientists from the University of California, San Francisco to gain insight into the unique psychological and physiological stressors that affect police officers nationwide. In “NYU’s Police Stress and Health Program Gains Insight Into Stressors Police Officers Face,” author Rebecca Fabbro details their findings and highlights the ways in which PTSD affects the minds, and eventually the lives of American police officers. 47 The Ebola Epidemic and its Fallout in West Africa By Alina Popkova 51 Political Conditions on Humanitarian Aid: How Health and Political Relations Mix and Why It Concerns You By Andrea Martinez 55 The Ebola Time Bomb By Mariya Reztsova This article explores the Ebola virus from its ancestry and make-up to its effects on the countries in western Africa where the virus is prevalent. Reztsova goes on to make the call of action for further intervention by the UN in partnership with nations around the globe, threatening that if such intervention does not occur, the epidemic can spread and become a global problem. Artwork by Alina Popkova Volume 15 MEDICAL DIALOGUE REVIEW 5 Jean-Philippe From Drug-High to SugarHigh: Recovering Drug Addicts Turn to Sugar By Kayana Jean-Philippe “The idea of using sugar as a replacement drug is called a ‘transfer addiction.’ This is an issue for many recovering addicts, as they use sugar consumption to mask their cravings for drugs.” At 21 years old, Rodney Zimmers became heroin and cocaine-free and weighed 135 pounds. In the following three years, although he had remained sober, he gained a whopping 115 pounds, now weighing in at 250 pounds. Zimmers blamed his 115-pound weight gain to another drug--sugar. The idea of using sugar as a replacement drug is called a ‘transfer addiction.’ This is an issue for many recovering addicts, as they use sugar consumption to mask their cravings for drugs. Why sugar? Sugar releases opioids, a chemical that produces euphoria; and dopamine, a neurotransmitter that controls the brain’s reward and pleasure centers. According to Brooke Alpert, M.S., R.D., CDN, author or The Sugar Detox and founder of B Nutritious, a private nutrition counseling practice in New York City, sugar has been shown to be as addicting as many hardcore drugs. “It activates the rewards and pleasure center in your brain to make you feel good each time you eat it,” said Alpert. “Unfortunately that feeling only lasts a short time so as that feeling leaves, it causes a person to want to reach for more sugar. This results in a continuous cycle with sugar highs and lows.” Sugar has been proven to yield the same addictive effect as cocaine. A study conducted by Yale University researchers found that the sight of a sugary chocolate milkshake activated the same reward centers of the brain as cocaine among people with addictive eating 6 MEDICAL DIALOGUE REVIEW habits. The addicting nature of sugar contributes to weight gain because instead of the sugar being used as energy, when consumed in excess, sugar is stored in the liver and is later converted into fat. This causes an increased risk of obesity, which can then lead to chronic health concerns such as high blood pressure and cholesterol, metabolic syndrome, diabetes, heart disease and certain types of cancers. The problem arises when individuals are not educated on what food items contain sugar. This hard-to-avoid substance is found in nearly every food item except meat, oil and butter. Try looking through your pantry to find a food item with 0 grams of sugar--it may not be easy. The American Heart Association recommends that men limit their sugar intake to nine teaspoons of added sugar per day and six teaspoons for women. As a point of reference, a standard 12-ounce can of Coca Cola contains eight teaspoons of sugar. Excessive consumption of this sweet toxin can also be linked to cataracts, Alzheimer’s disease and early wrinkling of skin and weight gain, which may result in further decline of self-esteem. But like many recovering drug addicts, Zimmer was not taught the negative effects of using sugar as a ‘transfer addiction’ drug and he was unaware that he was doing so. In his testimonial on the Solutions Recovery Center website, he stated, “Once I got sober, I continued to eat all this awful stuff. I learned how to be sober, but I didn’t learn how to take care of all Fall 2014 Jean-Philippe of me. I didn’t know how to cook or grocery shop because I’d never done it. I didn’t learn any life skills or how to live like an adult.” For Zimmer, who is now the founder of Blueprints for Recovery, an all-male treatment facility in Arizona, the availability of sugary and fatty foods in the rehabilitation centers including vending machines, unknowingly contributing to his weight gain. He was not given the means to be able to choose nutritious foods and beverages, cook, and gain necessary skills to adopt a healthier lifestyle. In addition, there is a high likelihood that drug addicts were malnutritioned even before entering the facility. Those who have previously consumed excess beer, liquor or wine have high caloric intakes, leaving addicts with no appetite for eating nutritious meals. Oppositely, marijuana is shown to promote what is commonly known as the “munchies” due to its appetite-stimulating ingredient, tetrahydrocannanicol or THC. In a mice study conducted at the University of Bordeaux, researchers found that THC enhanced the smell and taste receptors and stimulated their appetite, which then increased their food intake. Another study published on the Journal of Biological Chemistry found that THC causes the release of ghrelin, a hunger-stimulating hormone, which increases cravings and food consumption. Alpert recognized the likelihood of malnourished people entering drug rehabilitation centers. She stated, “Many addicts have been living an unhealthy lifestyle, where nutrition and exercise were not the focus of their pre- vious life. A [Registered Dietitian] can help teach new lifestyle behaviors to help promote a new healthy life.” While some private elite rehabilitation facilities have dietitians on staff, many, especially public facilities do not take nutrition into consideration in the healing process. After suffering from a near-fatal drug and alcohol addiction, Christopher Kennedy Lawford, author of What Addicts Know: 10 Lessons from Recovery to Benefit Everyone, has maintained a life of sobriety for the past 24 years. In an interview with the New York Times, he stated, “You can’t get an addict into recovery until you deal with every aspect of their life. What you think, how you think, how you relate to people, what you put in your body, how you exercise – it’s all related. And we need to get smarter about it.” Nutrition education and awareness not only alleviates issues concerning ‘transfer addiction’ and weight gain, but also self-efficacy. The recovering drug addicts may have felt a lack of control over their drug usage, but they can have control over their food choices and how they treat their bodies. Dr. Gabor Maté, author of In The Realm of Hungry Ghosts: Close Encounters with Addiction wrote, “Methods for gaining selfknowledge and self-mastery through conscious awareness strengthen the mind’s capacity to act as its own impartial observer.” By educating recovering drug addicts on proper nutrition, eating habits and exercise, they will be empowered to make healthful decisions, live a healthier lifestyle and achieve self-sustainability. Volume 15 MEDICAL DIALOGUE REVIEW 7 Jean-Philippe REFERENCES "5 Stomach-Turning Side Effects of Sugar." Addiction Treatment Magazine. Addiction Treatment in Food Addiction, 28 Aug. 2013. Web. 12 Nov. 2014. Callahan, Daniel. "Healthy Habits - Solutions Center." Solutions Center Healthy Habits Comments. N.p., n.d. Web. 12 Nov. 2014. Ellin, Abby. "Off the Drugs, Onto the Cupcakes." Well Off the Drugs Onto the Cupcakes Comments. The New York Times, 15 Sept. 2014. Web. 12 Nov. 2014. E, Stice, Burger KS, and Yokum S. "Relative Ability of Fat and Sugar Tastes to Activate Reward, Gustatory, and Somato sensory Regions." National Center for Biotechnology Information. U.S. National Library of Medicine, 16 Oct. 2013. Web. 12 Nov. 2014. Go, A. S., D. Mozaffarian, V. L. Roger, E. J. Benjamin, J. D. Berry, W. B. Borden, D. M. Bravata, S. Dai, E. S. Ford, C. S. Fox, S. Franco, H. J. Fullerton, C. Gillespie, S. M. Hailpern, J. A. Heit, V. J. Howard, M. D. Huffman, B. M. Kissela, S. J. Kittner, D. T. Lackland, J. H. Lichtman, L. D. Lisabeth, D. Magid, G. M. Marcus, A. Marelli, D. B. Matchar, D. K. Mcguire, E. R. Mohler, C. S. Moy, M. E. Mussolino, G. Nichol, N. P. Paynter, P. J. Schreiner, P. D. Sorlie, J. Stein, T. N. Turan, S. S. Virani, N. D. Wong, D. Woo, and M. B. Turner. "Heart Disease and Stroke Statis tics--2013 Update: A Report From the American Heart Association." Circulation127.1 (2013): E6-E245. 2013. Web. 12 Nov. 2014. Klein, Sarah. "Is Sugar The New Tobacco?" The Huffington Post. TheHuffingtonPost.com, 05 Aug. 2014. Web. 12 Nov. 2014. Kola, Blerina, Erika Hubina, Sonia A. Tucci, Tim C. Kirkham, Edwin A. Garcia, Simon A. Hawley, D. Graham Hardie, Ashley B. Grossman, and Marta Korbonits. "Redirecting." Redirecting. The Journal of Biological Chemistry, n.d. Web. 12 Nov. 2014. M, Peet. "Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, May 2014. Web. 12 Nov. 2014. Stromberg, Joseph. "A Scientific Explanation of How Marijuana Causes the Munchies." Smithsonian. Smithsonian.com, 9 Feb. 2014. Web. 12 Nov. 2014. "Study Identifies Neural Activity Linked to Food Addiction." ScienceDaily. ScienceDaily, 5 Apr. 2011. Web. 12 Nov. 2014. "The Importance of Nutrition in Addiction Recovery - Promises Addiction Treatment | Alcohol Drug Rehab Malibu." Promises Addiction Treatment Alcohol Drug Rehab Malibu. N.p., 11 Dec. 2012. Web. 12 Nov. 2014. 8 MEDICAL DIALOGUE REVIEW Fall 2014 Tailor Oasis in the Desert By Diptesh Tailor “The farm facilitates long-lasting change, fostering beneficial trends which can sustainably mitigate and prevent disease disparity at its roots for generations to come.” The thought of deserts usually invokes images of endless, evanescent dunes of sand swirling to zephyrs swiveling amongst the scorching backdrop of the Saharan sun - not the dense urban foliage that is the steel skyscrapers and subways, bodegas and bustle, and people of colors and culture which typifies the metropolitan landscape. However, closer inspection reveals the very real presence of ‘deserts’ in the concrete jungle familiar as New York City. Manifesting in both rural and urban locales, food deserts are neighborhoods lacking ready access to healthy, fresh, and affordable foods.1,8 Although there are many variables that define a food desert, the Economic Research Service division of the United States Department of Agriculture reported in August 2012 that food deserts are associated with “smaller populations, higher rates of abandoned or vacant homes, and residents who have lower levels of education, lower incomes, and higher unemployment.”13 In addition to these variables, urban food deserts, such as the South Bronx in New York City, are correlated with greater levels of minority groups.13,14 Epidemiologists at the University of North Carolina reported in a 2002 publication that four times more supermarkets (as a measure of relative food accessibility) were located in predominantly white neighborhoods compared to predominantly black ones in a study spanning four states.14 and obesity.15 Unfortunately, this outcome is disproportionately felt by minority, immigrant, and other lower socioeconomic status (SES) inhabitants as they are already limited in their consumer awareness and choice capacities (e.g. health knowledge gaps, lack of automobile ownership, more limited purchasing power), aug- Due to the consistent lack of access to affordable, healthy food options, such as fresh fruits, vegetables, whole grains, lowfat milk, and wholesome snacks, food desert phenomenon contributes to poor diet, which can increase one’s risk of noncommunicable diseasNYC Supermarket Need Choropes such as cardiovasleth Map.26 cular disease, diabetes, obesity, and cancer.1,2,3,12 menting the burden of limited Empirical evidence support- supermarket options and high ing this intuitive trend was ob- food prices characteristic of tained in a 2014 publication in food deserts on the long-term the American Journal of Preventive health of our neighbors. 16,17 Medicine in which researchers found a statistically significant Indeed, medicine has positive correlation between discovered a number of addistance to stores / food prices vanced treatments to address Volume 15 MEDICAL DIALOGUE REVIEW 9 Tailor noncommunicable diseases. Among these include insulin therapy, angioplasty, weightloss surgery, and the development of targeted chemotherapy, which have all maintained revolutionary implications in the short-term addressing of chronic illnesses and their impending courses. However, a sense of superficiality promulgates into the discussion as these conventional approaches mitigate symptoms but fail to deracinate the vicious roots, the fundamental causes, which perpetuate chronic disease pervasiveness. This can be attributed to the fact that modern medicine intervenes with proximal risk factors for disease, such as abnormal blood glucose levels, hypertension, unbalanced cholesterol profiles, and excess adiposity, instead of addressing the distal risk factors for chronic illness. As contended by researchers Jo Link and Bruce Phelan in their landmark publication “Social Conditions as Fundamental Causes of Disease,” the fundamental, root causes of disease disparity are implicated with distal risk factors, such as low socioeconomic status and limited purchasing power, lack of education and awareness, poor community development, and poor social networks, all of which influence multiple disease outcomes.7 These distal, rather than proximal, risk factors are the subtle yet systemic and persistent causes of disease disparity.7 Treating proximal risk factors does not ensure true long-term 10 solution nor prevention as distal risk factors would continue to inhibit access to resources which could allow for disease intervention, retaining diseases within the populations. More- low SES populations who may find such expenditures overwhelming.2,5,19 Moreover, the CDC has reported that medical costs linked to obesity, diagnosed diabetes, cardiovascular La Finca del Sur.27 over, there are tremendous social costs associated with merely treating manifested cases and their immediate, proximal causes. According to a 2010 report by the Johns Hopkins Bloomberg School of Public Health in conjunction with the Robert Wood Johnson Foundation, healthcare spending for an individual with one chronic disease is three times greater than a that of a healthy individual.18 With chronic diseases accounting for 75% of health expenditures, the cost per affected American totals nearly $7,900.20,21 These rising healthcare costs can be significant burdens, especially since chronic disease disproportionately affects minorities and other MEDICAL DIALOGUE REVIEW Fall 2014 disease, and cancer amounted to, respectively, $147 billion (2008), $245 billion (2012), $315.4 billion (2010), and $157 billion (2010).22-25 There are also serious human costs associated with noncommunicable diseases, which cause 70% of deaths in the United States. Chronic illnesses can be seriously disabling and can sharply decrease one’s autonomy and quality of life.20,21 Thus, this underwrites the need for a more fundamental approach to preventing chronic diseases and reducing their incidence and prevalence. Proximal risk factors are analogous to the leaves of a weed plant while the distal factors are associated with the roots. Intervening by removing Tailor the leaves (proximal factors) would be a temporary intervention; only razing the roots (distal factors) would provide long-term solution. Increased knowledge, enhanced community infrastructure, and mutual social networks would augment health through multiple modalities, such as by improving the populace’s dietary options and consumption, preventing noncommunicable disease incidence within food deserts.1,2,3,12 Although noncommunicable diseases can be immediately addressed by medicine, it would be a mirage to view such intervention as all-encompassing. It is the above strategies which would provide long-term treatment and prevention of multiple disease outcomes. However, distal risk factors cannot be addressed as simply as proximal counterparts; more pervasive roots require more pervasive involvement. Therefore, they require the active involvement of the entities affected - individual & communal. It requires the uplifting of vicious roots, and ingraining of nurturing, curative ones. What better way to translate this metaphorical conceptualization into a physical reality than through the art of farming? Indeed it was this very thirst that led to the creation of an oasis in the stagnant food desert than is the South Bronx.8 In 2009, under the leadership of a group of women of color, a rotting 2.5 acre lot located between a highway ramp and Metro- North train tracks in the South Bronx was transformed into New York City’s first womenrun, non-profit community farm named La Finca del Sur.9 Today, La Finca del Sur is a beautiful urban farm “committed to building healthy neighborhoods through economic empowerment, increased nutritional awareness, training and education, and advocating for social and political equality and food justice in low-income communities.”9 Indeed, this farm is not merely an oasis for its evident and significant impact on the urban food desert phenomenon, but more fully because of its impact in addressing distal risk factors fundamental causes of disease - which cause disease disparity in minority and low SES communities. Among the distal risk factors addressed are the lower purchasing power (directly proportional to SES) and educational gaps amongst the population, limiting their access to resources such as healthy foods, which could curb more proximate risk factors (unhealthy body weight, high blood pressure, high blood sugar levels), and fullblown chronic disease.7 La Finca del Sur addresses this limited access by allowing community members and neighbors to grow and harvest their own foods and sell them at local markets, further augmenting the accessibility of affordable, fresh, healthy produce for the neighbors and their community.9,10 The farm also Volume 15 educates school groups and neighbors on proper diet and nutrition to amplify its impact on these food desert regions and increase consumer awareness and discretion.11 Through these strategies, La Finca del Sur addresses the distal risk factors for disease, preventing the development of proximal risk factors and, ultimately, illness, such as obesity, diabetes, and cardiovascular diseases. Other distal risk factors addressed include poorly developed communities and social networks. With its name translating to “Farm of the South” in Spanish, La Finca del Sur serves as an epicenter of cultural heritage for many of the immigrant volunteers, supporters, and growers, nostalgic of the crucial role of agriculture in Hispanic countries. Through poetry, music, film festival, open mic, storytelling and various other cultural programmings, La Finca del Sur serves as a commune for South Bronx and neighboring communities.11 The lack of meaningful, positive, bidirectional relationships, especially for immigrants posed with cultural and linguistic barriers, can amplify unhealthy and uninformed decision and behaviors such as sedentary lifestyle, poor dietary choices and mental health issues.7 However, through the presence of a community center like La Finca del Sur, members can form positive, lasting relationships in an open, friendly, and serene environment. These social networks in turn allow MEDICAL DIALOGUE REVIEW 11 Tailor for disease prevention both directly (e.g. promoting active, outgoing lifestyle & developing supportive social relationships) and indirectly (e.g. fostering advancement and progress, such as via community initiatives and projects) to enable communities to adapt, grow, and thrive in a food desert oasis. La Finca del Sur addresses distal risk factors for disease such as low socioeco- nomic status and limited purchasing power, lack of education and awareness, poor community development, and poor social networks through robust farming and harvesting opportunities, communal education and awareness programmings, and community-building cultural events. La Finca del Sur exemplifies a self-sufficient neighborhood movement which addresses fundamental causes of disease disparity, as experienced by populaces in food deserts. The farm facilitates long-lasting change, fostering beneficial trends which can sustainably mitigate and prevent disease disparity at its roots for generations to come. Indeed, the sprouting of cultivation, culture and community has allowed the people of the South Bronx to transfigure a desert into an oasis, planting inspiration once thought only a mirage. REFERENCES 1. Agricultural Marketing Service (n.d.). Food Desserts. United States Department of Agriculture. Retrieved from https://apps. ams.usda.gov/fooddeserts/foodDeserts.aspx 2. CDC (2014, May 9). Chronic Diseases and Health Promotion. Centers for Disease Control and Prevention. Retrieved from http://www.cdc.gov/chronicdisease/overview/index.htm 3. Singh, M. (2014). Mood, food, and obesity. Frontiers in Psychology, Vol. 5: 925, pp. 1 – 20 4. Drewnowski, A., & Specter, SE. (2004). Poverty and obesity: the role of energy density and energy costs. American Society for Clinical Nutrition, Vol. 79: 1, pp. 6-16. Retrieved from http://ajcn.nutrition.org/content/79/1/6.long 5. CDC (2013, Nov 22). CDC Health Disparities and Inequalities Report - United States, 2013. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report, Vol 62: 3. Retrieved from http://www.cdc.gov/mmwr/pdf/ other/su6203.pdf 6. WHO (2011, April). Global status report on noncommunicable diseases 2010. World Health Organization. Retrieved from http://www.who.int/nmh/publications/ncd_report2010/en/ 7. Link, B.G., & Phelan, J. (1995). Social Conditions as Fundamental Causes of Disease. Journal of Health and Social Behavior, Vol. 35, pp. 80-94. 8. Mansour, I. (2013, Aug 15). How access to fresh food divides American. FortuneMagazine. Retrieved from http://fortune. com/2013/08/15/how-access-to-fresh-food-divides-americans/ 9. La Finca del Sur - South Bronx Farmers: About La Finca del Sur. (n.d.). Retrieved from http://bronxfarmers.blogspot. com/p/about-la-finca-del-sur.html 10. News12 The Bronx. (2014, April 4). La Finca del Sur to bring new Bronx farmer’s market to Alexander Avenue. News12 The Bronx. Retrieved from http://bronx.news12.com/news/la-finca-del-sur-to-bring-new-bronx-farmer-s-mar ket-to-alexander-avenue-1.7610105 11. Gonzalez, D. (2011, October 7). At Harvest Time, Bronx Farm Works Through a Tough Patch. New York Times: City Room. Retrieved from http://cityroom.blogs.nytimes.com/2011/10/07/at-harvest-time-bronx-farm-works- through-a-tough-patch/ 12 MEDICAL DIALOGUE REVIEW Fall 2014 Tailor 12. Walsh, B. (2008, June 12). It’s Not Just Genetics. Time. Retrieved from http://www.time.com/time/magazine/ar ticle/0,9171,1813984,00.html 13. Dutko, Paula, Michele Ver Ploeg, and Tracey Farrigan. Characteristics and Influential Factors of Food Deserts, ERR- 140, U.S. Department of Agriculture, Economic Research Service, August 2012. 14. Morland K, Wing S, Diez Roux A, Poole C. (2002). Neighborhood characteristics associated with the location of food stores and food service places. American Journal of Preventive Medicine, Vol 22, pp.23-9. 15. Ghosh-Dastidar B, Cohen D, Hunter G, Zenk SN, Huang C, Beckman R, Dubowitz. (2014). Distance to store, food prices, and obesity in urban food deserts. American Journal of Preventive Medicine, Vol47, pp.587-95 16. Ward BW, Schiller JS. Prevalence of Multiple Chronic Conditions Among US Adults: Estimates From the Nation al Health Interview Survey, 2010. Prev Chronic Dis 2013;10:120203. DOI: http://dx.doi.org/10.5888/ pcd10.120203 17. Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA. 2012;307:491-7. 18. Robert Wood Johnson Foundation. Chronic Care: Making the Case for Ongoing Care. Princeton, NJ: Robert Wood Johnson Foundation; 2010:16. http://www.rwjf.org/content/dam/farm/reports/reports/2010/rwjf54583.Accessed November 11, 2014. 19. Crook ED, Peters M. Health disparities in chronic diseases: where the money is. Am J Med Sci. 2008;335(4):266-70 20. Centers for Disease Control and Prevention. Chronic Disease Overview: Costs of Chronic Disease. Centers for Disease Control and Prevention Web site. Available at http://www.cdc.gov/nccdphp/overview.htm. Accessed Novem ber 11, 2014. 21. Triple Solution for a Healthier America (2014). The Impact of Chronic Diseases on Healthcare. GlaxoSmithKline. Re trieved from http://www.forahealthieramerica.com/ds/impact-of-chronic-disease.html 22. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer- and service- specific estimates. Health Affairs. 2009;28(5):w822-w831. http://content.healthaffairs.org/content/28/5/w822. full.html. Accessed November 11, 2014. 23. American Diabetes Association. The Cost of Diabetes Web site. http://www.diabetes.org/advocate/resources/cost-of- diabetes.html. Accessed November 11, 2014. 24. American Heart Association. Heart Disease and Stroke Statistics—2014 Update. AHA Statistical Update Web site. http://circ.ahajournals.org/content/early/2013/12/18/01.cir.0000441139.02102.80.full.pdf . Accessed Novem ber 11, 2014. 25. National Cancer Institute. Cancer Prevalence and Cost of Care Projections Web site. http://costprojections.cancer. gov/. Accessed November 11, 2014. 26. New York City Department of Health & Mental Hygiene [Publisher]. (2008). Supermarket Need [Choropleth Map], Retrieved Nov 14, 2014, from: http://foodmapper.wordpress.com/2008/05/13/nyc-food-deserts-talk-and- action/ 27. Citizens Committee for New York City [Publisher]. (n.d.). [Volunteers tending to garden beds]. Retrieved Nov 14, 2014, from: http://www.citizensnyc.org/grantee/la-finca-del-sursouth-bronx-farmers Volume 15 MEDICAL DIALOGUE REVIEW 13 Schneider The Threat of Misdiagnoses: Are There Forms of Dementia That Could Be So Similar That They Are Nearly Indistinguishable? By Julia Schneider “With the evolution of case studies showing ways to differentiate a reversible form of dementia from an irreversible type using radiographic findings, neurologists are able to see the differences. Since AD is more widely recognized all across the world compared to NPH, doctors jump to the former to make a clinical diagnosis.” There are many forms of dementia but Normal Pressure Hydrocephalus (NPH) and Alzheimer’s disease (AD) are the two types that are the most similar. Their overlapping symptoms engenders a hindrance for physicians to make a definitive diagnosis. Even though AD is more prevalent and widely known, there has been a plethora of misdiagnoses. It turns out that what physicians thought to have been AD was, in fact, NPH. Though they are very close on the pedigree chart of dementias -- practically siblings -- NPH and AD have been differentiated in a number of ways that have contributed to changing a patient’s life forever. AD is the most widespread cause of dementia with about 5.3 million Americans diagnosed per year.1 Despite how common AD is, there are no treatments to reverse this disease. Cholinesterase inhibitors are used to alleviate symptoms such as memory loss and cognitive deterioration, and despite attempts to halt the progression of AD, a patient usually has 4 to 6 years, on average, to live.1 Although AD is an irreversible form of dementia, NPH is reversible. It is characterized by a triad of symptoms: gait disturbance, cognitive impairment, and urinary incontinence.2 NPH’s prevalence is not as high as AD’s -- being responsible only for a meager 5% of dementia cases. However, the correct numbers are not known exactly since the range 14 MEDICAL DIALOGUE REVIEW of NPH cases is anywhere between 2 to 20 million cases per year.2 Furthermore, NPH’s etiology is interesting because there are two types: idiopathic and secondary which can be caused by a subarachnoid hemorrhage, aneurysms, or any type of brain traumas.2 Despite the technical differences between AD and NPH, their relationship tends to be overlooked. It is common for physicians to diagnose an elderly person—sixtyfive years or older—with AD, but NPH seems to be forgotten about. In a way, it is a hidden form of dementia. Unless NPH’s symptoms are comprehensively analyzed, a patient may be misdiagnosed with AD for the rest of his life. In order to examine the similarity and overlap between AD and NPH, a case study was conducted using 761 brains that were autopsied.3 Based on neuropathologic evidence, 563 of these cases were found to have had dementia and of those 563, almost half -- 56% -were diagnosed with AD. However, of the 563 cases, only nine patients had a clinical diagnosis of NPH. Eight of these patients were found to have met the National Institute on Aging and the Reagan Institute criteria of AD.3 These results suggest that AD pathology is present in NPH cases which shows how challenging it is to distinguish the two forms of dementia. Furthermore, AD and NPH are even more difficult to differentiate on a molecular Fall 2014 Schneider level. In the brain, the choroid plexus is the main tissue that secretes cerebrospinal fluid (CSF), which continuously circulates in order to get rid of noxious metabolites. If CSF circulation fails to serve its role, then amyloid-beta peotide and microtubuluar associated protein tao (MAP- tao) accumulate, and this failure and associated accumulation seems to occurs in AD and NPH patients.4 This in turn may result in the overproduction of CSF in the brain which causes the excess fluid to enter the ventricles, or the spaces in the brain. Once this occurs, ventricles become enlarged. Using an MRI would show enlarged ventricles for both AD and NPH patients; this overlap shows another example of a similarity between AD and NPH that makes diagnosing and differentiating between the two difficult and uncertain. Neurologists have difficulty differentially diagnosing NPH and AD because NPH’s triad of symptoms are common occurrences in the elderly. Studies have shown that gait disturbance occurs in 20% of people over the age of 75; cognitive decline occurs in about 4.5 million people over the age of 65; and urinary incontinence reportedly occurs in 38% of women and in 17% of men over the age of 60.5 Also, ventricle size tends to increase with age.5 Thus, NPH seems to have commonplace symptoms that do not seem anomalous. However it is the combination of the symptoms acting together that becomes an eye-opener for neurologists since this triad of “Wet, Wacky, Wobbly” is the hallmark of NPH. Despite the triad of symptoms standing out in a patient thought to have NPH, there are detailed ways to differentiate NPH from AD radiographically. Usually radiographic findings show ventriculomegaly and normal CSF pressures in NPH patients.2 Since CSF fluid flows into the ventricles of the brain, it would be expected for CSF pressure to change as well as intracranial pressure, but this covert type of dementia is so sneaky that it doesn’t present with any significant change in pressure. Typically, an MRI is used to pinpoint NPH, but a case study has proven successful for the use of Positron Emission Tomography (PET) to differentiate NPH from AD using [18 F]Fluorodeoxyglucose (FDG).6 This study included 3 NPH patients, 17 AD patients, and 7 elderly controls. NPH showed lower cortical rates of FDG use than AD. Between the AD and NPH categories, the former indicated bilateral temporoparietal hypometabolism, yet the latter showed an even distribution of cortical activity which showed a global lack of glucose utilization.6 The PET scan is much more useful in ruling out a patient who may seem to have NPH but in actuality has AD. Hypometabolism in the temporoparietal junction is a notable marker for identifying AD. On an MRI, AD would be noted to have a sulcal enlargement, unlike the focally dilated sulci over a convex or medial surface of a hemisphere, which would indicate NPH. Also, a higher Sylvian CSF volume would further corroborate NPH.5 Radiographic findings continue to distinguish AD from NPH since they both exhibit the enlargement of ventricles. Specifically, MRI’s have shown that AD patients usually present with atrophy mostly in the CA1 region of the hippocampus in conjunction with dilation of the perihippocampal fissures (PHFs).7 On the other hand, NPH patients do not present with enlarged PHFs, especially after being surgically treated with a Ventriculoperotineal shunt (VP), a catheter that changes the route of CSF flow. In this case, excess CSF goes into the peritoneal cavity. It is specifically important to examine PHFs in post-VP shunt NPH patients to see if the shunt does its job. If it doesn’t, then it would be clear that the patient doesn’t have NPH and PHFs may have been enlarged; this suggests AD since these patients do not respond to shunts and are not surgically treatable.7 In order to avoid surgically placing a shunt, two common methods are used: the first being a Lumbar Tap test which consists of a lumbar puncture removing 30-50 mL of CSF.2 The patient is observed about an hour afterwards to see if his gait disturbance and cognitive function improves. A similar procedure, called a Lumbar Drainage, encompasses the continuous drainage of CSF at 5 to 10 mL per hour with the drainage system attached to a patient.2 He is then observed for two to three days to see if his symptoms improve. If each procedure shows improvement, with the Lumbar Drainage being more reliable due to its lengthy and thorough examination, then Volume 15 MEDICAL DIALOGUE REVIEW 15 Schneider a shunt would most likely work as well. NPH patients have had success with shunts. Although it is mercurial to predict if a shunt will malfunction, a case study, that followed fifty-five patients three years after the surgical placement of a VP shunt; indicated that fifty-three percent of those patients did need revision.2 Thus a shunt, as of now, is the most ideal solution for patients with NPH. Fortunately, a shunt works well, which is why NPH is a reversible type of dementia; the symptoms subside indefinitely, until the shunt must be replaced. AD and NPH are two similar forms of dementia. They both show enlarged ventricles and cognitive decline. However, there has been much concern with regards to overlooking NPH symptoms and nuances in the presence of AD competitors. With the evolution of case studies showing ways to differentiate a reversible form of dementia from an irreversible type using ra- diographic findings, neurologists are able to see the differences. Since AD is more widely recognized all across the world compared to NPH, doctors jump to the former to make a clinical diagnosis. Consequently, not only is this misdiagnosis detrimentally covert, but this deleterious mistake hinders a patient from improving his health. Fortunately, more differences are being discovered with an augmentation in case studies so that NPH will be more widely recognized. Consider a rudimentary example: You go to a restaurant and order a salad that has green vegetables, but unfortunately, you are allergic to avocados. You make sure that the salad is bereft of any. In fact your allergic reaction is so extreme that if you do eat an avocado, it will prove fatal. If you were to have not seen that an avocado inadvertently ended up in your salad you would die. This is like not being able to recognize NPH though it would makes things infinitely easier. REFERENCES 1. Russell, T, and S Richards. "Alzheimer's Disease." (2013): CINAHL Plus with Full Text. Web. 17 Nov. 2013. 2. Siraj, S. "An Overview Of Normal Pressure Hydrocephalus And Its Importance: How Much Do We Really Know?." Journal Of The American Medical Directors Association 12.1 (2011): 19-21. Scopus®. Web. 17 Nov. 2013. 3. Cabral, Danielle, et al. "Frequency Of Alzheimer's Disease Pathology At Autopsy In Patients With Clinical Normal Pres sure Hydrocephalus." Alzheimer's & Dementia: The Journal Of The Alzheimer's Association 7.5 (2011): 509-513. MEDLINE. Web. 17 Nov. 2013. 4. Silverberg, Gerald D, et al. "Alzheimer's Disease, Normal-Pressure Hydrocephalus, And Senescent Changes In CSF Circulatory Physiology: A Hypothesis." Lancet Neurology 2.8 (2003): 506-511. MEDLINE. Web. 17 Nov. 2013. 5. Graff-Radford, Neill R. "Normal Pressure Hydrocephalus." Neurologic Clinics 25.3 (2007): 809. MEDLINE. Web. 17 Nov. 2013. 6. Jagust, W J, R P Friedland, and T F Budinger. "Positron Emission Tomography With [18F]Fluorodeoxyglucose Differ entiates Normal Pressure Hydrocephalus From Alzheimer-Type Dementia." Journal Of Neurology, Neurosurgery & Psychiatry 48.11 (1985): 1091. Publisher Provided Full Text Searching File. Web. 17 Nov. 2013. 7. Holodny, A.I. ( 1,3,5 ), et al. "MR Differential Diagnosis Of Normal-Pressure Hydrocephalus And Alzheimer Disease: Significance Of Perihippocampal Fissures." American Journal Of Neuroradiology 19.5 (1998): 813-819. Scopus®. Web. 17 Nov. 2013. 16 MEDICAL DIALOGUE REVIEW Fall 2014 D’Alessio Has the Medical Field Acknowledged Artists Make Better Doctors? By Nicole Marie D’Alessio “There has been a rise in the number of medical schools which acknowledge the edge artistic applicants might have over those who do not have a background in the arts.” The medical community is beginning to believe artists make better doctors. There has been a rise in the number of medical schools which acknowledge the edge artistic applicants might have over those who do not have a background in the arts. “Being accepted into medical school used to mean selecting time-honored disciplines such as biology or chemistry, taking a more traditional route as a “pre-med” to gain entrance…to be the most prepared for the onslaught of biochemistry, pharmacology, anatomy and science-related material that has traditionally permeated the first several years of medical school…” says Robert Glatter, MD for Forbes magazine. As the selection process has become increasingly competitive, schools are looking for students who not only have a high GPA. They are looking for applicants who have an edge. For many of schools, one of the best advantages is a background in the arts and related creative experiences. Prominent medical institutions such as Columbia, Yale, and Brown have implemented programs which teach students medicine while explaining the importance of an artistic mindset. For example, Columbia’s program in Narrative Medicine, describes their mission to be that it “…fortifies clinical practice with the narrative competence to recognize, absorb, metabolize, interpret, and be moved by the stories of illness.” At The Irvine College of Medicine, a program has been implemented with a mission stating: “The Program in Medical Humanities & Arts at the University of California, Irvine, College of Medicine has been in existence for five years. The program was implemented to enhance aspects of professionalism including empathy, altruism, compassion, and caring toward patients, as well as to hone clinical communication and observational skills.” --“Can Poetry Make Better Doctors? Teaching the Humanities and Arts to Medical Students and Residents at the University of California, Irvine, College of Medicine.” Brown University holds an annual lecture series entitled “Creative Medicine Lecture Series.” Collaboration between the fields of medicine and art emerged as the focal point of the lecture by guest speaker, Alexa Miller, who develops alliances between medical schools and art museums through her company, Arts Practica. “Realizing the benefits of the arts in medical education emerged as a school of thought around 15 years ago,” Miller said. Initial research at Yale revealed that medical students enrolled in a modest art education program demonstrated greatly increased sensitivity to visual information. Miller’s research at Harvard heralded similar results – medical students who took part in a 10-session museum observation workshop increased their amount of written clinical observation by 38 percent,” writes Phoebe Draper, senior staff writer for The Brown Daily Herald. Rutgers University has introduced an Volume 15 MEDICAL DIALOGUE REVIEW 17 D’Alessio interdisciplinary humanities course designed to graduate better doctors last year. “We need to address the educational foundation of health care providers by making them rethink how they view the human body,” says Bachmann, interim chair of the Department of Obstetrics, Gynecology and Reproductive Sciences and the director of the Women’s Health Institute at Rutgers Robert Wood Johnson Medical School. The course, which combines art history, medical courses, and narrative writing, will be offered for the first time to Robert Wood Johnson medical students the spring semester of 2015. They cite their ultimate goal as to “Prepare better doctors by making them more observant diagnosticians and more effective communicators.” Some of the cited reasons supporting artistic applications in doctoral training include the theory that artists may be more empathetic or humane; and since the study of medicine is largely a visual learning experience, when it comes to understanding the human body and its intricacies, artists may have an element that others do not. Or, as Pheobe Draper for The Brown Daily Herald describes, the idea that the longer you look, the more you see. The practice of medicine benefits from physicians who observe, think counter-intuitively, and think creatively. At tradition-minded Harvard, faculty members were fairly skeptical when proposed with the idea of using art in the curriculum. Doctor Joel Katz proposed his class of Harvard Medical School students meet regularly at the Museum of Fine Arts, “especially since the firstand second-year students who enroll are already overwhelmed with work.” But Katz’s belief that physicians can improve their diagnostic skills by observing art was bolstered…when he and his colleagues published a study in the Journal of General Internal Medicine showing that after completing the class, students’ ability to make accurate observations increased 38 percent.” Previous experience with critical thinking in the sciences has been a common theme for success in curing others. Characteristics including strong talents for imagery, imagination, thinking “outside the box” and compassion towards humanity may actually prove to be just as valuable as a scientific mindset in the eyes of some experts. REFERENCES "Columbia University Medical Center | Program in Narrative Medicine."Program in Narrative Medicine. N.p., n.d. Web. 15 Sept. 2014. Department of Family Medicine, Program in Medical Humanities & Arts, Orange, CA 92868-3298, USA. [email protected]. "Can Poetry Make Better Doctors? Teaching the Humanities and Arts to Medical Students and Residents at the University of California, Irvine, College of Medicine." National Center for Biotechnology Information. U.S. National Library of Medicine, 10 Oct. 2003. Web. 19 Sept. 2014. Draper, Pheobe. "Lecture Stresses Art's Impact on Medicine." Brown Daily Herald. Brown University, 21 Sept. 2013. Web. 17 Sept. 2014. Gladdix, Robert, MD. "Can Studying Art Help Medical Students Become Better Doctors?" Forbes. Forbes Magazine, 20 Oct. 2013. Web. 16 Sept. 2014. Kowalczyk, Liz. "Monet? Gauguin? Using Art to Make Better Doctors."Boston.com. The New York Times, 20 July 2008. Web. 19 Sept. 2014. Pugh, Rachel. "Art and Literature Could Make Doctors More Competent and Humane." The Guardian. The Guardian, 19 Nov. 2013. Web. 16 Sept. 2014. Verbinas, Patti. "Training the Doctor's Eye Through the Study of Art." Rutgers, A World of Discovery. Rutgers University of New Jersey, 27 Oct. 2013. Web. 19 Sept. 2014. 18 MEDICAL DIALOGUE REVIEW Fall 2014 Rahman Stem Cell Therapy – A Novel Treatment for Duchenne’s Muscular Dystrophy By Syed Rahman “The new discovery could lead to new therapies for degenerative diseases like muscular dystrophy, which is characterized by progressive weakening of skeletal muscle tissue.” Duchenne Muscular Dystrophy (DMD) is a recessive disease that results from a mutation in the dystrophin gene. This gene, located on the X chromosome, codes for the protein dystrophin- an important component in muscle tissue. People with this mutation suffer from muscle degeneration and death. DMD currently affects 1 in 3600 males in the United States, with most of the affected individuals receiving rigorous corticosteroid treatments (Goldring et al., 2002). However, this treatment is not curative; DMD ultimately leads to death as a result of complications arising from lack of muscular function, such as the impairment of cardiovascular function due to weakened cardiac tissue (Galli et al., 2000). This concept that multipotent stem cells can be derived from bone marrow had led the notion of actually using them as a potential treatment option to replaced damaged muscle tissue in individuals suffering from DMD. One of the areas of focus has been the usage of these so-called muscle stem cells to replace diseased tissue with cells that are capable of renewal and maintenance characteristic of normal muscle cells. This has led to a great deal of research looking into the efficacy of using stem cell therapies in order to regenerate functional muscle tissue, much of which will be explored in this article. The idea of using muscle stem cells as a potential treatment for patients suffering from DMD could lead to research for other muscular degenerative diseases. scription factors - or proteins that bind to gene regulatory elements in order to regulate gene expression., researchers can specify cell type, inducing stem cells to enter particular lineages. In its application as a treatment for DMD, this technique would replace the muscle For the past decade, researchers have attempted to find apFigure 1. Skeletal Muscle Cells. plications for stem cells in regenerating certain cell types. As cells cells patients have lost by using that have not yet entered the stem cells to create functional differentiation process, stem muscle cells. New findings cells have the potential to be- concerning muscular stem cells come one of a multitude of dif- have increased the potential efferent cell types. By controlling ficacy of this technique (Goldthe expression of certain tran- ring et al., 2002). Volume 15 MEDICAL DIALOGUE REVIEW 19 Rahman A 1999 study by Jackson and Goodell found that adult neural stem cells (ANSCs) derived from the central nervous system can differentiate into myogenic cells in the absence of certain inhibitory signals from the cellular environment (Jackson and Goodell, 1999). Jackson and Goodell found that certain signals from embryonic stem cells, can induce the expression of myogenic markers in ANSCs, ultimately resulting in their differentiation into skeletal muscle cells. These new cells can potentially be implanted into patients lacking functional muscle cells (Figure 1). The discovery that ANSCs that are clustered together stay undifferentiated has lead scientists to postulate that signaling between ANSCs may inhibit myogenic signaling and myogenic differentiation. Additionally, culturing ANSCs with undifferentiated embryoid bodies has the potential to produce a diverse array of skeletally derived myogenic cells in-vivo and in-vitro. The myogenic cells produced from ANSCs were shown to retain the ability to differentiate into a wide variety of muscle cells, thus giving these ANSC derived myogenic cells the capacity to replace a wide variety of muscle cells in-vivo (Jackson and Goodell, 1999). Later studies have come to similar conclusions (Galli et al., 2002). In February of 2014, Natalia Sych conducted a study 20 with a large group of DMD patients suffering from a wide range of muscle pains such as weakness in the wrists, lower extremities, pelvic muscles, and chest. Patients received a suspension containing preserved fetal stem cells expressing myogenic markers. The control group patients underwent the normal treatment for DMD, which included a rigorous treatment of corticosteroids and muscle supporting medications such as L-carnitine, vitamins, and amino acids. Based on an arbitrary point scale, patients who received fetal stem cells therapy (FSCT) scored on average 5 points higher in terms of physical functioning, mental health, vitality, and emotional health when compared to the control group of patients throughout the course of 6 months. The FSCT patients also had increased levels in all these categories in 12 months as opposed to 6 months, demonstrating the long lasting effects of FSCT. It was previously known that a lack of dystrophin (characteristic of DMD) leads to increased CPK (creatine phosphokinase) penetration from the damaged muscle cells into the bloodstream, thus making CPK levels a good indicator of DMD. However, in this study, the FSCT patients showed a much lower level of CPK in the blood stream when compared to the control group, results that persisted as long as 12 months after the stem cell treatment took place. This demonstrates the potential long-term benefits that FSCT can offer to patients suffering MEDICAL DIALOGUE REVIEW Fall 2014 from DMD (Sych et al., 2014). The next problem is finding a way to culture the large numbers of stem cells necessary to give rise to muscle cells. A study by Rudnicki found that mouse muscles contain two types of precursors to skeletal muscle cells, or satellite cells (Swaminithan, 2007). 90% of the cells are preprogrammed to become muscle tissue while another 10% are undifferentiated (Swaminithan, 2007). The researchers in this study found that the gene Myf5 codes for a protein that functions as the “first genetic entry point into the muscle lineage” (Swaminithan, 2007). When stem cells had a functional and positive Myf5 gene inserted, they went on to become muscle cells. Thus, the activation of Myf5 can increase the production of muscle cells from stem cells (Swaminithan, 2007). Another study by Akizawa in 2013 showed that the up-regulation of MYOD1 transcription factors in mesenchymal stem cells leads to the activation of Myf5, which in turn leads to increased levels of dystrophin. This shows that up-regulation of MYOD1 can increase the production of muscle cells specifically capable of combating the decreased levels of dystrophin characteristic of DMD (Akizawa et al, 2013). Overall, stem cell therapy can have long term benefits for patients suffering from DMD. However, simply giving functional muscle cells to DMD patients isn’t enough Rahman to ensure survival. Professor Simone Spuler of the Experimental and Clinical Research Center (ECRC) argues that a genetic muscle disease such as DMD requires treatment with a healthy gene that repairs or masks the defective gene. This is essentially the basis for gene therapy (Bactler, 2014). While stem cell therapy shows potential as a treatment for DMD, the complications of immune rejection of the muscle cells have prevented it from its widespread uptake. Further re- search must focus on combining the stem cells with a healthy gene that can replace the defective DMD gene and create muscle cells that can evade the risks associated with immune rejection. REFERENCES Akizawa, Y., et al. "Enhanced expression of myogenic differentiation factors and skeletal muscle proteins in human am nion-derived cells via the forced expression of MYOD1." Brain Development 35.4 (2013): 349-55. Print. Bachtler, Barbara. "New Research Method Opens Door to Therapy with Human Muscle Stem Cells Scientists and Physi cians in Germany Collaborate to Develop Promising Method." MDC. N.p., 27 Aug. 2014. Web. 18 Oct. 2014. <https://www.mdc-berlin.de/43612981/en/news/2014/ 20140827 new_research_method_opens_door_to_ therapy_>. Clarke DL, Johansson CB, Wilbertz J, et al. Generalised poten- tial of adult neural stem cells. Science 2000; 288: 1660–1663. Galli R, Borello U, Gritti A, et al. Skeletal muscle potential of human and mouse neuronal stem cells. Nature Neurosci 2000; 3: 986–991. Goldring, Kirstin, Terence Partridge, and Diana Watt. "Muscle stem cells." Journal of Pathology 197.1 (2002): 457-67. Print. Jackson, K. A, Mi, T. & Goodell, M. A. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc. Natl. Acad. Sci. USA 96, 14482–14486 (1999) Swaminithan, Nikhil. "Newfound Stem Cells May Lead to Regenerative Therapies for Damaged Muscles." Scientific Ameri can. N.p., 31 May 2007. Web. 18 Oct. 2014. Sych, N., et al. "Efficacy of fetal stem cells in Duchenne muscular dystrophy therapy." Journal of Neurorestoratology 2014.2 (2014): 37-46. Print. Volume 15 MEDICAL DIALOGUE REVIEW 21 Torres Coconut Oil Unmasked By Chris Torres “This confusion and skepticism in the scientific community has led neither the American Heart Association or the U.S. government’s Dietary Guidelines to suggest that coconut oil is any better or preferable over other saturated fats over other saturated fats.” Coconut oil is not a recently discovered health source. Coconut oil is an edible oil extracted from the kernels of extracted coconuts harvested from the coconut palm trees. The uses for coconut oil existed for as long as 4000 years ago in Sanskrit texts. Yet, even One theory proposed by Ancel Keys states that a major intake of saturated fats can lead to high cholesterol and heart failure. However, these findings may be flawed since, they hydrogenated coconut oil when they fed it to animal subjects. Hydrogenation of the unsaturated fatty acids converts it to saturated fatty acids which leads to more production than the original 92% saturated fat makeup; it also leads to less absorption of essential amino acids. With a more saturated coconut oil testing, animals would intake the transformed coconut oil and have different results than those who would intake normal amounts of saturated fats in coconut oil. To answer this question whether coconut oil is a healthy or an unhealthy fat, one must investigate the pathway for absorption of cholesterol. When humans consume fats, our body breaks it down Figure 1: Mortality Rate from Heart Disease. into cholesterol. However, cholesterol cannot be readily absorbed in the bloodwith knowledge about this oil in history, the oil’s stream without the help of carrier proteins. Two documented uses throughout history has been different types of carrier proteins exist, called less known. There has been much modern de- low-density lipoprotein(LDL) and high-density bate about its true health benefits. Coconut oil lipoprotein(HDL). LDL proteins are known as contains a mixture of short and medium chain the “bad” kind because they cause the formation fatty acids primarily lauric acid (44%) and my- of plaque inside the arteries and HDL proteins ristic acid (16.8%) (Zelman). The oil’s high satu- are the “good” kind because they are known to rated fat content (about 92%) has lead many to remove LDL cholesterol from the arteries. Yet, fear that coconut oil can lead to atherosclero- a study showed that coconut oil had a “combisis (Schardt). Atherosclerosis occurs when fats nation of fatty acids [that]improved the ratio of total build up on the walls of the arteries, forming cholesterol: HDL (good) cholesterol but they also raised plaques that eventually clog the arteries and LDL (bad) cholesterol (Zelman).” Therefore, the chemicauses problem with blood flow. This excessive cal makeup of coconut oil proved to show that levels of intake of lipids may in fact lead to heart disease. both good and bad cholesterol increased. However, epi22 MEDICAL DIALOGUE REVIEW Fall 2014 Torres demiologic studies were conducted in several itchy. Coconut oil’s affinity for hair protein and Asian countries where coconut oil was used in its ability to enter deep into the hair shaft gives their daily diets. The 1978 Demographic Year- the oil its beneficial effects. book of the United Nations claimed that in Sri However, researched conducted by Lanka 1 in 100,000 Florencio showed people die of heart that 40 obese womdisease. In a suben who consumed sequent study, 16 coconut oil had rehealthy Sri Lanka ductions in blood males replaced lipid levels and abtheir consumption dominal obesity. of coconut oil with Yet, researchers are corn oil. After 6 skeptical about the weeks, researchers benefits of the infound higher levtake of coconut oil. els of LDL (bad “There are a lot of Figure 2. Coconut Oil. cholesterol) in the claims that coconut blood of those who oil may have health had consumed corn oil as opposed to those con- benefits, but there is no concrete scientific data suming coconut oil. Furthermore, Filipinos in yet to support this,” said Dr. Daniel Hwang, a the Bocal region consume a large amount of research molecular biologist specializing in lauric coconut oil, about 26 grams daily. But a nutri- acid at the at the University of California, Davis. tional survey taken in different regions of the This confusion and skepticism in the scientific Philippines showed that though the Filipinos community has led neither the American Heart of the Bocal region eat more coconut oil, their Association or the U.S. government’s Dietary diets contain fewer calories than the typical US Guidelines to suggest that coconut oil is any betdiet. By calculating their dietary intake, the sur- ter or preferable over other saturated fats over vey revealed that out of all regions, the Bocal other saturated fats. According to both agenregion had less heart disease reported. This was cies, “Coconut oil, like all saturated fats, should recorded by overseeing the amount of cases of be limited to 7 percent of daily calories because heart disease reported. In accordance with this it can increase risk for heart disease.” Overall, study, Figure 1 shows that the Philippines, as a the studies conducted are short-term studies and whole, have lower rates of death due to heart need further investigation and long-term projdisease compared to the USA, Australia, and ects to be more validated. New Zealand. More research must be conducted to Although there is much scrutiny of give a final validated answer to ensure the safety studies showing the health benefits of consum- of consuming coconut oil regularly. However, ing coconut oil, there are supporters of the ben- heart disease is caused by more than dietary inefits of the external uses of coconut oil. One take but it also has other influences that can lead study showed that topical application of coco- one predisposed to it. Hence, there are many nut oil improved skin and hair conditions. In factors that can lead to such diseases and more a follow-up investigation, moisturization with research must be performed in order to see how coconut oil was shown to relieve xerosis, a skin coconut oil can fit into the web of factors. condition in which the skin is dry, rough, and Volume 15 MEDICAL DIALOGUE REVIEW 23 Torres REFERENCES Assunção ML, Ferreira HS, dos Santos AF, Cabral CR Jr, Florêncio TM. Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity. Lipids. 2009 Jul;44(7):593-601. Epub 2009 May 13. Agero AL, Verallo-Rowell VM. A randomized double-blind controlled trial comparing extra virgin coconut oil with mineral oil as a moisturizer for mild to moderate xerosis. Dermatitis. 2004 Sep;15(3):109-116. Coconut Oil. Digital image. HealthJunk. N.p., n.d. Web. Kaunitz H: Biological and therapeutic effects of “MCT” (Medium Chain Triglycerides) from Coconut Oil. Coconuts Today 1983: 27-30. "Mesnick, R. American Journal of Clinical Nutrition, May 2003; vol 77: pp 1146-55.. "Good vs. Bad Cholesterol." Good vs. Bad Cholesterol. N.p., n.d. Web. 15 Oct. 2014. Blackburn GL, Kater G, EA Mascioli, M Kowalchuk,. VK Babayan and BR Bistrian: “A reevaluation of coconut oil’s effect on serum cholesterol and atherogenesis” February 1990, Philippine Medical Association, 24-31 Keys A: Atherosclerosis: a problem in newer public health. J Mt Sinai Hosp 1953: 20; 118-139 David, Schardt, "Coconut Oil." Coconut Oil. N.p., n.d. Web. 14 Nov. 2014. 24 MEDICAL DIALOGUE REVIEW Fall 2014 Buttar Controlling the Control Center of the Body By Sally Buttar “Even though the location of this SWS-promoting/EEG-synchronizing circuitry is still a mystery, the activation of this sleep node could potentially allow scientists to discover a method where humans can trigger their own SWS. ” Sleep disorders, such as insomnia, affect the lives of 10-15% of the whole population. Associated symptoms include: inability to fall asleep, inability to sleep soundly through the night, and fatigue. Although sleep disorders are not headlining the news, they are more prevalent in today’s society than before. We live in a stress-filled environment, which contributes to insomnia. This, in turn, induces more stress as an individual with insomnia is continuously in a sleep-deprived state; the cycle never ends. Physicians employ a variety of methods in an attempt to inhibit this disorder. One of these methods includes paradoxical intention, which is a method that encourages the patient to address their most feared behavior, for example staying awake. The goal of this method is to “alleviate performance anxiety,” which attempts to reduce an individual’s stress level, and allow them to sleep (Saddichha 2010). Another method includes changing the patient’s beliefs and attitudes about sleep. Insomnia has different characteristics for each person, thus individuals may respond to different approaches (Saddichha 2010). While these methods seem to work for some patients, there are still no certain cures for most sleep disorders, leaving patients to resort to taking various pills. Scientists are now exploring new methods that may allow us to operate the brain ourselves, which will potentially be able to alter the lives of many who endure sleep disorders. Before Horace Magoun and Giuseppe Moruzzi shared their research, sleep was described as passive. Passive sleep was the idea that if we diminished all of the arousal activity from the brainstem, it would lead to the stability of the neural activity in the central nervous system. Now, following Magoun and Moruzzi’s research, we acknowledge sleep as an active phenomenon due to the neurons that are found to promote sleep. In the brain, the hypothalamus is responsible for managing the body’s sleep. While neuronal activity is increasing during wakefulness, sleep regulatory substances add up to eventually trigger the ventro-lateral prepotic nucleus (located in the anterior hypothalamus), which allows sleep to occur. Thus, many support the hypothesis that sleep is triggered due to many sleep regulatory substances that helps regulate slow-wave sleep (SWS) (Coulon et al 2012). In 1949, Moruzzi and Magoun discovered that the electrical stimulation of the reticular formation, a set of interconnected nuclei that are located through the brain stem (Gleitman et al 228), leads to a generalized arousal reaction in the cortex of the brain, which is what they found controls the sleep-waking cycle. Their experiment results indicated that the interaction between the thalamus neurons and the cortex neurons produces these sleep-wake cycles. Moruzzi and Magoun also identified the ascending reticular formation system, which sends electrical stimuli to produce wakefulness, and reduces electrical stimuli to produce sleep(Moruzzi et al 1949). There are four stages of sleep. In stage one, an individual is in light sleep; light enough to be woken up by a sound. If stage one sleep is not Volume 15 MEDICAL DIALOGUE REVIEW 25 Buttar disrupted, sleep starts to deepen, and within an hour that individual will go through stage two. Stage two is characterized by rapid brain wave activity called sleep spindles. The individual continues to fall into a deeper sleep as they move through stage three, where slow, large waves emerge in the electroencephalogram (EEG). These large waves, known as delta waves, take Figure 1. Each stage of sleep is defined by brain wave patterns (Bryant et al 2004). over and stage four occurs. Stages three and four are referred to as slow-wave sleep (SWS). “Slow, rolling eye movements, low cortical arousal, and slowed heart rate and respiration,” characterize sleep waves (Gleitman et al, 235). SWS has been discussed in great deal, and hypotheses have been made that show that SWS can be triggered, and the enhancement of those waves induce sleep (Roth 2009). The trigger mechanism involves interactions between sleep inducing neurons in the ventrolateral prepotic area (VLPO), and wake inducing neurons in the brainstem and hypothalamus (Anaclet et al 2014). Researchers at University of Buffalo School of Medicine and Biomedical Sciences and Harvard School of Medicine have recently discovered the second sleep node identified in the mammalian brain. This sleep-promoting circuit, located deep in the parafacial zone (PZ) in the brainstem, appears adequate and necessary to produce deep sleep (Goldbaum, 2014). SWS is crucial for deep sleep to occur, and the recently discovered PZ GABAergic neurons have shown to enhance and promote SWS waves. This new GABA neuron, which makes the neurotransmitter gammaaminobutryic acid, is reported to be 26 MEDICAL DIALOGUE REVIEW responsible for deep sleep (Goldbaum 2014). Researchers at Harvard and University of Buffalo tested the PZ GABAgeric neurons in mice. Researchers injected a virus containing an excitatory modified muscarinic G proteincoupled receptor, expressed in a Cre-dependant manner, into the paraficial zone of Vgat-IREScre mice and their non-Cre-expressing littermates (Anaclet et al 2014). Vigorous cell-surface expression of the G protein-coupled receptor was exhibited on the GABA neurons of the Vgat-IRES-cre mice, but was not detected in the non-Cre-expressing mice. This data confirms that Cre activity is required for receptor expression to be enabled in PZ GABAgeric neurons. Although it was then demonstrated that without the agonist clozapine-N-oxide (CNO), a chemical that binds to receptors to make them effective, the mice with the G protein-coupled receptors in their neurons did not show any different hourly sleep-wake, or difference in their EEG, than the mice that did not express the G protein-coupled receptors. Thus, it is apparent that the ligand (CNO) is needed to bind with the G protein-coupled receptors to induce PZ neuron activity. The induction of PZ neuron activity releases the GABA neurotransmitter, and results in deep sleep (Anaclet et al 2014). These injections of CNO did not seem to have an affect on the mice that did not express the G protein- coupled receptors. To test the effectiveness of the ligand CNO on the receptors, researchers first injected the mice with an interaperitoneal (IP) vehicle injection, a solution without CNO. Results following the injection show high electromyogram (EMG) activity, and low EEG slow wave activity (SWA). The higher the EMG activity and the lower the SWA, the more periods of wakefulness are occurring. Adversely, when the IP CNO was injected the mice fell asleep in a short period of time and had low EMG activity, along with high SWA. The slow wave sleep occurred in bouts 1-10 minutes with the IP vehicle injection, while the IP CNO mice had SWS that occurred in bouts longer than 5 minutes, with 35% occurring in bouts longer than 20 minutes. This shows that the activation of PZ GABAergic neurons by CNO results in higher SWS delta waves, which occur during sta- Fall 2014 Buttar ges three and four of sleep (Anaclet et al 2014). Even though the location of this SWSpromoting/EEG-synchronizing circuitry is still a mystery, the activation of this sleep node could potentially allow scientists to discover a method where humans can trigger their own SWS. As more discoveries about the brain, such as this sleep node, are revealed, humans will begin to see that we are in control of our own bodies. With the uncovering of only two sleep nodes scientists are able to unlock many mysteries about the brain—imagine what the discovery of the rest of the brain will allow humanity to achieve. REFERENCES Anaclet, Christell, Loris Ferrari, Elda Arrigoni, Caroline E. Bass, Cliford B Saper, Jun Lu, & Patrick M Fuller. “The GAB Aergic parafacial zone is a medullary slow wave sleep-promoting center” Nature Neurosciene. 17.9 (2014): 1217 1224. Web. 18 Oct. 2013 Bjorness, Theresa E and Robert W Green. “Adenosine and Sleep”. Current Neuropharmacology. 7.3. (2009): 238-245. Web. 18. Oct. 2014 Coulon, Philippe, Thomas Budde, and Hans-christian Pape. "The Sleep Relay--the Role of the Thalamus in Central and Decentral Sleep Regulation." Pflügers Archiv - European Journal of Physiology 463.1 (2012): 53-71. ProQuest. Web. 18 Oct. 2014. Goldbaum, Ellen. "No Sedative Necessary: Scientists Discover New “sleep Node” in the Brain." No Sedative Necessary: Scientists Discover New "sleep Node" in the Brain. University of Buffalo News Center, 16 Sept. 2014. Web. 19 Oct. 2014. Levi-Montalcini, Rita, Marco Piccolino, Nicholas J. Wade. “Giuseppe Moruzzi: A tribute to a ‘formidable’ scientist and a ‘formidable’ man.” European Brain Ressearch Institute. (2010). Web. 18. Oct. 2014 Roth, Thomas. “Slow Wave Sleep: Does It Matter?” J Clin Sleep Med. 5.2 (2009): S4-S5. Web. 18 Oct. 2014 Saddichha, Sahoo. “Diagnosis and treatment of chronic insomnia” Ann Indian Acad Neurol. 13.2 (2010): 94-102. Web. 18 Oct. 2014 Volume 15 MEDICAL DIALOGUE REVIEW 27 Robles-Long From Degeneration to Regeneration By Mark Robles-Long “Although the human brain appears to be this ominous, mysteriously impossible object (which it undoubtedly is), it is nothing without its equally divine counterpart in the central nervous system– the spinal cord.” An Introduction to Multiple Sclerosis The central nervous system earns its name as the core headquarters of the human body, regulating everything from voluntary movement of your eyes down the width and length of this paper to the involuntary retinal processing of these objects in the thalamus and primary visual cortex. It enables us as humans to have the evolutionarily advanced ability to sense one thing, visually, and then perceive it as much more than just what it appears to be: seeing a white object in the sky while feeling a chilling sensation on our noses and hands may induce nostalgia, reminiscence, recollection of a past event in our life and followed perhaps by a discrete smile or laugh. This is how we create our reality, through perception and interpretation of the physical world rather than simple sensation. Oftentimes, we create a reality in which we feel invincible for we can conjure up profound, ethereal ideas. Although 28 the human brain appears to be this ominous, mysteriously impossible object (which it undoubtedly is), it is nothing without its equally divine counterpart in the central nervous system–the spinal cord. It is no breaking news the brain and spinal cord communicate: receiving, processing, and sending signals that alert us of environmental cues, warnings or rewards, and our own internal disruptions. In fact, if it were not for signaling at the microscopic, synaptic level, we would not walk, sense the world, or even breathe. Without axonaldendritic communication, that is, the signaling of neuronal cells that comprise the nervous system, we would not be alive. Thus, rationally speaking, neurodegenerative diseases, those that degrade these crucial neurons, cannot simply be cured by a few therapy sessions, monthly prescriptions, and hope; but rather, they necessitate a much more in depth remedial process, one perhaps characterized by rehabilitating the entire nervous system. Neurodegenerative disease af- MEDICAL DIALOGUE REVIEW Fall 2014 ter all is a matter of life and death...or so it appears. One such disease is only a matter of life and death in rare cases. Multiple sclerosis makes it excruciatingly clear that neurodegenerative diseases are not explainable through a three-word ultimatum–“life or death”. Rather, MS expounds itself as an autoimmune disease, akin to a virus in that it destroys its host’s human qualities such as extremity comfort, articulation, sense of collectivity with others, and a peace of mind all without quite destroying its host. About the Disease Multiple sclerosis translates to “many scars”. These scars refer to lesions in the brain comprising a path of destruction created by the selfinflicting immune system as it devours and degrades the myelin lining of axons, necessary “insulation” of all axons that allows saltatory conduction of action potentials.1 Without myelin, action potentials would not propagate sufficiently Robles-Long down an axon, resulting in a loss of signal. These lost signals could vary between not feeling a prick of the finger to developing problems with simple or complex cognitive processes. In this case, autoimmune reactions against myelin are induced by inflammatory cytokines, proteins involved in signaling and thus stimulation of T cell proliferation and differentiation.6 Proliferation and differentiation of T cells are typically beneficial and necessary aspects of a healthy, normal immune system. These cells are involved in maintaining our well-being by engulfing bacteriophages that would otherwise cause sickness. However, these processes are utterly detrimental to humans plagued with MS. These T cells attack myelin sheaths and the oligodendrocytes, cells responsible for myelination, thereby exposing delicate axons, which are then damaged in the degenerative process.1 It only seems reasonable to find a solution using one’s gut intuition: stop the cytokines. Inhibiting the true primary source of demyelination, the cytokines, may seem like a plausible and obvious solution; however, doing so would decrease the proliferation of T cells altogether. This would perhaps result in a decrease of demyelination, but more definitely a decrease in the formidability of the immune system, leaving the patient vulnerable and prone to disease. This approach is clearly ineffective seeing as the patients are seeking an escape from an incapacitating disease rather than a potential introduction to a plethora of new ones. Effects and Symptoms MS entails an unmatched stock of its own sustained illnesses, ranging from physical disability to cognitive impairment. Trigeminal neuralgia is just one neuropathic pain that accompanies multiple sclerosis. It affects the 5th cranial nerve, the trigeminal nerve, as a result of demyelination.7 This particular nerve branches three ways throughout the face, encompassing chin to forehead, spanning countless amounts of nerves. This neuralgia is described as both physically and mentally incapacitating. To the likeness of a toothache and presumably a migraine, a bilateral effect can occur. This is a combination of the extreme and episodic pains of Type 1 and the atypical, persistent aching and burning sensations of Type 2.7 This type of pain is one of extreme magnitude, and although not all pains caused by MS are of the same scale, the disease knows no limits and grips nearly every facet of the human body, even extending into the human psyche. According the National Multiple Sclerosis Society, MS affects virtually every sensory system. Vision malfunction is oftentimes a very first sign of MS. From temporary blurs to pain, seeing double to having trouble deciphering contrast,5 MS affects the nerves and signaling involved in sensing the world. Damage to nerves implies irregular Volume 15 muscle function as well. This is seen in the difficulties had with speaking, swallowing, and even breathing wherein MS patients may articulate poorly or slur their speech and have trouble breathing as a result of nerves that control chest muscles being damaged.5 As for extremity discomforts, damage to the myelin sheath results in muscle weakness (i.e. numbness), pain and complications with preserving balance and hand-eye coordination.5 In terms of bladder and bowel function, 80% of MS patients struggle with constipation, diarrhea, or loss of bowel control.5 Additionally, damage to nerves may lead to kidney or urinary tract infections. While the reproductive and circulatory systems are only rarely or not directly affected at all, certain components are nonetheless affected, invoking difficulties in experiencing orgasm/arousal or administering sufficient oxygen to the brain.5 This insufficiency is associated with the inability to breathe deeply due to weak chest muscles and therefore prompts cardiac problems and stroke.5 As is the case with most diseases, while the physical body is barraged with symptoms and begins to gradually decline in wellness, the emotional state follows in shadow of it, becoming darker with each new slope. Oftentimes, patients with MS experience depression or low-self esteem as a result of their disabilities, particularly sexual and/or hygienic. When we look toward the child/adolescent popula- MEDICAL DIALOGUE REVIEW 29 Robles-Long tion of MS patients, there is an increase in effects already stated as well as on academic performance and relationships with either family or classmates.5 Having experienced pre-teen years and the conventional rocky adolescent blossoming like the majority of young adults, it is no surprise younger MS patients may experience a phase of self-image discontentment magnified tenfold. Susceptibility and Risk Variability Studying children typically provides insight to researchers as they seek to answer questions pertinent to their study; in the case of MS, these questions are intricate and abundant, probing deeply into the core cause and early detection of neurodegeneration. As we have seen already, neurodegenerative diseases know no limits when it comes to the human body or the human soul; however, it is also true it knows no age limits, targeting children due to their immature immune and nervous systems. MS is thought to be a disease dependent on demographics such as age, gender, ethnicity, and geography, rather than genetics like most other autoimmune diseases though genetics does have its role in inferring how MS comes about.8 While Relapse-Remitting Multiple Sclerosis (RRMS) diagnosis occurs between 20’s and 30’s, this particular type of MS can occur in childhood.5 Diagnosis of children is even more prob30 lematic than diagnosing adults, however, due to the ubiquitous irregularities associated with childhood having similar symptoms as MS (i.e. puberty, growing pains, etc.). Relapses of inflammation along with more brain lesions containing inflammatory cells characterize RRMS.5 Children experience more inflammation and relapse responses than adults as well as a slower disease progression, which may cause a significant disability accumulation.5 It is also in this type of the disease that developmental cognition such as learning, memory, and information processing is affected, hence the prevalence among growing brains of children. Statistically speaking, 18,000 to 25,000 children have been diagnosed with MS or have reported feeling symptoms resembling those of MS.5 Yet how exactly does MS target the immature, vulnerable systems of children? The answer is not clearly known. Research suggests chemical exposure to a certain environmental trigger such as a virus during childhood, prior to the age of 15, may determine risk of MS contraction.4 Since viruses play a virulent, inflammatory role in the destruction of myelin as well as in autoimmune disease (e.g. human immunodeficiency virus preceding acquired immune deficiency syndrome), it is likely a virus is responsible for the onset of MS. Connecting dots such as these, however, does not establish causation; it is necessary that a longitudinal study be in practice in order to help elucidate the mystery of MEDICAL DIALOGUE REVIEW Fall 2014 MS triggers. What more might we look toward to understand MS triggers? The onset of MS is popularly attributed to demographics: prevalent in the Pacific Northwest of the United States,4 in areas of greater latitudes (regions away from the equator) around the world, among women versus men at a ratio of 2-3:1, and most common among Caucasians of Northern European descent.8 However, there are correlation conflicts. MS is not prevalent in areas like southernmost New Zealand, and Norway of northern Europe though the two countries are exceedingly distant from the equator and Norwegians are Northern Europeans.8 While it is believed inhabitants of equatorial regions are not susceptible to MS due to Vitamin D sufficiency and thus a year-round supported immune system and protection against autoimmune disease, it is more likely geography acts in hybridization with ethnicity and other demographic variables8 to explain MS prevalence around the world. Migration, for example, show trends of immigrants and their descendants taking on either higher or lower risks of MS development depending on the area to which they move.8 Childhood prevalence is exemplified further in these migratory trends where if migration occurs early in childhood results in immigrants taking on the geographic-dependent chance themselves whereas if it occurs later in the life of an individual, the risk factor is passed Robles-Long down to the next generation.8 As for the asymmetry between men and women with MS, it is supposed hormones may play a role in the risk factor.8 Demographic trends even coincide with the genetic influence. While an average American has a 1% chance of disease development, a first-degree relative to someone with MS, such as a child or sibling, has an increased 2.5-5% chance.8 This perchance is due to the likelihood of the environment in which the family lives containing chemical triggers. One case of reverse causation suggests that a person may be born with a genetic predisposition, such as a weak immune system or otherwise endangering trait, that essentially makes him or her a susceptible, vulnerable target to MS development.8 who do not have MS as so. Thus more people are diagnosed than actually have the disease. This is not necessarily a terrible situation. Relative to the other option of diagnosing fewer people than actually have MS, this excessive diagnostic technique is the safer option. Though professionals know what types of lesions demonstrate MS affliction such as those of the corpus callosum, to name one, other similar but unrelated white matter lesions may distort their view.13 Aside from lesion congestion in MRI scans, overlapping symptoms of unrelated disease or disorders further convolute patient examinations. This is particularly true, as stated earlier, for children and teens experiencing drastic physical and emotional changes.5 Problematic Diagnoses Stem Cell Therapy–A Potential Treatment While deducing and speculating the causes and triggers of MS seems a mess of intermingled strings, connecting some things but not others, the actual diagnosis of MS is even hazier. MRI scans display the residual “scars” of the immune-mediated destruction, the white brain matter lesions indicative of MS whose degree of spread and circulation aid in professionals diagnostics. What makes MRI a helpful yet inadequate method of detection is its inability to detect lesions necessarily caused by MS. The increase in sensitivity, diagnosing people actually having MS correctly, results in a decrease of specificity, diagnosing people 13 Undoubtedly, multiple sclerosis compromises human functionality in nearly every facet of the physical and emotional body. Infiltration of the delicate brain cells spells disaster for the misfortunate person living with MS. However, with the relatively recent advent of stem cell therapy, this disaster could not only be halted but also reversed with new advances in oligodendrocyte understanding. One neurology department in Greece attempted to completely eradicate the immune-mediated reactive cells via rabbit-derived antibodies against human T cells (ATG–antithymocyte globulin) Volume 15 and install a new immune system derived from an allogeneic donor.2 The method used was HSCT (hematopoietic stem cell transplantation) in an autologous setting, where stem cells from the patient’s peripheral blood were transplanted into an MS patient, mobilized, and their feasibility as appropriate MS treatment and toxicity assessed. The experimenters utilized an autologous setting rather than allogeneic due to the potential GVHD (graftversus-host disease) problem, where the donor cells attack a new host. According to previous reports, autologous procedures involving BMT (bone marrow transplant) resulted in short and occasional long remissions; that is, malignancies disappear temporarily. Thus autologous HSCT was the safer alternative. The transplantation was performed in 15 patients, 8 male, 7 female, all in the progressive phase of MS with characteristic abnormalities on MRI scans, and only with ineffective past therapy. Upon mobilization, experimenters closely observed the nervous system to monitor toxicities, intensification of either preexisting symptoms of MS or new ones brought about as a result of the transplantation. In order to evaluate the wellbeing of the subjects, two tests were used, assessing impairments of daily activities or overall improvement of disabilities. What these experimenters found was that aside from episodes of infection due to unrelated bacteria, no neurotoxicity or deaths MEDICAL DIALOGUE REVIEW 31 Robles-Long were noted, nor were any adverse effects lasting longer than 1-2 days and being more than mild in their effects. There were several cases of aggravation and allergic reactions due to the transplant of both ATG and stem cell infusion; however, no patient had been re-admitted to a medical facility for a prolonged procedure-related disorder. Experimenters noted significant improvement in disability, especially in one patient who continued to improve 9 and 15 months post-procedure, ranking a 2 on the EDSS (Expanded Disability Status Scale where 0 indicates no disability and 10 indicates death) at 18 months from an original entry ranking of 5. While worsening did occur on this scale, no worsening occurred on the SNRS (Scripps Neurologic Rate Scale where 100 points indicates maximum efficiency). This scale is more reliable, according to researchers, due to reliance on more than just walking ability on which EDSS solely relies. However, two patients relapsed after having improved on this scale. One such relapse can be attributed to the receipt of a minimal dose of ATG. We might infer the original, malignant T cells still existed, reacting against myelin and perpetuating MS. 32 Although economic feasibility and late adverse effects must be taken into account, these researchers believe this therapy can suppress MS progression, reducing disability, or, in the best case, totally eradicate the disease. One important finding of this experiment was that MS progression depends on the circulation of lymphocytes. This disease thrives on the presence of intact, reactive T cells as well as the presence of myelinated axons. While this study provides a possible solution to fixing the immunemediated response, it does not give insight into how damage may be repaired. Neuroscience researchers at the University of California, San Francisco have recently discovered an effective way to screen potential therapeutic compounds for the treatment of MS.3 Micropillar arrays serve as a pseudoaxonal substrate upon which myelination by oligodendrocytes can occur. The real question is, however, under what conditions does myelination occur most efficiently. Upon screening of multiple compounds, researches came to the conclusion that clemastine, an antihistamine, promotes differentiation of oligodendrocyte precursor cells into oligoden- MEDICAL DIALOGUE REVIEW Fall 2014 drocytes, thereby promoting remyelination in organisms by inducing formation of concentric rings about the micropillars. Fortunately, clemastine is an FDA-approved compound and therefore reserves pharmaceutical potential. A Valuable Foe We, even in 2014, are unclear about the vast majority of biological functions, particularly dysfunctions and malfunctions. Yet this fact does not detract from the desire to research and experiment. Multiple sclerosis, though a terrible disease in some unparalleled aspects, is more valuable than it is detrimental. It not only prompts rigorous study in the medical field and public awareness, but it is one of the many diseases that remind us that we are not invincible. From physical disability to emotional incapacitation, MS usurps power of the human body. However, it is unlikely this disease will remain in reign much longer. The scientific community remains confident in the progressing interest, concern and subsequent research in neurodegenerative diseases, that it may one day provide a remedy. Robles-Long REFERENCES 1: "About MS." National Multiple Sclerosis Society. N.p., n.d. Web. 14 Nov. 2014. 2: Fassas, A., et al. "Peripheral Blood Stem Cell Transplantation in the Treatment of Progressive Multiple Sclerosis: First Results of a Pilot Study." Bone Marrow Transplantation 20.8 (1997): 631-38. Web. 3: Mei, Feng, et al. "Nature Medicine." Micropillar Arrays as a High-throughput Screening Platform for Therapeutics in Multiple Sclero sis (2013): n. pag. Web. 4: "Pediatric MS Cases Rise in the Northwest." InvestigateWest. N.p., n.d. Web. 14 Nov. 2014. 5: "Pediatric MS." National Multiple Sclerosis Society. N.p., n.d. Web. 14 Nov. 2014. 6: "TH1/TH2 Cytokine Profile in Relapsing-remitting Multiple Sclerosis Patients Treated with Glatiramer Acetate or Natali zumab." BMC Neurology. N.p., n.d. Web. 14 Nov. 2014. Volume 15 MEDICAL DIALOGUE REVIEW 33 Pang Orthognathic Surgery 101 By William Pang “Orthognathic surgery truly exemplifies the mission of oral & maxillofacial surgery: saving faces, changing lives.” Orthognathic literally means straight jaws. This particular type of surgery is unique within Oral & Maxillofacial Surgery, a dental specialty. Patients with misaligned bites that cannot be corrected by orthodontics alone are prime orthognathic candidates. Orthognathic surgery, or corrective jaw surgery, can be performed to spatially manipulate the upper jaw(maxilla) and/ or the lower jaw(mandible) in order to improve harmony between the jaws and the teeth in addition to the considerable enhancement in patients’ quality of life. The maxillofacial region is comprised of the face, mouth, tongue, and jaws. Many deformities occur in this area as a result of heredity and/or environmental factors. The most prevalent irregularities pertain to the congenital jaw structure. Jaw discrepancies are largely due to uneven growth in one or both jaws. This misalignment of the jaws, or malocclusion, can impair function and impact the patient’s appearance. Resulting functional problems include difficulty eating, speaking, and breathing properly. In cases of slight deviation, orthodontics can be used to treat the problem in its early stages. However, if the occlusion or bite is deemed too severe for conservative treatment, plans for orthognathic surgery begin when the patient is done growing. Usually growth plates fuse at age 16 for females and at age 20 for males. Another benefit of orthognathic surgery is the improvement of facial aesthetics; particularly of the lower third portion of the face. Facial aesthetic is related to symmetry and proportions. In regards to the frontal facial view, a face that is more symmetric when split midsagittally, or into two halves between the eyes, is universally deemed more attractive. This component also includes the dental midline. Teeth appear most aesthetic when the maxillary and 34 MEDICAL DIALOGUE REVIEW mandibular midlines match each other. It is very common for patients with jaw deformities to exhibit various degrees of asymmetry. A maxillary cant, or a slight tilt in the Figure 1. Vertical line divides the face into two halves to assess symmetry. maxillary occlusal plane, can affect the aesthetics of the entire jaw. Since the mandible is the only freely articulating, or moving, bone in the skull, the maxillary cant is detrimental to the symmetrical development of the mandible. Since the dimensions of soft tissue are strongly correlated to the underlying skeletal structure, maxillary cants will often cause a crooked appearance of the lips. Functionally, this can lead to a host of problems including Temporal Mandibular Disorder (TMD) and bruxism, or aggressive clenching of teeth. TMD is a painful condition that is localized at the Temporal Mandibular Joint (TMJ). Symptoms include aching pain in the maxillofacial region, jaw stiffness, and clicking during elevation (opening) and depression (closing) of the mandible. The dysfunction in the jaw joint is highly detrimental to a patient’s ability to speak, eat, chew, breathe, and make facial expressions. The patient featured in figure 2 exhibits a visible maxillary cant with mandible Fall 2014 Pang aesthetically favored. Convex profiles are characterized by a softer look, due to weak chin projection. Bart Simpson’s profile, for example, helps demonstrate this characterization. Lastly, concave profiles display a prominent chin, which juts anteriorly. A prime example of someone who exemplifies this type of profile is Jay Leno. The two major facial bones that oral Figure 2. Cephalometric analysis. Facial profile: (A) Convex, (B) Straight, (C) Concave Convex Profile - Lines form an angle pointed away from the face. Straight Profile - Lines form a straight line. Concave Profile - Lines form an angle pointed towards the face. Figure 3. Front view of soft tissue. deviating to the left side. TMD symptoms are present in the left condylar joint. As seen in figure 3, the soft tissue is reflective of the underlying skeletal discrepancies. The facial profile is the side view of a patient’s face. Three main facial landmarks along with two straight lines are used in the assessment of the profile. The landmarks include the soft tissue nasion, subnasale, and soft tissue pogonion. The nasion is the point directly between the eyes; the subnasale is the point below the base of the nose; the pogonion is the most anterior point of the chin. There are two lines that connect from the nasion/subnasal and subnasal/ pogonion segments with the resulting angle being the determinant for facial profile. In classification, there are three main facial profile categories: straight, convex, and concave. A straight profile is aesthetically ideal and can be characterized as being neither convex nor concave. Males with a straight profile are considered most attractive. On the other hand, females with a slightly convex profile are and maxillofacial surgeons operate on in orthognathic surgery are the maxilla (upper jaw) and the mandible (lower jaw). Each jaw contains certain unique features that are interconnected with blood vessels and nerves. The most commonly damaged nerve is the inferior alveolar nerve (IAN). This sensitive nerve passes through the mental foramen in the body of the mandible. Injury or trauma to the IAN can cause pares- Figure 4. The inferior alveolar nerve transverses through the mandibular canal. Volume 15 MEDICAL DIALOGUE REVIEW 35 Pang thesia or numbness of the lips, chin, and other surrounding areas immediate to the mandible. Such disturbances can have both functional and psychological consequences that decrease quality of life. Careful measures, such as proper retraction and deliberate surgical instrumentation must be used to protect this nerve during the more invasive mandibular osteotomy (bone cut) procedures. Skeletal Disharmonies Figure 5. I:Class I Occlusion; II1:Overbite with proclined anterior teeth; II-2:Overbite with retroclined anterior teeth; III:Underbite. is when the mesiobuccal cusp of the upper 1st molar lies anterior to the mesiobuccal groove of the lower 1st molar. Typically, the mesiobuccal cusp sits between the 1st mandibular molar and 2nd premolars. There are two subtypes of this bite: division 1 and division 2. In division 1, the anterior teeth are protruded or flared outwards. In division 2, the anterior teeth are retroclined or pointed into the mouth. Class II’s are usually accompanied by a weak chin projection and a relatively small mandible. They can be disguised or even corrected by orthodontics if treatment is done at a young age. However, for optimal longterm results, orthognathic surgery is usually recommended when the patient is done growing. Class III: Underbite Class III (prognathism) is the most severe of the malocclusions. In this case, the mesiobuccal cusp of the maxillary 1st molar lies posteriorly to the mesiobuccal groove of the mandibular 1st molar. In other words, the lower teeth sticks out in front of the upper teeth. The underlying culprit behind a Class III malocclusion is usually a large mandible and/or a short maxilla. Classifying occlusions is essential in treatment planning, as it distinguishes the morphology of dental and skeletal discrepancies from what is considered normal. In modern day dentistry, Angle’s classification of malocclusion is the gold standard. This system is based on the location of where the buccal groove of the mandibular 1st molar makes contact with the mesiobuccal cusp of the maxillary 1st molar. Class I Class I is representative of a normal occlusion in regards to the maxillary first molar. However, there may be slight issues such as spacing, crowding, and/or over/under eruption of teeth. This occlusion is the most prevalent and can be solely corrected with orthodontic treatment. Figure 6. Open bites exhibit a prominent gap between front teeth. Apertognathia Open Bite An open bite is characterized by an absence of anterior occlusion in addition to the premature occlusion of posterior teeth. Early childhood habits such as thumb sucking may contribute to the formation this bite. Class II: Overbite Class II (retrognathism), or overbite, 36 MEDICAL DIALOGUE REVIEW Fall 2014 Pang Figure 7. Cross bites appear crooked and have uneven occlusal force. Cross Bite A cross bite is the lateral misalignment of the maxillary and mandibular arches. It may involve a single tooth or a set of teeth that are skewed, thus placing tremendous stress on particular areas. This leads to an uneven distribution of occlusal force and an unaesthetic smile. Orthodontics The presurgical phase begins with the placement braces. The braces used to treat orthognathic patients aim to decompensate the dentition. Over time, teeth tend to migrate or compensate to touch their opposing side for maximum surface area contact. In the case of an underbite, the maxillary teeth will be proclined or flared out while the mandibular teeth will be retroclined in order for the top and bottom teeth to meet each other. Proper orientation of the teeth are pertinent during the final stages leading to orthognathic surgery. Therefore, the orthodontist will decompensate the bite, making the patient’s condition appear even worse until it is fixed by the surgeon. It may take anywhere from 6 to 12 months for the patient’s bite to be ready for surgery. During the week before surgery, the orthodontist will place surgical hooks between the brackets to act as an anchor for the surgeon to fixate wires onto in order to hold the splint in place. The splint is a custom made wafer that guides and stabilizes the patient’s new bite. Orthodontic treatment continues after surgery when the bones have been fully healed. This phase lasts from 3 to 6 months before the braces can be removed, leaving behind an aesthetic smile and functional bite. Orthognathic Surgery Usually, the patient’s General Dentist will spot out the malocclusion and will refer the case to an orthodontist. The orthodontist will then determine if the irregular bite is the result of a tooth or skeletal problem. More mild cases such as Class I with crowding/spacing, Class II, and crossbites, can be conservatively corrected with dentofacial appliances such as braces or headgear. Less commonly, severe Class II malocclusions, or overbites, and Class III malocclusions, or underbites, will require correction using orthodontic treatment in conjunction with orthognathic surgery at the end of the patient’s growth. Orthodontists will refer orthognathic cases out to an oral & maxillofacial surgeon. Oral & maxillofacial surgeons are specialists who combine their expertise in both dentistry and medicine to effectively treat patients with skeletal abnormalities within the maxillofacial region. Becoming a full-fledged OMFS is a long and arduous journey with many rewards. College graduates attend four years of dental school before training in OMFS at a hospital based residency program. There are two residency paths that may be taken to be board certified: a fouryear certificate program or a six-year combined MD/certificate program. Lately, there has been a shift towards dual degree OMFS. With extensive training in anesthesiology, dentistry, ENT, and plastic/reconstructive surgery, oral & maxillofacial surgeons are uniquely qualified to operate on the jaws. Imaging Radiology Surgeons use imagery to observe the nuances of the patient’s maxillofacial anatomy. The position of surrounding structures, such as the Inferior Alveolar Nerve, to the shape of the mandible are crucial information that the surgeon will use to determine which surgical procedures will yield optimal functional and aesthetic results. CT scanning of the maxillofacial region allows the surgeon to see the skull in floating 3D format. In a submentovertex radiograph, the xray beam enters behind the chin and exits at Volume 15 MEDICAL DIALOGUE REVIEW 37 Pang Figure 8. The blue and red regions highlight the maxilla and the mandible, respectively. Dolphin Imaging Surgeons may use advanced software to predict the final look of the patient. Skeletal movements of the jaws will lead to drastic changes in facial appearance, and soft tissue movement is often difficult to accurately predict due to factors that include swelling and accumulation of fat tissue. It is expected for patients undergoing orthognathic surgery to look different from before. the top of the head as the patient looks up. The Submentovertex view is used to see the curvature and thickness of the mandible in planning for lower jaw surgery. For thinner mandibles that require a setback, the surgeon will perform an IVRO (intraoral vertical ramus osteotomy). Otherwise, BSSO (bilateral sagittal split osteotomy) will be performed. Models The average time of pre-surgical orthodontics ranges from six to twelve months. When the teeth are fully decompensated, the orthodontist will meet with the surgeon to make models of the patient’s bite. The surgeon will then conduct a mock surgery on the models and use CT guided imagery to fabricate an intermediate and final splint. The intermediate splint is only used in double jaw surgery. It is placed on the maxillomandibular occlusion immediately following the first jaw that was operated on. The final splint is placed at the end of the case to maintain the occlusion. Depending upon the procedures used, the splint may or may not be removed for a set duration of time. Figure 10. The purple wafer is the intermediate splint used to reposition the first jaw. The blue wafer is the final splint used to fixate the second jaw. These splints are tied to the patient’s surgical hooks as the jaws are being moved. Figure 11. The innovation of Dolphin allows patients to visualize their expected outcome. Figure 9. X-ray beam enters the posterior region of the mandible. 38 MEDICAL DIALOGUE REVIEW Procedures Lefort I Osteotomy The most commonly used procedure of the maxilla is the Lefort I osteotomy. A transverse or horizontal bony cut is made in the maxilla until it separates from the skull. The surgeon Fall 2014 Pang Figure 12. The versatility of the Lefort I osteotomy in maxillary repositioning make it the primary option for upper jaw surgery. usually down-fractures the maxilla by gently ripping it towards the mandible with a figure-eight motion. It is a versatile procedure that allows the surgeon to rotate, advance, push back, and tilt in varying degrees to give the patient optimal aesthetics and function of bite. BSSO (Bilateral Sagittal Split Osteotomy) Figure 13. Rigid fixation of titanium screws and plates are used to stabilize the mandible during healing. These metal components remain in the patient’s face unless an infection warrants its removal. Bilateral means two sided, and sagittal refers to the anatomical plane in which the osteotomy or bone cut will be made. The tooth-bearing segment is split from the condyle-bearing segment attached to the skull, akin to sliding open and closing a drawer. The condyle-bearing segment is lateral to the tooth-bearing segment. BSSO may be used to correct Class II and Class III malocclusions. Its versatility gives the surgeon the option of advancing forward or pushing backward the mandible. This flexibility of movement allows the BSSO to correct mandibular asymmetries with great success. The disadvantages of using BSSO to move the mandible lie in the cuts’ close proximity to the IAN. BSSO procedures carry a 9-10% incidence of permanent numbness. BSSO requires rigid fixation with titanium plates and screws, which increase the rate of infection post-op. However, this fixation allows the patient to open their mouths immediately following surgery. They may drink liquids and follow a soft diet, unlike patients who have undergone an IVRO. IVRO (Intraoral Vertical Ramus Split Osteotomy) Figure 14. The IVRO features an oblique cut made in the ramus of the mandible, completely avoiding the IAN. Surgical hooks facilitate mandibulomaxillary fixation (MMF or wiring of the jaws) during the healing process. Volume 15 MEDICAL DIALOGUE REVIEW 39 Pang Intraoral means inside the oral cavity. Vertical refers to the anatomical plane through which the osteotomy is made. In IVRO, the ramus is split down in the coronal or vertical plane. Since this procedure is done far away from the IAN, the incidence of permanent numbness is much lower at 2%, compared to the 9-10% BSSO. Unlike the BSSO, the jaws must be wired shut for 6-8 weeks following IVRO due to the lack of rigid fixation. Instead, the segment containing the mandibular condyle is everted or flared outwards laterally to allow bony contact with the mandible. Due to the dependency of bony contact, the IVRO may only be used in mandibular setbacks. Therefore, they are only performed on prognathic patients who exhibit Class III malocclusion. At least 3 months is required for full bony union following an IVRO. A patient must take extreme caution and care during this vulnerable time as any trauma to the jaw will require another operation to correct. Figure 15. A horizontal cut is made across the inferior border of the mandible. Genioplasty A genioplasty or chin osteotomy may be done for purely cosmetic reasons. The chin is a vital component of the face that helps balance and frame the other features. A small chin may accentuate the prominence of the nose, whereas, a large chin may be too overbearing and masculine for female patients. The oral surgeon must take into account the patient’s race and gender in the determination of the chin’s final location. In most cases, the navigation of this fine balancing act is varied due to the patient’s and surgeon’s 40 MEDICAL DIALOGUE REVIEW Figure 16. Rigid fixation is used to secure the newly positioned chin. preference. The best genioplasty are the ones that leave no indications of surgery and instead appear natural to the public. In the case of a Class III malocclusion, the chin tends to lose its prominence due to retraction of the mandible. Thus, a small osteotomy can be made at the inferior border of the mandible to give the patient back his/her chin projection. Conclusion Orthognathic surgery is a common treatment modality used to correct skeletally related jaw discrepancies such as overbites, underbites, open bites, and cross bites. Treatment planning involves close collaboration between the patient’s orthodontist and oral & maxillofacial surgeon. With the assistance of advanced imaging, the oral & maxillofacial surgeon will know which procedures to perform and the degree of movements required in repositioning the patient’s jaw(s) for the final occlusion. The orthognathic journey is long and arduous, but worth it. The majority of orthognathic patients rave about its life changing effects. Increases in quality of life due to optimal bite functionality and closer symmetry in facial aesthetics are the two most noted differences that are made. Gone are the times when their skeletal disharmonies interfered with their livelihood. Newly found comfort in smiling, chewing, and interacting with peers have given patients their confidence back. Orthognathic surgery truly exemplifies the mission of oral & maxillofacial surgery: saving faces, changing lives. Fall 2014 Pang REFERENCES Aofoundation.org/wps/portal/surgery. Ed. Chris Colton, Steve Krikler, Joseph Schatzker, and Peter Trafton. Web. <https://www2.aofoundation.org/AOFileServerSurgery/MyPortalFiles?FilePath=/Surgery/en/_img/ surgery/05-RedFix/95b/X300-SpecCond-PlanningOrthSurg/95_X300_i260_540.gif>. "Dolphin Imaging & Management Solutions." Dolphin Imaging & Management Solutions. Web. <http://www.dolphinimaging. com/3dsurgery.html>. Gunson, Arnett. "Grafting Materials." Orthognathic Surgery. Web. <http://www.arnettgunson.com/technology/grafting- materials>. "Orthognathic Surgery, Education, and Research." Orthognathic Surgery. Web. <http://www.arnettgunson.com/>. Premkumar, Sridhar. Prep Manual for Undergraduates: Orthodontics. New Delhi: Elsevier, 2008. 163. ROBINSON, MD, DDS, RANDOLPH C., and REBECCA L. HOLM, RN, MSN, CNOR. "Orthognathic Surgery for Patients with Maxillofacial Deformities." AORN Journal 92.1 (2009): 28-49. Web. <http://isgweb.aorn.org/ ISGWeb/downloads/CEA10053-4017.pdf>. Volume 15 MEDICAL DIALOGUE REVIEW 41 Fabbro NYU’s Police Stress and Health Program Gains Insight Into Stressors Police Officers Face By Rebecca Fabbro “Can science tell us anything about how urban police departments can better select and train police officers to make critical decisions, particularly when lives are at stake?” On a hot August night, a 28-year-old white police officer named Darren Wilson approached an unarmed black teenager named Michael Brown and shot him to death. We do not know, and may never know, the details of what transpired that night or exactly what Darren Wilson was thinking when he pulled the trigger. But as the impact of the tragedy continues to reverberate beyond Ferguson, Missouri, it underscores why it is so important to better understand the stressors police officers confront—and what departments can do to equip police to make difficult decisions under pressure. Can science tell us anything about how urban police departments can better select and train police officers to make critical decisions, particularly when lives are at stake? For the past eight years, research into the unique psychological and physiological stressors police officers face— as well as the protective factors that equip some officers to show resilience under stress— has been taking place just a few blocks northeast of NYU’s main campus at NYU Langone 42 Medical Center (NYULMC). Under the leadership of Lucius N. Littauer Professor Dr. Charles R. Marmar, who also serves as chair of NYLMC’s department of psychiatry, NYU’s Police Stress & Health Program has been working in collaboration with researchers at the University of California, San Francisco to answer four primary questions: what are the unique stressors faced by law enforcement professionals; what are the positive and negative ways that officers cope with duty-related stress; is there a way to develop tools to maximize the emotional and physical health of police officers; and is there a way to test for genetic markers that may indicate vulnerability to— or resilience to—developing stress-related disorders (Police Stress & Health Program). Dr. Marmar brings to this work a quarter century of experience in research on trauma and PTSD with Vietnam and Iraq War veterans, fire departments, and disaster relief teams—including research on the prevalence of PTSD in 9/11 first responders. Like soldiers, Police officers must maintain high MEDICAL DIALOGUE REVIEW Fall 2014 performance even in the face of distressing events, making them an especially important group in which to understand risk and resilience to stress-related disorders. This article will focus on two of the center’s many findings and will discuss their implications for law enforcement personnel selection and training. Police Officers Face Particular Stressors For the average student, taking final exams may seem extraordinarily stressful, but serving as a police officer is without a doubt one of our country’s most stressful occupations. Within their first year on the job, New York’s new police recruits are exposed to potentially traumatic events, and it’s no secret that an officer’s job description entails the use of lethal force. In fact, Weiss et al. found that a quarter of police officers reported having to kill or seriously injure someone during the course of their careers (2010). Until the past few years, little research had been done on how this use of force affected police office- Fabbro rs psychologically. Studies of Iraq War veterans who have killed in combat, however, have found that an individual’s prior use of deadly force can increase his or her risk of developing some of the more serious forms of PTSD (Maguen, 2014). In addition to these risks, police officers on active duty also face potential threats to their own lives. The prevalence of these stressors, combined with a myriad of others, takes a severe toll on law enforcement professionals’ mental health. Between 7 to 15 percent of police officers develop duty-related Posttraumatic Stress Disorder over the course of their lifetimes with more showing symptoms of pre-PTSD, compared to an estimated 6.8 percent of individuals in the general population (Maia et. al, 2007; Kessler). While a small percentage of police exposed to critical incidents go on to develop PTSD, the condition has serious repercussions; PTSD is correlated with increased likelihood of divorce, inability to perform job duties, lifetime suicidal ideation and other major impairments in life function (Maia et al., 2007). To maximize the effectiveness of the police force, therefore, it is critical that officials develop a better understanding of the factors that protect recruits from stress-related mental health conditions. Certain psychological factors predispose police officers to developing PTSD after critical incidents; others appear to be protective To help understand which factors might predispose officers to developing stress-related mental health disorders--as well as which factors promote resilience Dr. Charles Marmar and colleagues conducted one of the first longitudinal studies of police. The research team followed 400 police officers in four cities— New York, Oakland, San Francisco and San Jose—during and after their academy training—and examined several factors (2010). One group, led by Chengmei Yuan at the University of California, San Francisco assessed a subgroup of 233 officers to determine which factors might promote resilience: the ability to “bounce back from negative emotional experiences and by flexible adaptation to the changing demands of stressful experiences” (Tugade and Fredrickson, 2004). These are also known as protective factors. Previous studies of protective factors in other subgroups have found that certain personality attributes, social networks and skills, basic attitudes of an individual toward him/herself and the world, and specific coping skills can all be protective factors that promote resilience. The research team set out to see which, if any, of these factors demonstrated a protective effect against stress in police. Officers were assessed using the NEO FiveFactor Inventory to measure five factors of personality: neuroticism, extraversion, openness, agreeableness and conscientiousness. They were also Volume 15 assessed on the World Assumptions Scale, a 32-self-reported questionnaire designed to assess an individual’s assumptions about his/her self-worth, the benevolence of the world and the meaningfulness of the world (Yuan). Finally, officers completed two measures of social support and functioning: The Sources of Social Support Scale (SOS), a 10-item test to measure social support previously used in the National Vietnam Veterans Readjustment Study; and The Social Adjustment Scale-Self Report (SAS-SR), a measure of social functioning. Two years later, the team assessed the same officers for symptoms of PTSD using the Civilian Mississippi Scale, a revised version of the Mississippi Scale for Combat Related PTSD, designed to capture associated traits of PTSD as specified by the DSM-III by asking officers to rate how often they had thoughts such as, “I have nightmares of experiences that happened during my police service.” Officers were also asked about their exposure to critical or traumatic incidents during the past two years, such as using lethal force of witnessing a death during duty. After controlling for demographic factors (a smaller percentage of Caucasian police officers, for example, go on to develop PTSD than do officers of color), the researchers determined several factors that appeared to be promote resilience in all officers. Surprisingly, differences in personality traits were not significantly co- MEDICAL DIALOGUE REVIEW 43 Fabbro rrelated with officers’ abilities to cope. Other results were less surprising. Officers with lower exposure to “critical incidents” during duty, such as having their life threatened, watching someone die, or being involved in a car accident, were predictably at less risk of developing PTSD. But of the officers exposed to traumatic experiences, the two traits that appeared especially protective against stress-related disorders were “greater assumptions of benevolence in the world” and “better social adjustment during training” (Yuan). While these traits promoted resilience, others placed officers at greater risk of developing PTSD and other stress-related mental health disorders. Another study associated with the longitudinal study revealed several traits that significantly increased the likelihood that officers would develop PTSD following a critical incident. The subgroups most likely to develop PTSD included: police officers with a history of childhood trauma, a family history of anxiety, a lack of social support, a history of mood disorders, or a history of substance abuse (Johnson). While these studies are some of the first into which factors may increase the risk of stress-related disorders or promote resilience in police officers, a few preliminary recommendations for police departments can be drawn. First, police academies may be able to better prepare officers from stress by adding instruction to help officers adjust socially dur44 ing training as well as to adopt assumptions of benevolence; previous studies have demonstrated that both traits are malleable, given the right conditions (Yuan). Second, an assessment of whether or not an officer candidate displays protective factors against or risk factors for developing PTSD could be conducted as additional criteria for place officers in best fit roles. A person with more protective factors against developing PTSD might be a better fit for a stressful active duty post than someone without those protective traits. One particular trauma that the researchers paid special attention to is how killing and injuring others in the line of duty affected police officers’ health. Komarovskaya et al. assessed 400 police officers of New York during academy training, and again five times during their first three years of service (2011). During those initial years, nearly 10 percent of officers self-reported that they had to kill or seriously injure someone in the line of duty and more than two thirds of officers reported that they had experienced at least one event in which they felt a direct threat to their own lives. After 36 months of duty, researchers assessed officers’ mental health symptoms using the Beck Depression Inventory-2nd edition to measure symptoms of depression and the Mississippi Combat Scale-Civilian Version for symptoms of PTSD. They also conducted two tests to measure levels of social adjustment and alcohol abuse. MEDICAL DIALOGUE REVIEW Fall 2014 Komarovskaya and colleagues found that injuring or killing another person in the line of duty, while only marginally associated with depression symptoms, was significantly associated with developing PTSD (p < .01). These results were the first to highlight the severity of the mental health impact of killing or seriously injuring someone in the line of duty. Hopefully one result of the study will be to draw greater mental health services to officers following exposures. Physiological risk factors While mental health conditions have long been viewed as conditions of the mind that do not manifest in physical symptoms, we now know that there are several physiological signs of stress. Dr. Marmar and his team have recently focused on documenting physiological symptoms of stress and studying their connection to mental health diseases in police. To do so, Pole and others tested to see how quickly officers in training would startle—and then reassessed officers following one year of duty (Pole et al.). All participants were brought into the laboratory and shown videos of real-life, dangerous police situations. Following the viewing, several physiological reactions were measured, including an individual’s tendency to blink, a person’s heart rate, and changes in salivary 3-methoxy-4-hydroxyphenylglycol (MHPG) and cortisol from the baseline, after contro- Fabbro lling for demographic factor. At the start of the study, none of the initial group of 400 officers had a significant chronic axis 1 psychiatric disorder. During the years covered by the study, the initial recruits experienced several critical events: subjects had an average of seven potentially traumatic incidents including encountering a dead or dying body (nearly 9 in 10 officers), witnessing another officer’s injury or death (more than 1 in 5), being seriously injured (more than 1 in 10) and having to shoot to kill. The research team found that officers who startled most easily during training were more likely to develop PTSD, after controlling for the number of incidences they had encountered and for other demographic factors. The most profound effect was seen in officer candidates who had been exposed to trauma in childhood. Twentyfive percent of new police recruits had experienced trauma prior to the age of 13, from exposure to violence, abuse or accident. While this rate was similar to that measured in the general population, the study observed that recruits who reported a history of trauma in childhood showed initial changes in psychological and biological reactivity compared to their peers, including a tendency to startle more quickly when exposed to videos of dangerous police situations, that were predictive of developing PTSD 4 years later. At the start of the study, new recruits who had experienced early childhood trauma already showed upregulated endocrine responses to the videos of police trauma (including sustained 3-methoxy-4-hydroxyphenylglycol reactions and elevations of salivary catecholamine). They were also more likely to demonstrate a startle response to sound in the form of blinking eyes or increased heart rate compared to officers who had not experienced childhood trauma, even though neither group had a measurable psychiatric illness. When assessed four years later, the officers who had been exposed to childhood trauma were more likely to show a greater reactivity (as measured by adrenergic and glucocorticoid reactivity) to real-life trauma while on duty. According to Johnson, “Officers who followed trajectories of resilience and recovery over 4 years mounted significant increases in cortisol in response to the experimental stressor, while those following a trajectory of chronic increasing distress had no significant cortisol change in response to the challenge.” The team concluded that a “blunted cortisol response to a laboratory stressor is a risk factor for later vulnerability to distress following significant life stressors. This is another trait that could be measured by police academies when determining where to place officer candidates. Some mental health professionals have expressed Volume 15 concern that data on which factors predispose officers to developing PTSD could be used to “screen out” potential officers from active duty. Associate Director of Clinical Training at the University of Pennsylvania's Department of Psychology, Melissa Hunt, in Philadelphia, expressed concern that, “ultimately, this kind of research will be used for screening people out of certain professions: 'That kid shouldn't be a Green Beret, maybe this one shouldn't be a police officer’” (Johnson). However, Dr. Marmar maintains that the aim of the program is not to weed out officers, but to provide them with better training and placement. As he explained the aims at a conference for Anxiety Disorders of America in 2012, “I think the view is that this kind of information could be used not to exclude people from service, but to provide resilience-building training and/or triage people into different roles” (Johnson). At the moment, the research continues, as officers continue to be assessed later in their careers to see if trends established during their time in the academy and several years out continue to hold. The hope is that a better understanding of the stressors officers face—as well as the genetic, physiological and psychological factors that allow them to be resilient despite stress, will lead to healthier and effective police departments for our urban areas. MEDICAL DIALOGUE REVIEW 45 Fabbro REFERENCES Brunet, A., Weiss, D., Metzler, T., Best, S., Neylan, T., Rogers, C., Fagan, J. & Marmar, C. The Peritraumatic Distress Inven tory: a proposed measure of PTSD Criterion A2. Am J Psychiatry 2001; 158(9), 1480-5. Galatzer-Levy, Isaac R. et al. Cortisol response to an experimental stress paradigm prospectively predicts long-term distress and resilience trajectories in response to active police service. (2014). Psychiatric Research, 56(September 2014), 36-42. Retrieved November 18, 2014, from http://www.journalofpsychiatricresearch.com/article/S00223956(14)00133-2/abstract?showall=true= Johnson, K. (2012, April 17). Childhood Trauma 'Profound' Predictor of PTSD. Retrieved November 18, 2014, from http://www.medscape.com/viewarticle/762166 Kessler, R.C., Berglund, P., Delmer, O., Jin, R., Merikangas, K.R., & Walters, E.E. (2005). Lifetime prevalence and age-of onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62(6): 593-602. Komarovskaya I., Maguen S., McCaslin S. E., Metzler T. J., Madan A., Brown A. D., Galatzer-Levy I. R., Henn-Haase C., Marmar C. R. (2011).The impact of killing and injuring others on mental health symptoms among police of ficers. Journal of Psychiatric Research, 45(10), 1332-1336. doi: 10.1016/j.jpsychires.2011.05.004 Maguen, S., Madden, E., Bosch, J., & Galatzer-Levy, I. (2013). Killing and latent classes of PTSD symptoms in Iraq and Afghanistan veterans. Journal of Effective Disorders, 145(3), 344-348. Retrieved November 18, 2014, from http://www.sciencedirect.com/science/article/pii/S0165032712005903 Maguen, S., Metzler, T.J., McCaslin, S.E., Inslicht, S., Henn-Haase, C., Neylan, T.C., & Marmar, C.R. (In press). Routine Work Environment Stress and PTSD Symptoms in Police Officers. Journal of Nervous and Mental Disease. 1480-5. Maia, D.B., Marmar, C.R., Metzler, T., Nobrega, A., Berger, W., Mendlowicz, M.V., Coutinho, E.S., Figueira, I., 2007. Post traumatic stress symptoms in an elite unit of Brazilian police officers: prevalence and impact on psychosocial functioning and on physical and mental health. Journal of Affective Disorders 97, 241–245. Pole, N., Neylan, T., Best, S., Orr, S., & Marmar, C. Fear-potentiated startle and posttraumatic stress symptoms in urban police officers. Journal of Traumatic Stress 2003; 16(5), 471-479. Police Stress & Health Program. (n.d.). Retrieved November 18, 2014, from http://policestressandhealth.med.nyu.edu/ Tugade, M.M., Fredrickson, B.L., 2004. Resilient individuals use positive emotions to bounce back from negative emotional experiences. Journal of Personality and Social Psychology 86, 320–333. Weiss DS, Brunet A, Best SR, Metzler TJ, Liberman A, Pole N, et al. Frequency and severity approaches to indexing expo sure to trauma: the critical incident history questionnaire for police officers. Journal of Traumatic Stress 2010;23: 734-43. Yuan, C., Wang, Z., Inslicht, S.S., McCaslin, S.E., Metzler, T.J., Henn-Haase, C., Apfel, B.A., Tong, H., Neylan, T.C., Fang, Y., & Marmar, C.R. (2010). Protective factors for posttraumatic stress disorder symptoms in a prospective study of police officers. Psychiatry Research, 188(1), 45-50. 46 MEDICAL DIALOGUE REVIEW Fall 2014 Popkova The Ebola Epidemic and its Fallout in West Africa By Alina Popkova “As of August 2014, only about 2200 medical staff were sent…by Doctors Without Borders, the World Health Organization, and the Center for Disease Control and Prevention to work with local medical practitioners… this number is far from enough for the nearly 203 million people who live in these countries and therefore some Ebola patients go untreated.” For the first time since its recognition as a virus more than 40 years ago, Ebola has been confirmed in multiple countries. The fear of contamination has increased coverage of Ebola and has had a surging effect on its international response in West Africa from health agencies such as Doctors Without Borders. While these efforts have had some successes, many of the people in West Africa continue to die from Ebola and the spread of the virus is nowhere near diminishing. It is believed that the Ebola virus first spread from animals that were infected by contagious bats nearly 40 years ago and has been able to infect humans by using a specific biomedical Figure 1. mechanism. In 2008, the researchers at the University of Texas Medical Branch at Galveston were able to determine this mechanism. They found that upon entering the body, the virus infects a host cell by activating the phophoinositide-3 kinase pathway on the cell membrane which makes the cell draw in the virus in an endosome capsule. Once the virus is inside the cell, it can replicate and then burst through at an appropriate time to infect others. Current research focuses on developing an antibiotic against Ebola by blocking this PI3 kinase pathway so that the virus becomes trapped inside its capsule and cannot escape to replicate. However, there has been little success in this endeavor. One such treatment to stop the virus once a patient is infected is ZMappTM. which is currently being developed by Mapp Biopharmaceutical Inc. The drug, which was first identified as a candidate against Ebola in January 2014, is a combination of three monoclonal antibodies that are grown by inserting the genes for the antibodies into a DNA vector and developing the DNA in the Nicotiana benthamiana plant. It is believed that Zmapp works by binding to the Ebola virus and stopping it from continuing its infection of the patient. However, since the drug is fairly new, not enough trials have been run to know whether or not it is effective against Ebola. Furthermore, only a small amount of the drug had been manufactured and is available for use on patients in West Africa so other methods are used to prevent the spread of the virus. Organizations such as Doctors Without Borders, the World Health Organization and the United Nations have built up an international response in the form of doctors, medical supplies and donations to West Africa to stop Ebola’s spread in West Africa. Trained doctors Volume 15 MEDICAL DIALOGUE REVIEW 47 Popkova go on missions and visit villages in the West African countries affected by the Ebola outbreak to isolate and treat the patients. They visit the people who are suspected of having Ebola and look for the symptoms associated with the disease such as severe hemorrhagic fever, muscle pain, weakness, and vomiting which can show up anywhere from 2 to 12 days after a patient becomes infected. The patients then have to be taken from their villages to specialized Ebola hospitals where they are treated. At the Ebola hospitals, the patients are diagnosed using an array of tests such as the ELISA, polymerase chain reaction or virus isolation method which can show if the virus is pres- Figure 2. ent in a blood sample belonging to the patient. Once it is established that a patient does indeed have Ebola, he or she is isolated and cared for until the disease goes away. The doctors give patients intravenous fluids, balance their electrolytes levels, maintain oxygen and blood pressure levels and cure them of any infections they may have besides Ebola, since the symptoms of other infections will have a cumulatively worse effect on the patient’s health and chances of survival. Once the symptoms subside, the patients are tested for antibodies against the Ebola virus and if they do have them, then they are cured of the virus and are returned home. The patients are given a certificate proving that they are cured so that the villagers will be more acceptable of them and more likely to welcome them back. Although this is how the procedure used for containing Ebola is structured, in real 48 MEDICAL DIALOGUE REVIEW life the response effort has had many setbacks. Most of the organizations such as Doctors Without Borders and the World Health Organization keep every doctor’s mission to West Africa short, lasting only 6 to 8 weeks. This is because the doctors can become fatigued, which would not help the effort to fight the outbreak, and there are not enough doctors to replace those that return. As of August 2014, only about 2200 medical staff were sent to regions of Guinea, Sierra Leone, Liberia and Nigeria by Doctors Without Borders, the World Health Organization, and the Center for Disease Control and Prevention to work with local medical practitioners there. This number is far from enough to for the nearly 203 million people who live in these countries and therefore some Ebola patients go untreated. Along with a limited amount of doctors willing to go, there is also a limit in the number of hospitals and supplies available to accommodate Ebola patients. According to the World Health Organization, there are only 14 hospitals and Ebola treatment centers available in Sierra Leone, Liberia and Guinea, which is not enough to account for the people living in the outbreak regions. Ebola patients are being turned away once hospitals become overcrowded. This again leads to some Ebola patients who are missed by the medical staff and go untreated. As for the patients who are received by the hospitals, there is not enough food and water available because of the limited donations. This means that not every patient in the hospital receives the care that is necessary for full recovery from Ebola. The cases where not enough medical staff, hospitals or supplies are available to the Ebola patients shows a major fault in the international healthcare and disease response system in its ability to organize an effective response to an infection as deadly as Ebola, for which the survival rate is approximately 50%, according to the WHO. Along with the setbacks in the international response to Ebola, there have been setbacks with gaining the trust and cooperation of the people living in West Africa. Many of the people do not understand the dangers of the Ebola virus and the safety measures that should be taken to prevent its spread. For example, Fall 2014 Popkova Figure 3. some of the Ebola patients lie and say they do not know others who are infected in order to protect them. Although the Ebola patients have a valid cause for this since as mentioned previously, the hospital conditions are very rough and difficult to live in, the Ebola hospitals are also the best possibility many of the people infected with Ebola have for making a recovery. Yet another example is that the villagers of West Africa are also not aware that their daily routines can further spread Ebola. For example, the death burial rituals of many villages require that the body be washed before burial but this can spread the virus to living people. The Ebola virus spreads from person to person through contact with bodily fluids such as urine, saliva or sweat or through contaminated objects such as syringes. Here the health organizations such as Doctors Without Borders can offer a solution by increasing awareness of how the disease spreads and how to avoid infection. This shows that the health organizations are able to isolate and treat present Ebola patients and prevent new ones by informing the people living in outbreak areas of ways they can limit the infection spread. But this can only happen if they have the resources necessary to fund their missions in West Africa. As of October 12, 2014, there have been 8,997 cases of Ebola in West Africa and 4,493 reported deaths. This is largely due to the lack of resources available from the governments to provide the necessary aid to the affected communities. This is where government funds and private grants and loans come into play to provide fiscal aid, such as those just approved by the World Bank Group. On September 16, 2014, the World Bank Group approved the United States to provide $105 million for the Ebola containment effort in Sierra Leone, Liberia and Guinea. These countries have been hit heaviest by the Ebola outbreak and have no medical infrastructure to fight the disease. For this reason, most of the donations are expected to go towards funding for an Outbreak Response Plans and towards obtaining enough international workers to carry out the health services. Without aid, there were only 50 doctors available in Liberia alone to respond to the beginning of the Ebola outbreak back in March 2014. Liberia has been most affected by the Ebola virus and shows just how insufficient Figure 4. the sources for aid to West Africa were. Since March, international health organizations continue to send what resources they have, whether it is workers, donations or medical supplies, to West Africa in an effort to contain the outbreak. As of now, it is clear that the Ebola outbreak is nowhere near diminishing and a new approach is needed towards containing and treating the virus. At the end of this year, relief funds are beginning to be sent to West Africa in an effort to contain and treat patients who have Ebola. Furthermore, there is now a push towards increasing the production and testing of the drug ZMappTM so that it will hopefully become available to patients in West Africa as another resource. However, these efforts are new and it is still unclear whether they will have a lasting effect and end Ebola. Volume 15 MEDICAL DIALOGUE REVIEW 49 Popkova REFERENCES "Africa." Ebola: Economic Impact Could Be Devastating. “http://www.worldbank.org/en/region/afr/publication/ebolaeconomic-analysis-ebola-long-term-economic-impact-could-be-devastating” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 16 Oct. 2014. “http://www.cdc.gov/ vhf/ebola/” Ebola:World Bank Group Approves US$105 Million Grant for Faster Epidemic Containment in Guinea, Liberia, and Sierra Leone. “http://www.worldbank.org/en/news/press-release/2014/09/16/ebola-world-bank-group-approves- grant-faster-epidemic-containment-guinea-liberia-sierra-leone” James Harding Giahyue and Bate Felix. "Ebola Patients Keep Escaping Liberian Hospitals." Business Insider. Business Insider, Inc, 06 Sept. 2014. “http://www.businessinsider.com/r-ebola-outbreak-stirs-anger-in-fragilelibe ria-2014-9” “Mapp Bio.” Mapp Bio. Mapp Biopharmaceuticals, Inc., 2012 “http://www.mappbio.com” Population of All Countries of the World / All National Populations Largest to Smallest - Worldatlas.com." Population of All Countries of the World / All National Populations Largest to Smallest - Worldatlas.com “http://www.worldatlas. com/aatlas/populations/ctypopls.htm” University of Texas Medical Branch at Galveston. "Ebola Cell-invasion Strategy Uncovered." ScienceDaily. ScienceDaily, 5 September 2008. www.sciencedaily.com/releases/2008/09/080903172428.htm Weintraub, Karen. "Doctors and Nurses Risk Everything to Fight Ebola in West Africa." National Geographic. “http:// news.nationalgeographic.com/news/special/features/2014/08/140829-ebola-caregivers-doctors-nurses- west-africa-sierra-leone/” "What Is the Ebola Virus's Survival Rate? And Other Key Questions About the Epidemic." National Journal. 50 MEDICAL DIALOGUE REVIEW Fall 2014 Martinez Political Conditions on Humanitarian Aid: How Health and Political Relations Mix and Why It Concerns You By Andrea Martinez “Why help anyone who hasn’t helped us? Why make it easy on a humanitarian aid organization that helps the people who killed, or will kill, our own people?” It seems as if anywhere we go, people ask for money from us. On the streets, we are asked for donations. A cashier asks for money in exchange for a Big Mac. During commercials of popular television shows, advertisements ask for money. They do not ask for much; some are even content with spare change. And after we donate money, we feel good about ourselves, as if we are making an impact on the world. Despite the existence of humanitarian aid, issues like poverty and world hunger remain unsolved. Even considering all the money we have seen donated, it is almost as if nothing has been done in support of these issues. Recently the UN declared that the fight against Ebola fell short of its fundraising goal. Out of the desired billion, only 250 million dollars were collected. This is interesting, as President Barack Obama called Ebola “a growing threat to regional and global security”. A shortage of money for humanitarian aid— considering the amount of suffering and death West Africa is experiencing—should come as a surprise. Collecting from all the major powers in the world should be an easy task. Yet nobody should be surprised as to why only 25% of the money has been collected. This is not the first time a fundraising goal has not been met, and this will certainly not be the last time. The International Red Cross was founded in 1863, in Geneva, by Henry Dunant and Gustave Moynier. Dunant and Moynier strived to create an organization that preserved the lives and dignity of war victims. Today, the International Red Cross receives help from around 97 million volunteers around the world. Médecins Sans Frontières (MSF) was founded over one hundred years afterwards. Even the United Nations (UN) was created after World War II to show international cooperation, a way to facilitate aid and discussion in a peaceful setting, but in the short years following its creation, the UN lacked the proper administration to be effective, even though it was terribly needed right after a devastating war. Luckily, the United States stepped in and led the reconstruction of Volume 15 Europe. Yet there was a more insidious reason behind this aid, for no country ever takes an action without a higher motive. The Marshall Plan was the United States’s response to the growing threat of communism during the Cold War, in which the United States gave the equivalent of 160 billion dollars in current dollar value in economic support to help rebuild European economies; developmental and humanitarian assistance filled the void left by the withdrawal of diplomacy. At one point, Soviet deputy foreign minister Andrei Vyshinsky said the Marshall Plan violated the principles of the UN, accusing America of trying to impose its will on independent states by using economic resources distributed as relief to needy nations as an instrument of political pressure. Indeed, Vyshinsky was not wrong in his assumption, as the Marshall Plan countries remained capitalist amidst the growing amount of communist states in Eastern Europe. Humanitarian aid not only requires effort from the volunteers and donations, but there is also another side many MEDICAL DIALOGUE REVIEW 51 Martinez do not account for: politics. Starting with the conflict in Iraq, the Humanitarian Practice Network writes about the conditions humanitarian agencies experience from security crises to policy quandaries to the need to interact with forces that the international community deems as illegitimate. Especially in areas like Iraq and Afghanistan, humanitarian agencies are seen as taking sides. This comes from their unique political position, where they need to work with an occupying power, which also happens to be the agency’s primary funder as well. This is the main issue dubbed as the Samaritan’s Dilemma: can a humanitarian aid agency be neutral? Fabric Weissman, one of the co-authors of the book Humanitarian Negotiations Revealed: The MSF Experience, mentioned the reality in the Taliban-held Afghanistan, stating that they claim responsibility of the goods and services that humanitarian groups are providing, which allows the Taliban to appear to the local population as effective governors. “On many occasions,” Weissman continues, “the MSF, like other organizations, uses combatants to ensure the safety of its teams and convoys.” Just by existing in areas of conflict, the agency inadvertently influences the behavior of policy decisionmakers, a coveted advantage not many have. Added to the fact that humanitarian agencies need money from large benefactors, it seems as if we found a match made in heaven. But this assumption has complica52 tions. The humanitarian principles of humanity, neutrality, and impartiality serve to create an ethical framework that defines and dictates the humanitarian sphere in which relief agencies operate. This definition is then contorted by the involvement of politics. Once humanitarian aid covered a narrow set of relief activities carried out by a small group of agencies. Now it has become a more complex activity involving rehabilitation work. This transformation created a whole new set of standards for the performance in the field, and led to increasing uncertainties on the quality of humanitarian responses and its accountability. This accountability has even worsened in the advent on 9/11. Since the “North” becomes more focused on terrorism and its real or perceived ramifications, humanitarian agencies are affected by the double standards applied by the North to the South. This is how humanitarian agencies become extensions of the security and foreign policy objectives of the North in crises such as Afghanistan, Kosovo, and Iraq. The “North” also makes it hard for aid groups to fully operate. US counter-terrorism laws that have entangled humanitarian organizations in a web of regulations and requirements, which add to their costs, slow down their transactions, and sow distrust between them and their local partners. The laws further stipulate that providing support resources to terrorists, even if not for ter- MEDICAL DIALOGUE REVIEW Fall 2014 rorist purposes, could result in criminal prosecution. Humanitarian organizations are stuck between a rock and a hard place. They want to save lives, but saving these lives involves having relationships with enemy organizations that the international community may not agree with. But if they don’t create these relationships, the humanitarian aid will never actually benefit the people who need it. This entanglement is one of the main reasons why not many countries donate money to these organizations, or why the transactions to accessing the money are so muddled in paperwork and bureaucracy. Though the Islamic State of Iraq and the Levant (ISIS) has stolen the spotlight as the newest story from the Middle East with their grotesque acts of violence, the Syrian civil war is not over, and the death count continues to rise. Even if the conflict is no longer at the forefront of the media outlets, chilling facts of humanitarian involvement still remain. Claimed to be 60 percent underfunded in 2012 by the United Nations, the Syrian Civil War is not the only instance of catastrophes that receive minimal aid. Even MSF complained about lack of resources, citing that medical assistance is at risk for thousands of Syrians living in overcrowded conditions, suffering psychological distress, and unable to afford medical care. But the Syrian Civil War is not the only instance of underfunded aid. Iraq, South Sudan, Martinez Afghanistan, Colombia, Israel, and Myanmar are but the few amount of examples of countries with underfunded aid. Many of the deaths the Rwandan Genocide in 1994 could have been avoided if the international response had been better. What all of these conflicts have in common is a lack of resources, but the reason behind this lack is simply politics and its influence on humanitarian aid. Then again, we hear stories about all this suffering and, though a horrified reaction is perfectly normal, we eventually move on and do not think much about them until the media bombards us with images and videos and dollar signs accompanied by trailing zeroes and a body count. Why should we care what is going on outside of this country, this continent? Each government only has an obligation to its constituents, its citizens. Syrians don’t pay taxes to the American government. Afghani children won’t become the next American soldiers, doctors, engineers. American history was not built by Colombians. Why help anyone who hasn’t helped us? Why make it easy on a humanitarian aid organization that helps the people who killed, or will kill, our own people? These are perfectly reasonable questions to have, and it isn’t inhumane to think this way. Worrying about a person thousands of miles away over the person standing next to you is almost impossible for some of us. Yet, with the advent of globalization, the people living in Iraq are interconnected with us by an invisible link. It’s impossible for us to see it or even predict the ramifications, but the link exists. We established the link when we built ships to sail the oceans, when we conquered the New World, when we forcibly opened Japanese harbors, when we connected everyone with the Internet. As much as we want to go back to the days where we didn’t even know what Saudi Arabia was, Volume 15 we live in an era in which children travel on airplanes before they’re five and teenagers have smartphones. Recently people have expressed much concern with Ebola, a disease that surged in West Africa and has started to spread throughout the world. Ebola is a link of globalizations whose effects we can see. The media saturates us with doomsday scenarios in America, but Ebola is not a problem in developed countries, but more of a problem in countries that lack proper hygiene and nutrition. West Africa needs the money more than we need it, and the money goes to save lives, and we can see the effects of our money because we are interconnected. Disease is just one of the effects globalization has brought, and it isn’t the only one. Containment in West Africa did not stop Ebola from spreading, and at least the disease can be monitored. The seeds of hatred for our Western lifestyle can only be stopped by humanitarian aid. MEDICAL DIALOGUE REVIEW 53 Martinez REFERENCES “AID POLICY: The Politics of Humanitarian Principle.” IRINnews. IRIN, 28 Oct. 2011. Web. 14 Nov. 2014. Curtis, Devon. “Politics and Humanitarian Aid: Debates, Dilemmas and Dissension.” Politics and Humanitarian Aid: Debates, Dilemmas and Dissension - HPG Reports 10 - Research Reports and Studies (n.d.): n. pag. ODI. ODI, Apr. 2001. Web. Donini, Antonio, Larry Minear, Peter Walker, and Feinstein International Famine Center. “Humanitarian Exchange Maga zine.” Iraq and the Crisis of Humanitarian Action. Humanitarian Practice Network, 26 Mar. 2004. Web. 14 Nov. 2014. Eriksson, John R., Tor Sellström, Howard Adelman, Astri Suhrke, Bruce Jones, John Borton, and Krishna Kumar. The In ternational Response to Conflict and Genocide: Lessons from the Rwanda Experience. Copenhagen?: Steering Committee of the Joint Evaluation of Emergency Assistance to Rwanda, 1996. OECD. OECD, Mar. 1996. Web. "Making US Humanitarian Aid to Syria a Political Tool Is Ineffective and Dangerous." The Christian Science Monitor. The Christian Science Monitor, 13 June 2013. Web. 14 Nov. 2014. Mollins, Julie. "Cb1f21c7-7d98-4ea3-903f-c5de10e41700." Thomson Reuters Foundation. Thomas Reuters Foundation, 11 Sept. 2012. Web. 14 Nov. 2014. Nakamura, David. "Obama: Ebola Is 'growing Threat to Regional and Global Security'" Washington Post. The Washington Post, 25 Sept. 2014. Web. 14 Nov. 2014. Nelson, Anna. "Six Underfunded ICRC Operations." ReliefWeb. N.p., 26 June 2014. Web. 14 Nov. 2014. Pallage, Stephane. Recognizing the Political Side of Humanitarian Aid Stéphane Pallage , ESG UQAM (n.d.): n. pag. CIR PEE. CIRPEE. Web. "Trust Fund Factsheet - Ebola Response MPTF." Trust Fund Factsheet - Ebola Response MPTF. United Nations, n.d. Web. 14 Nov. 2014. Vynshinsky, Andrei. "Vyshinsky Speech to U.N. General Assembly." Vyshinsky Speech to U. CNN, n.d. Web. 14 Nov. 2014. 54 MEDICAL DIALOGUE REVIEW Fall 2014 Reztsova The Ebola Time Bomb By Mariya Reztsova “It is apparent that without further intervention by the UN in partnership with nations around the globe, the epidemic can reach its tipping point and can develop into a global problem.” Abstract: The Ebola virus has made headlines around the world with its gruesome and shocking images. However, what the general public isn’t informed about is how the virus outbreak occurred and how people got infected in the first place. This article explored the virus from its ancestry and structure to its effect on impoverished countries of western Africa. It is apparent that without further intervention by the UN in partnership with nations around the globe, the epidemic can reach its tipping point and can develop into a global problem. In recent news the Ebola virus seemed to be holding the spotlight. With thousands dead and the virus reaching American shores, a growing panic has been brooding. But where did this new virus come from? And how was it able to become an epidemic? The Ebola virus is not a newly discovered disease. According to a report by Joseph McCormick in the Journal of Infectious Diseases, it is one of the genera of the Filoviridae viral family and has circulated amongst primates and mammals in the central African rain forests for many years. Ebola haemorrhagic fever, as the virus is formally known, Figure 1: Ebola Virus Structure (Source: Swiss Institute of Bioinformatics). was discovered 30 years ago. The first genus of the Filoviridae family, the Marburgvirus, was discovered in 1967 during an outbreak in Marburg, Germany (CDC, “Outbreak of Ebola Viral Hemorrhagic Fever”). At the time, laboratory workers were infected while working on infected tissues recovered from the Circopithecus aethiops monkeys imported from Uganda (McCormick, “Ebola Virus Ecology”). The subtype filovirus the Ebola haemorrhagic fever, was discovered in 1976. Two outbreaks of the disease occurred simultaneously in southern Sudan and northern Zaire (now the Dominican Republic). It was ascertained later on that the two outbreaks were caused by two different species of Ebola, the Ebola-Sudan virus and the Ebola-Zaire virus. Ebola-Zaire the more fatal of the two had an 88% fatality rate and killed 280 people (WHO, “Ebola virus disease”). In 1994, a third Ebola virus species was discovered in Cote d’Ivoire. The virus was discovered in an ethnologist who was exposed to the virus while working with chimpanzees in the Tai Forest reserve. As scientists later discovered there was a recurring theme of the filovirus spreading from primates to humans through close contact with the tissues and fluids of infected primates. Though the virus has infected humans, historically filovirus’ have wrecked havoc on populations of primates such as the mandrills and baboons and causing outbreaks in remote areas of Africa (McCormick, “Ebola Virus Ecology”). The largest outbreak of the Ebola virus in humans occurred recently in Liberia, Sierra Leone, Guinea, and Nigeria around March 2014. The current Ebola virus shares 97% resemblance to Ebola-Zaire strain first discovered in 1976 (Ansari A. “Clinical features and Pathobiology of Ebolavirus Volume 15 MEDICAL DIALOGUE REVIEW 55 Reztsova Figure 2: (Source: U.S. Centers for Disease and Control & BBC). infection”). According to the World Health Organization (WHO), thousands of people from western Africa have been infected and with almost a 50% fatality rate. Ebola virus is an RNA virus; its genome contains only RNA strands and has a method of infection and replication similar to HIV. The structure of the virus is referred to as the virion and consists of four parts: the nucleocapsid, the matrix, the RNA polymerase complex, and the lipoprotein membrane envelope (Figure 1). The virion is rod-shaped and 650-14,000 nm in length with a diameter of 80 nm (Konstantinov I. et la. “The Ebola Virus”). The RNA of the virus is transcribed into cDNA in the host cell using an enzyme called Reverse Transcriptase. The seven genes on the cDNA are then translated into four structural proteins (VP24, 30, 35, 40), an RNA polymerase (L), a glycoprotein (GP), and a nucleoprotein (NP) that are all about 19,000 nucleotides in length (Ascenzi P. et la., “Molecular Aspects of Medicine”). The lipoprotein membrane of the virion contains multiple copies of the glycoprotein (GP) which are seen as spikes in X-ray analysis and NMR spectroscopy. It is this lipoprotein which allows the cell to fuse into a host cell. The high lipid content and glycosylation of the membrane also help in penetration of the host cell by producing viral proteins that contribute to suppressing the host’s immune system (Ansari A., “Clinical Features and Pathobiology of Ebolavirus infection”). One of the staple characteristics of the virus 56 MEDICAL DIALOGUE REVIEW that seems to contribute to its high virulence is its ability to vary its shape and size in response to environmental stimuli. The Ebola virus enters a host when there is direct contact with the body fluids (blood, semen, mucus, urine, saliva, and feces) of an infected person (Ghayourmanesh S, & Hawley H., “Ebola virus”). Usually this occurs when eating bush meat or wildlife meat that is infected, using unsterilized needles, contact with dead infected bodies, and unprotected sex. The route of infection is usually through mucosal surfaces, breaks/ abrasions in the skin, and/or pregnancy (Feldmann, Heinz, & Thomas W. Geisbert, "Ebola Haemorrhagic Fever."). When the Ebolavirus enters the body it disables the immune system and the vascular system. It does this through infecting important cells of the immune system such as dendritic, macrophage, and endothelial cells (Ansari A., “Clinical Features and Pathobiology of Ebolavirus infection”). The dendritic cells are responsible for presenting antigens to T-cells and lymphocytes in order to initiate an immune response (Steinman, “Introduction to Dendritic Cells”). When these cells are infected it is difficult for the body to recognize infections and create a rapid response to ward off the infection. Macrophage cells are immune cells that function to recognize, engulf, and destroy target cells. Macrophage cells are part of the body’s second line of defense; they secrete a chemical called cytokines to attract more macrophages and inducing feverish symptoms (Mandal, A. “What is a Macrophage?”). When these cells are destroyed and infected by a virus the body cannot as effectively protect itself from virulent viruses or even simple infections. Endothelial cells are cells that form the lining of blood vessels. They function to provide blood to cells of the body. When these cells are infected low blood pressure and internal bleeding can occur within the body (Alberts B, Johnson A, Lewis J, et al., “Blood Vessels and Endothelial Cells”). According to the World Health Organization (WHO), once a human is infected by the Ebola virus symptoms arise in 2-21 days. Only when symptoms are onset can the virus be transmitted on to others. The first sign of infection are usually symptoms of fever, headache, Fall 2014 Reztsova sore throat, muscle pain, and fatigue (WHO). Since these symptoms are highly similar to the flu the Ebola virus can be difficult to detect without adequate blood tests for white blood cell and platelet counts. The second and more severe symptoms that follow are vomiting, diarrhea, impaired liver and kidney function, rash, and in some cases internal and external bleeding (Figure 2). In some cases severe symptoms such as seizures, heavy bleeding, and brain damage can occur. There is a 50% and higher mortality rate once a person is infected. The countries which currently have critical outbreaks of the Ebola virus are Guinea, Sierra Leone, and Liberia (Figure 3). These countries are highly impoverished with some of the lowest PPP per capita in the world. For example, Guinea is the fourth poorest country in the world with a PPP per capita of $394.25 (Valentina Pasquali, Global Finance Magazine). With high poverty rates and high corruption these countries have inadequate health care systems to treat many diseases much less to deal with critical outbreaks. Liberian President Ellen Johnson Sirleaf stated “We were not prepared to really fight this battle in terms of the material, the training, the people, the expertise,” (qt. Time “Racing Ebola”). The inadequate health care plus the close proximity within rural villages and the large populations living within villages created a dangerous scenario. Once a person developed Ebola it lit a spark that spread through the country like wild fire. According to The New England Journal of Medicine the first person who contracted the disease, or Patient Zero, was possibly a two year old boy from a village in Guinea. How the disease was contracted in the first place is currently unknown. In a TED talk called “Contagion,” Dr. Todd Disotell commented that the most common ancestry of the current Ebola virus is the Zaire virus. In fact the Ebola virus has a 97% resemblance to the Ebola-Zaire strain first discovered in 1976 (Ansari A., Journal of Autoimmunity). According to Dr. Disotell the Zaire virus is most commonly found in bats and can spread to primates. It has been known that some species of the fruit bat carry the Ebola virus without exhibiting any symptoms. It is theorized by scientist and reported by Time magazine that the Ebola virus was contracted from the consumption of an infected fruit bat, a type of bush meat eaten in rural African countries. This created a spillover event or the first animal-to-human transmission of the virus. According to Madison Park a reporter for CNN, when the boy died on December 6, 2013 near Gueckedou, Guinea the virus spread to his family members. When these family members died and had open funerals the people who attended contract the virus from the exposed dead bodies and spread it to people within their villages. Without adequate treatment and the isolation of the infected the virus spread to Sierra Leone and Liberia. There is currently neither a cure nor a vaccine for Ebola. Infected individuals are put on supportive therapy, a system maintenance method in which doctors administer IV fluids and try to balance the bodies electrolytes. Doctors try to maintain oxygen and blood pressure levels and treat other present infections (CDC). That is of course if there is an adequate medical facility available. In the majority of areas that Ebola has affected do not. The only thing that Figure 3: Map of Outbreaks (Western Africa) (Source: U.S. Centers for Disease Control). Volume 15 MEDICAL DIALOGUE REVIEW 57 Reztsova impoverished areas can do is try to contain the disease so that it doesn’t spread farther. The Centers for Disease Control (CDC) recommends that three steps should be taken to prevent the spread of an epidemic. First, infected patients are isolated and their disease confirmed. Then, people who have been recently in contact with the infected person are tracked down Figure 4: Fighting Ebola (Source: Time Magazine “Racing Ebola”). and identified, a process known as contact tracing. Finally, the people who were in contact are watched for symptoms. The incubation period for Ebola is 21 days, so if the contact does not exhibit symptoms in three weeks they’re released (Time, “Now Arriving”). But even this process is difficult to follow through because of the densely populated areas of western Africa and widespread confusion. Another problem is that many people live in fear of the disease and try to hide their sick loved ones (Time, “Racing Ebola”). This has caused many cases to go unreported and the virus to spread as uninformed people handled infected bodies without protection and 58 MEDICAL DIALOGUE REVIEW cared for sick loved ones, contracting the infection themselves. A late response to contain the disease also allowed the Ebola virus to reach epidemic levels. The virus first struck a Guinean village in March 2014 but many health officials believed the virus would stop on its own accord. However, their latent response allowed the virus to spread to Liberia and Sierra Leone. Just like that an epidemic ensued. By the time the UN, top officials within the country, and nonprofit groups were informed the virus was already in three countries infecting hundreds with a 50% fatality rate. Panic spread, people locked infected individuals in empty buildings, and hospitals were overwhelming with incoming cases. As nurses treated the sick without adequate equipment, they contracted the disease themselves and may have spread it further. In September, the CDC reported that if the amount of care given was to continue, the amount of infected people could double every 20 days and potentially infect 1.4 million people by mid-January (Figure 4; Time, “Racing Ebola”) President Obama issued a statement to the UN General Assembly emphasizing the risk of not stopping the virus. On September 25, Obama stated “If this epidemic is not stopped, this disease could cause a humanitarian catastrophe across the region. And in an era where regional crises can quickly become global threats, stopping Ebola is in the interest of all of us” (qt. Time). The thing that has health officials around the globe worried is that Ebola will reach its tipping point soon. According to epidemiologists there exists a tipping point in all epidemics that point is reached when the number of infected patients is so large that no number of health workers could isolate each person and stop the spread of the virus. Viruses spread exponentially, for each person that is infected and not properly treated/ isolated a multiple more are infected. According to the CDC, there is still time for the Ebola virus epidemic to be extinguished. Currently Red Cross, the World Health Organization (WHO), and many other nonprofit organizations are providing essential supplies to countries affected by Ebola. However, though there is no shortage of protective gear there is Fall 2014 Reztsova much more than supplies that are needed by the countries to stop the epidemic. For example, 2,122 more beds for patients, 50 more deadbody management teams, and 734 million dollars in funds are needed. More crucially 500-600 more health experts are needed. Without expertise on how to deal with outbreaks and set up treatment centers the epidemic has little chance of being extinguished (Time, “Racing Ebola”). The only silver lining of the Ebola epidemic seems to be what experts can learn from the virus. As reported by Bryan Walsh and Alexandra Sifferlin for Time, one thing we can learn is to be weary of diseases that can spread from animals. These zoonotic diseases are currently more frequently subject to spillovers, where the virus spreads to humans. These spillover events seem to occur more frequently as “deforestation and development bring humans and animals closer together” (Time, “After Ebola”). Another pattern that was pointed out by Dr. Disotell in his TED talk “The Contagion,” was that as the Earth’s climate gets warmer more infectious insects such as mosquitoes will migrate north towards North America. In fact, recently there has been a reemergence of highly infectious viral disease such as the Chikungunya virus and other viral Caribbean viruses. Another lesson from the virus is the need for research funding. Consider this, in 2001 after 9/11 there were various research teams looking for a vaccine or cure for the Ebola virus because they feared that it could be used as biowarfare. However, because the research was underfunded many of these research laboratories had to scrap their work. Another lesson to be learned is how critical a quick response to an epidemic is needed. As Dr. Disotell stated if the funds and supplies were provided to the infected countries in April the epidemic would have been distinguished by now. A final note to take away from this is what can be learned from the Ebola strain. How did it spread from primates or fruit bats to humans? What ancestry is it related to? These and many other scientific inquiries can provide information for current and future viral outbreaks. REFERENCES Aftab, A. A. Clinical features and pathobiology of Ebolavirus infection. Journal of Autoimmunity. 2014. doi:10.1016/j.jaut.2014.09.001. Feldmann, H., and Geisbert, T. W. "Ebola Haemorrhagic Fever." The Lancet 377.9768 (2011): 849-62. ProQuest. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Sci ence; 2002. Blood Vessels and Endothelial Cells. Ghayourmanesh, Ph.D., S, Hawley, M.D., HB. Ebola virus. Sinclair Remote Database Authentication Page. Ansari A. Clinical features and pathobiology of Ebola virus infection. Journal Of Autoimmunity [serial online]. September 23, 2014; Available from: MEDLINE with Full Text, Ipswich, MA Ascenzi, P., Bocedi, A., Heptonstall, J., et al. Ebolavirus and Marburgvirus: Insight the Filoviridae fam ily. Molecular Aspects of Medicine. 2008;29(3):151-185. doi:10.1016/jmam.2007.09.005. Joseph B. McCormick. Ebola Virus Ecology. The Journal of Infectious Diseases, Vol. 190, No. 11 (Dec. 1, 2004), pp. 1893 Konstantinov I. et la. Poster The Ebola Virus. Visual Sci ence. 2014. Park, M. Report: Ebola outbreak . CNN. 2014. Mandal, A. What is a Macrophage? News-Medical. 2014. Steinman, R. Introduction to Dendritic Cells . Laboratory of Cellular Physiology and Immunology. Baker, A. Racing Ebola . Time . 2014;184(14):40-45. Centers For Disease Control and Prevention (CDC). Up date: Outbreak of Ebola Viral Hemorrhagic Fe ver — Zaire, 1995. Morbidity and Mortality Weekly Report, Vol. 44, No. 20 (May 26, 1995), p. 381 Walsh, B, Sifferlin, A. After Ebola. Time . 2014;184(7):3639. WHO. Ebola virus disease. World Health Organization. 2014. Drehle, D. Now Arriving. Time . 2014;184(14):36-37. Volume 15 MEDICAL DIALOGUE REVIEW 59 Artwork by Michelle Shi 60 MEDICAL DIALOGUE REVIEW Fall 2014