UChicago PULSE Issue 5.2: Winter 2019

PULSE VOLUME 5, ISSUE 2. WINTER 2019.

THE FIRST

CRISPR BABIES

from the editor-in-chief Dear reader,

2019 has finally rolled around, and with it a hailstorm of developments throughout science, medicine, and policy (along with the polar vortex that blustered through at the beginning of the year). With the beginning of the year, we've also had an influx on articles on the beginning of us people as well – namely, babies. From an introduction to opioid addiction in newborns, to a baby born from three parents, to a closer look at the controversial CRISPR babies that sparked worldwide discussion late last year, this winter quarter issue of PULSE delves deeper into the many nuances of this first stage of life. just as how health does not end there, our topics grow from this narrow focus to a broader perspective as well – a global look at women's health is featured in our Policy section, as well as further analysis of the many aspects of life onwards: from sex, clinical practice, and biotechnology and more.

Spring is coming (hopefully), a new beginning of its own kind. As the winter quarter draws to a close and a new quarter approaches, we hope you enjoy this issue of PULSE and have a wonderful spring break!

With regards, Irena Feng

editors

writers

production

Purujit Chatterjee Anya Dunaif Yassmin Elbanna Areeha Khalid Jui Malwankar Yifan Mao Linus Park Abhijit Ramaprasad Lindsay Romano Fatima Sattar Allan Zhang

Swathi Balaji Victoria Bigdelle Sophia Cao Natalie Choi Ryan Choi Allison Gentry Nikki Kasal Malaika Mathias Edwin Santos Corinne Stonebraker Abby Weimer

Purujit Chatterjee (cover design) Irena Feng Sophia Korotev

GENERAL EDITORS Scott Wu

PULSE Magazine

other contributors Gold Standard Kaplan Test Prep The Princeton Review

CONTENTS EDUCATION 10 BENEFITS OF TAKING A GAP YEAR BEFORE MED SCHOOL MCAT MATH TRICKS KAPLAN MCAT PRACTICE PROBLEM SAVING OSCAR

2 4 5 6

POLICY THE HIDDEN DANGERS OF DIETARY SUPPLEMENTS NEONATAL ABSTINENCE SYNDROME THE SECOND SEXUAL REVOLUTION WOMEN'S HEALTH: A GLOBAL LENS THE FUTURE OF BIOSENSORS

10 14 16 19 26

RESEARCH CUT & PASTE: THE FIRST CRISPR BABIES HUMAN MOVING FORWARD A COCKTAIL OF DRUGS

28 32 36

CLINIC TRANSCRANIAL MAGNETIC STIMULATION CHILD AND ADULT ACUTE MYELOID LEUKEMIA

40 44

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10 BENEFITS OF TAKING A GAP YEAR BEFORE MED SCHOOL Is taking a gap year before medical school right for you?

During a typical pre-med timeline, students apply to medical school the summer before their senior year. But students who take a gap year delay the application process to the summer after their senior year – giving them time to work on the weakest areas of their med school application before they apply. Some students even take longer gap periods of two years (or more!), which give them the chance to work and save for med school tuition. In fact, the average age of applicants to med school for the 2016-2017 cycle was 24-25 years old.

Learn how taking a gap year before medical school can benefit your application.

1. Improve your MCAT score

It can be hard to prep for the MCAT with a full schedule of classes. Maximize your score by devoting time to an MCAT prep course – without the additional pressures of school obligations.

2. Finish up any missing prerequisites

Post-baccalaureate programs are excellent options for filling required pre-med courses you might be missing. If you were a non-science major, for example, you can take your science requirements on a streamlined schedule.

3. Gain research experience

A full year of working in a lab can be a boon to your med school application. Transfer the time you would have devoted to your primary/secondary applications to an extended research experience.

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4. Boost a low GPA with a science-based master's program

If you don’t have an undergraduate GPA that’s competitive for med school, completion of a sciencebased master's program will demonstrate your competency at the graduate level. You’ll want a full year of course work under your belt before you apply to med school.

There are also Special Masters Programs (or SMPs) affiliated with medical schools that are intended for college graduates who want to enhance their transcript for eventual application to medical school. SMP students often take science courses alongside actual med students.

5. Volunteer or work in a medically-related field

The majority of successful med school applicants have some experience in a hospital, clinic, hospice or other health care setting. If you don’t have medical experience, using your gap year as an introduction to the field is a smart move.

EDUCATION

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6. Take a break from academics

Med school is an intense – but ultimately rewarding – experience. Before diving into that pressure cooker, take your gap year to get an education in the real world. You could work full time, teach, travel, or commit to a personal project.

9. Do more research on potential schools and career paths

You can browse school profiles by major, location, concentration and more using our med school search.

Make sure you have reach, target, and safety schools on your med school application list.

7. Set up preceptorships with local doctors

10. Reflect on your goals

8. Get better letters of rec

THE BOTTOM LINE: CONSISTENCY IS KEY

Clinical shadowing, or preceptorships, is another way to gain experience within the medical profession. If you’ve shadowed doctors in only one kind of speciality, the gap year is an opportunity to branch out!

Your gap year experiences may put you into contact with professors, researchers, and doctors who will get to know and your abilities Building these kinds of relationships in the field can help you if you are missing a key recommendation letter.

Why do you want to be a doctor? If you don’t have a good answer, take the time to think about your background and ambitions. Another year in school or a year out in the workforce can help you decide if an MD is right for you.

However you decide to spend your gap year, stay engaged in clinical experiences and community service. Med schools want to see that your volunteer efforts extend past your college graduation!

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MCAT MATH TRICKS Do you know that you can make “magic” with numbers on the MCAT? In fact, since you are not allowed to use a calculator on the MCAT, understanding some basic principles of math can make certain aspects of the MCAT easier saving you testing time in the long run. All you have to know is that your power comes from being efficient and recognizing patterns.

1.

Pay attention to multiples.

2.

Know your perfect squares.

3.

Keep it easy as pi.

Even without context, if you see 44.8 or 11.2 on the MCAT, you should think: “I’m dealing with 2 moles (or ½ a mole) of a gas at STP.” Without reading the question, you must recognize that both of those numbers are multiples of 22.4, the molar volume according to Avogadro’s Law. Also, anything times 10 to the power of 23 should bring to mind Avogadro’s number of particles, a multiple or fraction thereof. Now, this does not mean that the answer will always depend on your response!

Instead, this exercise shows you how to look for trends and likelihoods that appear in answer choices.

AAMC exams often contain a similar trend. Do the numbers 1.44 and 1.69 ring a bell? They are simply decimal forms of perfect squares (12 squared equals 144; 13 squared equals 169)! A great MCAT math technique is to memorize all the squares between 1 and 15. You have probably known 1 through 10 since elementary school. So, save yourself a future headache and memorize 11 through 15.

Then, the next time you see 1.44 on a practice exam or the actual MCAT, you can use your pattern recognition to mentally identify the square root as 1.2.

Do you recall that pi equals 3.14, the square root of 2 is 1.4, and the square root of 3 is 1.7? Do not be surprised if the MCAT asks you to calculate the circumference (2 times pi times r) or area (pi times r squared) of a circle. And get comfortable with estimating the square root of any number. What is the square root of 17? Well, you know it will be between 4 (the square root of 16) and 5 (the square root of 25), but much closer to 4. Do not waste time calculating if there is just one answer that falls between 4 and 4.5.

4. Rely on fractions and variables.

To minimize stress and maximize time, avoid using decimals until you have no choice. Fractions are much more efficient to use and think about intuitively on the MCAT. Also, get comfortable with using scientific notation for very large and very small numbers. Whenever possible, hang onto variables as they often cancel out or help you in selecting the correct answer.

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EDUCATION

Kaplan MCAT PRACTICE PROBLEM QUESTION An ambulance, sounding its sirens, travels with a velocity of v towards a car. The car is traveling in the same direction as the ambulance, but at a velocity of 0.5v. Which of the following would NOT increase the car driver's perceived frequency of the sound emitted by the sirens?

A. Decreasing the speed of the car B. Decreasing the speed of the ambulance C. Decreasing the wavelength of the sound wave emitted by the sirens D. Reversing the direction of the car

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B. There is no real need to use the Doppler equation here, as long as the concept is familiar to you. The ambulance is the source of the sound, the car driver is the detector. So, if source and detector are travling in the same direction with the source behind the detector, then speeding up the source will increase the perceived frequency by the car driver. So choice (B) is our answer, since that will NOT increase the perceived frequency. Choice (C) is incorrect since a decrease in wavelength will increase the actual frequency of the sound wave, also increasing perceived frequency.

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SAVING OSCAR

THE ROLE OF FIDELITY IN MEDICAL SIMULATION

By

SWATHI BALAJI PURUJIT CHATTERJEE The untouchable became tangible, as I held the da Vinci robot controls in my own hands, manipulating my wrists and fingers ever so carefully to move virtual objects. The da Vinci Surgical System uses robotic technology to translate our hand movements into the fine, precise movements of small instruments, which we can visualize on a console. Never had I imagined that I would have the opportunity to use a $2.7 million robot operated by renowned surgeons, but in the Simulation Center at the University of Chicago, the inaccessible became accessible, and the unimaginable became a reality.

In the Simulation Center, physicians, residents, medical students, emergency medical responders, and undergraduates can access worldclass equipment such as the da Vinci robot and high-fidelity simulators (manikins that can speak, react, emote, and move), which inform us and allow us to prepare for clinical encounters and medical procedures, including CPR, defibrillation, childbirth, and traumatic injury. These simulators are categorized and perceived based on their engineering fidelity (the degree to which a simulator can reproduce the effects it is designed to produce), environmental fidelity (ability to replicate sensory information and respond to visual cues in an expected way), and psychological fidelity (the degree to which the simulator is perceived as a “real” person). Some of the models, such as Trauma Man, are very high-fidelity models, ranking highly in the three categorizations of fidelity, in that practitioners and students can obtain ultrasounds, insert chest tubes, feel realistic skin, see and touch blood coming from a gunshot wound, and hear the model’s groans and screams.

(top) I (Swathi Balaji) use the da Vinci surgical system, making fine movements with my wrists to manipulate the objects shown in the console; (bottom) Console for the da Vinci surgical system

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EDUCATION

(left) High fidelity pediatric simulator; (right) Moderate fidelity childbirth simulator

These simulators are highly useful for medical training, and numerous studies have shown that high-fidelity simulator practice is associated with improved learner outcomes (McGahie et al., 2006).

Practice with simulators offers a safety net for providers to practice sensitive procedures, such as pelvic examinations, without endangering any patients. However, this can also be problematic – what are the stakes if no lives are directly at stake? Are the simulators real enough to appropriately frame the mindset of practitioners and students in clinical encounters? In other words, do we have to view the simulators as bodies who can sense and be sensed in order for our practice to be beneficial in actual patient interactions?

I first visited the Simulation Center for one of my class sessions in the “Body in Medicine and the Performing Arts,” during which we were encouraged to explore the extent to which bodily simulation felt “real” and consider its clinical and performative aspects.

“Oscar, don’t die on me!” I exclaimed, as we used a defibrillator and performed CPR to revive one of the manikins in the Simulation Center. Oscar had a pulse, felt warm, had audible lung sounds,

and could blink, scream, constrict his pupils, groan, have seizures, have asthma attacks (wheezing lung sounds), and experience hypoxia (blue light on his tongue).

All of these factors contributed to Oscar’s great psychological fidelity.

Oscar also had high engineering and environmental fidelity, since he could respond to stimuli, displaying pupil constriction in response to light and having a seizure. Oscar’s sensing of my touch or body temperature was limited, but his pupils constricted in response to light (so he could sense me in that regard). The aspects that kept the realness of the experience in check were that (1) we could physically attach leads to his body, (2) his movements were restricted, and (3) his materiality was plastic rather than skin-like. However, I saw Oscar, not as a mere manikin, but almost as a person. He was someone who could sense me and be sensed by me, and he was someone that I wanted to save and successfully saved with my peers.

In contrast to Oscar and Trauma Man, the basic adult and baby models that we performed CPR on were all low-fidelity. I was not motivated to “save the lives” of these models but was instead

focused on obtaining a good score for my compressions. These models are and feel plastic, and the texture and lack of response of these models made them seem unrealistic. As a result, I did not consider these simulators to be entities that needed to be saved and just focused on learning CPR – pressing hard enough on the chest to go 2.5 inches deep and releasing to allow full recoil. When the models had low psychological fidelity, I no longer perceived the simulator as a model for the actual encounter with a patient, but rather just as a training tool.

When I returned to the Simulation Center for the second time with the Pre-Medical Students Association, I knew what to expect. I expected Oscar to wheeze before it started wheezing, expected the pupils to contract, and expected to observe lung sounds and a pulse. I was more excited to practice the procedures than to interact with Oscar and could not help wondering where the magic of my first encounter with Oscar had vanished. The engineering and environmental fidelity were still present, but the psychological fidelity was gone. A model that once possessed high fidelity now had low fidelity – for

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(left) Students listen to Oscar’s heartbeat [Chloe Mesa, Sabrina Foster]; (right) Xiya Wu performs CPR on Oscar.

me, at least.

And this is the problem that Hamstra et al. (2014) point out: that the term “fidelity” is imprecise and can be described as high or low for the same simulator depending on the context. Hamstra et al. argue that we should abandon use of the term and focus more on the functional abilities of the simulator than on its physical resemblance. Furthermore, Hamstra et al. indicate that functional alignment with the learning objective, the instructor, and the instructional design have more of an impact on immediate learning, retention, and application of knowledge in clinical settings. In other words, the human inter-

actions between learner and instructor outweigh the physical resemblance of the simulator.

With a well-designed curriculum, even low-fidelity simulators work well, but studies have shown that high-fidelity simulators contribute to reduced mental strain, higher successful delivery rates, and reduction in total applied force on a simulator

(Meurling et al. 2014). So, while the functional component of simulation arguably has more educational value, we cannot dismiss the role that psychological fidelity, engineering fidelity, and environmental fidelity play in shaping interactions with the simulator, making the situation a more realistic representation of a clinical encounter.

Hector Toro, Simulation Technical Coordinator, explains Trauma Man’s functional abilities and juxtaposes Trauma Man (foreground) with the Basic Adult CPR model (background)

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EDUCATION

Simulation of the full environment recreates realistic scenarios, and adding an emotional component (which can be enhanced by physical resemblance of the simulator) can cause emotional changes in participants, thereby leaving a lasting impression. For instance, according to Corvetto et al. (2013), the death of a simulator can be a useful tool because it allows learners to practice end-oflife care, see how their actions affect simulator outcomes, learn how to communicate difficult news with the patient’s family, and cope with their own emotions in a less stressful setting. Of course, with simulated death, pre-briefing and debriefing sessions with guided reflection must be held to prevent psychological harm to the learner (unexpected or punitive death should not be used as a training tool). If a simulator did not seem real enough to the learner, the emotional component would no longer be as significant, and the mindset of the learner would not be appropriately framed for such an encounter involving distress, communication, and death. While the learner may still be able to learn how to perform a procedure, the death of an unrealistic simulator would not have as much bearing as a realistic simulator with an emotional effect on the learner.

A simulator seems real to a learner when there is suspension of disbelief, defined by Hamstra et al. as a “mechanism that learners engage in to project the learning objective onto the physical structure.” When learners suspend disbelief, they can ignore

features of the simulator that are not relevant to the task at hand.

Since we can still suspend disbelief, the simulators may not have to be perceived as bodies who can sense and be sensed for our practice to be beneficial in actual patient interactions. For instance, I was still able to perform CPR and visualize the manikin as a body in need of cardiac compressions.

It is thus possible that physical resemblance may only play a small role in the ability of a learner to suspend disbelief and that it is more useful in cases of interpersonal skills, communication, and emotional learning.

What are the stakes when patient’s lives are not directly in our hands? The stakes don’t disappear when we work with simulators – they become embodied in the simulators, when we suspend disbelief and prepare ourselves to transfer knowledge to the clinical setting. If I had to save Oscar again, I definitely would save him.

Join the Pre-Medical Students Association for a tour of the Simulation Center at the University of Chicago!

Corvetto, M. A., and J. M. Taekman. 2013. “To die or not to die? A review of simulated death.” Simul Healthc 8 (1):8-12. doi:10.1097/ SIH.0b013e3182689aff.

Hamstra, S. J., R. Brydges, R. Hatala, B. Zendejas, and D. A. Cook. 2014. “Reconsidering fidelity in simulation-based training.”

Acad Med 89 (3):387-92. doi:10.1097/ ACM.0000000000000130.

McGaghie, W. C., S. B. Issenberg, E. R. Petrusa, and R. J. Scalese. 2006. “Effect of practice on standardised learning outcomes in simulation-based medical education.” Med Educ 40 (8):792-7. doi:10.1111/j.13652929.2006.02528.x.

Meurling, L., L. Hedman, K. J. Lidefelt, C. Escher, L. Fellander-Tsai, and C. J. Wallin. 2014.

“Comparison of high- and low equipment fidelity during paediatric simulation team training: a case control study.” BMC Med Educ 14:221. doi:10.1186/1472-6920-14-221.

Students from the Pre-Medical Students Association pose with the da Vinci Surgical System [Chloe Mesa, Deanna Tang, Xiya Wu, Sabrina Foster, Swathi Balaji (left to right)]

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THE HIDDEN DANGERS OF DIETARY SUPPLEMENTS By

NIKKI KASAL AREEHA KHALID

In 1978, at only two years old, Chad Green was diagnosed with acute lymphocytic leukemia. He immediately began chemotherapy treatment at the University of Nebraska Medical Center in Omaha, and for a while it seemed that his condition was improving as the cancer entered remission. His parents, however, balked when his doctors suggested harsh radiation therapy and decided to move to Massachusetts to place their son under the care of Dr. John Truman, a pediatric cancer specialist at Massachusetts General Hospital.

The negative effects of chemotherapy still took their toll on Chad, and his parents began to look into the possibility of treating his condition with unconventional cancer therapies. One of these was the drug Laetrile, which was a chemical similar to cyanide that many at the time believed could cure cancer through a metabolically-based mechanism. It has since been declared ineffective and even dangerous, and despite

Amygdalin, a cyanide-producing compound, is found in fruit pits and bitter almonds.

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the warnings of Chad’s doctors that he would die without chemotherapy, the Greens opted to switch to a fully Laetrile-based treatment course. A legal battle with the state of Massachusetts to take the child as a ward of the state ensued when Chad began to show symptoms of cyanide poisoning, which prompted his parents to flee to Tijuana, Mexico so they could freely continue the Laetrile “treatments”. Chad’s condition only became direr, until he died of leukemia on October 12, 1979. He was three years old.

Though the history of Laetrile is long and convoluted, it is sufficient to say that it is a man-made, purified form of the compound amygdalin, which is found in many fruit pits and bitter almonds. Laetrile became popular as a cancer treatment in the 1960s and 70s, under the claim that its breakdown by our digestive system produces cyanide, which kills harmful cancer cells. While it is true that the breakdown of amygdalin produces hydrogen cyanide, it has no effect on cancer cells and is actually a potent toxin: 50 grams of Laetrile can be a lethal dose.

When the government began to crack down on the advertisement of Laetrile as a cancer-preventing drug, its proponents were quick to rebrand it as a cancer-preventing vitamin (termed Vitamin B17) in order to circumvent the stringent restrictions surrounding disease treatment sale. It was finally banned in the US by the FDA in 1980; however, “Vitamin B17” is to this day touted as a natural supplement and readily available to buy online and in other countries.

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To this day, “Vitamin B17” is available for purchase online.

The fact that Laetrile was readily available in the United States, first as a treatment and later as a vitamin, from its discovery in the mid-1940s until 1980, points to the ease with which untested and unproven substances are able to gain massive ground in the dietary supplement industry. This is largely due to the fact that while the FDA has strict regulations surrounding the marketing and sale of treatments or disease preventatives in the USA, its policies surrounding the distribution of vitamins and supplements are significantly more relaxed. This is because they aren’t classified as drugs, but rather as foods, a designation which extends to all vitamins, minerals, and botanicals. This classification means that supplements are not subjected to the extensive safety and efficacy testing that all disease treatments must undergo prior to marketing. It even goes so far as to include a disclaimer on its website: “The FDA is unable to test and identify all products marketed as dietary supplements on the market that have potentially harmful hidden ingredients.”

Though its regulations do attempt to prevent vitamin manufacturers from distributing a product that is mislabeled or has been tampered with, the fact that no research or proof regarding the safety of the supplement is required for its sale, leads to inevitable adulteration of the vitamin with potentially unsafe active ingredients.

In fact, research published by the California Department of Public Health found that from 2006 to 2016, 776 dietary supplements on the shelf contained active ingredients that were either unstudied or explicitly known to be dangerous. Some of these included dapoxetine and sibutramine, respectively an

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antidepressant and appetite suppressant which have been banned in the US since 2010. “Adulteration with active pharmaceutical ingredients does not happen by accident and poses a serious public health risk as consumers unknowingly ingest these drugs,” says Dr. Madhur Kumar of the California Department of Public Health in Sacramento.

However, adulterated drugs are not the only underlying issue in the $35 billion dietary supplement industry. By virtue of the lack of restrictions surrounding FDA testing of vitamins, the vetting process can approve a variety of untested, dangerous homeopathic remedies similar to Laetrile. These herbal supplements often find their fame in being touted as “all natural,” whether they come as a pill, oil, ointment, tincture, rub, or tea. However, “all-natural” does not necessarily translate to benevolent or even safe. “Most herbs we use in the U.S. are pretty benign, but some are dangerous and others are if not taken correctly,” says Dr. Adriane Fugh-Berman, an expert on medicinal herbs and supplements and professor at Georgetown University School of Medicine. Though Laetrile’s metabolic pathway leads to cyanide production in the body, this is far from the only harmful pathway through which herbal drugs can do harm. Most common are the risks of liver and kidney damage, as well as dangerous interactions with other pharmaceuticals. For instance, kava (Piper methyscitum), an herb advertised as helpful

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for those experiencing anxiety, can lead to serious illness, liver damage, and even death in as little as one to three months, according to the National Institutes of Health. “Heavy kava use has been linked to nerve damage and skin changes,” warns Dr. Andrew Weil, the founder of the Arizona Center for Integrative Medicine. It can also lead to dangerous interactions with other drugs, including Xanax and sedatives.

Another example is comfrey, which may have efficacy in treating inflammation when applied to the skin, but can cause severe liver damage when ingested orally. Most customers seeking these types of vitamins and supplements are unaware of the nuances of the ways they should be administered, which can make even potentially benevolent herbs dangerous. "My local coffee shop serves comfrey tea, and when I told them it was a liver-toxic herb, they said, ‘Oh, we sell a lot of it,’” Dr. Fugh-Berman says.

From homeopathic remedies to adulterated drugs, a variety of potentially risky or outright dangerous products are currently circulating in the extensive US dietary supplement industry. However, the market may take a safer turn as increased consumer and medical provider concerns force government agencies to turn their attention to potential reforms.

For instance, in February 2019, the FDA finally announced plans for a massive overhaul of the industry in what FDA Commissioner Scott Gottlieb calls “one of the most significant modernizations of dietary

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supplement regulation and oversight in more than 25 years.” A major aspect of this initiative involves an online “rapid-response tool” that can quickly alert the public about potentially unsafe drugs or ingredients.

The agency also intends to update its compliance policies regarding new dietary ingredient notifications (NDIs), which require manufacturers to update the FDA about any ingredients in their products that weren’t sold in the US before 1994. With regards to homeopathic remedies, it’s also launching a new Botanical Safety Consortium, which joins public and private sectors to better evaluate the safety and use of herbal remedies.

In an industry that has grown from offering 4,000 products to over 80,000 products in the last 25 years, it can be difficult to monitor every new drug or ingredient which arrives on the market. “As the popularity of supplements has grown, so have the number of entities marketing potentially dangerous products or making unproven or misleading claims about the health benefits they may deliver,” concedes FDA Commissioner Gottlieb. Nevertheless, both the FDA and private supplement manufacturers have a duty to consumers to allow only those supplements which contain safe and studied ingredients to permeate the market. Chad Green died from a combination of Laetrile-induced cyanide poisoning and leukemia only a year before the drug was officially banned for sale in the US, but this was too little, too late

for the boy whose parents had succumbed to the lure of alternative medicine. With the market now more saturated with supplements than ever before, it is particularly crucial to remain aware of the US’s complicated history with unstudied supplements and ensure no one else will fall victim to their risks.

Bloom, Josh. “Laetrile, Amygdalin, Vitamin B17: Different Names, Same Poison.” Millennials, the Deaf Generation? | American Council on Science and Health, 7 May 2018, www.acsh.org/news/2018/04/17/why-laetrilekills-you-12853.

Bluth, Rachel. “Hidden Dangers Lurk in over-the-Counter Supplements, Study Warns.” NBCNews.com, NBCUniversal News Group, 2018, www.nbcnews. com/health/health-news/hidden-dangers-lurk-over-counter-supplementsstudy-warns-n919731.

Davey, Melissa. “Herbal Medicines Can Have Dangerous Side Effects, Research Reveals.” The Guardian, Guardian News and Media, 5 Feb. 2017, www. theguardian.com/australia-news/2017/feb/06/herbal-medicines-can-havedangerous-side-effects-research-reveals.

Mozes, Alan. “Many Dietary Supplements Contain Unapproved, Dangerous Ingredients, Study Finds.” CBS News, CBS Interactive, 2018, www.cbsnews. com/news/many-dietary-supplements-contain-unapproved-dangerousingredients-study-finds/.

“Laetrile/Amygdalin.” Little Fighters Cancer Trust. Np, nd. http://www. mennerchiropractic.com/nutritional-supplements.

“Nutritional Supplements.” Menner Chiropractic. Np, nd. http://www. mennerchiropractic.com/nutritional-supplements.

“Vitamin B17.” ShopShape. Np, nd. https://www.shape.com/shop/apricotpower-apricot-power-vitamins-b17-amygdalin-500-mg-100-tablets-pde9c 5fcd5b036809a780f39a3c4b035f.html.

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NEONATAL ABSTINENCE SYNDROME

AMBIGUITY AND OPIOIDS

By

ABBY WEIMER ABHIJIT RAMAPRASAD

We all come into the world kicking and screaming, and it’s not news that babies cry. Sometimes, though, those screams combine with shivering, vomiting, and seizures to alert physicians to the extension of a mother’s opioid addiction: Neonatal Abstinence Syndrome (NAS). While its definition and set of symptoms is sometimes debated, NAS is generally recognized as a disorder that involves the negative reaction of the central and autonomic nervous systems and the gastrointestinal systems after a fetus’ exposure to opioid drugs.

According to McQueen and Murphy-Oikonen’s 2016 article titled “Neonatal Abstinence Syndrome” featured in The New England Journal of Medicine, NAS saw a five-fold increase in diagnosed infants in the United States from 2000-2012 due to a variety of factors. First and foremost, pregnant women are more liberally prescribed opioids to manage pain during pregnancy.

As a result, there has been an

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increase in opioid substitution programs being used to treat opioid addiction in pregnant women. For instance, if a pregnant mother is addicted to heroin, she may be given either methadone or buprenorphine to treat her addiction and hopefully prevent her newborn from suffering from addiction to other illicit drugs.

However, even though these medications are meant to improve the outcome of the pregnancy and the baby’s well-being, methadone and buprenorphine can also lead to NAS. Within the context of these common pain treatments, buprenorphine’s outcomes aren’t as dire as methadone’s. In a 2010 study published in The New England Journal of Medicine, Dr. Hendrée E. Jones et al. documented how withdrawal symptoms from buprenorphine in nonpregnant adults are much milder than those from methadone, making it a more popular consideration than the once-standard methadone.

Right after birth, babies whose

mothers had been prescribed methadone suffered longer hospital stays and extensive pharmacological intervention to curb the symptoms of NAS brought on by methadone use. Buprenorphine, on the other hand, has a lower risk of overdose because its receptors have a lower efficacy in response to the drug’s presence. Therefore, its effects are not as potent and patients are less likely to become addicted.

The newborn’s health issues don’t stop in the hospital room; infants with NAS are most often born to mothers in low income areas of the US that have high rates of long-term unemployment.

According to a recent study from the Vanderbilt University Medical Center and the RAND Corporation published last month, babies who are born with NAS are more likely to be born in urban parts of the United States that have higher rates of unemployment and less access to substantial mental health support services. Bradley D. Stein, the senior author of the study and

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director of the RAND Opioid Policy Center, noted how those with mental health issues, who are more likely to use opioids, are usually living in places with higher persistent levels of unemployment. This correlation translates to babies being born with the same issue. NAS therefore finds itself nested within a complex triangle of problems – the opioid crisis, long term unemployment, and lack of mental health resources – that highlights the intricacies of fighting its effects. In order to combat the increased incidence of NAS in the US, there must be a cohesive effort to treat the myriad of problems that ties NAS to the places it’s found and the people it affects.

As with any complex health condition, the first step to

understanding and treating the ramifications of NAS should begin with a cohesive and sound definition of the symptoms presented that qualify as the syndrome.

Without a clear starting point, there is no way to develop standardized diagnoses and treatment protocols. The issue involves many different moving parts that include not only the patients themselves, but the socioeconomic and healthcare systems with which the patients interact in dealing with the syndrome. Indeed, there is much work being done on reaching a consensus about the nature of this disease. Due to the myriad causes and symptoms of NAS-born children, the path ahead to a directed treatment remains to be discovered, but at the very least, this first step is clear.

Jones, Hendrée E., and Andrea Fielder. “Neonatal Abstinence Syndrome: Historical Perspective, Current Focus, Future Directions.” Preventive Medicine, vol. 80, 2015, pp. 12–17., doi:10.1016/j.ypmed.2015.07.017.

Jones, Hendrée E., Karol Kaltenbach, Sarah H. Heil, Susan M. Stine, Mara G. Coyle, Amelia M. Arria, Kevin E. Ogrady, Peter Selby, Peter R. Martin, and Gabriele Fischer. "Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure." The New England Journal of Medicine 363, no. 24 (2010): 2320331. doi:10.1056/nejmoa1005359.

McQueen, Karen, and Jodie Murphy-Oikonen.

2016. “Neonatal Abstinence Syndrome.”

The New England Journal of Medicine 375 (25): 2468–79. https://doi.org/10.1056/ nejmra1600879.

Vanderbilt University Medical Center. “LongTerm Unemployment Linked to Increase in Neonatal Abstinence Syndrome.” EurekAlert!, 29 Jan. 2019, www.eurekalert.org/pub_ releases/2019-01/vumc-lul012419.php.

(Image) Ap. "Hospital Announces New Unit for Babies with Neonatal Abstinence Syndrome." Beckley Register-Herald.

February 26, 2019. Accessed March 04, 2019. https://www.register-herald.com/ news/hospital-announces-new-unit-forbabies-with-neonatal-abstinence-syndrome/ article_67cb744b-3517-57ab-b12b534e4a47788e.html.

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THE SECOND SEXUAL REVOLUTION Examining the Effects of Sexual Health Education on the Prevalence of Sexually Transmitted Infections in Young Americans By

NATALIE CHOI ANYA DUNAIF

Freddie Mercury. 2014 cult classic film It Follows.

Keith Haring. Pulitzer prize winning Broadway musical Rent. Magic Johnson. Hit TLC soft-scripted, semi-reality show 16 & Pregnant. The potential consequences of unprotected sex pervade the media consumed every day and are integral parts of iconic works of pop culture. Countless influential cultural figures – artists, musicians, politicians and everything in between – have been lost to syphilis and HIV/ AIDS. Others bear the burden of living with continuous treatment for diagnosed sexually transmitted infections (STIs).

Despite the recent movements working to raise awareness for safe sex practices and STI screening and treatment, formal education and mandatory educational programs about safe sex practices continue to be stigmatized and controversial. Overwhelming evidence reveal that contraceptives and safe sex practices decrease the chances of unplanned pregnancy and spread of STIs. Despite these facts, promotion of sexual health education programs and practices is still a polarizing, highly debated topic in both high school environments and at institutes of higher education.

Many notorious “party schools” like Texas Christian University continue to refuse provision of sexual health resources for students. In an interview with the student website TCU360, the university’s Director of Alcohol and Drug Education Yvonne Giovanni said, “There is no comprehensive program to address sexual health on campus, so… the Alcohol and Drug Education Center, Health Center, and Campus Life all provide resources for students.” While it may seem that the school provides a wealth of resources

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for students, the division of responsibility for sexual health education, screening, and treatment increases inaccessibility for students. This places an inordinate responsibility on students to navigate the convoluted system of student health services. Other large schools that should be addressing sexual health education for their many students, like the University of Notre Dame, do not have a mandatory sexual health education program for their students. In fact, the first line on Notre Dame’s website addressing “What You Can Do” about sexually transmitted infections reads, “You can abstain from all sexual activity, including vaginal, oral, or anal sex, outside the context of a committed marital relationship.” Although abstinence education sounds outdated, a relic from the conservative past, the lion’s share of federal funding for “teen” sexual health education programs in 2017 – one third, to be exact – was spent on abstinence education funding.

Sexual health education programs across the

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country are doing an inadequate job educating young people about minimizing the risk of contracting STIs. The statistics on STI epidemiology in young age demographics, from high school students to recent college graduates, reflect the stigmatization of sex and ensuing continuous increase in STI prevalence in young people. For the past four years, the number of reported cases of the three most common STIs – gonorrhea, chlamydia, and syphilis – have climbed to record-breaking levels. The Centers for Disease Control and Prevention (CDC) estimate that nearly 20 million new STIs occur every year in this country, half of which are among young people between the ages of 15 and 24. For context, one in four sexually active people in the United States are within that same age group – just a quarter of the sexually active population accounts for half of the newly diagnosed STIs each year. One in two sexually active persons will contract an STI by age 25. One in two people diagnosed with gonorrhea is under the age of 24.

One in two sexually active high school students have reported not using condoms during the last time they engaged in intercourse. These statistics should be shocking – but are they?

Considering the early exposure to sex and sexually explicit imagery that young people receive and the lack of education surrounding this topic, it’s no wonder the prevalence of STIs in adolescent age demographics has continued to increase. The importance of sex and its prevalence in our day-to-day media consumption has skyrocketed. Accessibility of explicit media as a result of advancements in technology and the relatively open-minded, sex-positive message sent by influential public personalities expose young people to sex earlier than ever before – but this exposure comes hand in hand with little education necessary to understand the risks that unsafe sex poses. This has resulted in a time lag: our culture has progressed and young people are becoming sexually active earlier, but legislation and education haven’t followed suit to address this advancement. Young adults are beginning their sexually active lives without receiving education about safe sex practices that should be made accessible, if not mandatory, even before college.

Throughout history, this delay between cultural progress and establishment of corresponding progressive legislation has resulted in political revolutions.

The sexual revolution of the 1960s began as a cultural movement, a reclamation of female sexuality and making a place for women in the workplace. The effects of the cultural revolution of the 1960s are felt today: increased accessibility to contraceptives, a

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more open-minded perspective on premarital sex and sexuality, and continuing advancements in medicine resulting in a plethora of contraceptive options.

Just like the sexual revolution of the sixties, though, in the midst of all this progress, there is an obvious crisis. Our culture may have progressed, exposing young people to sex at an earlier age, but there is an incongruous lag in policy making sexual health education resources available to those young people who need it most. Recent cultural movements may have opened up a dialogue about sex amongst young people, but it still has yet to be addressed properly in the most important place: the classroom. The end of this decade marks the beginning of a second sexual revolution – a cultural revolution just waiting for legislation and education policy to catch up.

Duncan et al. (2005) Duncan C, Harrison MG, Toldson IA, Malaka D, Sithole S. Social stigma, HIV/AIDS knowledge and sexual risk: a cross-cultural analysis. Journal of Applied Biobehavioral Research 2005;10:1–26.

Cates JR, Herndon NL, Schulz S L, Darroch JE. (2004). Our Voices, Our Lives, Our Futures: Youth and Sexually Transmitted Diseases. Chapel Hill, NC: University of North Carolina at Chapel Hill School of Journalism and Mass Communication U.S. Center for Disease Control. (2018). Reported STDs In The United States, 2017, High Burden of STDs Threatens Millions of Americans [Fact Sheet].

Retrieved from https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/ STD-Trends-508.pdf.

“A History of Federal Funding For Abstinence-Only-Until-Marriage Programs.” SIECUS, Sexuality Information and Education Council of the United States, Aug. 2018, https://siecus.org/wp-content/uploads/2018/08/ A-History-of-AOUM-Funding-Final-Draft.pdf.

“Statistics.” ASHA, American Sexual Health Association, 2018, www. ashasexualhealth.org/stdsstis/statistics/.

Beer L, Mattson CL, Shouse RL, Prejean J. Receipt of clinical and prevention services, clinical outcomes, and sexual risk behaviors among HIV-infected young adults in care in the United States. AIDS Care 2016;28(9):1166-70.

Kann L, Olsen EO, McManus T, et al. Sexual identity, sex of sexual contacts, and health-risk behaviors among students in grades 9-12–youth risk behavior surveillance, selected sites, United States, 2001-2009. MMWR 2011;60(7):1-133.

Image. United States, Centers for Disease Control and Prevention. “Sexually Transmitted Infections Among Young Americans.” Sexually Transmitted Infections Among Young Americans [Fact Sheet], U.S. Department of Health and Human Services: Centers for Disease Control and Prevention, 2017. www.cdc.gov/std/products/youth-sti-infographic.pdf.

Image. “Abstinence Education Programs: Definition, Funding, and Impact on Teen Sexual Behavior.” KFF, The Henry J. Kaiser Family Foundation, 1 June 2018, www.kff.org/womens-health-policy/fact-sheet/abstinence-educationprograms-definition-funding-and-impact-on-teen-sexual-behavior/.

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WOMEN'S HEALTH: A GLOBAL LENS

HOW DOES HEALTH EQUITY AFFECT WOMEN ON A WORLDWIDE SCALE?

By

CORINNE STONEBRAKER YASSMIN ELBANNA

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CONTENT WARNING: This article includes discussion of themes of violence against women and female genital mutilation (FGM).

Throughout the globe, health disparities across sexes are evident. However, these disparities are magnified in resource-poor countries, where women lack basic healthcare and face life-debilitating and life-threatening health issues. Some of these health issues never even existed in the West, while some were eliminated as major obstacles over decades ago. Human immunodeficiency virus (HIV)/AIDS, maternal mortality, female genital cutting, and violence against LGBTQIA+ women are a few of the problems that are prevalent women’s health issues. This article introduces some of these challenging health problems and seeks to explore them with a global and intersectional lens.

What is global women’s health? What are some issues in global women’s reproductive health?

Women’s health and reproductive rights have received a significant amount of discourse in the past year in the United States, shedding light on topics such as the current administration’s anti-abortion agenda and doctors’ tendency to downplay women’s health concerns, such as endometriosis. In industrialized countries, although the gender gap in life expectancy has greatly improved, women still face more severe diseases with poorer outcomes. Gender is an important social determinant of health, and women’s health is influenced not just by biology, but by confounding social factors like poverty, employment, and family responsibilities. A history of social and economic disadvantage for women has resulted in restricted access to necessities like health care and access to medical resources. The issues we face in women’s health in America are only exacerbated in developing countries, where the gender gap in health is even more acute as women are relatively more disadvantaged. Understanding how these disadvantages impact women’s health issues from a global perspective is necessary to address critical global challenges in healthcare in low-resource settings and to catalyze resources for improving practices in women's health care worldwide. Most necessary to a global perspective on women’s health is a nuanced understanding of the social and cultural determinants of health in developing regions.

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The transmission of HIV and maternal health are problems which have been globally pervasive for at least a half-century. These are both issues that, while prevalent in the United States and Western countries, disproportionately affect women in low- and middle-income countries.

Young women in countries lacking health infrastructure struggle to access options for both prevention and treatment, compounding the risk of contracting HIV and the likelihood of dying from AIDS-related complications. Tuberculosis, one of the complications often associated with AIDs, is one of the leading causes of death in low-income countries of women 20–59 years. Three million people died from AIDS-related causes in 2001, with 2.2 million of these deaths occurring in sub-Saharan Africa. Now, AIDS is the leading cause of death in this region, which consists of about 16 countries and stretches from Ethiopia down the east side of the continent through South Africa. However, rates of HIV in West Africa are nowhere near that of countries in eastern and southern Africa, indicating some driving force behind this particular “belt-like” epidemiological pattern across the continent. This is where the importance of understanding cultural and social factors enters. Countries in West Africa with conservative Islamic traditions and a large proportion of Muslims in the population often have lower rates of HIV/ AIDS as religious values tend to circumscribe sexual

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HIV prevalence as percentage of the total population. Sub-Saharan Africa suffers from the highest prevalence of HIV as a share of the population, with 15% or more of the population between 15 and 49 years old infected with HIV. Data is sourced from UNAIDS estimates.

networking more so than in eastern and southern Africa. For example, Algeria and Morocco, countries with 99.75% and 99.5% Muslim populations, have only a 0.1-0.5% prevalence of HIV/AIDS. HIV/AIDS disproportionately affects women and adolescent girls because of vulnerabilities created by unequal cultural, social and economic status. Barriers like denial of access to female-only services, discrimination from providers due to views regarding female sexuality, and subpar services prevent women from fully accessing sexual and reproductive healthcare services. In fact, in 29 countries women need their husband’s consent to access sexual and reproductive health services. Laws like these especially disadvantage women who are victims of domestic abuse, who may need consent to seek treatment from the same person who is harming them. Additionally, early

education about HIV and sexual health is crucial – in Botswana, UNAIDS reports that every additional year of school a girl completes has been shown to reduce her risk of HIV infection by 11.6%. Finally, access to lifesaving antiretroviral treatment (ART) is also limited. A study of around 2,000 women living with HIV from Western Europe, Canada, Central and Eastern Europe, Latin America and China found 88.2% were currently taking ART. However, in countries like South Africa, that number is only 51%. PrEP, another treatment which is taken preventatively in case of HIV exposure, is also less accessible. In the United States, double the proportion of the population is taking PrEP than in South Africa.

In addition to conditions like HIV/AIDS that have a primarily sexual transmission, non-sexual reproductive health concerns are also an important

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component of global women’s health. Across the globe, significant strides in healthcare during pregnancy and childbirth have been made post-World War I. However, these improvements have not necessarily spread equally throughout the world, with marginalized groups still facing concerningly high maternal mortality rates. For example, Sub-Saharan Africa and South Asia together account for 86% of maternal deaths across the world. In fact, the WHO estimates that 99% of these deaths, the majority of which occur within 24 hours of childbirth, would have been easily preventable if equal and fair access to the appropriate infrastructure, training, and facilities were available. In countries where access to prenatal and perinatal care is limited, maternal health is further undermined by poverty and adverse economic factors that impair the development of health infra-

structure. According to the United Nation’s 2015 Millennium Development Goals Report, only 52% of deliveries in South Asia were attended by skilled medical personnel, compared to 100% in Eastern Asia and 92% in Latin America. Furthermore, this percentage decreases when you assess the rural regions of South Asia, where only 42% of deliveries were attended by skilled health personnel. Women in rural regions are most at risk for birth complications, due to a lack of access to skilled medical personnel as well as pervasive traditional cultural attitudes towards sexuality, contraception, child marriage, and home birth. While access to resources during delivery are crucial, prenatal care is just as important, and a lack thereof can be just as deadly. The WHO recommends at least four prenatal care appointments during a women’s pregnancy to protect neonatal and mater-

HIV prevalence as percentage of the total population. Sub-Saharan Africa suffers from the highest prevalence of HIV as a share of the population, with 15% or more of the population between 15 and 49 years old infected with HIV. Data is sourced from UNAIDS estimates.

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nal health. These visits should provide basic care advice, nutritional guidelines, and information about warning signs and safeguards for possible pregnancy complications that may arise. According to the same 2015 United Nations report, only 39% of women in South Asia aged 15 to 49 attended four or more prenatal visits, compared to 89% in North Africa and 97% in Latin America. Although the South Asia, Latin America, and North Africa regions all encompass developing as well as developed countries, South Asia has far more statistically alarming evidence of maternal health issues than Latin America or North Africa. Several countries in the South Asia region are experiencing relative prosperity, middle-class affluence, and unprecedented economic development, yet this clearly does not associate with improvements in maternal and child health. To understand why this is occurring, it is necessary to look at both epidemiological and sociocultural factors.

Malnutrition in South Asia, reflected by a lower average body mass index and subclinical micronutrient deficiencies, is higher than the rest of the world.

Maternal malnutrition is consistently linked with low birth rate and infant mortality. It is also strongly correlated in the South Asian region with a dietary lack of green leafy vegetables, which provide essential B vitamins, and high maternal energy expenditure and workload during pregnancy. Dietary deficiencies and consistent laborious work despite pregnancy are common in women from regions stricken by poverty, a clear empirical example of how poverty is a social determinant of women’s health. In addition to poverty, the poor social status of women and lack of empowerment reinforce poor reproductive regulation and snowballing population rates. Termed the “feminization of poverty”, the disproportionately higher rates of poverty among women in this region contribute to the gender gap in healthcare, forming a formidable social barrier to the development of adequate healthcare services for women. This barrier is only further compounded by an absence of safety nets, and healthcare industries that fail to implement basic services at a grassroots level.

What are the non-reproductive issues in global women’s health?

Female genital mutilation (FGM), is defined by the WHO as “all procedures that involve partial or total removal of the external female genitalia, or other injuries to the female genital organs for non-medical reasons". The degree of mutilation can range from removal of only the clitoral glands all the way to entire removal of the external genitalia and almost complete closure of the vaginal opening.

While concentrated in some 30 countries in Africa, the Middle East, and Asia, FGM is most prevalent in North Africa, particularly on the Northwest coast.

In Gambia and Mauritania respectively, 56% and 54% of girls under 14 have undergone some form of FGM. More than 200 million girls and women alive today have been subjected to this painful and dangerous procedure. Rather than conferring any type of medical benefit, FGM is actually incredibly unsafe and often performed with no anesthesia. Young girls are held down by relatives, while the “cutter” uses an unsterile knife, scissors, or sharpened piece of glass to remove parts of the external anatomy in a way that is intensely painful and traumatic. FGM is often performed with the intention to “force” the girls to remain virgins until they are married, after which the closure is re-opened. In regards to a physical sense, it does not exactly “force” virginity, but rather, removes pleasure from their sex lives and further stigmatizes female sexuality, discouraging girls from becoming sexually active before marriage. Short-term complications of the procedure include hemorrhage, infection, sepsis, and even death, while long-term effects include dyspareunia, dysmenorrhea, vaginitis, and cystitis. Given the gravity of the act, the numerous health complications, and the blatant human rights violations (as it is perpetuated mostly against young girls by force), why does FGM still occur?

The practice is rooted in gender inequality and the marginalization of women, and is tied to cultural ideals of femininity and modesty. The main argument for FGM is that it is considered “necessary” to prepare a girl for adulthood and marriage by ensuring her

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virginity and making sex more pleasurable for her husband, motivated largely by beliefs about what is considered acceptable sexual behavior. In rural and low-income regions, restricted access to accurate information about the female reproductive system and the perpetuation of myths about virginity and sexuality, along with a social obligation conferred by traditional and religious norms, have helped continue to enforce this practice.

Women’s health encompasses not just an absence of disease, but also physical, mental, and social well-being. Given this, it is important to understand how violence and prejudice impact women’s health on a global scale, and to analyze this impact with intersectionality. Violence against women takes many forms, including sexual assault, domestic violence, and human trafficking, and almost always disproportionately affects women of color and LGBTQIA+ women. Violence against transgender women, especially transgender women of color, is alarmingly common in both developed and developing countries.

For these women, intersections of racism, sexism, homophobia, and transphobia combine to make them more vulnerable to violence via deprivation of employment, housing, healthcare and other necessities. According to a 2017 Human Rights Campaign report, of the 102 murders of Americans identifying as transgender between 2013 and 2017, 86% of the victims were black, Hispanic or Native American.

Violence perpetrated against trans women is also prevalent outside of America, especially in Brazil, which saw 167 trans people reported murdered in the past year alone. Brazil lacks anti-discrimination legislation, trans-inclusive hate crime legislation, and recently saw the election of Jair Bolsonaro, a self-admitted “proud homophobe” who promised to strengthen persecution of LGBTQIA+ people.

Despite hosting thriving pride scenes in most major cities, Brazil remains deeply divided, with rampant

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homophobia and transphobia along with a Catholic Church that is frequently critical of gay and trans rights. In addition to high risks of transphobic violence, trans women also face discrimination from healthcare providers who lack training in treating transgender patients or just refuse to treat them at all. The goal of global women’s health initiatives is to empower women in underserved communities and remove barriers to healthcare access. This goal is only accomplishable if it is intersectional and inclusionary.

What can we do?

Empowering women and closing the global gender gap in healthcare requires a multifaceted approach.

The United States has established national initiatives and offices to promote women’s health, including the Offices of Women’s Health established in the CDC and the Department of Health and Human Services.

International organizations like the WHO, UNICEF, and the UNFPA have implemented specific programs on maternal, sexual, and reproductive health. Ultimately, global women’s health aims to empower women in underserved communities and contribute (financially and otherwise) to resources that cause a systemic change in women’s health in developing countries. Challenges to reaching this goal, like a lack of gender equity in research studies and a lack of representation in healthcare and health research, as well as in government, centers of higher learning, and in the private sector, must be addressed. Finally, it is important to emphasize short-term impacts with long-term outcomes. This includes bringing urgent healthcare to individual women in need worldwide, educating medical professionals and communities on women's health issues, investing in sustainable global women's health educational programs, fostering international partnerships and opportunities, and creating media campaigns to raise awareness and educate the global community.

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Scene from the closing of the 62nd Session of the Commission on the Status of Women. The UN's largest annual gathering on gender equality and women's rights concluded with the strong commitment by UN Member States to achieving the empowerment of rural women and girls. (Source: UN Women/Ryan Brown) 1.

Nour, Nawal M. “Preparing for Global Women’s Health Work.”

Obstetrics and Gynecology in Low-Resource Settings, 2016, 6-22. doi:10.4159/9780674974180-002.

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“HIV and AIDS in East and Southern Africa Regional Overview.”

AVERT. December 10, 2018. https://www.avert.org/professionals/ hiv-around-world/sub-saharan-africa/overview.

2.

“Violence against Women.” World Health Organization. November 29, 2017. https://www.who.int/news-room/fact-sheets/detail/violenceagainst-women.

7.

“Antiretroviral Therapy (ART) Coverage among All Age Groups.” World Health Organization. August 29, 2018. https://www.who.int/gho/hiv/ epidemic_response/ART_text/en/.

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Human Rights Campaign. “Violence Against the Transgender Community in 2018.” Human Rights Campaign. https://www.hrc.org/ resources/violence-against-the-transgender-community-in-2018.

8.

Goliber, Thomas. “The Status of the HIV/AIDS Epidemic in Sub-Saharan Africa.” Population Reference Bureau. March 2, 2017. https://www.prb. org/thestatusofthehivaidsepidemicinsubsaharanafrica/.

4.

“Female Genital Mutilation/Cutting: A statistical overview and exploration of the dynamics of change.” UNICEF. July 2013. https:// data.unicef.org/resources/female-genital-mutilationcutting-statisticaloverview-exploration-dynamics-change/.

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“Women and Girls, HIV and AIDS.” AVERT. August 21, 2018. https:// www.avert.org/professionals/hiv-social-issues/key-affected-populations/ women.

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El-Saharty, Sameh. “South Asia’s Quest for Reduced Maternal Mortality: What the Data Show.” Investing in Health. January 13th, 2015.

10. Bustreo, Flavia. “Ten Top Issues for Women's Health.” World Health Organization. January 04, 2016. https://www.who.int/life-course/news/ commentaries/2015-intl-womens-day/en/.

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THE FUTURE OF BIOSENSORS

AN ANALYTICAL LOOK AT THE POTENTIAL CONSEQUENCES OF NEW BIOTECHNOLOGY

By

RYAN CHOI LINUS PARK

The ER responds to an emergency call indicating that a boy’s father is under cardiac arrest.

There were no previous signs of heartburn, chest pain, or any other symptom related to heart failure, and yet two hours later, he is dead.

In the United States alone, the five most common causes of death are heart disease, cancer, respiratory diseases, unintentional accidents, and strokes – three of which are often unforeseen, sudden deaths. Most of the time, like the boy’s father, we never see it coming. Only when we feel certain symptoms do we suspect there to be anything wrong. We react to these unforeseen changes, and if we are unlucky, we are too late.

But what if we are able to predict these accidents, to prevent health conditions before they even arise? What if we knew precisely the condition of our bodies, and the direct consequences of our daily decisions, like the impact a cheese pizza can have on our propensity for heart failure? How would this shape our decisions?

This is precisely what biosen-

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sors, analytical devices that detect the amount of a specific chemical substance in our body, seek to achieve – to analyze the dynamics within our body and calculate the direct implications of the data received. As medical technology evolves, some form of biosensors will become a common norm in our society. Biosensors may sound like an innovative panacea to the modern medical dilemma; however, there are potential problems that can cause greater damage than the health benefits associated with this technology.

To broaden the perspective for biosensor use in the future, we will discuss potential benefits of this new biotechnology as well as the potential shortcomings associated.

Benefits

The modern health dilemma usually involves an ambiguity with our present health condition. Individuals tend to lack awareness about the conditions of their respective bodies. When we eat healthy, we feel “good”; when we have a cold, we feel

“sick”; when we work out, we feel “strong”. These are all categorical descriptions that depend on the subjective experience of the individual. But what if people had access to precise analytical data on the dynamic of their physical states? Biosensors can pinpoint the amount of cholesterol in our body and inform us on the amount of cholesterol that could cause heart failure. It could potentially detect cancer cells, and alert us early on to take the steps necessary to prevent its growth. What we lack is precise, continuous, and objective data that tell us the exact condition of our body.

This is the greatest benefit of biosensors: a device that provides users with precise objective data on their bodily conditions. It can supplement daily decision-making by optimizing goals and managing nutrient intake. Precise data can help unfold medical mysteries. With an extensive database, doctors can rely on a number of cases to help diagnosis their patients. Biological data can also identify people’s susceptibility to

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different health conditions that are not identifiable by genetics, such as cystic fibrosis. Perhaps one day, we can even predict exactly when and how we get Alzheimer’s based on our current lifestyle.

In the present, we have already developed tremendous data analytical techniques that can inform predictions of the future – we can predict stock market fluctuations, our preferences in our next Netflix show, even a very accurate model of future weather patterns.

It seems counterintuitive, then, that we haven’t developed the tools necessary to gather data in using these analytical techniques in the medical arena. When those tools become sophisticated enough, the possibilities will be revolutionary and will surely change the dynamics of our society. But tremendous benefits come with equally large risks. While we can be optimistic of this technology, we similarly have to question and anticipate the pitfalls associated with it.

Shortcomings

The greatest problem in the short term will be social issues, in that the inequality gap between the upper and lower class is bound to widen. Undoubtedly, this technology will be a costly venture, and only the upper class will be able to afford and integrate biosensors seamlessly into their daily lives.

Already, the income inequality is immense and gaining analytical data is expensive (the average cost of an MRI is $2,500 in the US). In the future, while the upper class has access to various forms of this biotechnology, and thus becoming even more productive and successful, the lower and middle class will be left behind, increasing the inequality gap to irreparable levels.

This is a complication that should be solved, either through policy, accessibility, etc. before biosensors become accessible to consumers.

Following is an issue of our privacy. Who should hold the rights to this medical data? The greatest dilemma involves insurance companies. If they have access to, say, the likelihood of when we get cancer or when we will get a stroke, wouldn’t they raise insurance costs exponentially to fit those calculations? They would be able to make immense profits while leaving consumers broke. On the contrary, if medical data is restricted from insurance companies, then individuals can manipulate when they purchase insurance based on medical predictions. This could, in turn, bankrupt insurance companies.

Aside from insurance, medical privacy is already an issue that is bound to become even more complicated with biosensors and their medical counterparts. Do

companies have access to the medical profile of an applicant?

Will people alienate others with certain diseases? The question then is how much medical data should be available to the public and how much should be private?

All this leads to an important point – do we really want to know these calculations? Big data already, without biosensors, can accurately predict to the week, when we will die based on our current lifestyle and genetic data.

Do we really want to know when we die? This gives us complications that need to be addressed.

The human body always has some form of problems. Yet, we can live comfortably without much consideration. With access to this data, we may know too much of our health, and we may not be able to live freely, restricted by the knowledge we have.

Center for Disease and Control. https://www.cdc. gov/heartdisease/facts.htm.

Estrela, Pedro. NCBI. https://www.ncbi.nlm.nih. gov/pmc/articles/PMC4986445/.

Nichols, Hannah. Medical News Today. https:// www.medicalnewstoday.com/articles/282929. php.

Scheller, FW, A Yaman, T Bachmann, T Hirsch, and S Kubick. https://www.ncbi.nlm.nih.gov/ pubmed/24196315.

Sinha, Shubham. Edureka. https://www.edureka. co/blog/big-data-applications-revolutionizingvarious-domains/.

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CUT & PASTE Gene Editing in Humans and the First CRISPR Babies By

ALLISON GENTRY LINDSAY ROMANO

Dr. He Jiankui announces his research while at the Second International Summit on Human Genome Editing in Hong Kong.

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Our imaginations have always been captivated by the ability of science to change our world. Sci-fi books and movies such as Gattaca, Blade Runner, and Jurassic Park have indulged our curiosity about the darker side of science where the abuse of genetic research alters the entire universe. While these worlds may seem outrageous, society is on the verge of scientific research that prompts us to ask difficult questions about our power to change the natural order.

The broad leaps in our understanding of genetics made in the past century have enabled us to learn about our history through the study of phylogeny and our present through the examination of DNA to understand genetic disorders. Now we must face the question of how these discoveries will affect our future.

The study of genetics spans back to the nineteenth century, when Gregor Mendel began to investigate how traits are passed from organism to organism by studying pea plants. His research opened the doors to understanding that our physical traits, or phenotypes, arise from the universal genetic code found within the DNA of our cells. This discovery set the groundwork for monumental genetics research such as the Human Genome Project, which consisted of researchers mapping out the entire span of the human genome and was completed by the late 20th century. With the development of faster and more comprehensive scientific technology, drastic strides in genetic

The CRISPR-Cas9 technique and the processes used to edit genetic material in laboratory settings.

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research are continuously being made, including the discovery and research into the use of a gene-editing technique called CRISPR-Cas9.

The CRISPR-Cas9 process emulates the ability of bacterial cells to produce small segments of RNA called “CRISPR assays� that attach to the DNA of invading viruses, which is then cut by

the enzyme Cas9. Scientists are now able to harness CRISPR-Cas9 within laboratories, which allows them to alter specific genes in a DNA sequence. This is done by creating small segments of RNA that match with the code of a specific gene within a DNA sequence. After the complementary RNA lines up with the DNA, Cas9 is able to cut that gene out

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of the DNA strand. This process has been used to alter the genes of bacteria and other organisms within various lab and research settings, and for the first time in history, one researcher has used it to alter the genome of two human beings.

In November of 2018, the scientific community was set into a frenzy by the announcement of the birth of twin girls in China.

These girls are unlike any other humans in existence because they are the first to have embryonic genes edited by the CRISPR-Cas9 technique. The scientist behind this project, Dr. He Jiankui, announced at the Second International Summit on Human Genome Editing in Hong Kong that he had successfully edited the genome of human embryos using CRISPR-Cas9 to provide the twin girls with resistance to HIV. Dr. He’s project centered on using CRISPR-Cas9 to remove the CCR5 gene from embryonic cells, a gene which creates a protein that HIV needs to replicate itself and infect human cells. Several couples were recruited to participate in the study, in each of which the father had HIV, the mother was uninfected, and the couple wished to have children. Using the CRISPR-Cas9 technique, researchers were able to create a small strand of RNA that attached to the CCR5 gene within the DNA of the embryos, and the CCR5 gene was cut out by the Cas9 enzyme. Dr. He chose to edit the germline cells of the embryos, and these cells are the first to replicate during development; therefore, the changes made to the embryonic DNA were replicated and reproduced within every somatic cell in the body.

This radical change made to the genome of the twins’ bodies also means that these edits made to their cells could be passed down to all of their descendants for each subsequent generation.

As with most things in modern science, there are downsides that accompany the potential benefits of these methods. The CRISPR-Cas9 process does not always perform with perfect accuracy, and many times will inadvertently alter other genes as well, which is known as “off-target editing” and can lead to genetically different cells throughout the body, or “mosaicism.” A review of the twins’ genomes showed signs of mosaicism, and the effects this may have on the health of the girls later in life is still being analyzed.

Another issue being addressed is that the editing process also did not go to completion, as only one of the twins had both copies of the gene removed, while the other still has a single copy in her genome.

The result of this incomplete process means that she does not have complete resistance against HIV. Many scientists familiar with this process have expressed concern with Dr. He’s procedures, as they believe he could have been more meticulous by stopping the gene editing process when issues arose. It is also contested whether or not a resistance to HIV is so necessary that gene editing would be required. There are currently methods that prevent HIV from infecting embryos such as washing off sperm before in vitro insemination. These issues with the gene editing process that occurred in this instance call into question the moral principles that Dr. He has violated.

Ethical boards of review have looked into Dr. He’s paperwork and found that he evaded monitoring in order to continue his research without disruption, and he is now being faced with charges for violating national guidelines for scientific studies.

The health of the twins is now being constantly monitored, and another woman who was part of the trial is currently pregnant with another genetically modified embryo and is being monitored as well. The ethics of this research has begun an important conversation about gene editing in the scientific community, and questions of morality raised by Dr. He’s project will continue to arise as scientific research and technology continue to develop.

“CCR5 Gene - Genetics Home Reference - NIH.” U.S. National Library of Medicine. Accessed February 21, 2019. https://ghr.nlm.nih.gov/ gene/CCR5#resources.

“CRISPR Graphic.” PLOS Ecology Community.

Accessed February 21, 2019. https://blogs. plos.org/onscienceblogs/2017/08/04/ successful-gene-editing-of-a-viable-humanembryo-lots-and-lots-of-links/crispr-graphic/.

Davies, Kevin. "He Jiankui Fired in Wake of CRISPR Babies Investigation." GEN. January 21, 2019. Accessed February 21, 2019. https:// www.genengnews.com/news/he-jiankui-firedin-wake-of-crispr-babies-investigation/.

“Doctor behind Gene-edited Babies Acted on His Own, China Says.” NBCNews.com. Accessed February 21, 2019. https://www.nbcnews.com/ health/health-news/china-says-dr-he-jiankuibehind-gene-edited-babies-acted-n960926.

Kolata, Gina, Sui-lee Wee, and Pam Belluck.

"Chinese Scientist Claims to Use Crispr to Make First Genetically Edited Babies." The New York Times. November 26, 2018. Accessed February 21, 2019. https://www.nytimes. com/2018/11/26/health/gene-editing-babieschina.html.

Saey, Tina Hesman. "The Researcher Who Created CRISPR Twins Defends His Work but Fails to Quell Controversy." Science News.

November 29, 2018. Accessed February 21, 2019. https://www.sciencenews.org/article/ researcher-defends-creating-crispr-babies-failsquell-controversy.

“What Are Genome Editing and CRISPR-Cas9?

- Genetics Home Reference - NIH.” U.S. National Library of Medicine. Accessed February 21, 2019. https://ghr.nlm.nih.gov/ primer/genomicresearch/genomeediting.

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HUMAN MOVING FORWARD Ethical Discussion Regarding Creation of 3-Parent Children By

EDWIN SANTOS FATIMA SATTAR

Amidst the sudden shift from the dream of DNA sequencing to the reality of procedures like gene therapy, our relationship with DNA has changed with remarkable speed over the past few decades. At first, the desire to sequence DNA was out of scientific curiosity and research-focused goals. With ever-improving technology, however, humans have moved beyond merely learning about our DNA to the point of outright altering DNA. Embryonic techniques allow us to go so far as to alter DNA prior to birth, such that deleterious diseases passed down from parent to child can be eradicated before birth.

One of the most recent and groundbreaking uses of this new technology is seen in the story of a Jordanian family who emigrated to America. The mother passed on Leigh syndrome, a fatal disease, through mutated mitochondria in her eggs to her children in previous pregnancies. The couple sought out Dr. John Zhang in an attempt to bear children free of this malady. At first when the couple consulted Dr. Zhang, they were put off by the methods of his technique of pronuclear

Steamlined diagram of pronuclear transfer

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transfer: the mother and a donor’s egg cells are both fertilized with the father’s sperm cells, then the mother’s nucleus is moved into the donor’s egg cell while the donor’s egg cell nucleus is discarded.

For some time, the couple held onto the hope of conceiving a child naturally free of the disease.

Because only 25% of the mother’s DNA was mutated for Leigh syndrome and mitochondrial DNA is randomly placed in egg cells, it was possible, with luck, that the mother could have a child with a relatively unmutated egg cell and not pass down the fatal illness. After a lack of success, the couple returned to Dr. Zhang, who agreed to execute an altered version of the procedure: instead of fertilizing both eggs, he used tiny pipettes to remove the nuclei from both egg cells prior to fertilization. The mother’s nucleus was then placed into the egg of the donor for fertilization, and the donor’s nucleus was discarded. This allowed the procedure to better suit the parents’ religious values. As Muslims, the parents were initially put off by the loss of a fertilized egg cell, but the adaptation of the procedure meant only an unfertilized egg (the mother’s egg carrying the compromised mitochondria and the donor’s nucleus) was discarded.

Once born, the baby appeared to be healthy and lacking the adverse health effects that plagued the couple’s previous children. Dr. Zhang and his colleagues tested the boy’s mitochondria for mutated mitochondrial DNA (mtDNA) and found that only 1% of the mtDNA was mutated. This is substantially below what is considered the threshold for serious adverse health effects, but continuous monitoring of the child’s condition must be done to ensure that the

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percentage of defective mtDNA does not increase.

Policy and Ethics

Procedures for mitochondrial replacement face stigma and caution that in part reflects societal concern over DNA and embryonic manipulation as a whole. Additionally, there are legitimate ethical concerns regarding the nature of the procedure and consequences to the health of the children born of the procedure.

One ethical concern is over the propagation of dangerous mtDNA mutations or other complications from the procedure if the baby produced is female.

Since females pass on their mtDNA to their children, any issue of mtDNA in the female baby may be passed on to her children. Here, the issue is mitigated by the fact that the child born to the Jordanian couple is a boy, who will therefore never pass on any of his mitochondrial DNA to potential children. However, Nadiya Clinic in Kiev, Ukraine, has offered pronuclear transfer procedures to women and brought four babies to term through this method, one being a girl.

On the front of public presentiment, there is the association of embryonic procedures such as this one with DNA manipulation to the extent of what some call “designer babies.” There is public concern among some that DNA manipulation could lead to parents deciding on the genetic profiles of their children through artificial means. An important distinction to draw between Dr. Zhang’s procedure and gene editing is that DNA itself was never manipulated during the procedure. The mother and donor’s egg cell nuclei were both healthy and unaltered, while the donor’s

mtDNA was without dangerous mutation. The majority of the mother’s mtDNA was discarded along with the majority of her contributed egg cell. None of the DNA itself was altered, simply that the combination of mtDNA with nuclear DNA in the mother and donor cell was switched to give the mother a cell with her nuclear DNA and predominantly the donor’s mtDNA. Certain reservations people have with the procedure can be considered in part more practical matters that have to do with the technology of the procedure.

For example, when there is concern of mtDNA issues with the final fertilized egg cells, one of the issues people fear is that residual mtDNA will make its way from the mother’s egg cell to the donor’s egg cell and still result in complications. This fear is grounded by the fact that the ban placed on mitochondrial replacement in the US stemmed from a procedure in the 1990s where mitochondrial DNA from a donor was injected along with the sperm of the mother’s partner into a mother’s egg cell, such that the egg cell contained both the mother and the donor’s mtDNA. The two fetuses born of the procedure had genetic disorders thought to be the result of carrying two different sets of mtDNA. As with the child born to the Jordanian parents, current procedures are imperfect and the child still carried some of the mother’s mutated mtDNA. Moreover, there is risk simply in having two sets of mtDNA, and the more carryover of the mother’s mutated mtDNA there is in procedures, the greater the risk to the child. While one approach to this threat is banning the procedures, ultimately not all

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countries take this approach nor would be firm in their regulation, such that doctors such as Dr. John Zhang can simply go to other countries to conduct the procedure. A ban will not eliminate the risks of the procedure, mainly because a ban will likely not become uniform and well-regulated worldwide.

Therein, a ban simply reduces funding and research into such procedures while some find ways to circumvent the ban and continue the procedure, though the procedure could be developed to limit functional issues such as carryover of the mother’s mtDNA. A ban ultimately will not solve any issues associated with the procedure itself but merely aggravate those issues by halting development by restricting research and funding.

With other countries such as the UK legalizing pronuclear transfer, and places like Nadiya Clinic and John Zhang’s New Hope Fertility Clinic practicing these procedures, it is evident that these types of alterations will become less the exception and more the norm. The US has one of the most advanced healthcare systems in the world. To turn away physicians who would practice in the US is to force them to go to countries with lesser regulations, just as John Zhang did. To ban the procedure stops physicians

from executing the procedure in regulated hospitals that have health requirements as stringent as in the USA, and have ready access to research, funding, and technology. When physicians head to places with more lenient regulations in healthcare, they also risk the safety of their patients who may face negative consequences from the less strict health standards.

While many may have moral qualms as to the nature of the procedure, bans will only drive such activity underground and out of the country, which could aggravate many of the dangers that initially resulted in the ban. The USA, as one of the nations most capable to drive the field of embryology forward, must reassess the validity of the stigma surrounding procedures such as this. The nation must recognize the full ramifications of the ban and all the improvements to the procedure that can be made if proper resources are gathered for the development of pronuclear transfer and other techniques.

As the biological sciences develop further with the aid of new technology, our ability to change our DNA and alter our physical life will only increase. We must take responsibility so that such technology can be regulated for the protection of patients and children, and that such applications may be appropriate.

Mitochondrial DNA

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Barfield, Jennifer. "How Can a Baby Have 3 Parents?" D-brief. June 18, 2018. Accessed February 22, 2019. http://blogs.discovermagazine.com/ crux/2018/06/15/how-can-a-baby-have-3-parents/#.XFMyrrhME2w.

“Fact Sheet 12 | MITOCHONDRIAL INHERITANCE.” Centre for Genetics Education. Updated September 30, 2015. Accessed February 22, 2019. http://www.genetics.edu.au/publications-and-resources/facts-sheets/factsheet-12-mitochondrial-inheritance. Mitochondrial DNA diagram.

Hamzelou, Jessica. "Exclusive: World's First Baby Born with New "3 Parent" Technique." New Scientist. September 27, 2016. Accessed February 22, 2019. https://www.newscientist.com/article/2107219-exclusive-worldsfirst-baby-born-with-new-3-parent-technique/. Approximated publishing date.

Kolata, Gina. "Birth of Baby With Three Parents' DNA Marks Success for Banned Technique." The New York Times. December 21, 2017. Accessed February 22, 2019. https://www.nytimes.com/2016/09/28/health/birth-of3-parent-baby-a-success-for-controversial-procedure.html.

Sample, Ian. "World's First Baby Born from New Procedure Using DNA of Three People." The Guardian. September 27, 2016. Accessed February 22, 2019. https://www.theguardian.com/science/2016/sep/27/worlds-firstbaby-born-using-dna-from-three-parents.

Stein, Rob. "Her Son Is One Of The Few Children To Have 3 Parents' DNA." NPR. June 06, 2018. Accessed February 22, 2019. https://www.npr.org/ sections/health-shots/2018/06/06/616334508/her-son-is-one-of-the-fewchildren-to-have-3-parents.

"VECTOR - Pronuclear Transfer in Human Embryos." 123RF Stock Photos.

Accessed February 22, 2019. https://www.123rf.com/photo_71587580_ stock-vector-vector-pronuclear-transfer-in-human-embryos.html.

Pronuclear transfer diagram.

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A COCKTAIL OF DRUGS

New research shows cancer treatment starts in the kitchen

By

MALAIKA MATHIAS YIFAN MAO

“One way or another, I’m going to die.” Kathy Mydlach-Bero was suffering from the final stage of breast cancer, and with 21 months of life left on the clock, this was not the way she had planned to go. Her organs were failing, her hair was falling, and new tumors were growing – until one day, the cancer stopped growing. Researchers around the United States were yearning for her secret, and were shocked by its simplicity.

The magical recipe, she says, is actually just that. A combination of food that she put into her body actually had effects potent enough to alter the cellular pathways of tumor cells. The common procedure of digestion that we learn about often overlooks the impact of interactions between food and bacteria in the digestive pathway.

As we age, the nearly 10 trillion bacteria that find their homes in our guts evolve and play a complex

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role in tuning our immunity over time.

How do these bacteria work against cancer? For one, harmful bacteria metabolize cancer drugs, such as chemotherapies, hindering efficacy and deterring treatment. New research, however, is showing promotive effects of bacteria on immunotherapy and other targeted therapies. Immunotherapy is a set of novel cancer treatments that work to stimulate the body’s own immune response to act against cancer, rather than having external drugs work directly on the tumor. This streamlines treatments to target tumor cells, while ideally leaving the rest of the patient’s tissues unaffected and healthy.

The influence of bacteria has been heavily researched – most prominently in melanoma cancers, but also in lung, bladder, and kidney cancers – by teams

across the world, including here at the University of Chicago. In both human patients and mouse models, those who responded better to immunotherapy are seen to have greater microbial biodiversity than those who responded poorly. Furthermore, germ-free mice injected with fecal samples from humans who exhibited positive responses to immunotherapy had similar positive responses, in contrast to those mice that were administered bacteria from human non-responders.

Correspondingly, antibiotics inhibiting bacterial growth can have negative effects on treatment as well. Specifically, a lack of microbial diversity leads to decreased activation of dendritic cells, cells required for the activation of T-cells by presenting antigens from tumor cells on their surface for T-cell recognition. In other words, with fewer

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Pathways by which bacteria interact with tumor cells

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bacteria present, dendritic cells’ efficiency at processing tumor cells decreases, and thus T-cells are not activated to the same extent. In addition, certain engineered bacteria have also been used to attack tumor cells themselves.

Drugs aside, our nutrition influences the growth and apoptosis of various bacterial strains, of which each has its own functional impact on tumor cells. One of the ways by which bacteria does this is through immunostimulation, in which they trigger lymphocytes to attack tumors. They also selectively colonize regions of tissue that are low in oxygen and experiencing failure due to disease to stimulate an inflammatory response those regions. Furthermore, bacteria are motile organisms, making it easier

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for them to move toward and attach to tumor cells. Finally, they can act as a vector in delivering molecules involved in the immune response to the tissue, such as cytokines which lead to necrosis of cancerous tissue.

Clostridium, for example, while being a bacterial genus of which a strain is known for causing diarrhea, can actually work in the attack against cancerous cells by increasing the number of T-cells in the body. This works by affecting bile acids, which stimulate liver cells to produce the protein CXCL16, which subsequently triggers T-cell proliferation.

While it is widely known that obesity often acts in favor of diseases and their prevalence, new research further shows that long-

term calorie deficit can actually have anti-carcinogenic properties. Specifically, this is done by promoting the growth of Lactobacillus bacterial strains, many of which have anti-cancer properties.

Thus, to carry this research forward, understanding how our bacteria interacts with therapies means that we can tailor the microbiome to respond best to the treatments we make. The next steps include clinical trials where “good” bacteria, or probiotics, are fed as drugs to tumor patients in order to measure their change in response to immunotherapies as compared to before the bacteria were administered. Meanwhile, there are also ongoing clinical trials using fecal matter transplant (FMT) from “healthy” donors –

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determined by the diversity and composition of their microbiome – into cancer patients receiving immunotherapy. This could potentially further concur with data from previous studies about the strong impact of commensal microbiota.

Yet, there are ways we can incorporate these findings outside a hospital or laboratory to promote our own defense against cancer, starting from the food we eat.

Low-fat diets are not only beneficial to stave off obesity, but they also act against promoting cancer.

Alternatively, diets high in fat and low in fiber alter vitamins B7 and B12, which are closely related to microbial metabolism. As a result, high-fat diets increase inflammation and induce carcinogenesis.

With about 38.4% of people receiving a cancer diagnosis during their lifetime, we sometimes neglect the notion that we can directly impact our own susceptibility. Several studies have shown how our bacterial makeup can affect the efficiency of immunotherapies, but this is now extending even to prevention.

Since we can almost directly alter our microbiome through the foods we eat, it seems clear that our next steps involve our own awareness of nutrition. In doing so, we can mitigate our own risk of developing cancer and possibly even lower diagnosis rates on a broader scale.

Cancer Immunotherapy: A Brief Review of the History, Possibilities, and Challenges Ahead. https://jcmtjournal.com/article/view/2365.

"Can the Microbiome Affect The Effectiveness of Cancer Treatment?" UBiome. https://ubiome. com/blog/post/can-microbiome-affecteffectiveness-cancer-treatment/.

Choi, S. S., Y. Kim, K. S. Han, S. You, S. Oh, and S. H. Kim. "Effects of Lactobacillus Strains on Cancer Cell Proliferation and Oxidative Stress in Vitro." Current Neurology and Neuroscience Reports. May 2006. https://www.ncbi.nlm.nih. gov/pubmed/16620202.

Gajewski, Thomas F., and Jessica Fessler. "The Microbiota: A New Variable Impacting Cancer Treatment Outcomes." NCBI. April 26, 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC5627769/.

Geller, Leore T. et. al. "Potential Role of Intratumor Bacteria in Mediating Tumor Resistance to the Chemotherapeutic Drug Gemcitabine."

Science. September 15, 2017. http://science. sciencemag.org/content/357/6356/1156.long.

Gopalakrishnan, V. et. al. "Gut Microbiome Modulates Response to Anti–PD-1 Immunotherapy in Melanoma Patients."

Science. January 05, 2018. http://science. sciencemag.org/content/359/6371/97.

"Kathy Mydlach Bero." Kathy Mydlach Bero. https://www.kathymydlachbero.com/.

Krans, Brian. "6 Surprising Facts About the Microbes Living in Your Gut." HealthLine. September 7, 2013. https:// www.healthline.com/health-news/ strange-six-things-you-didnt-know-aboutyour-gut-microbes-090713#1.

Nci, Nci, and Nci. "Gut Bacteria Affect Response to Immunotherapy." National Cancer Institute. https://www.cancer.gov/news-events/ cancer-currents-blog/2018/gut-bacteriacheckpoint-inhibitors.

Rea, Domenica, Giovanni Coppola Coppola, Giuseppe Palma, and Antonio Barbieri.

"Microbiota Effects on Cancer: From Risks to Therapies." Oncotarget 9, no. 25. April 3, 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC5915165/.

"2nd Healing Story of the Month: May 2018."

Radical Remission Project. https:// radicalremission.com/healing-story-of-themonth-may-2018-2/.

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TRANSCRANIAL MAGNETIC STIMULATION

THE FUTURE OF DEPRESSION TREATMENT

By

VICTORIA BIGDELLE ALLAN ZHANG

Introduction

Depression is one of the most common mental disorders and disabilities in the U.S., affecting people across all ages, genders, and ethnicities. While depression can be seen as a spectrum, major depression has specific characteristics that vary little: persistent feeling of sadness, lack of interest, change in appetite, and a deregulated sleep schedule. However, that being said, depression is one large umbrella of a multitude of

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subtypes including: psychotic, postpartum, melancholic, and major depression. For the purpose of this article, the depression being spoken about will be major depression.

While depression is largely studied, with accounts of the disease dating back to the second millennium B.C., a panacea for the condition doesn’t exist: depression affects every individual in a different way. Therapies for depression, while being largely studied now,

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unfortunately are fairly recent – until recently, society did not look at depression and other mental illnesses as something worth treating, so instead, therapies were primitive and often times lethal.

Mental diseases were likened to insanity and patients were often subjected to “treatments” such as water immersion, lobotomies, insulin-induced comas, malarial infections, and even being placed in jail-like institutions.

The history of depression has a deep-rooted misunderstanding in how to go about treating the illness, which unfortunately is a stigma that, while lessened, is still ever present. Now, depression has affected millions and research in the past decade has been consistently progressing whether it be new drugs, therapy, and recently, transcranial magnetic stimulation (TMS).

The process itself is fairly simple: an electromagnetic copper coil is applied to the patient's forehead as the coil administers electromagnetic pulses meant to cause neural stimulation. Patients don't require any anesthesia, as they will simply feel slight tapping on their forehead for a few seconds. This continues until patient’s hands or fingers begin to twitch, signifying to the doctor or clinician that the correct magnetic dosage has been

administered. Typically, these treatments are administered for 30 to 40 minutes, 5 days a week.

However, like all medications or treatments, the TMS dosage can be altered to lessen the potential side effects. Some of the side effects include headaches, scalp discomfort at the site of coil placement, tingling, and in severe cases, seizures. However, since the treatment is noninvasive, most patients only experience side effects tempo-

Procedure

TMS, simply put, is a procedure that uses magnetic pulses to stimulate nerve cells of the brain. Only recently approved by the FDA, TMS has shown some success in patients with major depression.

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Clinical Trials and Future Research

rarily. At its core, TMS treatment works through the law of electromagnetic induction. As the coil is placed on the patient's forehead, it generates a rapidly changing magnetic pulse meant to penetrate the skull and reach the cortex. The current created by the magnet triggers action potentials in cortical neurons in the hopes of altering the excitability of inhibitory and excitatory circuits in the brain.

This depolarization of the cortical neurons and increased blood flow to the area of the applied coil is thought to be responsible for the therapeutic effects of TMS.

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Clinical trials of TMS have shown some success, and as such have encouraged researchers to continue with larger trials. Data shows that TMS has helped trial patients based on three major outcomes: severity of depression symptoms, response rate, and remission rate. On the Hamilton Depression Rating Scale used to determine a patient’s level of depression, TMS-treated patients averaged over a 4-point greater decrease than those given the placebo treatment. These results led to the conclusion that TMS was a suitable treatment in patients who have not had success with two or more antidepressant medication trials. Since then there have been many more clinical trials, each differing slightly in either their intensity of the dosage, the placement on the cranium of the coil, and even in treating different illnesses like schizophrenia. With the success scientists have seen in patients suffering from depression, TMS is trying to be expanded to help patients with schizophrenia.

There are clinical trials being done that focus on the reduced synaptic activity and dendritic connectivity between neurons associated with schizophrenia; however, as of now, there is no strong evidence.

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Conclusion

Science has clearly developed since the times of treating patients with depression like criminals, but it still has a long journey ahead.

TMS is an excitingly promising method that could potentially help millions of lives but that being said, the actual procedure is highly expensive and not yet at the point to be mass-marketed.

A single session can cost around $500, averaging about $15,000 for the entire treatment, and unfortunately, the treatment doesn't work on everyone. In those it has helped, remission is also possible.

This leaves scientists in a position to improve the treatment and hopefully encourages them to continue with research towards a better treatment and future for those suffering from depression.

This could mean trying to focus on the molecular biology of what happens in the brain when TMS is applied, or continuing to alter the existing procedure – this could be through changing the time of the treatment, the frequency or wavelength, position of coil placement, type of coil, or number of coils used at once. Regardless, TMS is not to be ruled out as the potential future of depression treatment as it is already pushing the boundaries of what science and medicine thought were possible.

Janicak, Philip G., and Mehmet E. Dokucu.

“Transcranial Magnetic Stimulation for the Treatment of Major Depression.” June 26, 2015. www.ncbi.nlm.nih.gov.

Kropotov, Juri D. “Transcranial Magnetic Stimulation.” NeuroImage. June 17, 2016. www. sciencedirect.com.

Lieber, Arnold, MD. “What Is Major Depression?

The Signs, Symptoms & Treatment.” PsyCom. net - Mental Health Treatment Resource Since 1986. Accessed February 15, 2019. www. psycom.net.

“Major Depression.” National Institute of Mental Health. November 2017. www.nimh.nih.gov/ health/statistics/major-depression.shtml.

Northwestern Medicine. “Transcranial Magnetic Stimulation.” Northwestern Medicine. www. nm.org.

Smith, Kathleen. “Transcranial Magnetic Stimulation (TMS) Therapy.” PsyCom.net Mental Health Treatment Resource Since 1986.

August 7, 2018. www.psycom.net/transcranialmagnetic-stimulation-tms-therapy.

Stern, Adam P. “Transcranial Magnetic Stimulation (TMS): Hope for Stubborn Depression.”

Harvard Health Blog. February 23, 2018. www. health.harvard.edu/blog.

“Transcranial Magnetic Stimulation.” Mayo Clinic.

November 27, 2018. www.mayoclinic.org.

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CHILD AND ADULT ACUTE MYELOID LEUKEMIA: WHAT’S THE DIFFERENCE? “It’s almost like comparing breast cancer to colon cancer.”

By

SOPHIA CAO JUI MALWANKAR

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According to the NCI-funded study’s senior investigator Soheil Meshinchi, acute myeloid leukemia differs greatly between pediatric and adult patients, demonstrating distinct genomic signatures. Acute myeloid leukemia (AML) is a cancer that starts from the bone marrow and then moves into the blood. AML is developed from cells that are presumed to turn into white blood cells, known as abnormal myeloblast cells. Symptoms of AML include fever, fatigue, musculoskeletal pain, and frequent bruising. According to the National Institute of Health, about 25% of children in the world with leukemia have AML while nearly 21,000 Americans over age 65 have been diagnosed with AML. It is assumed that acute myeloid leukemia treatments in adults can be used to treat younger patients as well, but studies from the Fred Hutchinson Cancer Research Center have shown that the biological characteristics of AML differ by patient development.

Better Understanding of AML in Children

To determine the genetic changes that drive Acute Myeloid Leukemia, the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Acute Myeloid Leukemia Project identified the genetic features of cancer cells in infants, children, and young adults through the analysis of subgroups. By doing so, the creation of targeted therapies would be established for younger patients aged 0-35. The TARGET AML Project team consisted of members from the National

Cancer Institute as well as the Children’s Oncology Group. From analyzing the pediatric patients’ tumors, it was evident that there were big changes in chromosome structure including deletions, duplications, or translocations.

This included the identification of fusion genes which are formed when part of the DNA from one chromosome moves to another chromosome, joining parts from two different genes.

There was a low frequency of the same mutations and alterations, signifying that there is an abundance of genomic characteristics in young patients. Reflecting off another study done by The Cancer Genome Atlas, there were nearly ten times more different structural alterations than DNA mutations in children with AML than adults with AML. In children, though, mutations in the NRAS gene that controls cell growth and death was found to be more common than in adults. Based off the TARGET researchers, no single treatment strategy is likely to be effective for all pediatric AML due to the unique features of each young individual.

Phenotypic Similarities, Different Genetic Diseases

In adults with AML, on the other hand, mutations are more common than structural alterations, with an accumulation of single-letter mutations in DNA over time. The study depicted that AML resulted from a huge part of the genome being moved, causing an effect of dysregulation.

Dysregulation is the impairment of a regulation mechanism towards

our physiological, metabolic, and/ or psychological process. AML in adults also develops from epigenetic dysfunction which is where the epigenetic changes that alter the structure of DNA lose their regulative behavior.

AML Treatments Between Children and Adults

Even though the development of drugs that have been approved to treat adult cancers are effective, this is not the same case with children. There have been continuous clinical trials to discover ways to cure AML in children. In one clinical trial performed by the TARGET researchers, a high-level protein known as mesothelin was discovered in lung cancer cells. Dr. Meshinchi, the TARGET coordinator, is currently working on creating a mesothelin-targeting drug that can cure children with relapsed AML. Additionally, the Children’s Oncology Group are continuously trying to improve treatment selection for pediatric patients, but there are still ongoing investigations on how to effectively cure children with acute myeloid leukemia. https://www.cancer.gov/news-events/ cancer-currents-blog/2018/genetic-differenceschildhood-adult-aml https://ocg.cancer.gov/e-newsletter-issue/issue-10/ childhood-and-adult-acute-myeloid-leukemiagenetically-distinct-diseases https://ocg.cancer.gov/programs/target/projects/ acute-myeloid-leukemia https://www.cancer.gov/publications/dictionaries/ cancer-terms/def/fusion-gene https://www.eurekalert.org/pub_releases/201811/w-lei112218.php

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