RaMedz

November 2016

Volume 8, Issue 1

The Medical Journal of the Ramaz Upper School

Vitamin D May Increase Survival for Breast Cancer Patients

by Tyler Mandelbaum ’17

New research suggests that vitamin D

might have a lasting effect in anticancer therapy for breast cancer, the most common form of cancer found in women.

The Centers for Disease Control and Prevention report that approximately 220,000 women are diagnosed with breast cancer every year in the United States. In 2013, 230,815 women were diagnosed with breast cancer, and 40,860 died because of it.

New studies suggest that the active metabolite of vitamin D – known as calcitriol – may be what helps to fight cancer. Researchers ran a test, in which they administered calcitriol to mice, and calcitriol hindered the proliferation and growth of Staff cancer cells, reduced tumor Editors-in-Chief blood vessel Gabriel Klapholz formation, and Jessica Fuzailof stimulated cell Rebecca Araten death.

While Faculty Advisor there are still Ms. Lenore Brachot not enough clinical trials in

humans for definitive proof, some clinical and preclinical studies say that making sure to always have enough vitamin D, specifically taking vitamin D supplements, might be a cost-effective and easy way to prevent cancer and improve the scenario in patients already diagnosed with breast cancer. A new study led by Dr. Song Yao, from the Roswell Park Cancer Institute in Buffalo in New York, analyzed data from 1,666 women diagnosed with breast cancer.

Researchers looked at levels of the vitamin D biomarker 25-hydroxyvitamin D (25OHD) at the time of the diagnosis, and associated them with survival prognosis. In addition, patients were checked at regular intervals: 12, 24, 48, 72, and 96 months.

Researchers found a lower level of the vitamin D biomarker in women with advanced-stage tumors. The lowest levels were found in premenopausal women with triple-negative cancer. Levels of 25OHD were found to be inversely proportional to disease progression and death rates.

Researchers are consistently finding that more vitamin D in a woman’s body usually means less of a chance of cancer, but it may be a while before we know definitively.

Healthy Living Can Overcome Genes Linked to Heart Disease

by Tammy Krikheli ’18

Many

people have had friends or family members who have passed away or been affected by cardiovascular disease. The thing that people usually don’t know is that there are ways to counter the disease. New research shows that by living a healthier lifestyle (eating better, exercising and quitting smoking are all examples), one can minimize one’s risk for a heart attack.

Senior researcher Dr. Sekar Kathiresan says that people can cut their genetic risk for heart disease almost by half just by changing their lifestyles. He also says that the opposite is true as well; if people are genetically born with an advantage protecting them, they could ruin their luck just by having unhealthy lifestyles.

For his research, Kathiresan used data on more than 55,000 participants in four large-scale health studies. He judged each person’s lifestyle based on four areas: smoking, body weight, diet, and exercise. The expectations for the

people involved included no smoking, maintaining a body weight that doesn’t cross into obesity, exercising weekly, and meeting some standards of a diet.

From this research, Kathiresan found that people with high genetic risk and a bad lifestyle raised their chances of a coronary event within ten years to nearly 11 percent. However, a person with high risk who had healthy lifestyles cut their risk down to five percent.

People with low genetic risk and good lifestyles had a three percent risk of a coronary event within ten years, but people with low genetic risk and bad lifestyles drove their risk to 5.8 percent.

The results of this research showed that though one may be more likely to have a heart attack or some sort of coronary event, one can always reduce his or her risks. The lifestyle one makes for oneself can be the difference between a long happy life and one strongly affected by disease.

The Science behind Peanut Allergies (and How to End Them?)

by Kyla Mintz ’18

Most of us have at least one friend or family

member that has a severe peanut allergy. We know not to eat peanut products near those with the allergy and to wash our hands before interacting with them if we’ve touched anything with peanuts.

But why are peanut allergies so severe? And what is actually happening when someone with a peanut allergy either comes into direct contact or cross contact with peanuts, or inhales a product with peanuts?

A food allergy response happens when your immune system overreacts to a food, identifying it as dangerous and triggering a response that is meant to protect you. There are at least seven peanut proteins that have been identified to cause allergies. The allergic reaction caused by peanuts is strictly an IgE mediated Type I hypersensitivity reaction. IgE is a type of antibody produced by the immune system. In the allergic response, peanutspecific IgE antibodies bind to receptors on mast cells and basophils. When the peanut allergens enter the mucosal barrier, cell-bound IgE and peanut allergens cross link, resulting in the break up of preformed allergic mediators. This leads to the activation of cells, which can then produce various cytokines and chemokines. The cytokines and chemokines then recruit other inflammatory cells. This all contributes to the IgE-mediated late phase allergic response.

The allergic response often causes anaphylaxis, which can be fatal if not treated immediately. The inflammatory mediator cells that are released in the allergic response cause increased vascular permeability, peripheral vasodilation, increased mucus production, and bronchial smooth muscle contraction. The airway becomes extremely compromised and the cardiovascular system can collapse. Anaphylaxis is a type of shock; the biggest issue is perfusion.

The primary treatment for anaphylaxis is epinephrine. Individuals with severe allergies carry an epinephrine pen for use in case of an allergic reaction. It helps to restore perfusion by constructing the blood vessels. The epinephrine also helps to re-establish the airway by relaxing the muscles of the airway. It is an extremely important life-saving medication. In some cases, individuals experiencing anaphylaxis may need to be intubated with an artificial airway if their own airway is too obstructed due to the swelling and edema that occurs. Patients in anaphylactic shock also need to receive large amounts of intravenous fluid.

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, have sponsored an ongoing trial to determine if an innovative patch may help people with peanut allergies. The treatment is known as epicutaneous immunotherapy. The patch lessens the stressful burden of having a peanut allergy by training the immune system to tolerate enough peanut to protect against accidental ingestion or exposure. The patch delivers small amounts of peanut protein through the skin. The study invoked 74 peanutLerwick volunteers between the ages of 4 and 25.

A third of the volunteers had a high dose patch, a third had a low dose patch, and a third had a placebo patch. The participants' peanut allergies were assessed before the study began in a supervised setting. Each day the participants put a new patch on their arm or between their shoulder blades. It was found, after a year, that participants were able to consume ten times more peanut protein than they were able to before beginning this patch therapy. Treatment was most effective for participants aged 4 to 11.

Although there is certainly more research to be done, this exciting development in immunology may be extremely promising.

Peanut allergies can be life threatening, and if this therapy proves to be effective based on further studies, families and children will have a significantly easier time navigating through our peanut-filled country.

Study Finds Young Athletes Should Wear Protective Goggles

by Gabriel Klapholz ’17

At Ramaz, athletics play a major role in

many students’ lives. From basketball team to volleyball team members, students are constantly frequenting the gym to practice, play, and compete. A recent scientific study indicated that eye injuries are more common in sports than one might think.

The study singled out youth sports as even more worrying, basing its conclusions on a nationwide analysis of emergency room visits related to eye problems among athletes. The research showed that those involved in youth sports should be very careful about protecting their eyes.

In general, team sports, while providing athletes with a wide range of health benefits, obviously include risk of injury. This risk does not discriminate between athletes with more or less experience, as even veteran athletes can trip, fall, or hurt themselves in some other way.

In recent years, sports injuries have been on the rise, namely concussions and anterior cruciate ligament (ACL) tears in the knee, but eye injuries have faced far less concern and worry from athletes (or their parents).

Eyes, however, are particularly at risk during sports because they are often “facing directly into the action,” stated a recent article in The New York Times.

Furthermore, eyes do not have a great deal of natural protection against projectiles and other sports-related dangers. They remain open and unprotected, leading to the recent study’s reports of a startling number of eye injuries.

JAMA Ophthalmology published the new study, which involved researchers from Johns Hopkins University, Harvard, and other institutions who decided to collect data from the Nationwide Emergency Department Sample. The database includes information from millions of emergency

room visits to over 900 hospitals nationwide, serving as a sample for the near 5,000 emergency rooms in the country. The researchers were working with data from 2010 to 2013 and found that around 30,000 sports-related eye injuries were treated each year at the emergency rooms that were involved in the database. The vast majority of these injuries were in athletes under age 18.

Researchers found that basketball was the most dangerous sport for eyes, and the sport caused more than a quarter of the injuries. Baseball and softball tied for second. Interestingly, football resulted in few eye injuries, most likely due to the protective headgear that players wear, which covers the face. In addition to basketball, cycling was also a major cause for eye injury, and for girls, soccer was too.

Fortunately, most of the reported injuries were relatively small and included mainly superficial damage around the eye or on the eyelid. Fractures of the bones that house the eyeball, however, required surgery and put the athletes at risk of impaired vision.

“Sports-related eye injuries can be quite serious,” noted Dr. R. Sterling Haring, the leader of the study and a doctoral researcher at Johns Hopkins and the University of Lugano in Switzerland. Dr. Haring also mentioned, “We had data only from emergency rooms” – so the numbers exclude all of the visits to eye doctors, urgent care facilities, and general practitioners. According to the leader of the study, taking these other categories into account would double or triple the total number of eye injuries.

Ultimately, Dr. Haring said, “If you’re dealing with projectiles or fastmoving objects,” he said, “protective eyewear is definitely worthwhile.

Wraparound glasses with shatterproof

lenses can keep out a lot of undesirable objects.” The doctor continued, “Knowing what we know now about how many eye injuries occur during sports, especially

youth sports, let’s try for a cultural shift and convince the kids they look really good wearing those glasses.”

3D Printing Can Lead to Printable Organs

by Oriya Romano ’17

Could you ever imagine that it would be possible, using your own cells, for doctors and scientists to recreate an identical copy of your organs using a printer? Now, although there is some time until that dream can be a reality, with recent studies done by Tsingua University in China and Drexel University in Philadelphia, the preliminary steps towards this world-changing ability are in motion.

While bioprinting with embryotic stem cells is not entirely new, the team of scientists who published their study in Biofabrication introduced a new technique for printing a grid-like 3D structure laden with stem cells.

Embryotic stem cells are used because they can develop into any cell type. Thus, they are ideal for use in regenerative medicine. In the lab, the embryotic stem cells are placed in a solution that contains the biological ‘cues’ that tell the cells to develop into a specific tissue type. The printer creates 3D spheroids using delicate embryonic cell cultures floating in the solution or "bio ink" medium. They end up looking like little bubbles. Each droplet can contain as few as five stem cells. The cell printer uses compressed air to squirt out this "bio-ink" containing cells and nutrient-rich fluid. At first, scientists had trouble creating this “ink” since pluripotent cells are hard to maneuver and were only able to create twodimensional sheet cells. For this new method, the researchers mixed the embryotic stem cells with hydrogel, and printed a tiny sixlayered grid square, 8 millimeters across and 1 millimeter thick. The whole system was then cultured, and researchers watched the cells grow into ball-shaped embryotic bodies without leaving their spots in the grid. This

development meant that the cells were dividing and remaining separate instead of randomly clumping together all over the place.

The result was a uniform collection of cell spheres.

Dr. Will Shu, who is part of the research team working on the project and one of the lead authors of the paper said, "In the longer term, we envisage the technology being further developed to create viable 3D organs for medical implantation from a patient's own cells, eliminating the need for organ donation, immune suppression, and the problem of transplant rejection." The possibilities for this type of machine are truly endless and so are the opportunities it brings. For example, scientists will be able to print out viable tissues and organs on which to practice medicine.

They will also be able to test new drugs on these printed organs, thus eliminating the risk of animal and human trials. Biomedical engineer Utkan Demirci, of Harvard University Medical School and Brigham and Women's Hospital, has done revolutionary work in printing cells and thinks the new study is taking it in an exciting direction. "This technology could be really good for highthroughput drug testing. However, building whole organs is the long-term goal and may be quite far from where we are today."

The Dangers of Simultaneous Physical Exertion and Emotional Tension

by Rebecca Araten ’18

While a run may seem like a healthy way

to combat life's stress and emotion, studies show that one must be cautious when doing so. An international study recently found a correlation between heart attacks, high emotions, and physical exertion. While physical exertion and emotional tension had been previously known to trigger heart attacks, data collected from people around the world suggest that when combined, they cause more heart attacks than they do individually. The common denominator between these two triggers is that they lead to an increased heart rate and blood pressure, which can ultimately break the plaque in the heart and disturb normal blood flow.

Scientists have concluded that the risk of triggering a heart attack mainly exists when one runs or exercises beyond

the amount to which one's body is accustomed. While the definitions of high emotion and physical exertion are very subjective, scientists have come to the agreement that if a person becomes distressed and suddenly decides to push his or her body to the limit, it could potentially trigger a heart attack.

However, the important thing to remember is that these conclusions only apply to one who already has heart disease and either does not realize or simply decides to exercise intensely despite previous issues. If one does not have heart plaque, there is no fear of it bursting, in which case it should be perfectly acceptable to use a jog as an outlet for excess emotion. Nevertheless, it is vital to respect bodily limits and norms and to not deviate too greatly from our normal routines and patterns.

Race for a Zika Vaccine

by Jessica Fuzailof ’17

This

past Friday, the World Health Organization declared that Zika virus is no longer a world health emergency. Zika is continuing to spread, and the new plan is to take a long-term prevention approach to defeat the virus. Most people infected by Zika typically experience only minimal symptoms, but can suffer from fevers, rashes, and joint pain. The larger concern is the birth defects caused by the virus, including microcephaly, which causes infants to be born with abnormally small heads and incomplete brain development.

Scientists all over the world are clamoring to find a vaccine for the virus.

Vaccines typically take over a decade to develop, but hopeful estimates place a vaccine for Zika arriving in 2018. Many independent companies, as well as government-sponsored labs and organizations, are employing various different methods to find the vaccines. The most common and effective type of vaccine, the killed vaccine, involves a dead virus sample being injected into the body. The body crafts a defense against the virus and learns to fight off the live virus that way.

Many organizations are attempting to create a killed vaccine for the Zika virus.

However, while effective, the killed vaccines normally take decades to develop.

Other teams are attempting a newer approach, involving manufacturing a harmless piece of the virus’s DNA that, once injected, tells human cells to create Zika proteins. These proteins will assemble into harmless virus-like particles and thus prompt the body to develop antibodies against the virus.

This newest method is difficult in practice, because the vaccine’s DNA often

fails to reach the nucleus of the human cell in time to order the creation of Zika proteins. Some companies are looking for ways to adapt this method to RNA instead, since it is more flexible than DNA, and the vaccine would not need to reach the nucleus to trigger the immune response.

Researchers are taking advantage of Zika’s rapid spread to make use of ideal testing grounds for a vaccine. Zika has now spread to more than seventy countries.

There is a financial incentive to find the vaccine, as well—the virus is not limited to poor regions of third world countries; it exists in wealthy countries like the United States and Brazil, where the governments can afford public vaccination campaigns and the people can afford treatment. In addition, with governments paying for much of the early development for a vaccine, any company that succeeds in creating a vaccine will reap billions in profits.

Once a vaccine is developed, no time can be wasted in testing it. The timing is crucial; the trials must occur at the height of summer in Latin America. The vaccine, if used for anything other than outbreaks, runs the risk of allowing Zika to become routine in some parts of the world.

The National Institutes of Health (NIH) has already begun testing in a clinic at the University of Maryland’s School of Medicine. Hopefully, a successful vaccine can be found soon.

Wireless Brain Implant Allows “Locked-In” Woman to Communicate

by David Grinberg ’19

Locked-in syndrome (LIS) is a condition

in which a patient is unable to move or communicate due to complete paralysis but is aware of his or her surroundings.

Nearly all voluntary muscles in the body, except for the eyes, are paralyzed. Damage to specific portions of the lower brain and brainstem, with no damage to the upper brain, is usually the cause for LIS, which is different from a persistent vegetative state.

Caretakers are currently assisting an anonymous 59-year-old patient who is suffering from LIS. They care for her 24/7.

However, a new wireless device has enabled her to select letters on a computer screen using her mind alone. She can spell a word at the rate of one letter every 56 seconds. According to neuroscientist Erick Aarnoutse, the signals from her brain no longer reach her muscles because her condition has damaged the motor neurons that relay them. There has not been any practical way for patients with LIS to communicate. Before this wireless implant, one would use an infrared camera to track the patient’s eye movements in order to communicate. After surgically installing all of the equipment in this anonymous patient, scientists used “beta” (low frequency) and “gamma” (high frequency) brain waves. They measured the ratio of gamma to beta wave power in continuous brain waves sweeping through the patient’s motor cortex. The computer would then detect when she was imagining closing her fingers. The patient then learned how to use her finger as a stylus to sweep over letters in a sequence on the tablet/computer screen to communicate.

However, many doctors and researchers believe that noninvasive methods should be used to help these patients. Niels Birbaumer, an expert in brain-computer interfaces at Tubingen University, said, “Implantations like the one reported here may carry an unknown risk for advanced ALS patients.” This instance is not the first time that doctors have implanted devices in patients. In 2015, researchers led by neuroscientist Leigh Hochberg at Brown University implanted a 96-channel electrode array into the cerebral cortex of a 58-year-old woman with locked-in syndrome. Those implants helped her to communicate by enabling her to select words that appeared on the computer screen.

The anonymous patient’s procedure is not practical, and a team of highly specialized technicians completed it as part of their research. It is unlikely for most caretakers to specialize in this procedure, and it would also be expensive.

Neurologist Philip Kennedy said, “One to two letters per minute is not justifiable [for doing a craniotomy] unless they can improve it.” A year after the device was implanted in our anonymous patient’s head, she still lives a happy life with her husband and child. This device may not be the answer to the problems that these people face every day, but it does relieve some of the painful and bothersome moments that come when an LIS/ALS patient tries to communicate with others.

Correlation Between Sleep Disruption and Liver Cancer

by Matthew Hirschfeld ’17 Since the 1980s, the rate of occurrence of liver cancer has tripled – a significantly higher increase than the simple, expected increase in frequency due to population growth. In a recent study conducted by a team from Baylor College of Medicine in Texas, researchers discovered that consistent sleep deprivation in mice causes liver disease and ultimately leads to liver cancer. The study is published in the journal, Cancer Cell.

Regarding the practical relevance of this discovery, senior author of the study and associate professor at Baylor College of Medicine, Loning Fu, noted, “Recent studies have shown that more than 80 percent of the population in the United States adopt a lifestyle that leads to chronic disruption in their sleep schedules.” Professor Fu adds that this trend has also reached “an epidemic level in other developed countries” where it has been “coupled with the increase in obesity and liver cancer risk.”

According to David Moore, a professor of molecular and cellular biology and co-lead author of the study, “Liver cancer is on the rise worldwide, and in human studies we’ve now seen that patients can progress from fatty liver disease to liver cancer without any middle steps such as cirrhosis.” Professor Moore explains, “We knew we needed an animal model to examine this connection, and studies in the Fu Lab found that chronically jet-lagged mice developed liver cancer in a very similar way as that described for obese humans.”

In terms of how sleep disruption can translate into liver cancer, the essence of connection revolves around the fact that every person has a “master clock” in their brain.

This biological temporal reference frame regulates the circadian (twenty-four-hour-

cycle) rhythms in tissues and organs around the body, which are very significant in terms of not only sleep but also normal metabolic function.

Already, work that takes place on a schedule outside of the traditional 9am-5pm work-day, commonly referred to as “shift” work – because it is assigned in shifts, like the night shift, evening shift, etc. – has been linked to the disruption of normal circadian function. An extreme example of this causal relationship is a study that was reported earlier this year by Medical News Today. In the study, researchers linked simulated shift working patterns in mice with an increased development of nonsmall cell lung cancer.

Now, researchers have associated sleep disruption specifically with an increased risk of liver cancer.

Per statistics reported by the American Cancer Society, 700,000 people are diagnosed worldwide with liver cancer each year. Men are more prone to develop liver cancer than women and the American Cancer Society estimates that over 18,000 men and nearly 9,000 women will die from liver cancer this year.

Another crucial element of one’s risk for liver cancer is obesity. Obesity is a major risk factor in the development of hepatocellular carcinoma (HCC), which is the most prevalent form of liver cancer. When excess fate accumulates in the liver, it results in nonalcoholic fatty liver disease (NAFLD), which has an elevated incidence rate in obese individuals. According to most experts on the matter, NAFLD is expected to become the predominant cause of HCC in the 21st century.

With the purpose of modeling the physiological impact of chronic sleep

disruption, which the research team refers to as “social jet lag,” mice were exposed to disrupted light and dark cycles over the course of nearly 2 years, which induced prolonged disruption to their normal sleep cycles. Consequently, the mice developed a variety of conditions, which included skin disorders, neurodegeneration, and cancer.

These conditions were not observed in a control group of mice, which experienced regular light and dark cycles. All of the mice in the study received a normal diet.

Although both male and female mice in the study developed HCC by the age of 78 weeks, the rates of incidence were much higher among males, as it is with humans. 78 weeks of age in mice is proportional to 67-72 years of age in humans, which is the stage of life when the spontaneous development of HCC is mostly observed. By the age of 90 weeks, a staggering 96 percent of jet-lagged mice exhibited NAFLD and 9 percent of those had developed HCC by then. In general, the jet-lagged mice experienced a severe disruption of normal liver function. Their development of NAFLD was accompanied by severe inflammation and fibrosis, even prior to the development of HCC. When the researchers examined global gene expression in the livers of the jet-lagged mice, they observed a pattern rather akin to that found in humans with HCC. This evidence shows a direct effect of chronic jet lag on gene expression, including genes involved in the regulation of circadian rhythms (Bmal1, Clock, Per1, Per2, and Nr1d1), despite the absence of the mutations in typical cancer genes. The sleep deprivation also disrupted cholesterol and bile acid pathways, which are critical for normal liver function. The nuclear receptor, CAR, which is involved in sensing toxic compounds, was constitutively activated, while FXR, the bile acid receptor, was suppressed – a pattern that is very similar to HCC in humans.

Professor Fu commented, “To us, our results are consistent with the what we already knew about these receptors, but they definitely show that chronic circadian disruption alone leads to malfunction of these receptors.” She thus concluded that “maintaining internal physiological homeostasis is really important for liver tumor suppression.”

The team surmises that the development of HCC due to the disruption of normal liver function can be addressed using drugs, which target these specific receptors.

Professor Moore reflected on the study, “This experiment allowed us to take several threads that were already there and put them together to come to this conclusion.

We think most people would be surprised to hear that chronic jet lag was sufficient to induce liver cancer.”

Works Cited “Vitamin D May Increase Survival for Breast Cancer Patients” http://www.medicalnewstoday.com/articles/314017.php “Healthy Living Can Overcome Genes Linked to Heart Disease” http://www.medicinenet.com/script/main/art.asp?articlekey=199761 “The Science behind Peanut Allergies (and How to End Them?)” https://www.sciencedaily.com/releases/2016/10/161026105052.htmhttps://www.ncbi.nlm.nih.gov/p mc/articles/PMC154188/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC154188/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683407/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954079/ “Study Finds Young Athletes Should Wear Protective Goggles” Reynolds, Gretchen. "Eye Injuries in Youth Sports Are Surprisingly Common." New York Times 9 Nov. 2016, Well sec.: n. pag. Print.

“3D Printing Can Lead to Printable Organs” http://www.sciencealert.com/scientists-have-found-a-way-to-3d-print-embryonic-stem-cellbuilding-blocks http://www.livescience.com/26865-3d-printed-embryonic-stem-cells.html http://www.cnet.com/news/3d-printing-with-stem-cells-could-lead-to-printable-organs/ “The Dangers of Simultaneous Physical Exertion and Emotional Tension” Reynolds, Gretchen. "Think It's Cathartic to Run Angry? Think Again." New York Times 19 Oct. 2016, Phys Ed sec.: n. pag. Print.

“Race for a Zika Virus” http://www.usatoday.com/story/news/2016/11/18/who-zika-no-longer-world-emergency/94079718/ http://www.nytimes.com/2016/11/20/business/testing-the-limits-of-biotech-in-the-race-for-a-zikavaccine.html?rref=collection%2Fsectioncollection%2Fhealth&action=click&contentCollection=hea lth&region=rank&module=package&version=highlights&contentPlacement=2&pgtype=sectionfro nt “Wireless Brain Implant Allows ‘Locked-In’ Woman to Communicate” https://www.scientificamerican.com/article/wireless-brain-implant-allows-ldquo-locked-in-rdquowoman-to-communicate/ “Correlation Between Sleep Disruption and Liver Cancer” http://www.medicalnewstoday.com/articles/314318.php