It’s a challenge to watch TV for any length of time these days without coming across a commercial for drinks like Gatorade and Red Bull, beverages usually marketed with adrenalized advertisements featuring athletes and daredevil feats. Though these commercials always feature adults, the tone and pacing is clearly aimed at a younger audience more susceptible to quick-cut, extreme-sports salesmanship. The message appears to be connecting, as a 2003 study found that more than half of adolescents use sports drinks and nearly half used energy drinks. Simultaneously, such beverages are becoming more and more accessible to kids, as some schools removing soda from their vending machines for health reasons are replacing them with sports drinks.

But are their dangers for kids ingesting sports or energy drinks? And how should parents treat their child’s consumption of these beverages? Guidance was provided this week in the journal Pediatrics by a panel of physicians co-led by Holly Benjamin, associate professor of pediatrics at the Medical Center. Their report is a stern warning, particularly on the effects of caffeine-packed energy drinks in young consumers and the casual use of sports drinks intended for replenishment after rigorous exercise. Here are the main take-home points from the report:

1) Sports Drinks ≠ Energy Drinks

A common misconception on the part of both parents and children is equating sports drinks such as Powerade with energy drinks such as Monster, despite their very different ingredients and purpose. While sports drinks purport to rehydrate and restore electrolytes after a long run or game of basketball, energy drinks are high-calorie and filled with stimulants such as caffeine, ginseng, and guarana. Despite these differences, adolescents often mix up the two beverages, expecting thirst-quenching and energy boosts from either one - a misconception encouraged by the  advertising for the various brands of drinks, the report concludes.

2) Boring is Still Best

Of the two types of drinks, sports drinks pose fewer health risks than the energy drink side of the aisle. But the claims made by sports drinks - to replenish electrolytes, provide muscle-repairing protein, and rehydration - are just as effectively, if not better, performed by plain old water and a balanced diet, the authors write. Sufficient amounts of the electrolytes sodium and potassium, which are important for brain and muscle activity, are provided by a healthy diet (the kind to be promoted by the new USDA “plate” on Thursday), and are only significantly depleted after lengthy or intense exercise. As such, “sports drinks offer little to no advantage over plain water,” the authors write. But they do offer a significant disadvantage compared to H20 - calories. Even the relatively low calories-per-serving of a sports drink (10 to 70 calories, the report says) can increase a child’s daily carbohydrate intake. In the absence of the exercise the drink is intended to offset, that could contribute to the risk of a child being overweight or obese.

3) A Dangerous Buzz

The calorie count of energy drinks is even higher - as high as 270 calories per serving, and often served in multiple-serving cans or bottles. But the even scarier figure cited by the report is the 500 milligrams of caffeine that some cans and bottles of energy drinks contain. To put that amount in perspective, it’s equivalent to roughly 14 cans of caffeinated soda! Energy drinks can also hide their stimulant content behind unusual ingredients other than caffeine. Each gram of guarana, which is included in drinks such as Rockstar and Power Trip, is equivalent to 40mg of caffeine.

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Anyone with a video game console at home can simulate  a variety of occupations: airplane pilot, race car driver, baseball player, Old West zombie hunter. As technology improves, the experience that can be created for these tasks grows ever more accurate and immersive, causing some experts to wonder whether simulation can be used for actual education as well as vicarious thrills. In the aeronautics field, this is old news - pilots have been trained on flight simulators for decades, gaining experience on high-risk, low-frequency tasks such as landing a damaged plane on a river. But in medicine, the use of simulation has only started picking up speed in the last decade, employing a mix of high-tech and low-tech to prepare doctors and nurses for both the usual and unusual.

In their Department of Medicine Grand Rounds presentation last week, Ernest Wang and Morris Kharasch from our partners at NorthShore University HealthSystem described the current state of simulation in medicine on the eve of their state-of-the-art simulation center’s grand opening. But while the idea might sound modern, it’s actually been around for more than 40 years, as Wang illustrated using a clip from the 1972 film Future Shock, narrated by Orson Welles.

Welles’ portentous warnings were a bit premature, it turned out. Never mind the leap from medical simulation dummy to humanoid robot, a generation would pass from when the first dummies were engineered in the late 1960’s before the broader field would accept simulators as a valid training tool for doctors.

“It looked pretty much what our current high-fidelity simulators look like, but didn’t have traction,” said Wang, a clinical associate professor at NorthShore. “There’s a Chinese saying: ‘When the student is ready the teacher will appear,’ and clearly they were too far ahead of their time and the conditions weren’t right.”

However, since 2000 the use of simulation in medicine has gathered momentum. A wide range of technologies are currently used for teaching sessions, from complex simulation environments that fully recreate the experience of being in an operating room to computer programs and table-top gadgets that rehearse medical decision-making and the performance of specific tasks. Medical simulation has grown to the point where a new specialty - the simulationist - may need to be created, Wang said.

“This would be a practitioner of simulation, who takes a recipe of clinically important cases, lessons learned from other industries, computer-driven full body simulators, realistic task trainers, and a dash of theater, to create a memorable learning experience that can be transferred directly to patient care,” Wang said. “In the end, that’s what this is about: education and patient care.”

Winning acceptance for medical simulation involves proving its success and determining its most effective uses. At the NorthShore center, educators have focused on designing simulation courses around “high-liability, low-frequency” events, said Kharasch, clinical director of the Center for Simulation Technology & Academic Research. The students in these courses might be residents encountering these situations for the first time, or older doctors who need a refresher on tasks they haven’t performed in many years before serving as an attending on the wards or in the emergency room.

“We’ve learned that as the years go on after you come out of residency, you are less able to do things that you once did as residents,” Kharasch said. “We spend a lot of time training on simple tasks that can be life-saving.”

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A Magic 8-Ball for Cardiac Arrest

Cardiac arrest is one of the most common ways that people die, and hospitals need to be constantly vigilant about the threat of heart stoppage in their patients. So physicians have long sought to develop a way of predicting who is most at risk for cardiac arrest when checked into the hospital, such that extra care and surveillance can be taken. At the 2011 international meeting of the American Thoracic Society, held this past week in Denver, two Medical Center fellows presented research refining these early warning systems to make them a more effective hospital tool.

In the first study, pulmonary and critical care fellow Gordon E. Carr connected cardiac arrest with another frequent sight on the hospital ward: pneumonia. Carr’s study found that patients admitted with pneumonia are at elevated risk of cardiac arrest over the next three days after admission, and that almost 40 percent of these cardiac arrests occurred while the patient was outside of the intensive care unit. “We found a compelling signal that some patients with pneumonia may develop cardiac arrest outside of the ICU, without apparent shock or respiratory failure,” Carr said in a press release. “If this is true, then we need to improve how we assess risk in pneumonia.”

Adding extra caution about cardiac arrest to the care of patients with pneumonia is a specific way to improve surveillance. But to apply to more patients, a broader scale is needed, one that can be easily assembled from the vital signs that are already routinely measured in the wards. One such scale, called the Modified Early Warning Score or MEWS was tested by pulmonary and critical care fellow Matthew Churpek as a predictor of cardiac arrest, who found it to be better at predicting a cardiac arrest in the next 48 hours than any individual vital sign. But MEWS was designed for general risk of death, not specifically for cardiac arrest, and Churpek suggested a more specialized risk score could be calculated for use by hospitals. The benefits of such a measure, he said in a press release, would be immense.

“Rapid response teams are a complex and resource-intensive intervention, so providing evidence-based criteria for their activation is crucial,” Churpek said. “Our patients will do better if we can detect who is at high risk early enough to intervene and prevent a cardiac arrest.”

Doctors Against Ronald McDonald

Childhood obesity is a growing problem in the United States, and doctors point the finger of blame directly at increased consumption of junk food and fast food. Chains such as McDonalds have made noise about making their food healthier, especially for children, by posting calorie counts on menus and offering snacks such as apples and carrots instead of fries. But according to an open letter signed by over 500 health care professionals and placed in newspapers around the country this week, they have not done enough.

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Animal models are useful for testing and developing future treatments and procedures before they are tried in humans. Before bone marrow transplants were first tried clinically in the 1950’s for the treatment of radiation poisoning or leukemia, they had already been shown to work in rats, dogs, and primates. But even after the proven success of the method to replenish a patient’s hematopoietic stem cells - the precursors of all the different types of blood cells - animal models continued to be useful for improving the procedure and better understanding the system’s biology. Now, more than 50 years after those first experiments, a new animal model for transplanting marrow has been developed - under water.

Zebrafish, the tiny, striped fish often found in pet stores, lead a double life as scientific heroes. Because of their fast reproductive cycle, translucent embryos (seen above), and well-studied genome, zebrafish are an increasingly popular animal model for scientists to study embryonic development, genetics, and diseases such as cancer. The ability to easily mutate zebrafish genes and screen for interesting biological changes makes the species an ideal fit for studying the function of hematopoietic stem cells and how they can be better used in medical procedures. But there was only one problem for a team of researchers at the Harvard Stem Cell Institute: nobody had tried to do a marrow transplant in zebrafish before.

“We wanted to be able to have an assay where you could compare mutant marrow with wild type marrow and see whether the hematopoietic stem cells function differently,” said Jill de Jong, member of the Harvard research team and now assistant professor of pediatrics at the University of Chicago Medical Center. “The only way to do that was with a transplant assay. Since you’re talking about mutants in fish, it really would have to be a transplant assay in fish - and that didn’t exist.”

Translating a stem cell transplant procedure developed in mammals to fish required several modifications. For one, zebrafish do not carry their hematopoietic stem cells in bone marrow, but rather in their kidneys. In recipient fish, nobody had calibrated the amount of radiation needed to knock out the native marrow cells, or the amount of donor cells needed to successfully replenish the marrow and blood. And while it is easy to match mice for transplantation purposes - because they are inbred and immunologically identical - the fish require more precise matching of donor and recipient, just like humans. The low success rate in the first batch of zebrafish transplants reflected this difficulty.

“These fish were like random donors, they were not immunologically matched at all,” de Jong said. “In some ways, it’s kind of miraculous that it even worked at all.”

But one by one, the kinks were worked out and the procedure was standardized (and published earlier this year in the journal Blood). A number of the immune system MHC genes, which are carefully matched in human bone marrow transplants, were located on chromosome 19 of the zebrafish genome. Each fish could then be genotyped and paired with a closer match for the transplant, which raised the success rate of the procedure.

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In taking care of sick patients, clinicians have two goals: treating the disease and treating the symptoms. In the case of an infection or a chronic illness, accomplishing this dual purpose is relatively straightforward. But what about when the symptom is something more complicated than pain or nausea? Some genetic disorders carry the consequence of short height, a condition that may have more serious social effects than medical. But clinicians are nevertheless finding new ways to “treat” short height, helping children approach, if not fully reach, the size of their peers.

One genetic syndrome that carries the symptom of short stature is Turner syndrome, the result of a missing or incomplete X chromosome that occurs in 1 in 2,000 female births. In addition to some physical and reproductive abnormalities, Turner patients grow to an average of about 4-foot-7, several inches below the typical height for an adult female. Since 1996, the FDA has approved the use of growth hormone to help Turner patients achieve a closer-to-normal height, and the treatment, while very expensive, has achieved some success. But a new study finds that a second hormone, once thought to stunt growth rather than promote it, might be a useful additive in the treatment of short stature.

Estrogen is prescribed for a variety of medical uses, such as birth control, hormone replacement during menopause, but also as a suppressor of growth in teenage girls. However, the doses of estrogen given via pills or patches are much higher than what the body normally releases into the bloodstream. Some clinicians, including Robert Rosenfield, professor emeritus of adult and pediatric endocrinology, believe that these lower doses of estrogen may actually promote growth, particularly in Turner girls who have a deficiency of the hormone. But many doctors have shied away from giving Turner girls estrogen, he said.

“It’s obvious that normal girls have a growth spurt, and it turns out to be due to estrogen,” Rosenfield said. “But because of this long history of estrogen being seen as a growth inhibitor, people have delayed given estrogen in Turner syndrome until girls were maybe 14 or 15 years old because they didn’t want to rob girls of the growth-promoting benefits of hormone treatment.”

That theory was put to the test in a long-running and controversial study published last week in the New England Journal of Medicine. Nearly 150 girls with Turner syndrome were divided into different height-treatment groups: growth hormone alone, estrogen alone, growth hormone and estrogen, or placebo (this fourth group created some of the controversy, as the girls were not aware that they were receiving no treatment). The treatments were started when the girls were as young as 5 years old until their growth slowed in their teens, signaling that they had reached their adult height.

Between 1987, when the study began, and today, when the study was finally completed and published, the use of growth hormone in Turner girls has become accepted and approved. In fact, as far as growth hormone use goes, the good news of this study was no news, as the effect of GH alone on height was right in line with other, less rigorous studies conducted in Turner girls. The average size of that effect was not staggering: about 5 centimeters, or 2 inches, over the 7 years of treatment.

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For some diseases, taking a census is easy. Most people who have cancer are diagnosed with the disease before they die and seek treatment, allowing for the collection of detailed national cancer statistics. But other diseases tend to hide in the shadows, undetected and under-counted due to infrequent diagnosis or an unwillingness of patients to seek treatment. Into this latter group falls the eating disorders: anorexia nervosa, bulimia nervosa, and other conditions. Because many of these patients try to avoid treatment, psychiatrists have long suspected the numbers are skewed because only a subset of people suffering from eating disorders find their way to their clinical practice.

“We only see the tip of the iceberg,” said Daniel Le Grange, professor of psychiatry and director of the University of Chicago Eating Disorders Program. “As clinicians and researchers, we’ve known that in the community there are thousands of people out there with eating disorder behaviors that we never see in our clinics.”

Hard data on the frequency of eating disorders in the broader community has been hard to come by. But a new survey study of over 10,000 adolescents, released last week in the Archives of General Psychiatry, confirmed that the iceberg of eating disorder prevalence among American teens is as broad below the surface as psychiatrists suspected. Almost 6 percent of those surveyed in the study met the criteria for one of the five eating disorders tested at some point in their lifetime, a number extrapolated by some media outlets to 500,000 teens in the United States.

But the total numbers were just one of the eyebrow-raising results of the research. Le Grange, a co-author on the study, sat down with ScienceLife and detailed the most significant findings of this long-awaited census, and discussed its implications for the nature of these diseases and the patients who are slipping through the field’s fingers.

1. The Myth of Rarity

Health care dollars are not infinite, and cynical as it may sound, diseases must compete for research funding and insurance reimbursements. So when conditions such as eating disorders are perceived as rare occurrences, the people who treat and study those conditions face an uphill struggle for attention and support. Thus, the under-reporting of eating disorder prevalence has held the field back from being considered as a priority concern in adolescents. The new numbers - lifetime prevalences of 0.3% for anorexia nervosa, 0.9% for bulimia nervosa, 1.6% for binge-eating disorder, and 3.3% for sub-threshold disorders - lift eating disorders into a higher tier of concern for teenage and adult health.

“The myth has been that eating disorders and especially anorexia nervosa are relatively rare disorders, and we constantly have to argue that they’re not, because that’s what it feels like when we sit in clinical practice and we are inundated by patients,” Le Grange said. “This is robust data to demonstrate that eating disorders are not rare.”

2. A Gender-Blind Illness

In the clinic, psychiatrists see far more girls with eating disorders than boys - a ratio of 9-to-1. But surprisingly, the community survey revealed roughly equal prevalence for anorexia nervosa in males and females, suggesting that boys are not less likely to suffer from the condition, but are much less likely to be diagnosed and treated. Le Grange said he suspects that physician bias may lead them to more quickly consider an eating disorder  when the patient is a she rather than a he.

“We are so convinced that anorexia nervosa is predominantly a female disorder that pediatricians and mental health professionals, when presented with a boy who’s lost weight, do not consider anorexia to be a legitimate  diagnosis,” he said. “When we do see boys in our clinic, they usually have had an extensive preliminary workup, as the clinicians don’t consider an eating disorder…until everything comes back negative.”

3. Effects Beyond Mealtime

Psychiatrists observe that eating disorders don’t typically occur in isolation, as patients often carry “co-morbid” psychiatric issues such as depression or anxiety. The community survey puts a number on this observation, finding that the majority of those that met the criteria of an eating disorder also met the criteria of at least one other psychiatric disorder. Perhaps most alarming was the very high occurrence of suicidal thoughts and attempts in adolescents with eating disorders - more than half of those with bulimia nervosa reported thinking about suicide, and more than a third reported attempts.

Also striking was that these associations were just as common for kids who exhibited “sub-threshold” eating disorders, those did not meet the full criteria for anorexia nervosa or bulimia nervosa. In the DSM-IV, the diagnostic bible of psychiatry, such patients would be lumped into the category of Eating Disorders Not Otherwise Specified (EDNOS). The health risks associated with these patients suggest that EDNOS should not be seen as any less severe an illness, Le Grange said.

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“If sleep does not serve an absolutely vital function, then it is the biggest mistake the evolutionary process ever made.” - Allan Rechtschaffen.

We spend approximately one-third of our lives asleep, and yet there is still much to learn about why. Modern sleep research only began less than a century ago, when Nathaniel Kleitman founded the world’s first sleep laboratory at the University of Chicago in 1925. Since then, many of the mysteries of sleep have been uncovered by UChicago researchers, including the discovery of REM sleep by Kleitman and Eugene Aserinsky in 1953, and the characterization of the first sleep disorder, narcolepsy, by Rechtschaffen and Gerry Vogel in the early 1960’s.

But in the last two decades, the study of sleep has shifted from how it works and doesn’t work to the serious consequences when sleep is lacking. Locally, the hub of this new wave of sleep research is Eve Van Cauter, who has linked insufficient or irregular sleep to a long list of chronic diseases including diabetes, obesity, and heart disease. Earlier this week, Van Cauter was doubly honored in receiving the Frederick H. Rawson Professorship and headlining the christening of the new University of Chicago Sleep, Metabolism, and Health Center (SMAHC, pronounced “Smack”). Sleep scientists from UChicago, Northwestern University, and Harvard University gathered to discuss the latest evidence on just how important sufficient sleep is for good health. The consensus message was frightening: From infancy to the golden years, the failure to get a good night’s sleep can cause a wide variety of problems - and may be a major contributor to today’s most worrisome health trends.

The importance of sleep starts with birth, said David Gozal in his talk, and maybe even before due to epigenetic imprinting during the mother’s pregnancy. Gozal reviewed his paper from last month on the elevated risk of obesity in children with shorter and less consistent sleep patterns, but also presented even newer findings, including altered expression of metabolic genes in children who snore and mouse studies that found frequently-disrupted sleep can cause animals to ingest more food and retain more fat tissue. Meanwhile, more and more studies are finding that young children are not getting nearly as much sleep as recommended.

“Sleep curtailment is not only a problem of our adult society, but clearly has pervasively infiltrated to infants and young toddlers,” Gozal said.

The effect of poor sleep upon children may go beyond metabolic issues such as obesity and diabetes, proposed neurobiologist Daniel Margoliash. In both humans and birds, Margoliash’s laboratory has found evidence that sleep helps the brain consolidate information learned during the day into memory. As young birds sleep after a day of practicing their distinctive song, the brain recreates its activity patterns from those earlier performances, presumably part of the process of making that newly learned skill permanent. For schoolchildren, the lesson is clear: lose out on sleep, and you could be losing what you were taught during the preceding day.

Later in life, the problems associated with insufficient sleep only appear to grow worse. In older adults, chronic insomnia has been linked to cognitive decline, perturbations in hormones associated with hunger, and insulin sensitivity, said Northwestern’s Phyllis Zee. Women with polycystic ovary syndrome, a condition marked by infertility, hormonal dysregulation, obesity, and diabetes, are more than 8 times more likely to suffer from obstructive sleep apnea, said David Ehrmann. And the medical effects of poor sleep can literally appear overnight - Vineet Arora’s study of poor sleep in noisy hospital wards found an average blood pressure increase of 6.2 mmHg for every hour of sleep lost. read more

The future of medicine, we are told time and time again, is genetic and personalized. Someday, physicians will call up the genetic code of a patient and determine their genetic risks and which treatments will work most effectively with the fewest side effects. That information can be organized into individual, unique medical plans for each patient, helping them avoid disease as much as possible and treat quickly and directly when illness does occur. Though completely personalized medicine remains years, if not decades, away, the first few glimpses of this future have arisen in recent years with gene tests that help inform decisions about blood thinners and cancer drugs.

But for all the talk of genetic medicine improving patient care, an important question lingers: what will it cost? The soaring costs of health care in the United States have been at least partially driven by the steep price tags attached to medical innovations. New drugs and tests tend to be expensive when they reach the market, and it remains to be seen whether the clinical advantages of personalized medicine will outweigh its potential costs.

To put this balance to the test, a team of University of Chicago researchers used one of the earliest successes of genetic medicine: monogenic neonatal diabetes. As profiled before on ScienceLife, some children who are born with a form of diabetes caused by a genetic mutation can be switched from daily injected insulin to a pill, with dramatic improvements to their quality of life and disease control. At last summer’s Celebrating the Miracles conference, the families of children who had successfully “transitioned” off of insulin spoke emotionally about how the switch had changed their lives for the better. But for all the heart-warming anecdotes, the financial benefits of testing for neonatal diabetes have not yet been assessed.

“Despite all the talk and the fact we have now sequenced the human genome, there are very few studies showing an actual benefit of all these tests,” said Siri Atma Greeley, instructor of pediatrics and first author of the study. “We have to prove to people that it can make a measurable and appreciable difference in dollars and cents.”

To test the cost-effectiveness of genetic testing in neonatal diabetes, Greeley and colleagues (many from the Kovler Diabetes Center) built a simulation of the costs and quality of life effects associated with the disease over 30 years. Beyond the daily costs of insulin and blood-sugar tests, children with diabetes are at risk of several complications, including blindness, stroke, and heart disease, that can further increase medical spending and decrease quality of life. But testing for the two most common genetic mutations in neonatal diabetes has costs too - roughly $2,800 at 2009 prices - and not every child tested will have a mutation that allows for switching from insulin to sulfonylurea pills. Children who develop diabetes before the age of 6 months have a high chance of testing positive for one of the mutations, but only 1-2% of children diagnosed between 6 months and 1 year old may have this form of monogenic diabetes.

Still, when the researchers ran the numbers, genetic testing clearly proved its worth. Alongside the health benefits one would expect to result from genetic testing of all children diagnosed with diabetes before the age of 6 months, the model also revealed dramatic financial savings over not performing the tests. By 10 years after testing, the average cost savings was over $12,000; by 30 years, the savings figure had climbed over $30,000. The results add a strong financial argument to the medical case for genetic testing of all infants with diabetes.

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Photo by woodleywonderworks/Wikimedia Commons

It’s a fight all parents are familiar with: the nightly battle to get their children to bed. Kids will try almost any tactic to avoid being tucked in for the night, and even then have long found ways to delay sleep with under-the-cover flashlights. But the deficit of sleep for today’s children and the degree to which that could be harming their short-term and long-term health was underscored last week by a new paper from University of Chicago and University of Louisville researchers. Led by David Gozal, professor and chair of pediatrics, and Karen Spruyt, assistant professor of pediatrics, the study used wristwatch-like activity monitors to objectively measure the sleep of more than 300 children between the ages of 4 and 10 for a week. Their results found that children are sleeping nowhere near the recommended amount of time, and that reduced or irregular sleep increases the risk of childhood obesity.

Like other studies dealing with sleep and weight gain, the research received a flood of media coverage, from sources such as CNN, the New York Times, and Time Magazine. ScienceLife conducted an extended interview with Dr. Gozal to dig deeper into the issues raised by the study, including how sleep deprivation is like an overdrawn bank account, how poor childhood sleep can predispose a child to a lifetime of health problems, and what parents can do to make sure their child is getting adequate rest at night. Here is an edited transcript of that conversation.

Q: What differentiates this study from previous studies of childhood sleep and obesity?

Gozal: Other investigators have conducted studies assessing sleep objectively using an actigraph, but the usual duration of those studies was either one day or three days. There was a study out of China where they actually identified for the first time that kids who slept more during the weekend were somewhat protected from the risk of obesity. Our study set out to look at a US population, to look objectively at both the week and the weekend, and to look at blood correlates of risk. This has never been done, to really look at what impact relatively short sleep or irregular sleep would have on the risk of disease later in life.

Q: What links did the study find between this lack of sleep and obesity?

We found that kids that slept the normally recommended number of hours were actually at the least risk. The kids that slept the least and had irregular sleep schedules were not only at very high risk, over fourfold, of obesity, but also showed a similar increase in metabolic and cardiovascular risk factors. When they tried to compensate during the weekends, the risk was less, but not eliminated. These kids were still at almost a threefold increased risk in obesity, but it’s better than a fourfold increased risk.

Q: The study revealed that he kids (aged 4-10) slept on average about 8 hours a night. Was this a surprise? Is it a concern?

It was a suspected surprise, because in the process of verifying the validity of actigraph recordings in children, we already became fully appraised of the misclassification that parents will assign to the duration of their own children’s sleep. On average, parents tend to overestimate the duration of sleep that their kids get by between 60 and 90 minutes. The moment parents close the door on their children, when they’re a certain age and above, they really don’t know what’s happening. They assume that 15-30 minutes later their kids will be asleep, when in fact it’s not true at all. I remember as a kid myself telling good night to my mom and then taking a little flashlight and book and reading for a long time. Now I’m sure what kids do is pull out their gadgets: phones, computers, mini-TVs, and video games.

The other thing that actually is rather remarkable is that over 80 percent of our kids in our country don’t wake up by themselves, they actually need to be awoken by their parents, which indicates that they still need more sleep, but aren’t getting it. There’s a paper from 1913 which measured and observed that kids of this age would sleep, on average, 10 hours. So the recommendations of all the organizations that are involved in sleep coincide on the need in this age group being 9-1/2 to 10 hours.

I’ve always said you need to look at this as if you were running a bank account. Call it a sleep account. If kids on average have an overdraft every night of two hours of sleep, by the end of the week, after five days of school, they will owe themselves and owe the account about 10 hours. If they continue doing the same during the weekend because they have friends, they want to do all these activities, and sleep is not perceived by the family as important, then they will further owe themselves an additional 4 hours, which gives an overdraft of 14 hours.

Q: So is “catch-up” sleep on the weekend an advisable way to recover from a sleep deficit?

Even if kids are catching up on sleep during the weekend, and let’s say they over-sleep two hours, then they would only reduce the debt of 10 hours accumulated during the week to about 6 hours. In both cases, they’re on overdraft, and long-term their credit history is gone. Also, you must remember, like a real bank account you’re going to pay a penalty every time you are going into overdraft.

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(photo by Wakinnebis/Wikimedia Commons)

At many levels of medicine, it’s important for physicians to make predictions about their patient’s future. Will their disease or condition worsen? Will this treatment or that treatment be more effective in curing them? How much longer does a patient have to live? Such decisions are especially important for pediatricians in the NICU, the neonatal intensive-care unit, where infants born prematurely can be put in incubators and given oxygen for the early days of their life. In the gray area of extremely premature infants born between 22 and 25 weeks of pregnancy, important decisions need to be made by physicians and parents at birth and in the following days about whether to pursue all possible medical interventions for a child that may not survive. Reliable predictions are crucial for these decisions.

William Meadow, professor of pediatrics at the University of Chicago Medical Center, is dedicated to improving the accuracy of that important early-life prognosis. In a recent editorial, Meadow and colleagues from Children’s Memorial Hospital, the Medical College of Wisconsin, and Children’s Mercy Hospital found an unexpected guiding analogy for that effort: the world of sports betting. To illustrate the fluctuating odds of a premature infant’s survival, Meadow chose the competitions on the European football or soccer pitch, where life-or-death stakes are mere hyperbole.

“For premature babies, 24 weekers, we know that many do badly. But which “many” do badly? We need an algorithm to tell us this baby is probably going to do pretty well, this baby is probably going to do pretty badly,” Meadow said. “If we can envision an algorithm like that, then the world would be a better place.”

In sports gambling, the original odds are initially set using all the information available before the game begins. The record of the two teams, relevant statistics, recent streaks and momentum, injured players, and many more factors are part of the calculations of who is the favorite, and by how much. (Betting lines also take into account the influence of a team’s popularity on betting behaviors, but the authors put that factor aside for this analogy.) Similarly, neonatologists use a core set of factors at the time of birth to determine a premature infant’s chances of living, including gestational age, size, steroid levels, and sex. But oddsmaking, in both the sportsbook and the NICU, doesn’t need to end with the initial “betting line.”

“Both in the NICU and in football betting, the pregame odds of a particular outcome only get you so far,” the authors write.

In the boom industry of online sports gambling, the practice of in-game betting has grown more popular. As the game plays out and points go on the scoreboard, gamblers can bet on the eventual winner as odds change in real time. To test how the quality of predictions change as the game progresses, Meadow and colleagues (including his son, Xander Meadow), performed a common-sense experiment, testing how well the score at various intervals of a game predict the final outcome. Originally, they used data from more than 400 baseball games to test the premise. But when the British journal Acta Pediatrica agreed to publish the editorial, they asked that the analysis be repeated in a sport more familiar to their culture.

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A sickle cell (left) and a normal red blood cell (right). From carnegiescience.edu.

In 2006, Rice University football player Dale Lloyd II collapsed during a practice and later died. The cause of death was acute exertional rhabdomyolysis, a sudden breakdown of muscle tissue into the blood brought on by strenuous exercise. But the trigger for Lloyd’s death may have been sickle cell trait, the name for when a person carries one of the two genes required for full-blown sickle cell disease.

People with sickle cell disease form abnormal red blood cells that can lead to chronic pain, hypertension, stroke, and death, while people with sickle cell trait (approximately 2 million in the U.S.) are generally thought to be symptom-free. But Lloyd’s death drew attention to potentially fatal consequences for athletes with sickle cell trait, and a lawsuit filed by the player’s family led to the NCAA mandating testing for all Division I athletes in 2010.

But is screening for sickle cell trait the best preventive measure for college athletes? That was the topic on the table at the first Department of Pediatrics Grand Rounds of 2011 last week, where both the medical and ethical implications of the NCAA’s new policy were considered. Though mandatory sickle cell trait screening has previously been adopted by the military and the National Football League, the NCAA stance could cause a “trickle-down” effect to high schools and youth sports, leading to millions of tests that might cause more harm and expense than good.

At least fifteen NCAA athletes have died from sickle cell trait-related causes in the last 30 years. But given that there have been approximately 2 million total athletes over that time span, that’s only 1 death for every 400,000 people, said Holly Benjamin, associate professor of pediatrics and surgery. Compared to more common, harmful occurrences such as concussions and spinal cord injuries, that’s an exceedingly rare event.

Which is not to say that it shouldn’t be closely monitored. Sickling, the name for a sickle-cell-related attack, can develop after as little as 2 or 3 minutes of strenuous exercise, and can be exacerbated by heat, altitude, and dehydration, Benjamin said. Parents, coaches, and trainers should be vigilant about athletes who suddenly collapse, giving them fluids and oxygen and transporting them to the nearest emergency department.

But while screening athletes for sickle cell trait might improve the response to an athlete’s collapse, preventing that collapse in the first place would be even more beneficial. As a demonstration, Lainie Ross, professor of pediatrics, surgery, and medicine, used the history of sickle cell trait testing in the American military, which has faced similar tragedies and pressure to screen.

After 4 sickle cell trait-related deaths in 1970, a study found that African-American recruits with the gene were 30 times more likely to die during basic training. In response, the Armed Forces considered screening for carriers of the gene and restricting service in those with positive tests. Meanwhile, another study was started to test whether the danger could be reduced by using the wet-bulb globe temperature (WBGT) index, a measure incorporating temperature, humidity and other factors to determine how dangerous conditions are for physical activity. An intervention based around reducing exertion and increasing rest for basic training recruits on days with a high WGBT index was successful not only in completely eliminating deaths related to sickle cell trait, but reduced deaths in non-carriers as well.

“What this shows is that effective intervention does not require the identification of sickle cell trait,” Ross said.

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ScienceLife ran 219 posts in 2010, and choosing the best of them is as hard as picking a favorite gene.  So here’s a month-by-month scan of a busy year at the University of Chicago Medical Center, full of exciting discoveries in the laboratory and the clinic. The impact of some of this research is already being felt by patients receiving improved, evidence-based medical care. For other studies, the clinical benefit may be years in the future, and may take unpredictable forms. As a closing message for 2010, we’ll re-quote the recently departed Eugene Goldwasser, whose laboratory research isolating and purifying the hormone erythropoietin has helped millions of people worldwide.

“It is a particularly impressive example of how basic research can pay a dividend that could not be anticipated at the start,” Goldwasser wrote about his life’s work, “and it is a pity that the lesson still has not been learned by those who control public funding of science.”

January: Tong Chuan-He looked at how cancer may result from cells who don’t want to grow up. Scientists studied how sleep affects the language learning skills of starlings (with painstakingly acquired video of the experiment!). Richard Jones combined two laboratory staples - Western blots and DNA micro-arrays - to develop a new method for studying protein networks. While physicians such as Tammy Utset treat patients with lupus, UChicago scientists are looking for the genetic origins of the autoimmune disorder.

February: Many Medical Center employees returned from volunteering with relief efforts in Haiti, and we filmed video interviews with Rex Haydon, Tiffany Cupp, Richard Cook, and Dima Awad on their experiences. Most of the human genome is “junk” between protein-encoding regions, but Marcelo Nobrega developed a way to find important regulatory elements in that genetic sea. Like birds, human learning can be affected by sleep, and Leila Kheirandish-Gozal reported on the impact of obstructive sleep apnea upon learning in children. Can a single protein in the brain create behaviors associated with drug addiction in rats?

March: Everyone knows air travel is stressful, but did you know that eastbound flights cause stronger cortisol changes than westbound trips? The laboratory of Milan Mrksich found a way to direct stem cells to form fat or bone by shaping them into stars or flowers, a brilliant example of bioengineering. Computational neuroscientists discovered how touch is like vision in the brain, knowledge that could be used to someday re-engineer Luke Skywalker’s robot hand. Dartmouth president and Partners in Health co-founder Jim Yong Kim visited to talk about a new, needed area of research: health care delivery.

April: Researchers at the Field Museum and the University of Chicago teamed up for the Emerging Pathogens Project, an effort to find new viruses in animals before they jump to humans. Cardiologist Martin Burke tested out a new type of internal defibrillator device that can go under the skin, instead of into the heart (the clinical trial, reported in May, was a success). In a lecture to the MacLean Center of Clinical Medical Ethics, transplant surgeon J. Michael Millis described his efforts to bring American organ transplant practices to China.

May: A trial testing the erectile dysfunction drug Viagra for a rare, untreatable lung disease failed, but pulmonologist Imre Noth found a silver lining. Lauren Sallan and Michael Coates uncovered evidence of a previously unappreciated mass extinction event 360 million years ago that changed the path of life on Earth. Researchers from the University of Chicago and around the world presented science at the frontier of biotechnology at the annual BIO conference.

June: In a study that is literally the size of an entire country, epidemiologist Habibul Ahsan measured the toll of a tragic, accidental exposure of millions to arsenic in Bangladesh. Putting a gene from fireflies into the pancreas of mice isn’t mad science, it’s an imaging tool that will help study cures for diabetes. Epigenetics, the modifications that turn genes on and off, took off in 2010, and cardiologists Stephen Archer and Jalees Rehman linked one epigenetic factor to pulmonary artery hypertension.

July: Scientists don’t often get to see the fruits of their research in the flesh, but the Celebrating the Miracles gathering of diabetic children weaned off injected insulin thanks to genetic research was a moving exception (video of the event can also be viewed). Another hot topic in science and medicine this year was the use of computational analysis to sift through rapidly accumulating data, topics explored by Gary An and Andrey Rzhetsky. Or you can build a computer model of a brain network to study the dynamics of epilepsy, like neurologist Wim van Drongelen.

August: Air pollution is a problem indoors as well as outdoors in developing countries where dung and firewood are used to cook food - a problem being tackled in a project led by Sola Olopade. A study of the hormonal changes induced by a stressful test revealed a surprising protective effect of marriage and long relationships. Microbiologist Olaf Schneewind’s laboratory developed two new strategies against MRSA, the most-wanted cause of hospital-acquired infections.

September: To study multiple sclerosis, neurologist Brian Popko’ s laboratory developed a new mouse model that can replicate the disease, then spontaneously recover. Meanwhile, a new drug to treat MS, originally isolated from fungus found in wasps, was approved by the FDA and is being studied for broader uses at the Medical Center. The micro-organisms that live in humans were analyzed as part of a “microbiome” study looking at the protective effects of breast-feeding against a intestinal disease.

October: Common wisdom on quitting smoking says to stay away from cigarette-associated cues, but research from psychiatrist Harriet de Wit’s laboratory revealed that abstinence could make craving even worse. A study of how getting a good night’s rest affects dieting results suggested that “sleeping off the pounds” isn’t merely a fantasy. Graduate student Daniel Matute solved a 100-year-old riddle about how quickly new species become reproductively incompatible with each other.

November: In perhaps our favorite study of the year, geneticist George Perry found a way to acquire the genomic information of endangered species from…poop. The evolutionary biologist Leigh Van Valen passed away, but his Lewis Caroll-inspired Red Queen Hypothesis lives on. Sometimes statistics don’t tell the whole truth, as in the curious case of the aspirin paradox - why the cardio-protective drug may actually predict worse outcomes after heart attack.

December: Evolution textbooks may need a rewrite after geneticist Manyuan Long’s laboratory discovered that new genes can be just as essential as old genes. A study by neurobiologist Nicholas Hatsopoulos proved that the only thing better than a thought-controlled device is a thought-controlled device equipped with a robot arm. Ripped from the headlines: microbiologist Jack Miller weighed in on the hype over arsenic-based bacteria, and ethicist/physician/friar Daniel Sulmasy discussed the Presidential Bioethics Commission’s report on synthetic biology.

All told, it was a great year of science and medicine. Let’s do it again in 2011! Regular posting will resume Jan. 3rd. Happy Holidays.

Racial disparities have been described for almost every type of cancer, with the gap in outcomes widening or holding steady between black and white patients in breast, prostate, colorectal, and lung cancers. Much debate has occurred over the causes of these disparities, with most  focusing on the overlapping factors of socioeconomic status, access to health care, and compliance with treatments. Underneath these social contributors may lie biological differences as well, such as the increased prevalence of hard-to-treat triple-negative breast cancer in women of African origin. But separating sociology from biology is almost impossible in the large populational studies needed to measure cancer disparities.

However, the pediatric cancer of neuroblastoma may offer a unique exception to this problem. The cancer, which originates in the nerve tissue outside the brain, is the most frequently seen solid tumor in children, with most cases occurring before the age of 5. Because the cancer is rare - roughly 650 new cases are reported each year in the United States - a large-scale study of outcome disparities has been impossible. But through the combined efforts of the Children’s Oncology Group (COG), a coalition of more than 200 clinical sites for administering trials for pediatric cancer, data from over 3,500 children was collected over 9 years.

That data pool was used for the largest-ever study of neuroblastoma disparities, published this week in the Journal of Clinical Oncology. The analysis found that racial disparities do exist for neuroblastoma, with black children (and Native Americans) more likely to die from the disease than white and Hispanic children. But the reasons for that treatment gap may not follow the same formula that are seen in many adult cancers.

“In many cancers, disparities in outcome appear to be largely due to differences in socio-economic status and environment. For example, the lack of ability to be seen by a doctor in a timely manner and get appropriate care significantly impacts survival,” said Susan Cohn, professor of pediatrics at Comer Children’s Hospital and senior author of the study with Tara Henderson, instructor of pediatrics.

“While multiple factors are also likely to contribute to the disparities we observed in children with neuroblastoma, genetic factors are likely to contribute to the increased prevalence of high-risk tumors in the black cohort, which is quite unique.”

Unlike other cancers, which may grow deadlier and harder-to-treat with time, neuroblastoma almost always remains true to its original diagnosis, Cohn said. Based on a variety of clinical factors, children with neuroblastoma are designated as low, medium, or high-risk, and only rarely does that risk assessment change, even without treatment. So unlike other cancers, the delayed diagnosis of neuroblastoma due to poor health care access is an unlikely contributor to racial disparities.

The treatment of high-risk neuroblastoma also largely takes place in a hospital, involving procedures such as intravenous chemotherapy, radiation treatment, and stem cell transplants. With therapies administered under clinical supervision, issues of compliance and access to affordable medication that often enter the disparities discussion are also largely irrelevant.

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Fangs You Very Much, Evolution

Where did the snake get its fangs? It sounds like the lead-in to a Rudyard Kipling Just So stories, but it’s a legitimate evolutionary biology question about one of nature’s deadliest weapons, one that goes back 20 million years ago to the oldest snakes in the fossil record. But even those ancient snakes had fangs similar to the poisonous snakes of today, with a hollow tube running through the tooth to inject venom into some poor prey like a hypodermic needle. How snakes (and other venomous reptiles) evolved such an elegantly dangerous mechanism was a mystery, until a new study published this week by University of Chicago’s Jonathan Mitchell and colleagues.

To study the evolution of snake fangs, Mitchell and his team were forced to go to a non-snake reptile - the mysterious Uatchitodon, a roughly 200 million year old reptile known only by its teeth. But in this case, the teeth were what the scientists cared about, and they compared the dental fossils from Uatchitodons found in Virginia, North Carolina, and Arizona. Interestingly, the teeth of older specimens appeared to show a kind of proto-fang, with a “canal” running down the outside of the tooth for the delivery of venom. This style of venom delivery is more similar to the modern-day Gila monster, the authors wrote, which “chews” its venom into its victims (shudder).

Later Uatchitodon teeth display a new form more similar to modern snakes, with the once-external groove now hidden inside the tooth. “This fossil really suggests that you can’t get hollow fangs any other way,” says co-author Wolfgang Wüstertold Nature News. Indeed, modern snakes even demonstrate a fast-forward highlight reel of this evolution, with grooved “replacement fangs” that give way to the mature, tubular model. It’s also a demonstration of the kind of transitional, evolutionary process that intelligent design supporters absolutely hate, demonstrating that the highly successful fang mechanism didn’t just appear out of nowhere, but through a series of intermediate steps that were also functional in their own right.

Another Bridge to China

The effort to help Wuhan University revise their medical school curriculum, described here yesterday, is not the only current collaboration between the University of Chicago Medical Center and Chinese hospitals. Last month, a delegation from Comer Children’s Hospital and the Department of Pediatrics visited Shanghai, where they signed an agreement establishing an educational, clinical, and research collaboration with Shanghai Children’s Medical Center (SCMC).

The relationship between the two pediatric hospitals sprouted from a training program started by Donald Liu, professor of surgery at Comer, who has taught minimally invasive techniques to surgical fellows from the Shanghai hospital for the last 10 years. For a disease called gastroschisis, where an infant is born with their bowels on the outside of their body, Liu’s instruction helped SCMC improve survival rates from 30 percent to 95 percent in 10 years. The success of that informal program and a successful visit from SCMC leadership to Chicago last year inspired the expanded collaboration, which will begin next year.

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“In this sense, we may indeed say that medicine has saved the life of ethics, in that it has given back to ethics a seriousness and relevance which it seemed to have lost for good.”

-Stephen Toulmin, 1982

“The emergence of medical ethics in the latter half of the 20th century helped revive medicine, saved it…from its narrow focus on science and technology to restore to it its former human dimensions of care, compassion and case focus.”

-Mark Siegler, 2010

Did medicine save the life of ethics? Toulmin , a professor in the University of Chicago Department of Philosophy and Divinity School until 1986, argued that it did in his 1982 essay. But at the 22nd Annual Dorothy J. MacLean Fellows Conference - dedicated to the memory of Toulmin - his former colleague Mark Siegler, the director of the MacLean Center for Clinical Medical Ethics, said the opposite might also be true. His argument found support in the sessions of the conference’s second day, which examined medicine’s present and future from the angle of ethics, and occasionally recommended applying the brake to the runaway train of science.

The first session of the day focused on the genetic testing of newborns, the kind of medical concept that sounds great on paper, but loses some of its luster with close, careful scrutiny. In theory, the ability to quickly screen a baby for disease immediately after birth should be a medical wonder, allowing physicians to quickly react and treat the child for medical conditions. But the history of such screening is far from ideal, as Norman Fost of the University of Wisconsin presented.

Consider the case of phenylketonuria (PKU), a nutritional deficiency that can cause mental retardation in around 1 of every 10,000 births. Spurred by John F. Kennedy’s call to action against the causes of mental retardation, scientists developed a cheap, simple test for PKU in newborns that was made mandatory. However, the test was “one of the worst tests ever devised,” Fost said, with a 95 percent false positive rate. To make matters worse, the special diet used to treat PKU turned out to be as harmful to children as the original disorder. As an isolated case, that story is frightening enough, but the pattern of unreliable tests and ill-considered treatments has repeated itself several times over, Fost said.

“Santayana said, ‘Those who do not study history are not doomed to repeat it,’” Fost said. “In newborn screening, it doesn’t really matter if you study history, it just keeps getting repeated anyway.”

Rather than slowing down to correct these flaws, the field of newborn screening is poised to expand using the latest genetic technology. Lainie Ross, professor of pediatrics at the University of Chicago Medical Center, talked about the near future where all 3 billion base pairs of a newborn baby can be sequenced from a single blood spot. That data can then be matched against the library of all known genetic disorders and markers of disease risk, giving parents an avalanche of information about their child’s current and future health.

But can anything be done with that information? Will an inability to treat genetic disorders produce unnecessary anxiety in parents? How do you determine who should have access to that child’s information? What if the child, when they reach adulthood, wants that information withdrawn? How should that information be used by insurers, employers, or law enforcement, if at all? In light of all these questions, genetic testing appears more and more inadvisable, even if the science to do so is nearly there.

“Clearly many issues need to be addressed before newborn genetic profiling should become routine,” Ross said.

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