Ultrasound imaging is best known for pictures of developing fetuses; 3D is typically associated with monster movies. But when you put the two together and aim the technology at the heart, they create a valuable tool that is changing the way heart disease is treated. Three-dimensional echocardiography is a cutting edge imaging technique used to obtain a detailed look at a patient’s heart in motion, figure out what may be wrong, and determine the best way to fix it.

The high-definition images collected by “3D Echo” can detect holes in the heart, problems with the valves that let blood pass between chambers, and irregularities in muscle contraction and blood flow. Information gathered during an echocardiogram can help surgeons create detailed plans for procedures to correct heart problems and can give them immediate feedback in the operating room after the surgery to make sure it was successful. For the increasing number of procedures that can be performed with cardiac catheterization instead of open heart surgery, a 3D echocardiogram provides live information to help guide cardiologists in their repairs.

“This is progressing very quickly and in many diseases, it really, really changes the way that people think about cardiology,” said Roberto Lang, professor of medicine and the director of the Noninvasive Cardiac Imaging Lab at the University of Chicago Medical Center. “We can look at the heart and tell the surgeon what he or she is going to encounter at the time of surgery.”

At this month’s American Heart Association meeting in Chicago, Lang presented research and participated in panels on the latest uses of 3D echocardiography. Since its submarine-sonar-inspired origin in 1953, the sonogram has been applied to cardiac function in many ways, through 2D images (similar to today’s fetal ultrasounds), through 3D reconstructions built from 2D data, to today’s instantaneous 3D view. Though real-time 3D imaging was only made possible 8 years ago, it is rapidly sweeping into the hospitals around the world, and new uses are still being discovered as the technology improves further.

During the AHA meeting, Lang presented what he calls “fusion imaging,” a combination of 3D Echo and computed tomography (CT) scanning to help determine the best place to implant a pacemaker for restoring normal heart contraction. Another presentation focuses on how 3D Echo can collect information about problems with the mitral valve - the portal between the left atrium and left ventricle of the heart. The precise location of leaks and other abnormalities can be mapped from the same angle the surgeon will see during surgery, Lang said, minimizing surprises on the operating table.

The best way to grasp the value of 3D echocardiograms is to see one, and last year, a production company came to the Medical Center and filmed Lang at work and talking about his field. Watch the results below.

“When we do these studies, we use all the different modalities and integrate them into a simple study,” Lang says in the video. “You want to be a detective and find out exactly what is happening to the patient, so you use all the technologies available and integrate them in order to come up with a good question or a good answer.”

[Thanks to Philips and Tomorrow Media for the video footage.]

A spinal MRI of a patient with neuromyelitis optica (from BMJ.com)

Doctors classify diseases like zoologists classify animals. A new disease, discovered and described, is placed next to diseases with similar symptoms, causes, and prognosis, which helps inform physicians about the best treatments to initially try. Later, when more specific information is known about a disease, that classification may change - just as biologists have dramatically redrawn the Tree of Life thanks to genetic similarities that trumped surface comparisons.

A disease called neuromyelitis optica (NMO), or Devic’s disease, would seem like a pretty easy one to put in its proper place. Since its discovery in the late 19th century, the disease was considered to be a variant of the neurological disorder multiple sclerosis. As in MS, a patient with NMO suffers an autoimmune attack on their nervous system, with the body’s natural defense mechanisms mistakenly killing off the insulation that help neurons conduct signals.

But unlike MS, which occurs throughout the brain and spinal cord, the NMO attack is restricted to the spinal cord and optic nerve, causing the sudden onset of visual problems and muscular difficulties. Untreated cases can lead to blindness and paralysis, said Adil Javed, assistant professor of neurology at the University of Chicago Medical Center.

“The inflammation is very intense in the spinal cord and the eyes, as opposed to multiple sclerosis,” Javed said. “The patients go blind and become paralyzed very quickly as soon as the disease starts. Within a year or two, they can go from walking to a wheelchair or a stretcher.”

Yet the differences were not enough to convince doctors that NMO was anything other than a cousin to MS. Patients with NMO symptoms were sometimes misdiagnosed as suffering from multiple sclerosis, or correctly diagnosed and treated with drugs designed for MS such as interferons. However, during his time as a neurological fellow at the Medical Center, Javed and his colleagues began to notice that NMO might not be as close a relative to MS as the field had thought.

The first clue was in the treatment - “We learned over the years that the interferons, which are the standard treatment for many MS patients, doesn’t work with Devic’s disease,” Javed said. “In fact, in many cases it made them worse.” Another mystery was the symptoms NMO patients shared with another group of diseases, the rheumatological disorders of lupus and Sjogren’s disease. Symptoms of Sjogren’s, including dry eyes and mouth, joint pain, and some organ dysfunction, turned up in a high number of NMO patients, Javed noticed with interest.

“That’s pretty rare that you would have two of these diseases,” Javed said. “So we thought perhaps they are connected.”

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Thanks to its association with the Thanksgiving turkey, tryptophan has become probably the most popular amino acid. Whether it’s being blamed for the strong post-meal desire for a nap or being rhymed with “gravy in the pan” in a dancey clothing store commercial, tryptophan is the envy of its 19 peers in the standard amino acid family. But like most scientific crossover stories, public misperception has given turkey’s tryptophan something of a bad rap as a kind of natural sleeping pill - or a convenient excuse to not do dishes.

In fact, research has shown that turkey has no more tryptophan than any other poultry or ground beef; perhaps people should pull out the old “tryptophan” excuse the next time they eat a burger, as well. Simply eating a bunch of carbohydrates, such as the rolls, potatoes, and stuffing on the table next to the turkey, can spike a person’s tryptophan and insulin. The latter, a hormone best known for causing cells to absorb blood sugar, also causes the absorption of amino acids - except tryptophan, which crosses over into the brain. There, it is turned into the neurotransmitters serotonin and melatonin, which, yes, cause sleepiness, but also have a number of other interesting behavioral effects.

The powers of tryptophan are perhaps best depicted by what happens to a person when it’s not there. Tryptophan depletion is a frequently-used tool in psychiatry research, mostly as a shortcut to reducing the levels of serotonin in the brain. Because serotonin has been implicated in depression (many anti-depressant drugs are designed to increase brain serotonin) and impulsivity, some interesting things happen when you remove its key amino acid ingredient from a person’s diet.

In 2009, the laboratory of Emil Coccaro, chair of psychiatry at the University of Chicago Medical Center, used tyrptophan depletion to study an element of intermittent explosive disorder (IED). People with IED tend to have violent temper tantrums that do harm to themselves and others, and show signs of abnormal serotonin signaling, so Coccaro’s group, led by Michael McCloskey, studied the effects of tryptophan depletion in this group. Subjects with IED and controls without the disorder were given a tryptophan-depleting drink: a chocolate-flavored liquid that contained all the other dietary amino acids. Test subjects were then given a test where the punishment for failure was an electric shock; participants were allowed to choose the intensity of their shock.

Independent of the pre-test drink, IED subjects chose a stronger shock punishment than control subjects. But after quaffing the trytophan depletion drink, both IED and control subjects were more likely to choose a higher shock than when they consumed a placebo drink. That result suggests that lower one’s tryptophan, and by extension their serontonin, increases self-aggression and self-injury.

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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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Genomic sequencing has made incredible strides in recent years, with both the cost and the time required to sequence an individual’s entire DNA sequence dropping meteorically. Yet one rate-limiting step for securing an organism’s genome remains: in order to sequence a species’ genetic information, you need a sample to start with. In humans or laboratory animals, a sample of blood or tissue is easily obtained. But what if a scientist wants to do a genomic study on an endangered species population, in the wild, without having to “trap 0r dart” a number of the animals to take blood samples?

George Perry, a genetics researcher at the University of Chicago, pondered this dilemma in planning his own research on endangered lemurs in Madagascar. In discussions with colleagues, he considered whether a “non-invasive” sampling technique might be possible for the collection of genomic data useful for conservationists and evolutionary biologists. The process led him to an unorthodox idea.

“We started thinking, ‘Is there a way to use fecal samples but to still do genomics work?’,” said Perry, a postdoctoral researcher in the laboratory of Yoav Gilad. “Then everyone would have the flexibility to collect population genomics data from any species at any time, as long as you can collect poop.”

Believe it or not, the collection of genetic data from feces has a long scientific history. Alongside the unwanted parts of an organism’s diet, solid waste contains a small number of cells stripped from the lining of the organism’s digestive system. Scientists have extracted small segments of DNA from those cells for study, mostly from the intracellular structures called mitochondria, which have their own genes. But more extensive genetic mapping of nuclear DNA from fecal samples has been thwarted by another of its ingredients: bacteria. The dominance of bacteria over host DNA inside the digestive system carries over to its product, where an organism produces less than 2% of the DNA deposited in its droppings.

To apply the awesome power of next-generation sequencing technology to a fecal sample, the DNA you want has to be separated from all that DNA you don’t want. Perry decided to modify an existing technique known as DNA capture (which has also been used to sequence Neanderthal DNA), to accomplish this task. With DNA capture, custom-made RNA sequences are used as bait to fish specific stretches of DNA out of a mixture; metallic beads are attached to the RNA sequences, and a magnet separates out the target DNA from the unwanted material. Perry boosted the specificity of this model, incorporating extra washes and two separate rounds of DNA capture, to turn his lower-quality fecal sample into starting material sufficient for sequencing. In part, that means starting with a lot more DNA that typically used for DNA capture, which means starting with roughly 2 grams of poop from each animal. Fortunately, it’s an abundant resource.

“It’s not that you can only study rhinoceros because they have huge poop,” Perry said.

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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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Sarah-Anne Schumann with the first community health clerkship students.

Facing rising medical costs and shortages of physicians in rural and urban areas, a government calls for health care reform. Experts warn that more primary care and family medicine physicians are needed to meet the surging demand for first-line treatment, chronic disease management, and the promotion of prevention. In response, medical schools look for ways to adjust their programs to prepare new doctors for careers in family medicine and community health.

It’s a familiar story for Americans, but the same drama is playing out half the world away in China. With their population soaring past the 1.3 billion mark, the community health crisis is on an even larger scale than the one here in the United States. But in many ways, the country is farther away from a solution, with a national medical curriculum that heavily prioritizes inpatient care and specialization. In response, the Chinese government recently issued a mandate redirecting schools to start producing more front-line doctors.

But it’s no simple matter to create a new curriculum from scratch, and the University of Chicago Medical Center is helping one Chinese medical school with that process. Wuhan University, a school in the central Chinese province of Hubei, is working with Renslow Sherer, professor of medicine, and other faculty to revise their curriculum over five years. A key part of that collaboration - the creation of a family medicine department - recently reached a landmark in October as the first six Wuhan medical students began a one-month community health rotation designed by Wuhan and Chicago doctors.

Sarah-Anne Schumann and Mari Egan, assistant professors of family medicine, have spearheaded Wuhan’s construction of a new family medicine program, visiting the country three times between them in the last year. As leaders of the family medicine and community health programs at the University of Chicago’s Pritzker School of Medicine, both are experienced in creating partnerships between a hospital and the surrounding neighborhoods. But despite Wuhan’s original plan to import their Pritzker program wholesale to China, it became quickly apparent during the visits that a custom-fitting was necessary.

“We were constantly saying ‘You can’t create a community clerkship for the South Side of Chicago in China,’” Schumann said. “You have to look at what your patients need and design the clerkship around that. They needed to take ownership and make it work for their students.”

The pricelist at a community health center.

The main challenge was connecting the Wuhan medical school with the community health centers in the city, which are actually very impressive facilities, Schumann and Egan said. Care for chronic diseases such as diabetes or asthma, rehabilitation medicine, traditional Chinese medicine, and specialized care are all available at the centers, and doctors and nurses do home visits for those who can’t make it into the clinic. Physicians use electronic medical records to keep track of patients, statistics about blood pressure and glucose levels are posted on the wall, and a “menu” of procedures is prominently displayed in the front (pictured at right).

“You walk into the health center, and it’s like McDonald’s - there’s a neon sign that’s rotating, and it has all the treatments and how much they cost,” Schumann said.

But until now, students from Wuhan University did not have an opportunity to experience medical care in this environment. Nearly all of their patient encounters took place in the hospital, and the community health education amounted to hearing lectures about the neighborhood clinics without ever visiting them. That format is similar to what was commonly seen in American medical schools until the relatively recent push for more hands-on community health experience, Egan said.

“Until about 40 years ago in the United States, most of medical education was taught in the hospital, and we needed to learn how to teach students in the outpatient community setting,” Egan said. “Now we’re starting to do the same thing in China.”

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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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Anyone who dares make predictions about the future of the U.S. health care system in 2010 is standing on shaky ground. With the passing of the Patent Protection and Affordable Care Act (PPACA)- the legislative product of the health care reform debate - everyone knows that the rules are about to change in this country, but nobody is quite sure how. The changes included in the act will not be fully phased in until 2014, and the complicated business of determining exactly how those changes are implemented is currently underway in the bureaucratic halls of Washington. Throw in the Republican gains in this month’s election - won at least in part on promises to repeal aspects of PPACA - and uncertainty is rampant about the most important overhaul to American health care since the creation of Medicare.

That foggy vision of the future dominated discussion on the opening day of the 22nd Dorothy J. MacLean Fellows Conference, this year’s edition of the MacLean Center for Clinical Medical Ethics annual event. Though the topic of Friday’s sessions was nominally health disparities on the local, national, and global stages, the discussion was magnetically drawn again and again to PPACA, which was designed in part to narrow notorious health care gaps in the United States.  The physicians, ethicists, and social scientists at the conference unsurprisingly agreed that it was imperative that those disparities be reduced, but less consensus was reached on whether PPACA would be the magic bullet to do so.

On its face, the legislation makes several sweeping moves that would appear to directly confront health disparities in America. No PPACA component is more significant for underserved populations than the expansion of medical coverage for the country’s 47 million people without insurance, the majority of whom are minorities, said A. Eugene Washington, the dean of the David Geffen School of Medicine at UCLA. The other major aims of the bill, improving quality and reducing cost, may produce more mixed results for disparity reduction, as new payment measures based on outcome, rather than volume, could push health care providers to avoid communities with poor health at baseline. Much relies upon how the broad goals of the bill are truly implemented by federal and state agencies, he said.

“The legislation is really a framework, and it’s going to get shaped,” Washington said.

The (mostly) pessimistic view of that shaping process was provided by Harold Pollack, professor of social service administration at the University of Chicago. Pollack said the legislation, as written, is the most important AIDS and drug addiction policy ever passed in the United States and that expanded coverage will help address some disparities. But he was also critical of the slow roll-out of policies because it makes them contingent upon “bipartisan goodwill,” a scarce resource lately in Washington.

“We’re in for a wild ride, and it’s going to be a wild ride in a time of fiscal crisis and political gridlock in the short run, when the most difficult implementation challenges in our health care system will have to be resolved,” Pollack said.

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(photo by Lloyd DeGrane)

Here in Chicago, we’re entering the second of our two seasons: transitioning from “Construction” into “Winter.” The rampant highway repair that happens during warm weather months is largely due to the stresses of the cold weather months, which leave our roads cracked and potholed. But perhaps we’ll be saved from all that misery if a team of Dutch researchers are successful in their efforts to create biologically self-healing concrete. The process embeds calcite-precipitating bacteria into concrete paste, so that when cracks occur, the microorganisms can secrete a mineral that will fill those fractures. It’s a cool example of biology-inspired engineering, and was mentioned as part of the New York Times’ interesting “What’s Next in Science?” feature this week.

Two exciting studies from the other side of the University of Chicago campus came out in this week. In the first, Chuan He in the Department of Chemistry helped characterize the activity of “the most exciting protein family now in biology,” a DNA repair protein called AlkB. In charge of demethylating DNA, AlkB has the power to re-activate silenced genes, a valuable epigenetic function that could someday be harnessed to treat diabetes, obesity, and cancer. The study also utilizes a delightful science word to describe one of the protein’s intermediate states: “zwitterionic,” when an object has a neutral charge, but acts positive or negative when interacting with other objects.

In another study, University of Chicago psychologist Susan Levine found that a child’s early exposure to mathematics can influence later success in the subject. Researchers videotaped interactions between parents and their children when they were between the ages of 14 and 30 months, counting how many “number words” were used by the parents. When the children were given a simple math test at the end of the experiment, those that heard more about math from their parents tended to perform better.

Today and tomorrow, the MacLean Center for Clinical Medical Ethics will hold its 22nd annual conference, a two-day festival of ethical lectures and discussion. Today’s session will expand upon the local, national, and global health disparities theme of the center’s weekly seminar series, while the second day takes a broader approach with topics such as pediatric ethics, palliative care, transplant medicine, and a session dedicated to the memory of faculty member Stephen Toulmin. The schedule is available here (pdf), and we’ll have coverage of the conference next week.

ScienceLife is very excited to have gotten in during the very brief window that registration for Science Online 2011 was open this week. The “unconference,” held in North Carolina in January brings together a dream team of science bloggers for open discussions and workshops on the growing field of internet science journalism. Expect to hear more about it.

The past few decades have brought astounding progress in fighting the scourge of infectious disease in developing countries. It’s remarkable to think that a disease such as smallpox, which killed 50 million people a year only 50 years ago, has been successfully eradicated from the world. Similarly, polio has been stamped down to only rare outbreaks, and great strides have been made against HIV/AIDS and tuberculosis in poor countries.

But the fight against infectious disease is only half the battle in global health. In fact, it’s less than half, said Abdallah Daar of the University of Toronto in his Nov. 3 talk for the MacLean Center for Clinical Medical Ethics Seminar Series. More people in the developing world die from chronic, non-communicable diseases like diabetes and cancer than from infectious disease, nutritional deficiencies, or inherited conditions combined. While chronic diseases dominate health care in the United States and Europe, efforts to fight those disease in poorer countries have lagged far behind the funding for infectious disease.

“About 60 million people die each year, and people imagine that a lot of people in the developing world die from infectious diseases. Well, it’s not so,” said Daar, the Senior Scientist and Director of Ethics and Commercialization at the University of Toronto’s McLaughlin-Rotman Centre for Global Health. “Chronic disease…is an area that has been totally neglected in the developing world.”

To fill in this considerable gap, Daar’s group has helped coordinate new initiatives with the Canadian government and research agencies around the world. The Global Alliance for Chronic Disease, which brings together six scientific funding bodies from the US, Canada, China, India, England, and Australia, was created to address the priorities laid out by Daar and colleagues in a 2007 editorial. “Inaction is costing millions of premature deaths throughout the world,” they wrote.

The effort plans to go after worldwide chronic disease on several fronts, from modifying risk factors such as diet, exercise and smoking to advocating for healthier government policy and health systems to working with businesses to deliver cheaper, more effective care to underserved populations.

“We know how to treat hypertension in one person. We know how to treat hypertension in a classroom. But how do you treat hypertension in a whole country? We don’t know how to do that,” Daar said. “We need to learn how to take evidence and how to scale it up and interact with policymakers and get them to buy in. So if you do a screening program, and it’s very successful and you save many lives, how do you get the policymakers to say yes, we’ll do this on a national scale and save even more lives?”

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Scott Brady speaks at the Chicago Biomedical Consortium symposium, Oct. 29, 2010. (photo courtesy of the CBC)

Proteins are a little like laundry: folding matters. When folded properly, proteins can go about their intended business as the machinery of the cell, responsible for its structure and function. A misfolded protein or two can be an annoyance, temporarily throwing off the order of the cell but easily handled by a cell’s internal janitors. But when those misfolded proteins pile up like rumpled clothes across a messy room, the whole system can collapse, leading the cell to an early demise.

These catastrophic failures of folding may be the cause of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and Lou Gehrig’s Disease (amyotrophic lateral sclerosis). When pathologists look at the brains of people who die from these conditions, they find unusual changes, with missing neurons and/or abnormal deposits known by names like plaques, tangles, and Lewy bodies. As imaging techniques have improved, scientists have traced these abnormalities back to protein misfolding, with the accumulated defects leading to intracellular traffic jams and even cell suicide.

Experts in the protein folding field met October 29th at the University of Chicago as part of a special symposium organized by the Chicago Biomedical Consortium, a partnership between Chicago-area research institutions. A succession of experts talked about the intricate origami of folding polypeptide structures into functional proteins, the cellular mechanisms that help regulate that process, and the consequences when those mechanisms fail and misfolded proteins are allowed to aggregate into dangerous clumps.

“The ability of polypeptide chains in vivo to fold correctly into their native states with sufficient frequency for them to be able to execute their functions in a living organism is one of the most fundamental and remarkable phenomenons in biology,” said Sangram Sisodia, professor of neurosciences at the University of Chicago. “Despite these regulatory systems, protein misfolding and aggregation do occur, particularly as organisms age, and cause devastating diseases.”

Scott Brady of the University of Illinois at Chicago illustrated those diseases with the famous people they are associated with: Muhammad Ali and Parkinson’s disease, for example, or Woody Guthrie and Huntington’s. Brady then outlined the reasons why a pile of misfolded proteins can be so troublesome to neurons - many of which are long, skinny structures (as long as a meter in humans) that must transport proteins from one end to the other. Should an aggregate of erroneous proteins occur anywhere along that long stretch, it could cause a traffic jam fatal to the cell. Brady’s laboratory has repeatedly demonstrated this process in what is, thanks to their long, wide axons, a favorite animal model of neurobiologists: the squid.

“You may be wondering what calamari has to do with all this,” Brady said. “No, squids do not get Alzheimer’s disease, but they react to the toxic proteins in Alzheimer’s just as well as mammalian systems.”

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Originally developed in 1897 as a painkiller, aspirin has become a valuable cardiology tool in the 21st century for preventing and treating cardiovascular disease. Because of the drug’s ability to reduce blood clotting, doctors commonly recommend a daily aspirin to patients at high risk or with a history of heart attacks, strokes, and other cardiovascular ailments. Extensive research has largely supported the drug as a cheap and effective way to prevent these life-threatening events and to help nullify what remains the leading cause of death in the United States.

But in 2000, a group of Boston cardiologists trying to identify risk factors that might predict poor outcomes after a heart attack made a strange discovery. Most of the predictive risk factors they discovered and ultimately incorporated into their well-known 7-point “TIMI risk score” made perfect sense. For example, if you came to the emergency room with chest pain and had an abnormal electrocardiogram or elevated levels in the blood signaling heart damage, you were more likely to be at risk for future adverse events. But the team also discovered one risk factor for predicting worse outcomes that was far from expected: the prior use of aspirin. According to their analysis, patients who were taking aspirin to prevent cardiovascular disease actually did worse after suffering a heart attack.

“It seemed to make little sense, because aspirin had clearly proven itself in other settings to be protective against heart attacks,” said Jonathan Rich, an instructor of medicine in the section of cardiology at the University of Chicago Medical Center. “If you suffered a heart attack, to prevent you from having another, your doctor invariably puts you on aspirin. So this unexpected discovery caught everyone’s attention. Did this mean that aspirin use could actually be hurting people?”

Dubbed the “aspirin paradox,” this observation did not deter doctors from continuing to prescribe aspirin for the prevention of cardiovascular disease. But the mystery caused some to wonder whether there was a biological reason for aspirin’s unexpected role as a risk factor, such as “aspirin resistance” in some patients, or if there was instead an epidemiological or statistical explanation. While working in Boston with the TIMI study group, Rich took charge of an effort to comb through the data for a way to explain the paradox.

The research ultimately led to a study, published last month in the Journal of the American College of Cardiology, which seems to take aspirin off the hook. When researchers controlled for a long list of potential confounding variables such as age, sex, smoking, and previous history of cardiovascular events, the association of prior aspirin use with a higher chance of post-event mortality entirely disappeared. Aspirin, they concluded, was not directly causing worse outcomes after a heart attack. Instead, it was simply a common drug that people with previous cardiovascular disease - by definition, a population at high risk for poorer outcomes, were frequently taking.

“Aspirin is probably an innocent bystander,” Rich said. “The reason people who take aspirin do worse than those not taking aspirin is because those taking aspirin have already suffered a heart attack, a stroke, or have heart failure for which they were prescribed the drug. In actuality, when we looked closer at the heart attacks that people suffered, those who were taking aspirin actually had less severe heart attacks than those not taking aspirin, suggesting that perhaps aspirin was indeed beneficial, but simply insufficient to prevent the heart attack entirely.”

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Tuesday’s midterm election results appeared to deliver a strong message of discontent to the young Obama administration. With Republicans gaining control of the House of Representatives and closing the gap in the Senate, many analysts saw the election as a rebuke of the Democratic agenda of the last two years. Perhaps the highest-profile of those policies was the Patient Protection and Affordable Care Act, the product of the epic legislative battle over health care reform. Though many of the PPACA changes have yet to be activated, its opposition has loudly and repeatedly warned that the reforms will bring rationing of health care for the American public.

That’s a false bogeyman because rationing is already here, according to a commentary by the University of Chicago’s David Meltzer in last week’s Journal of the American Medical Association. Though the word “rationing” brings to mind making do with scarce resources during wartime, the term applies to any time a good or service is divorced from the economic forces of supply and demand. With the influence of government subsidies, private insurance companies, and managed care, the American health care system has long been subject to rationing.

“Attempts to resist change using the specter of rationing are not reasonable because rationing already exists and is inevitable,” Meltzer, an associate professor of medicine and economics, writes with Allan Detsky of the University of Toronto.

Because each individual’s personal demand for health care is unpredictable - a person could go the next year without needing to see a doctor, or get in a serious car accident tomorrow - insurance companies (and government programs such as Medicaid and Medicare) play the role of mediators, evening out the cost and lowering the risk. But that role gives insurers the power to make decisions about what care is appropriate and necessary, which may include the ability to ration health care through denial of coverage. Because a patient can pay for the procedure themselves, it’s not quite the same as the wartime rationing of goods, but when an unapproved procedure can run hundreds of thousands of dollars, the result may be no different.

The real debate then is over who should be making decisions about health care rationing: profit-driven private insurers, or politically-prone government officials, the authors write.

“I think it’s silly to talk about rationing without more subtlety,” Meltzer told ScienceLife in a separate interview. “We should absolutely have a debate about rationing, but it’s not a debate about whether, it’s a debate about how.”

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As discussed previously on ScienceLife, the microbiome is the ecosystem of billions of bacterial organisms living inside our bodies, influencing us in as-yet-undetermined ways. Most efforts to study the microbiome thus far have focused on how gut bacteria affect digestion and disease, but a paper this week in PNAS reveals a surprising new power for those microorganisms: the ability to shape sexual preference. Okay, so far it’s only been observed in fruit flies, but as Ed Yong at Discover Magazine’s Not Exactly Rocket Science explains, it’s still a remarkable example of how a change in diet can alter an organism’s behavior in unforeseen ways.

The relationship between science and films, Carl Zimmer writes in this week’s Nature, has largely been a one-way street. Science gives Hollywood the technology to make pictures move, talk, and appear to throw things at you (in the case of the recent 3D boom), but returns the favor by portraying scientists as mad, geeky, or both. Zimmer’s column was inspired by hosting the recent Imagine Science Film Festival, a New York event that showcases short films with scientific inspiration. And while Zimmer is skeptical about the use of Hollywood film to promote science - Citizen Kane “would not have been a masterpiece if Orson Welles had kept asking himself ‘Does this make journalism accessible to a broader audience?’,” Zimmer writes - he comes slightly around after seeing films portraying the sensory phenomenon of synaesthesia and the comedic adventures of a Norwegian cryonics laboratory.

Bad news: a new projection by former University of Chicago faculty member Nicholas Christakis predicts that 42 percent of Americans will be obese by the year 2050. Good news: the obesity rate will plateau at that ghastly figure; as the authors write, “While not great, this is a much more optimistic estimate than 100%.” As our own Elbert Huang calculated last year, that plateau will still mean billions more in health care costs to treat chronic diseases associated with obesity, such as diabetes and heart disease.

The health care reform measures passed last year, should they survive the new Republican-led House, put a greater emphasis on primary care and preventive medicine. But the question of who will provide that primary care remains unanswered, as Joanna Broder wrote in the Chicago Tribune this week. Broder leads her article with Pritzker School of Medicine graduate Nina Vergari Rogers, currently working at the Chicago Family Health Center as part of the University of Chicago Medical Center’s REACH program. Doctors enrolled in REACH can receive $40,000 a year toward their medical school loans - a serious incentive, given that the lower salaries paid to primary care physicians mean their expenses exceed their earnings for the first 3-5 years after residency.