A brain from a person with mad cow disease, caused by prions (compared to a normal brain).

A Place for Prions

We previously discussed the bizarre infectious proteins called prions in the context of kuru, the disease of muscle tremors and uncontrollable laughter spread by cannibalistic rituals in Papua New Guinea. In diseases such as kuru or mad cow disease, abnormal prion proteins wreak havoc by binding to native prions and other cellular elements, creating clumps that kill off cells in the nervous system. But one important thing I didn’t mention in the kuru article - nobody’s really sure what the native, normal prions actually do!

That mystery may have been somewhat dispelled by an article published by Nature Neuroscience last weekend from a team of scientists in Sweden and Germany. Those researchers knocked out or interrupted the gene for prions in a number of different mouse strains, a strategy that had previously yielded a pretty normal mouse without much to say about the prion’s purpose. But for the current experiment, the researchers were patient, allowing the mice to live to the grand old age of 60 weeks (mice typically live for about two years) before looking for deficiencies related to their lack of prions.

What they found in their elderly mice links back to another ScienceLife post - peripheral neuropathy, a motor disorder marked by the demyelination of peripheral neurons. The nerve cells running from the spinal cord to muscles of the prion-free mouse’s body were normal, save for a thinned-out sheath of myelin along the axon. As discussed previously for multiple sclerosis (where central nervous systems neurons are demyelinated), this loss of myelin leaves cells less insulated and like a frayed power cable, unable to transmit signals at optimum speeds. Hence, the motor difficulties associated with peripheral neuropathy, which in humans manifests itself as twitching, paralysis, and loss of dexterity.

That could be a promising finding for not just one field but two. Recall that motor difficulties are usually one of the first symptoms of prion diseases - “kuru” is the word for “shiver” in the Fore language of Papua New Guinea’s Eastern Highlands. Prion gene knockout mice may have their issues, but have the small consolation of being resistant to prion diseases. And the study of peripheral neuropathies (plural, because the term covers several different diseases) could benefit from the new identity of the prion as a mediator of myelin maintenance.

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The University of Chicago Medical Center team currently working in Jimani, Haiti. (L to R: Rex Haydon, Elvire LaPlanche, Richard Cook, Nicole Muse, Christian Theodosis)

More than two weeks after the earthquake that devastated the Caribbean nation of Haiti, the situation remains a humanitarian crisis as hundreds of thousands of injured and homeless seek treatment and shelter. There are more and more signs of hope: Hundreds of millions of dollars have been donated from around the world, some semblance of daily life is resuming on Haitian streets, and roughly 150 temporary hospitals and clinics - including a US Navy ship docked off the coast of Port-au-Prince - have set up to treat the wounded. Yet beyond the immediate triage, long-term health care worries about illness, infection and serious injuries persist, including the need for an estimated 200,000 amputations due to wounds suffered in the quake.

To bolster this continued effort to provide high-quality medical care in the coming weeks and months, two teams left the University of Chicago Medical Center for Haiti earlier this week. Made up of emergency medicine specialists, orthopedic surgeons, anesthesiologists and nurses, the teams are suited to assist both the immediate and long-term challenges of the medical crisis. One team, made up of physicians from the UCMC-affiliated North Shore University Health System as well as Northwestern University and Johns Hopkins University, flew into Port-au-Prince. Another team, with three physicians and two nurses (both Haitian natives), will set up in Fond Parisien, a town near the border between Haiti and the Dominican Republic that has become a hub of medical care to earthquake survivors. The team also brought more than 1,000 pounds of medical supplies with them, and additional teams of UCMC personnel will rotate into the camp every two weeks - more than 100 physicians and nurses have already volunteered for the effort.

The first dispatch from the arriving team underscored the urgency of the need for medical care and supplies. “Just finished getting crushed,” wrote team co-leader and emergency medicine physician Christian Theodosis the day after their arrival. “67 patients on 3 buses, after dark. Conditions quite intense, quite rough. Running short on tents, short on hands, several generators now, security intact. Many, quite vulnerable people. Hungry and tired.”

Updates from the latter team will be posted at Haiti Relief, a blog set up by the Medical Center’s Global Health Initiative. That space also hopes to start conversations among experts across the University of Chicago campus about how best to treat and rebuild Haiti, its health care, infrastructure and beyond. From there, you can read articles from UChicago anthropologist Greg Beckett on the underlying issues Haiti faced before the earthquake. If you would like to donate to efforts in Haiti, the University’s Chicago Studies project have set up a blog with links and information about local and global campaigns.

After the jump, some pictures from Dr. Theodosis of the Fond Parisien hospital camp.

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The protein structure of human interferon-alpha

As discussed yesterday, lupus is not an equal-opportunity disease. Ninety percent of lupus cases occur in women, the disease is three times more likely to affect African-American women than Caucasian women, and lupus is more common and severe in other minority populations as well. Given that the general cause of lupus remains unknown, the reason for these discrepancies is also mysterious. But a grant from the Lupus Research Institute recently awarded to Timothy Niewold, assistant professor of rheumatology at the University of Chicago Medical Center, hopes to turn the focus of science to this issue, looking for genetic factors that may explain why minority women are more seriously afflicted by lupus.

One of the few things that is clear about lupus is that it must have a strong genetic component. The disease is strongly inherited - if someone has a close relative with lupus, their own chances of having the disease are increased twenty-fold. Genetic linkage studies have found a number of promising genes and clusters of genes that are associated with an increased risk of contracting lupus. But while such results are promising, they also contain a couple of problems. 1) The genes don’t account for everything, suggesting an environmental role in triggering the disease. 2) The multiple linkages indicate that lupus cannot be traced back to just one gene, backing theories that the complexity of the disease is due to multiple genetic factors. 3) The linkage studies were conducted in patient populations that were predominantly Caucasian, obfuscating any genetic differences that could account for the increased incidence of lupus in minorities.

“We are excited that we are mapping a bunch of different genes, but it is kind of like we’re sketching some of the first maps of the continent,” Niewold said. “We’re getting something here, something there, and not everything is connected. It’s kind of a vague diagram.”

If all those caveats and complexities are giving you a headache, you’re not alone. But Niewold’s approach is to focus on particular portions of the map that look like they may be relevant to at least a large portion of lupus patients, while expanding genetic studies to start filling in some of the blank parts on the map.

One part of that effort is to focus on a likely suspect in lupus - cytokines. Small signaling molecules that play a role in the immune system, cytokines are normally responsible for helping marshal immune defenses to fight off infections. But one particular cytokine, called interferon-alpha, or IFN-α, may go awry in lupus patients, with elevated levels of the cytokine producing the disease’s characteristic overactive immune response. The theory is backed by both genetic linkage data (where several genes associated with the IFN-α pathway pop up) and acute measurements revealing high levels of IFN-α in lupus patients.

“One of the most common and consistent pathways dysregulated in lupus is type I interferon,” Niewold said. “It doesn’t give us a complete answer, but the data suggests that it’s an important pathway in lupus.”

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Autoimmune disorders are a strange type of disease, a case where the body’s biology isn’t breaking down but rather is functioning too well. In disorders such as Type I diabetes, arthritis and multiple sclerosis, the body’s natural defenses stage something of an internal coup, mistakenly attacking the body’s own tissues instead of viral or bacterial invaders. In a lot of these diseases, the immune system chooses just one system to mistakenly attack - the pancreas in diabetes, or the joints in arthritis. But one autoimmune disorder is less specific, striking out against multiple targets that can differ from patient to patient - lupus.

Known clinically by its longer name, systemic lupus erythematosus (SLE), lupus afflicts roughly 1% of the American population, according to CDC statistics. But that number could also be three times higher, the CDC cautions, an imprecise figure partially down to the difficulty of diagnosing the disease. As Tammy Utset, associate professor in the Section of Rheumatology at the University of Chicago Medical Center describes in the videos below, lupus can present with any number of different symptoms, from fever, rash and fatigue to hair loss, joint pain and kidney disorders.

“It’s a little tricky because the symptoms are so varied from person to person,” Utset said. “That’s why it can take a long time for lupus to come to diagnosis after the symptoms start, because the symptoms early on can be relatively non-specific.”

The diverse range of symptoms is only one of lupus’ mysteries. The disease also has a very skewed incidence between genders, with 9 out of 10 cases in women. Across ethnic lines, lupus strikes minority populations more often - the CDC states that the disease is three times more likely to strike African-American women than Caucasian women, and symptoms tend to be more severe in these populations. At the University of Chicago, the Gwen Knapp Center for Lupus and Immunology Research has been grappling with research questions regarding this discrepancy and potential genetic factors in the development of lupus. Tomorrow, I’ll discuss some of the genetic research coming from that group, but today, here are four videos of Dr. Utset talking about the unique clinical character of this unusual, but hardly rare, autoimmune disease.

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Illustration by Clint May

Most people who have spent any length of time in a laboratory know the pain and frustration of Western blots. There’s probably a little bit of PTSD in every cell biologist related to gels falling apart, leaky electrophoresis chambers, or bands that should be there but aren’t, causing you to wonder which of the preceding 40 steps went wrong.

But don’t hate the method, hate the human error - Western blots, for all the agony they’ve caused, have been one of the most widely-used and productive lab methods of the past 30-some years. Used to detect the amount of protein in a given cell or tissue sample, Western blots have furthered our understanding of the intricate machinery of the cell, from the assembly line that builds it to the defects that can lead to cancer and other diseases. More specific than another protein assay, mass spectrometry, Western blots are the weapon of choice for laboratories that want to characterize the amount and status of a specific protein.

Nevertheless, Western blots have their limits, and the key word is “protein,” singular. Due to the limited size of a Western blot gel and the expense of the antibodies needed to “visualize” the proteins within, blots can only assay, at most, a handful of proteins in each run. Given that the protein networks of cells can contain hundreds or even thousands of proteins, that’s like trying to figure out the image on a puzzle by looking at only one piece at a time. The search was on for a better method, one that could take a snapshot of hundreds of proteins from a cell sample simultaneously.

Such a breakthrough was announced over the weekend in the journal Nature Methods, where a team of scientists led by Richard Jones, assistant professor at the University of Chicago’s Ben May Department for Cancer Research and the Institute for Genomics and Systems Biology described a promising new technique: micro-western arrays.

“When you walk into a dark room and don’t have much information, it’s difficult to predict where everything is going to be,” Jones said. “If someone can simply turn on the light, you don’t have to progress one step at a time by bumping into things. With this new technology, you can potentially see everything at the same time.”

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Videogame Learning & Brain Size

Many a member of the older generations will tell you how video games are rotting our children’s brains, turning kids into button-pushing, drooling zombies. Such warnings linger on despite the fact that my generation - the one that desperately wanted a Nintendo for Christmas - turned out pretty okay…though obviously I’m a little biased. Heard less often are whispers that video games might actually be beneficial to players, helping them fine-tune hand-eye coordination, spatial learning and perceptual tasks. But such research is out there; last year, I wrote about research showing that video games and other parental bogeymen such as Facebook and texting might actually be improving people’s brains rather than destroying them.

Some new research in that community was released this week in the journal Cerebral Cortex, in a study that was rapidly misunderstood as merely Bigger Brains Mean Higher Video Game Scores. That’s not a false headline, but it does miss the subtle point. The authors, from 4 different schools including the University of Illinois and MIT, trained people without video game experience to play the vintage game Space Fortress. In those who learned the game faster (i.e. had achieved higher scores by the end of the training day), a brain area called the striatum was found to be larger on average than the slower learner’s striatum.

The striatum is actually a pretty interesting area, implicated in both movement (and movement disorders such as Parkinson’s and Huntington’s diseases) and addiction. The ventral striatum, including a region called the nucleus accumbens, is the focus of many addiction studies because it is the “reception area” for dopamine, the neurotransmitter increased by all drugs of abuse. With video games, the size of the ventral striatum correlated with early stages of learning, lending support to the idea that learning is enhanced by activities that are rewarding - or to put it more simply, fun.

That could explain why video games are powerful tools for improving a person’s attention and pereception, a phenomenon that researchers such as Daphne Bavelier at the University of Rochester are trying to corral to facilitate education. The study’s findings also may explain the limitations of that approach - some people appear to be resistant to the beneficial effects of video games, a fact that could be explained by brain architecture limiting their ability to learn the game. So next time I’m cursing these new-generation games for being so much harder to play than Super Mario Bros., perhaps I should blame my striatum instead of the developers.

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One of the major goals of the health care reform effort that has dominated political discussion for the past year has been reining in medical spending. Oft quoted is the fact that U.S. health care expenditures have tripled since 1990, that the health care industry comprises a whopping 16% of U.S. GDP, and that each American citizen spends over $7,000 per year on health care, higher than any other country, all despite ranking merely 50th in the worldwide competition for life expectancy. To many, these spiraling figures are a cause for concern, a runaway train that needs to be slowed down through government intervention and industry reforms. But to Robert Fogel, University of Chicago economist and 1993 Nobel laureate, these figures were not worrying omens, but positive signs of a healthier world and a thriving health care industry.

Fogel expressed these views during his talk to a packed room of doctors and ethicists Wednesday as part of the MacLean Center for Clinical Medical Ethics lecture series. Titled “Forecasting the Cost of U.S. of Health Care in 2040,” Fogel’s predictions and figures seemed to feed people’s worst fears about rising costs of health care - for example, during the Q&A portion following his talk, he estimated that health care will comprise 29 percent of the U.S. GDP by 2040, drawing gasps from the crowd. But uniquely, Fogel stressed that such an increase was not a bad thing, taking the minority position (albeit a very University of Chicago economics one) that there is no need to restrict health care spending because it’s what the people demonstrably want.

The key statistic that informed Fogel’s conclusion was that American households, when they gain an extra 1 percent of income, spend an average of 1.6 percent more on health care. Americans have a demand for higher quality health care, and as basics like food and shelter cost less, they choose to spend more of their income on attaining that medical quality - “the long-term inelasticity of the demand for health care,” as he put it in economicsese.

“Consequently, there is no need to suppress the demand for healthcare,” Fogel said. “Expenditures on health care are driven by demand, which is spurred by income and by advances in biotechnology that make health interventions increasingly effective…health care is the great growth industry of the 21st century.”

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Photo from haitiorphansproject.org

One of the unfathomably tragic numbers to come from last week’s earthquake in Haiti last week is the estimate about the number of orphans the disaster created. As many as tens of thousands of children may have been orphaned by the earthquake, according to United Nations estimates, a total that becomes even more shocking when it’s added to the approximately 380,000 orphaned children in the country before last week’s disaster. Some efforts have sprung up quickly to try and find homes for these children, but so far it’s only a trickle, restricted both by logistical difficulties from the earthquake and pre-existing legal obstacles to international adoption.

That real-time crisis lingered over a timely event held Saturday at Comer Children’s Hospital on the University of Chicago Medical Center campus. Organized by the hospital’s International Adoption Clinic as an informational and networking session for about a dozen families who have adopted or are on the verge of adoption, presentations and conversations kept veering back to the topic of Haiti.

“It’s hard today not to talk about international adoption and at the same time keep those images of Haiti out of your head,” clinic founder Larry Gray, assistant professor of pediatrics, told the room at the start of the event. “It’s sort of overwhelming at times.”

The International Adoption Clinic, which started in 2002, was set up to help children from countries such as the Ukraine, Ethiopia and China medically and developmentally transition to a new life with a new family. Gray and nurse practitioner Linda Walsh screen newly adopted children for a wide range of diseases and conditions that can be brought on by living in poverty or an overcrowded orphanage, directing them toward the treatment they need to recover. Many of the children are literally shrunken by the stressful environment they endured, charting as significantly shorter (stunting) or less heavy (wasting) than other children their age. In extreme cases, the child’s brain will even shrink from malnourishment, a condition called microencephaly.

Finding and addressing the causes of these medical issues requires extensive screening, Gray said.

“We think that to pull out a successful adoption transition, it needs to be a very multi-focused effort,” Gray said. “When a family arrives in the United States, it’s just the beginning of a network of processes that come into play.”

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Myelin is the secret weapon of the nervous system, the insulation that allows neurons to transmit electrical signals at the speed of thought. Wrapping itself around the long projecting axons of neurons, myelin acts like the insulation on a power cable, allowing electricity to travel more efficiently down nerve cells that can stretch for several feet. The importance of this function is revealed by diseases such as multiple sclerosis, where the loss of myelin causes severe movement difficulties and seizures.

The myelinating machines of the central nervous system have been known for decades: cells called oligodendrocytes, which produce myelin sheets that wrap around axons. But what genes and signals drive oligodendrocytes to do their work properly - and which of those factors go wrong in diseases like MS - remains a mystery. But the laboratory of Brian Popko, professor of neurology at the University of Chicago Medical Center, recently found a key piece of the myelination puzzle thanks to an odd, shivering mouse.

Published last week in the journal Genes & Development, Popko and his team used a method called forward genetics to launch an unbiased hunt for genes that had not previously been identified as important for myelination. Unlike reverse genetics, where researchers choose a gene of interest and make a knockout mouse lacking that gene, forward genetics relies upon the spontaneous creation of an interesting mutant. In this case, Popko and colleagues were looking for a mouse with the muscle tremors and seizures you would expect from deficient myelination.

“There were a number of knockout mutants available to us that disrupted the myelination process. They all resulted in mice that had a tremor, with names like shiverer, jumpy, trembler - you can get an idea of what the phenotype is,” Popko said. “Our screen was about as unsophisticated as you can imagine; we just selected for mice that have a tremor.”

Soon, Jackson Laboratory, a company that breeds and distributes mice for lab studies, came up with just such a mouse, who in its brief life (only about 3-1/2 weeks) has a chronic tremor in its hind legs, like it is constantly shivering in the cold.

Sure enough, when the brain and spinal cord of this mouse was dissected, it had little to no white matter, the informal term for myelinated neurons. Even more promising, the oligodendrocytes of this mutant were present, and appeared mature, but were frozen in the state just before actually initiating myelination - an interruption that resembles the malfunctioning oligodendrocytes in MS.

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If you’ll forgive the light posting today, I’d like to direct you to an article that appeared this week on the website of New Scientist magazine by Peter Aldhous, “Poor Neighborhoods Can Kill.” Aldhous gives a broad overview of a collaboration here at the University of Chicago that we’ve only barely nibbled at here on the blog, a team of biologists, clinicians, sociologists and epidemiologists that are grappling with a sobering statistic - breast cancer death rates of black women in Chicago are a shocking 68 percent higher than the rates for white women.

A frequent theme here has been the simultaneous promise and difficulty of translating animal research and laboratory findings to the real world, but this project offers a pretty remarkable example of how different types of research can be united. The effort builds bridges from Martha McClintock’s studies of social isolation worsening breast cancer in rats, to Suzanne Conzen’s studies of the genes that show increased expression in stressful or isolated conditions, to Funmi Olopade’s research on differences in breast tumors in populations of African-American and West African women.

Results from the collaboration indicate that social isolation and a fear of crime cause an overload of stress hormones that can change cell biology, sending tumours into overdrive. “We’re showing that your social environment can affect your health directly,” says Suzanne Conzen of the University of Chicago. “It goes into gene expression. That concept is really new.”

What’s more, sociologist Sarah Gehlert (now at Washington University in St. Louis) has taken those results out into the community, collecting surveys and hormonal measurements from South Side Chicago women diagnosed with breast cancer.

Gehlert suggests that the fear that comes with living in high-crime areas combined with scant social support causes overproduction of cortisol, similar to that seen in McClintock’s isolated rats. This eventually erodes the body’s ability to release the stress hormone, creating the flatline effect. Similar “burnout” patterns have been seen in patients with post-traumatic stress disorder.

It’s a great article on a great project, do check it out.

Elsewhere…

- The coolest science story of the week may have been the discovery that the Y chromosomes of humans and chimpanzees are much different than previously thought, suggesting dramatic evolution for both species on the chromosome that carries male-sex genes.

- While donations flood in to aid the people of Haiti after this week’s tragic earthquake, science writer Jonah Lehrer contributes a timely post on how the value of a charitable donation is reflected in the brain.

- The science blog NCBI ROFL moves to Discover magazine’s website, and given that their angle is one of my favorite time-wasters (searching for weird and funny articles on PubMed, the online library of scientific journals), it’s definitely going to be a regular visit. For a taste, enjoy the Onionesque “getting babies drunk” study, or the study that uses Pink Floyd-induced hallucinations to screen for a neurological disease.

The risks of being ahead of the curve in reporting on an experimental therapy: you never know when new information is going to shake loose from the scientific community. Tuesday, our Dr. FAQ series focused on platelet-rich plasma therapy, a treatment gaining popularity over the last year for a variety of sports-related injuries. J. Martin Leland, an assistant professor of surgery with our orthopaedic sports medicine team, explained the idea behind PRP therapy and the injuries it is currently being used on at the University of Chicago Medical Center and other health centers.

Leland also warned that PRP therapy remained experimental, without the double-blind, placebo-controlled trials that are the gold standard for proving that a medical treatment is effective. The day after I posted the videos, just such a trial was published in one of the leading medical journals, JAMA. The news was less than encouraging for PRP therapy. In a trial of 54 patients with an Achilles tendon injury called chronic achilles tendinopathy, PRP therapy in combination with a physical therapy technique called eccentric exercise was no more effective at reducing pain and increasing activity than a combination of placebo and eccentric exercise. News coverage of the research described the therapy as “no more effective than saltwater.”

The study itself highlights the difficulty of translating basic research into clinical application. Review articles, like this one, recommended the procedure based on promising results from lab-bench and animal studies, experiments which don’t always make the jump to the clinic. The authors also point out that invasive therapies, such as injections, can induce a potent placebo effect (even the participants in this study who received placebo showed significant improvement in pain and activity).

However, before PRP therapy is written off completely, it’s important to note that this study only tested the treatment in one specific kind of injury. After reviewing the JAMA, paper, Dr. Leland wrote the following statement to me about the current status of PRP therapy.

A Dutch study published in the Jan. 13, 2010 issue of the Journal of the American Medical Association (JAMA) found that an injection of platelet-rich plasma (PRP) performed no better than saline for chronic Achilles tendinopathy patients who were treated with eccentric exercises. This is an important study because it is one of the first of its kind regarding the effectiveness of PRP when used for the treatment of different issues in humans. However, this is only one of the first studies to come out and rash decisions should not be made based upon its findings alone.

I feel that physicians and patients should remain “cautiously optimistic” regarding the use of PRP. Over time, more and more studies will be published regarding the effectiveness of PRP. This study is a perfect example that PRP is not the solution to every problem. However, this is only one study on one specific disorder in the human body. Much more research is needed to determine if this study can be reproduced in other studies as well as what the effectiveness is of PRP on other parts of the body. In my opinion, the risks of PRP use are low and the benefits, in certain situations, may warrant its use. However, only research in the future will be able to specifically determine when and where PRP is specifically effective.

As the New York Times article linked above notes, a study showing encouraging effects of PRP therapy in combination with steroids for tennis elbow is forthcoming, and much more research is currently underway. So the story of PRP therapy is still just beginning, and it will be worth tracking which way the research tips on the procedure in the months and years to come.

If we’re lucky, we spend about one-third of our lives sleeping, a fact that appears on its face to be a colossal waste of time. Wouldn’t us humans  be able to get so much more done if we weren’t required to shut down for 8 hours a night? But the fact that the need for sleep is shared across the majority of animal species indicates that there must be some important role that the behavior plays, otherwise evolution would have likely done away with it millions of years ago.

The laboratories of Daniel Margoliash and Howard Nusbaum at the University of Chicago focus on how birds and humans learn to use language. But over the past decade, their research has also discovered some pretty interesting things about the role that sleep plays in language learning. In Margoliash’s laboratory, studies of juvenile zebra finches learning to sing found that the brains of birds will “replay” in sleep the symphony of neural activity that was present during the day when they listened to song. Separate human studies by Margoliash and Nusbaum found that sleep helped stabilize the learning of a language perception task - college students learning to comprehend computer-generated speech similar to heavily-accented English performed better on the task after a night’s sleep.

The latter experiment tested the principle of memory consolidation, the process by which short-term memories are stabilized into long-term storage. Sleep’s role in facilitating consolidation has been studied in many different ways in humans, including a 2008 paper by Timothy Brawn and Kimberly Fenn with Margoliash and Nusbaum that found that sleep enhanced people’s ability to learn how to play a first-person shooter video game. But despite accumulating evidence in humans that sleep-dependent consolidation was a real phenomenon, a true animal model had not yet been established. So Brawn once again used the unique partnership between Margoliash and Nusbaum to demonstrate that the stabilization of memories through sleep was not a uniquely human characteristic, but was also present in a bird species, the starling.

In the video below, you can hear Brawn, Margoliash and Nusbaum talk about the experiment, which was published today in The Journal of Neuroscience. You can also watch one of the experimental subjects - a starling - perform the learning task that was used in the experiment, called a “go-nogo” task. After a day of learning what birdsong cue signaled them to poke their beaks into a hole to receive food, and what cue meant to avoid poking, the starlings were tested before and after a period of sleep. As in humans, sleep improved the starlings’ performance of the task, suggesting that sleep-dependent consolidation is a common feature of at least two species.

“We really wanted to behaviorally show that these types of sleep-dependent memory benefits are occurring in animals,” Brawn said. “What was remarkable was that the pattern here looks very similar to what we see in humans. There wasn’t anything that was terribly different.”

Now that the similarities between birds and humans have been proven for this phenomenon, the story is just beginning. Further experiments in the starlings will look for the mechanisms of how sleep-dependent consolidation occurs, offering clues to how memories are stabilized in the brain that would be difficult or impossible to gather from human studies alone.

“The result suggests this is a very broad, general phenomenon that might be shared across a great many vertebrates,” Margoliash said. “It was quite important to show that and it now opens the possibility for mechanistic and behavioral experiments in animals that are difficult to do in humans.”

The latest in our video series where experts from the University of Chicago Medical Center answer frequently asked questions about popular medical topics. To suggest a topic or a question, please contact the editors.

If you’re a frequent reader of the sports pages, you probably have a pretty good familiarity with the terminology of sports medicine. Concepts like ACL tears, plantar fasciitis, Tommy John surgery and arthroscopic surgery are all frequent mentions of the injury report, lending sports fans at least a surface-level grasp of the common injuries and procedures. One treatment that has recently received a boost of mentions amid the box scores and locker room interviews is platelet-rich plasma therapy - PRP therapy for short.

Many first heard about PRP therapy in early 2009 after Pittsburgh Steelers stars Hines Ward and Troy Polamalu praised the procedure for helping them recover from injuries in time for their Super Bowl XLIII victory. Recently, a second uptick of attention has resulted, somewhat infamously, from news reports about the doctor that helped treat Tiger Woods’ knee injury in 2008 - Anthony Galea, a Canadian specialist under investigation for administering performance-enhancing drugs. But lest PRP therapy (a safe, legal treatment) be confused with the more unsavory treatments that also show up in those articles, I went to J. Martin Leland, an assistant professor of surgery in the orthopaedic sports medicine group at the University of Chicago Medical Center, to learn the facts.

Leland told me that the idea behind PRP therapy - using a patient’s own blood to assist the healing process - has been around for decades, but has gained momentum among sports medicine professionals over the past couple years. The procedure is easy (able to be completed in one doctor’s visit), safe, and relatively cheap (though not covered by most insurance plans). But Leland cautioned that PRP therapy is not a magic solution for all sports injury woes, and that much more clinical research must be done to determine just how effective the treatment is in combination with more established surgical procedures. Those topics, and more, are discussed in the videos below.

Update: On January 13, the day after we posted these videos, an article in the Journal of the American Medical Association found no significant effect of PRP therapy upon pain and activity in patients with chronic achilles tendinopathy. Dr. Leland commented:

A Dutch study published in the Jan. 13, 2010 issue of the Journal of the American Medical Association (JAMA) found that an injection of platelet-rich plasma (PRP) performed no better than saline for chronic Achilles tendinopathy patients who were treated with eccentric exercises. This is an important study because it is one of the first of its kind regarding the effectiveness of PRP when used for the treatment of different issues in humans. However, this is only one of the first studies to come out and rash decisions should not be made based upon its findings alone. I feel that physicians and patients should remain “cautiously optimistic” regarding the use of PRP. Over time, more and more studies will be published regarding the effectiveness of PRP. This study is a perfect example that PRP is not the solution to every problem. However, this is only one study on one specific disorder in the human body. Much more research is needed to determine if this study can be reproduced in other studies as well as what the effectiveness is of PRP on other parts of the body. In my opinion, the risks of PRP use are low and the benefits, in certain situations, may warrant its use. However, only research in the future will be able to specifically determine when and where PRP is specifically effective.

More information on the JAMA finding is available here.

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flickr photo by thepatrick

I’m spending today doing some intense video editing for pieces that will be on the site over the next two days, so here is science writer Greg Borzo with a guest post about a study released last month by University of Chicago researchers. The study proposes a new equation for calculating the survival expectations of patients with pulmonary artery hypertension, a disease sometimes observed in patients with COPD or sleep apnea. It’s also an interesting case study of how the equations doctors employ for prognosticating the course of disease or studying clinical treatments must be updated and adjusted as health care advances change the probabilities related to a disease.

Setting out to determine the survival of patients with pulmonary arterial hypertension (PAH), researchers at the University of Chicago Medical Center and their colleagues also discovered that an equation used for more than 20 years to predict survival is outdated. Accordingly, they developed and recently published a new survival prediction equation that will impact clinical practice and the drug development process.

In PAH, the pulmonary arteries, which carry blood from the heart to the lungs to pick up oxygen, become restricted, forcing the lower right chamber of the heart to pump harder. This leads to shortness of breath, limited exercise capacity, fatigue, heart failure and death. Often the condition goes undetected until it is advanced. Untreated, patients with PAH have a very poor prognosis.

That prognosis is determined using an equation developed by a landmark National Institutes of Health study published in 1987, well before there were any Food and Drug Administration approved therapies for PAH. The first such therapy was approved in 1995; today there are seven.

“Since 1987, great progress has been made in understanding and treating PAH, so a few years ago we decided that it was time to study contemporary survival,” said Mardi Gomberg-Maitland, associate professor of medicine and director of pulmonary hypertension. “Our results show that survival is vastly improved today. That led us to rework the NIH equation, which has been a standard measuring stick for more than 22 years.”

Gomberg and her colleagues at the Medical Center and Northwestern University’s Feinberg School of Medicine studied the survival of 576 PAH patients in their registry. Of these patients, 282 had idiopathic, familial, and anorexigen-associated PAH, which matches the conditions of the 187 patients in the pioneering NIH study.

Using the NIH equation, these 282 patients would have been expected to have one-, three- and five-year survival rates of 65%, 43% and 32%, respectively. In fact, their survival rates were much higher: 92%, 75% and 66%, respectively.

“This new formula is important for patients who want to know what, on average, to expect from their disease and for doctors who want to give accurate advice,” said Stephen L. Archer, Harold Hines Jr. Professor and chief of cardiology and co-author of the study. “We hope others will test our work. If it is validated by others it could be a very useful tool.”

The researchers were not able to determine why PAH patients survive longer today than in the 1980s, even though they measured the survival impact of many factors, including pulmonary function, demographics, medications, exercise treadmill, laboratory markers, echocardiography, and hemodynamics as well as the cause of the disease, which includes heart and lung disease, genetics, blood clots, connective tissue disease and other conditions.

None of these factors or causes had a significant impact on survival in multivariate analysis (when tested together statistically)-except hemodynamics. This explains why the new equation only incorporates hemodynamic parameters.

“Based on this result, physicians should stop drifting away from cardiac catherization, which is the gold standard test to determine exact hemodynamics,” Gomberg said. “Providers have been using more echocardiography and less cardiac catherization but we need to reverse that trend because until you know the hemodynamics you can’t accurately predict survival and or cure the disease.

“You can estimate hemodynamics with echocardiography but not accurately enough,” she added.

Many clinical trials in PAH used the NIH equation to suggest improvement in survival by comparing observed survival rates on a study drug versus survival rates predicted by the NIH equation, the study says. Since the NIH equation understates contemporary survival, it has led to more favorable comparisons of clinical trials testing new drugs to treat PAH, according to Gomberg.

“Our research suggests a reason that the drugs currently approved to treat PAH do not always work as well as we hope-because they were not held to a higher contemporary standard during their development and post-approval,” Gomberg said. “The new equation should ameliorate this bias.

“Although some of these drugs dramatically improve the condition of some patients, none of them improves hemodynamics to normal levels,” she added. “Therefore, we, as a medical community, have to acknowledge the fact that we have not yet cured PAH.”

Do Polish Tracks Trump Tiktaalik?

A bit of a firestorm with local significance was stirred up this week when a paper published in Nature purported to reset the clock on when marine animals took their first step out of water. Grzegorz Niedzwiedzki and colleagues from Warsaw and Sweden presented a fossil “trackway” made up of what the team identified as several hand and footprints from a tetrapod four-limbed vertebrates thought to be a key step in evolution from marine animals to land dwellers. The tracks, found in south-eastern Poland in a layer dated as 395 million years old (video), reveal some fascinating details in the authors’ analysis, including distinct hand and foot prints, toes and ankles - all critical aspects of the transition from fin to limb. It’s also the earliest known evidence for a tetrapod, predating fossil findings of “fish-with-limbs” such as Tiktaalik by nearly 20 million years.

While some are convinced of these conclusions, others are skeptical. Tiktaalik, discovered in 2004 in far northern Canada by a team led by University of Chicago paleontologist Neil Shubin, remains the earliest known tetrapod fossil, a remarkably complete specimen that clearly shows limb-like bone structure. Footprints, on the other hand, are acceptable as paleontological evidence, but much more open to question. Indeed, no tetrapod fossils - or any fossils, for that matter - were found near the trackway, which the authors attribute to the soil being a poor environment for preserving skeletons. Nevertheless, in a news article accompanying the Nature paper, other paleontologists express caution in accepting the veracity of the trackway fossil, and Phillippe Janvier of the Muséum National d’Histoire Naturelle in Paris suggested “a risk” that natural processes could have produced track-like markings.

Shubin, currently on sabbatical writing the follow-up to this award-winning Your Inner Fish, wasn’t immediately available for comment. But when he’s back, ask him what he thinks of the new discovery and how it changes our view of early tetrapod evolution.

The Cell Phone Treatment

In an almost too-weird-to-be-true piece of science news this week, a story started kicking around that the type of electromagnetic fields (EMFs) generated by cell phones was found to be effective at protecting against or even reversing the effects related to Alzheimer’s disease in mice. Studies of cell phone radiation - usually focused on proving that the phones’ electromagnetic waves cause harm - are notoriously unreliable. Time and again, studies have shown these waves do not cause brain tumors or other diseases…but in looking for damage from cell phone use, were scientists overlooking benefits?

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