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Stem cells implicated in Duchenne muscular dystrophy

Stem cells implicated in Duchenne muscular dystrophy

640px-Duchenne-muscular-dystrophyStanford researchers published a paper today in Science Translational Medicine describing how stem cells are involved in the development of Duchenne muscular dystrophy, a disease that results in progressive, often severe muscle weakness. It affects about one in every 3,600 boys born in the U.S.

The research team determined that the stem cells surrounding muscle tissue gradually became less able to create new muscle cells and instead begin to express genes that lead to connective tissue formation. Excess connective tissue accumulation, which is called fibrosis, occurs in many diseases. Thomas Rando, MD, PhD, a Stanford neurologist and one of the authors of the paper said in a release about the new study:

These cells are losing their ability to produce muscle, and are beginning to look more like fibroblasts, which secrete connective tissue. It’s possible that if we could prevent this transition in the muscle stem cells, we could slow or ameliorate the fibrosis seen in muscular dystrophy in humans.

The researchers also found that a drug already approved to treat high blood pressure in humans called losartin can slow these changes in stem cells in laboratory mice, although much more work is needed to find out if it could be helpful in children with Duchenne.

The researchers are focusing on how to get the drug to target only muscle cells, but they’re also interested in how they can apply their findings to other diseases. Rando, who directs the Glenn Center for the Biology of Aging at Stanford, also commented:

Fibrosis seems to occur in a vicious cycle. As the muscle stem cells become less able to regenerate new muscle, the tissue is less able to repair itself after damage. This leads to fibrosis, which then further impairs muscle formation. Understanding the biological basis of fibrosis could have a profound effect on many other diseases.

Previously: Working on a gene therapy for muscular dystrophy, New mouse model of muscular dystrophy provides clues to cardiac  failure, and Mouse model of muscular dystrophy points finger at stem cells
Photo of muscle cells affected by Duchenne disease by Edwin P. Ewing

Genetics, NIH, Research, Videos

DNA origami: How our genomes fold

DNA origami: How our genomes fold

Here’s an interesting factoid about our genomes: If you stretched out the DNA in a single cell, which is only a few millionths of an inch wide, it would span more than six feet. And another: DNA folding is a dynamic process that changes over time. Scientists have been trying to understand how DNA folds itself up so efficiently, and a recent post on the NIH Director’s Blog highlights new research illustrating how the human genome folds inside the cell’s nucleus, as well as how DNA folding affects gene regulation. The research team created this delightful video that demonstrates the principles involved using origami art.

Researchers have been working to determine how cells regulate gene expression for nearly as long as we’ve known about DNA. How, for example, do nerve cells know to turn off only nerve cell genes and turn off bone cell genes? DNA folding loops are part of the answer. This research team, which published their findings in a paper in Cell yesterday, found that the number of loops is much lower than expected. There are only 10,000 loops instead of the predicted millions, and they form on/off switches in DNA. As explained in the blog post:

[The] paper in Cell adds fascinating details to that map, and it confirms that DNA loops appear to play a crucial role in gene regulation. The researchers found that many stretches of DNA with the potential to fold into loops have genes located at one end and, at the other end, novel genetic switches. When a loop forms, placing a hidden switch in contact with a once-distant gene, the gene is turned on or off. In fact, the mapping work uncovered thousands of these “secret” switches within the genome—information that may provide valuable new clues for understanding cancer and many other complex, common diseases.

Previously: DNA architecture fascinates Stanford researcher – and dictates biological outcomes

Patient Care, Public Health, Research, Science

Finding cures for the most challenging diseases

640px-Drawing_Test_tubes_different_colorsThe recent Ebola outbreak and the subsequent race to find a vaccine and other treatment options has brought the topic of drug development back in the public spotlight. But despite the millions of dollars spent on these efforts and the technological advances in biomedical sciences in the last 20 years or so, the process is still time-consuming and prone to failure. A recent feature story from National Journal (which also appears on The Atlantic’s website today) describes the work of several scientists trying to find cures or treatments for some of the most challenging diseases, from infectious diseases, like AIDS and Ebola, to chronic diseases such as Alzheimer’s.

The first disease the article highlights is a rare disorder called progeria, which causes young children to age prematurely. Recent breakthroughs in treatment have come from a team led by Francis Collins, MD, PhD, who is more famous for leading the Human Genome Project and now serves as director for the National Institutes of Health. Collins worked briefly on progeria early in his career and the combination of Collins’s work and genomics made it possible for his team to crack the genetic secret of the rare disease: that it was caused by a single genetic mutation. That finding led to a treatment that extended the lives of patients with progeria by several years. But it also points to some of the overwhelming challenges of chasing down cures and treatments:

The doctors and scientists hunting for new cures and treatments work in a constant state of tension. They operate in a tremendously high-stakes environment, pouring years of their lives into research as the people who inspire them continue to suffer and even die. Drug hunters face failure after failure, almost never followed by success. Decades of work flame out. Promising ideas turn into dead ends. For every 10,000 compounds they explore, scientists wind up with just one drug approved by the Food and Drug Administration. Even when medical science moves as fast as it can—and today, it’s moving faster than ever before—it’s still an agonizingly slow process.

“As much as we say that failure is part of what we do—if you’re not failing, you’re probably not doing science that’s very interesting—it still hurts,” Collins says. “It is frustrating, because you want to come up with the answer. You want to save lives. That’s what we all get into this medical research area to try to achieve, and yet the challenges are immense. And we make progress, oftentimes, in very small baby steps, even though what we’re hoping for are big leaps.”

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Aging, Dermatology, Public Health, Videos

Don’t skip the sunscreen in wintertime

Don’t skip the sunscreen in wintertime

When you’re spending time outdoors during the wintertime, it’s easy to justify skipping the sunscreen when the sun isn’t beating down on you mercilessly and you’re bundled up instead of sporting a swimsuit. But UV rays from the sun can penetrate clouds and snow can reflect sun onto your face, hands and any other exposed skin. So it’s important to remember to take sun safety precautions even on cold or overcast days, too.

This  Stanford Health Care video featuring dermatologist Justin Ko, MD, MBA, includes important tips for preventing skin cancer year-round. As I, like many others, prepare for a family trip to Tahoe to take advantage of the recent snow, Ko’s reminder about sun safety habits during the winter comes at a good time. For example, I suspect I’ve been skimping on sunscreen: Ko says you need a shot glass-full to completely cover your body. If you’re using a spray-on sunscreen, you need to spray for a full 60 seconds.

Watch the video to learn more information about how to identify possible cancerous moles and preventing high-risk exposures, like tanning beds.

Previously: Skin cancer linked to UV-caused mutation in new oncogene, say Stanford researchers, Humble anti-fungal pill appears to have a noble side-effect: treating skin cancer, Skin cancer images help people check skin more often and effectively, and The importance of sunscreen in preventing skin cancer

Global Health, Infectious Disease, Microbiology, Public Health, Videos

'Tis the season for norovirus

'Tis the season for norovirus

The week before Thanksgiving, some kind of stomach bug, which I suspect was norovirus, spread like wildfire among my daughter’s daycare. Several of her classmates became sick and like dominos so did the parents, including us.

So I was more than sympathetic when I came across this video by John Green (of the vlogbrothers fame and author of “The Fault in Our Stars”) about his family’s Thanksgiving troubles with a norovirus infection that seems to have left no GI system untouched in their household.

Winter, from about November to April, is prime norovirus season. The treacherous illness, which as Green says “has amazing superpowers,” spreads when you come into contact with feces or vomit of an infected person. It can take less than a pinhead of virus particles to make this happen. Unlike other viruses, it can live on surfaces for surprising long periods, which is how a reusable grocery bag caused an outbreak among a girls soccer team in 2012. Plus, an infected person can continue to shed the virus for about three or four days after recovering. It’s possible to disinfect after an infection, but it’s a pretty intense job.

Given these characteristics it’s not surprising that this tiny virus (even by virus standards) causes about 20 million illnesses each year. Although for most people it’s a mild illness, for the very young,  old or those with compromised immune systems—it can be severe. About 56,000-71,000 people are hospitalized and 570-800 die from norovirus infections.

The situation is worse in developing countries, where, as Green points out, rehydration therapy is harder to come by for the most vulnerable. About 200,000 deaths are caused by norovirus infections in poor parts of the world.

In his typical funny and thoughtful style, Green talks about what lack of simple—and cheap—rehydration therapy means for many on our planet. It’s one more thing that it’s easy to take for granted, and one more thing to be thankful for.

Previously: Stanford pediatrician and others urge people to shun raw milk and products and Science weighs in on food safety and the three-second rule

Big data, Cancer, Health Disparities, Imaging, Public Health, Women's Health

A new way of reaching women who need mammograms

A new way of reaching women who need mammograms

black Woman_receives_mammogramI’ve taken cancer screenings for granted since I’m one of those fortunate enough to have health insurance, and it didn’t occur to me that many uninsured women were going without regular mammograms to screen for breast cancer. A story today on Kaiser Health News mentions this fact and highlights a partnership that Chicago public-health officials have forged with a company named Civis. The private company includes staffers that helped with the Obama campaign’s get-out-the-vote efforts, and then moved on to help find people eligible to enroll for health insurance through the Affordable Health Care Act. The company used its expertise to identify women who were in the right age group (over 40) and were uninsured in Chicago’s South Side area; those women then were then sent fliers about free screenings available to them.

The article describes some other cities using similar “big data” efforts for public-health purposes:

This project represents a distinctive step in public health outreach, said Jonathan Weiner, professor and director of the Johns Hopkins Center for Population Health IT in Baltimore. But Chicago is not the only city investigating how population data can be used in health programs, he added, citing New York City, Baltimore and San Diego as other examples.

“It’s a growing trend that some of the techniques first developed for commercial applications are now spinning off for health applications,” he said. So far, he said, “these techniques have not been as widely applied for social good and public health,” but that appears to be changing.

The early signs say that the new effort in Chicago, which started earlier this year, is working. One hospital saw a big jump in the number of free mammograms, from 10 a month to 31, though the full impact may not be understood for a few months. It’s not “a silver bullet” as one expert cited in the story notes, but it’s a much more precise tool than most public-health outreach programs have had access to until now.

Previously: Screening could slash number of breast cancer casesDespite genetic advances, detection still key in breast cancerStudy questions effects of breast cancer screenings on survival rates and New mammogram guidelines echo ones developed by physicians group
Photo by National Cancer Institute

In the News, Infectious Disease, Medical Education, Medicine and Society, Patient Care

A doctor’s attire – what works best?

A doctor’s attire – what works best?

Lab CoatsDoes what your doctor wear matter to you? You may simply want your doctor to be competent and compassionate, but a recent article in The Atlantic points out some subtle issues in the effects a doctor’s dress may have. Most people seem to prefer “formal” to “casual,” but the author recalls being put off by a well-coiffed female doctor dressed in a smart business suit. But if there’s such a thing as too formal, a doctor in cut-off shorts and a tee isn’t likely to get too many repeat patients either.

I’m pregnant and I have a toddler, so I’ve had more than the average number of visits to the doctor in the past couple of years. I also like clothes and notice what people are wearing, but even I had to stop and think about what, if anything, I remembered about what my OB/GYN or my daughter’s pediatrician (both women) wore during recent visits. Mostly I remember slacks and simple blouses, or in the unforgiving summer heat typical in this area, something a little lighter. My daughter’s pediatrician also has a couple of small Disney character toys attached to her name tag to entertain the youngest patients.

There’s a middle ground that doctors have to strike that may be tricky depending on their specialty, their hospital or clinic’s dress codes (Mayo Clinic requires all docs to dress in a business suit) among other things. And that’s not even considering the issue of how a doctor’s clothes can spread infectious disease. From the article:

The definition of what counts as professional clothing is also in flux, thanks to increasing knowledge of infectious risks. Earlier this year, the Society for Healthcare Epidemiology Association (SHEA) published new guidelines for healthcare-personnel attire in hospital settings. Their goal was to balance the need for professional appearance with the obligation to minimize potential germ transmission via clothing and other doodads like ID badges and jewelry and neckties that might touch body parts or bodily fluids. The SHEA investigators’ take-home points regarding infection: White coats should be washed weekly, at the minimum; neckties should be clipped in place (70 percent of doctors in two studies admitted to having never had a tie cleaned); and institutions should strongly consider a “bare below the elbow” (BBE) policy, meaning short sleeves and no wristwatches or jewelry. Although the impact on reducing the risk of infections remains to be determined, it’s considered potentially significant enough that a number of countries have adopted BBE requirements for all clinicians. (And it leaves me wondering: When will the Mayo clinic update its dress code to short-sleeved business suits?)

The other factor doctors have to consider is that the “business casual” that I’ve seen on most doctors may need to be upgraded for more formal meetings – something I’d never considered as a patient. Again from the article:

Last week, two days in a row, I ran into a colleague who’s a pediatrician. The first day, she wore a beige pantsuit (I’d label it formal, or business) and looked fairly corporate. I wondered to myself if she realized that her clothes were sending a message to her patients, a message that indicated that her medical practice was a business and that she wielded the power. The next day, she wore a loose-fitting knee-length navy dress (professional informal, perhaps, or smart casual). I asked her if she had seen patients the first day. She had not; it was a day of meetings, and when I told her I was writing about doctors’ clothing, she laughed. “When you’re seeing patients,” she said, “you have to look like you’re not afraid to get dirty.”

I’m not sure how I would have reacted if at our first appointment our pediatrician had worn a formal business suit. At the very least, I would have felt under-dressed (jeans and tees are my de facto uniform these days), but I would have likely judged her as cool or somehow distant, not suited to working with kids. Which may prove nothing, but only hint that that the best attire is the kind that your patients don’t notice.

Previously: NY bill proposes banning white coats, ties for doctors
Photo by Pi

Chronic Disease, In the News, otolaryngology, Patient Care

A look at one woman's long journey to diagnosis and treatment of rare disorder

VertigoThis week’s Medical Mysteries column in The Washington Post tells the story of a woman who lived with debilitating vertigo and odd tinnitus. Baltimore’s Rachel Miller lived with dizziness, the exaggerated sound of her heart and breathing and even anomalies with her vision for five years before she was diagnosed and treated. Many of the doctors she saw dismissed her symptoms as psychosomatic and Miller even went through a period when she stopped seeing doctors for her condition. Miller described her travails this way:

“I had started to feel like a person in one of those stories where someone has been committed to a mental hospital by mistake or malice and they desperately try to appear sane,” recalled Miller, now 53. She began to wonder if she really was crazy; numerous tests had ruled out a host of possible causes, including a brain tumor. Continuing to look for answers seemed futile, since all the doctors she had seen had failed to come up with anything conclusive.

But then she went to see David Zee, MD, who diagnosed her strange symptoms as a rare disorder called superior canal dehiscence syndrome (SCDS), when a small hole or a thin area of the temporal bone allows the fluid of the inner ear to touch the brain, transmitting sounds from the rest of the body, like our heartbeat or breathing, or even the movement of our eyeballs. John Carey, MD, operated on Miller, filling the small hole with bone and other tissue from the skull. As the piece notes, both Carey and Zee trained with Lloyd Minor, MD, now dean of the Stanford School of Medicine, when he was at Johns Hopkins University. Minor discovered SCDS in 1995 and developed the surgical treatment that Miller subsequently received in 2012.

Miller has recovered now, with only occasional problems when she gets a cold. But her story points out how difficult it can be to diagnose rare medical problems.

Previously: NIH network designed to diagnose, develop possible treatments for rare, unidentified diseases and Using crowdsourcing to diagnose medical mysteries
Photo by Mikael Tigerström

Genetics, In the News, Medicine and Society, Research

James Watson to put Nobel medal on the auction block

James Watson to put Nobel medal on the auction block

DNA Template molecular modelLooking for the perfect holiday gift for the science geek in your life? Have an extra $3 million sitting around? If so, you can bid on James Watson’s Nobel Medal, which will be auctioned off by Christie’s on December 4 and is expected to fetch between $2.5 and $3.5 million. Watson, now 86, won the Nobel Prize in Physiology or Medicine in 1962 for deciphering the structure of DNA, along with Francis Crick and Maurice Wilkins. An article in Reuters noted the significance of the medal’s auction and the 1953 finding for which it was awarded:

“It is recognition of probably the most significant scientific breakthrough of the 20th century and the impact of it is only being played out now in the 21st century,” said Francis Wahlgren, international head of books and manuscripts at Christie’s. “Whole industries have developed around it.”

Countless subsequent scientific discoveries in the last half century have their foundation in Watson and Crick’s work. Last year, Francis Crick’s Nobel medal garnered $2.27 million. Watson’s handwritten notes for his acceptance speech will also be auctioned the same day. He plans to donate part of the proceeds from the sales to charities and to scientific research.

Previously: Coming soon: A genome test that costs less than a new pair of shoes, NPR explores the pros and cons of scientists sequencing their own genes, and Image of the Week: Watson and Crick
Photo of thymine template from Watson and Crick’s 1953 molecular model by Science Museum London

Global Health, In the News, Public Health, Research, Science Policy

Gates Foundation makes bold moves toward open access publication of grantee research

Gates Foundation makes bold moves toward open access publication of grantee research

Bill and Melinda GatesLast week, the Gates Foundation announced that it will now require all grantees to make the results of their research publicly accessible immediately. Researchers will only be able to publish their research in scientific journals that make the published papers accessible via open access – which rules out publishing in many prominent journals such as Science and Nature.

Inside Higher Education detailed the new policy:

The sweeping open access policy, which signals the foundation’s full-throated approval for the public availability of research, will go into effect Jan. 1, 2015, and cover all new projects made possible with funding from the foundation. The foundation will ease grant recipients into the policy, allowing them to embargo their work for 12 months, but come 2017, “All publications shall be available immediately upon their publication, without any embargo period.”

“We believe that our new open access policy is very much in alignment with the open access movement which has gained momentum in recent years, championed by the NIH, PLoS, Research Councils UK, Wellcome Trust, the U.S. government and most recently the WHO,” a spokeswoman for the foundation said in an email. “The publishing world is changing rapidly as well, with many prestigious peer-reviewed journals adopting services to support open access. We believe that now is the right time to join the leading funding institutions by requiring the open access publication of our funded research.”

But the Gates Foundation policy goes further than other funding instutions. Once the papers are available publicly, they must be licensed so that others can use that data freely, even for commercial purposes. A news article in Nature explains the change:

The Gates Foundation’s policy has a second, more onerous twist which appears to put it directly in conflict with many non-OA journals now, rather than in 2017. Once made open, papers must be published under a license that legally allows unrestricted re-use — including for commercial purposes. This might include ‘mining’ the text with computer software to draw conclusions and mix it with other work, distributing translations of the text, or selling republished versions.  In the parlance of Creative Commons, a non-profit organization based in Mountain View, California, this is the CC-BY licence (where BY indicates that credit must be given to the author of the original work).

This demand goes further than any other funding agency has dared. The UK’s Wellcome Trust, for example, demands a CC-BY license when it is paying for a paper’s publication — but does not require it for the archived version of a manuscript published in a paywalled journal. Indeed, many researchers actively dislike the thought of allowing such liberal re-use of their work, surveys have suggested. But Gates Foundation spokeswoman Amy Enright says that “author-archived articles (even those made available after a 12-month delay) will need to be available after the 12 month period on terms and conditions equivalent to those in a CC-BY license.”

The Gates Foundation has funded approximately $32 billion in research since its inception in 2000 and funds about $900 million in global health funds annually. That’s a smaller impact than, say the U.S. National Institutes of Health, which funds about $30 billion in health research. But it does represent nearly 3,000 papers published in 2012 and 2013. Only 30 percent of those were published in open access journals.

Previously: Teen cancer researcher Jack Andraka discusses open access in science, stagnation in medicineExploring the “dark side of open access”, White House to highlight Stanford professors as “Champions of Change”Stanford neurosurgeon launches new open-source medical journal built on a crowdsourcing modelDiscussing the benefits of open access in science and How open access publishing benefits patients
Photo of Bill and Melinda Gates by Kjetil Ree

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