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Medical Education, Microbiology, NIH, Public Health, Research, Videos

Investigating the human microbiome: “We’re only just beginning and there is so much more to explore”

Investigating the human microbiome: "We’re only just beginning and there is so much more to explore"

The more scientists learn about the body’s community of bacteria, the more they believe that the human microbiome plays an important role in our overall health. For example, research published earlier this week suggests that a specific pattern of high bacterial diversity in the vagina during pregnancy increases a woman’s risk of giving birth prematurely.

Despite these and other insightful findings, researchers have a long way to go to understand the composition of our internal microbial ecosystems. As Keisha Findley, a postdoctoral fellow at the National Human Genome Research Institute says in the above video, “We’re only just beginning and there is so much more to explore.”

Findley and colleagues are working to survey all of the fungi and bacteria living on healthy human skin and develop a baseline to determine how these microbial communities may influence skin conditions such as acne, athlete’s foot, skin ulcers and eczema. Watch the LabTV video above to learn more about her work.

Previously: Drugs for bugs: Industry seeks small molecules to target, tweak and tune up our gut microbes, A look at our disappearing microbes, Exploring the microbes that inhabit our bodies and Diverse microbes discovered in healthy lungs shed new light on cystic fibrosis
Via NIH Director’s Blog

Mental Health, Pregnancy, Research, Women's Health

Study shows mothers receiving fertility treatments may have an elevated risk of depression

Study shows mothers receiving fertility treatments may have an elevated risk of depression

5088785288_9f7a23f17a_zAn estimated one in four couples in developing countries encounter difficulties trying to conceive. In the United States, more than 7 million women have undergone fertility treatments and, as a result, millions of babies have been born through in-vitro fertilization.

While many may assume that failed fertility treatments would increase a woman’s risk of depression more than successful attempts that resulted in a live birth, research recently published in the journal ACTA Obstetricia et Gynecologica Scandinavica shows that the opposite may be true.

In the study, researchers from the University of Copenhagen analyzed data on 41,000 Danish women who had undergone fertility treatments. PsychCentral reports that “investigators discovered women who give birth after receiving fertility treatment are five times more likely to develop depression compared to women who don’t give birth.”

Lead author Camilla Sandal Sejbaek, PhD, discusses the results in the story:

The new results are surprising because we had assumed it was actually quite the opposite. However, our study clearly shows that women who become mothers following fertility treatment have an increased risk of developing depression in the first six weeks after birth compared to women who did not have a child.

Our study has not looked at why the depression occurs, but other studies indicate that it could be caused by hormonal changes or mental factors, but we cannot say for sure. We did not find any correlation between the number of fertility treatments and the subsequent risk of depression.

Previously: Stanford-developed fertility treatment deemed a “top medical breakthrough” of the year, Ask Stanford Med: Expert in reproductive medicine responds to questions on infertility, Image of the Week: Baby born after mom receives Stanford-developed fertility treatment and NIH study suggests progestin in infertility treatment for women with PCOS may be counterproductive
Photo by Big D2112

FDA, Media, Research, Science Policy, Sexual Health, Women's Health

“A historic moment for women”: FDA approves the first drug to treat hypoactive sexual desire disorder

"A historic moment for women": FDA approves the first drug to treat hypoactive sexual desire disorder

20705116491_5351758c67_zRoughly 16 million women over the age of 50 suffer from low sex drive. Yet, until recently, there were no FDA-approved medications to treat the lack of sexual thoughts and desire experienced by women with hypoactive sexual desire disorder (HSDD).

That’s why the U.S. Food and Drug Administration’s recent approval of the drug flibanserin (sold under the brand name Addyi™) to treat women with HSDD, is such big news.

“It’s a historic moment for women,” said Leah Millheiser, MD, director of Stanford’s Female Sexual Medicine Program, in a story published today in the San Francisco Chronicle. HSDD, Millheiser explains, is more than the occasional loss of sexual desire that can result from changes in hormones, stress and discontent in a relationship. “These are women who want to have sex with their partner, they’re attracted to their partner and used to love having sex,” Millheiser said. “It’s as if someone turned off the lightbulb.”

It’s tempting to equate flibanserin to Viagra (the drug approved to treat erectile disfunction in men), but this is clinically inaccurate. As explained in the article, Viagra treats erectile dysfunction by increasing blood flow to the penis, while flibanserin works on the brain.

From the story:

The drug [flibanserin] was first developed as an antidepressant. Like other antidepressants, it works on the brain’s serotonin levels, but researchers say it works on different serotonin receptors than other similar antidepressants.

It didn’t work to relieve depression, as it turned out, but patients reported increased sexual desire.

In clinical trials, researchers said 53 percent of women who took the drug reported an increased desire for sex and 29 percent said the drug decreased their level of distress over their condition. In the trials, the number of “satisfying sexual events” reported by participants essentially doubled from an average of 2.5 per month before they received flibanserin to five while taking it.

Millheiser credits Viagra for helping to pave the way for this new approved treatment for HSDD.  “As a result of Viagra, there was an explosion in research and understanding into what sexual dysfunction is and how we treat it,” she said. “It took 17 years to … get to this day,” she said.

Previously: When hormonal issues interfere with mental healthFemale sexual health expert responds to delay in approval for “Viagra for women and Speaking up about female sexual dysfunction
Photo by Day Donaldson

Neuroscience, Pediatrics, Research

Stanford team uses brain scans to forecast development of kids’ math skills

Stanford team uses brain scans to forecast development of kids' math skills

multiplication-table-2Back in the third grade, I did not like math. It was boring! It was hard! Why did I have to memorize the times tables, anyway?

Did this mean I would have trouble with math for the rest of my life, or would I get over my eight-year-old’s funk and end up being good at it? At the time, there was no way to know. But now, in a longitudinal study published today in The Journal of Neuroscience, a team of Stanford researchers show that scans of third graders’ brains forecast which children will eventually do well in math and which of them will continue to struggle.

The resting MRI scans collected in the study evaluated the brain’s structure and connectivity between different brain regions in 43 eight-year-olds of normal intelligence. The researchers also gave the children several standardized tests outside the scanner. They then re-tested the kids’ math skills regularly for the next six years.

The brain scans were better than standard IQ, math or other tests at predicting how the children’s math skills would develop. Larger volume and greater connectedness of specific brain regions at age eight was linked to better math skills down the road. From our press release:

“A long-term goal of this research is to identify children who might benefit most from targeted math intervention at an early age,” said senior author Vinod Menon, PhD, professor of psychiatry and behavioral sciences. “Mathematical skills are crucial in our increasingly technological society, and our new data show which brain features forecast future growth in math abilities.”

In addition to identifying at-risk kids, the scans may help scientists design better ways to help them. Because the new work gives a baseline understanding of brain features in children with normal math skills, it may help guide efforts to strengthen the brains of kids with math difficulties. The researchers, who are now exploring how math tutoring changes the brain, encourage parents and teachers not to give up on children who have a hard time with math:

“Just because a child is currently struggling doesn’t necessarily mean he or she will be a poor learner in the future,” said [Tanya] Evans, [PhD, first author of the new study].

As for me, math never became my favorite subject. But I did eventually shake my early aversion to it. Since my job requires me to understand a range of mathematical concepts, I’m grateful — and I hope the new work being done at Stanford will allow today’s struggling third-graders to someday say the same.

Previously: A not so fearful symmetry: Applying neuroscience findings to teaching math, Peering into the brain to predict kids’ responses to math tutoring and New research tracks “math anxiety” in the brain
Photo by jmawork

Microbiology, Pregnancy, Research, Stanford News

Stanford microbiome research offers new clues to the mystery of preterm birth

Stanford microbiome research offers new clues to the mystery of preterm birth

preemie-holdinghandsPremature birth affects 450,000 U.S. babies each year and is the leading cause of newborn deaths. But in about half of cases, doctors never figure out what triggered premature labor in the pregnant mom.

Now, there’s a new clue: A Stanford study, published today, gives important details of how the microbiome – the body’s community of bacteria – behaves in women whose pregnancies go to the full 40-week term, and what’s different in women whose babies come three weeks, or more, early. A specific pattern of vaginal bacteria was linked to greater risk of preterm delivery, and the longer the pattern persisted, the greater the risk, the study found.

The work is one piece of a larger effort by the March of Dimes Prematurity Research Center at Stanford to bring experts from many branches of science together to work on preterm birth. The researchers collected weekly bacterial samples throughout pregnancy from four body sites for 49 pregnant women, of whom 15 delivered prematurely. Patterns of vaginal bacteria that were dominated by lactobacillus bacteria were linked to low prematurity risk. Such patterns had already been shown to be linked to health in non-pregnant women.

A pattern of high bacterial diversity, low lactobacillus and high levels of gardnerella and ureaplasma bacteria was linked to higher prematurity risk, the study also showed. This was especially true if the high-diversity pattern persisted for several weeks. From our press release about the new research:

“I think our data suggest that if the microbiome plays a role in premature birth, it may be something that is long in the making,” said the study’s lead author, Daniel DiGiulio, MD, a research associate and clinical instructor in medicine. “It may be that an event in the first trimester or early second trimester, or even prior to pregnancy, starts the clock ticking.”

The researchers also followed the women’s bacterial communities for up to a year after their deliveries and found that all new mothers shifted to the high-risk pattern, regardless of if their babies were born early or on time or if they had a c-section or vaginal delivery. This finding may help explain why women with closely-spaced pregnancies are more likely to have a preterm baby the second time around, however more work is needed to better understand this discovery, concluded researchers.

Ultimately, the research team hopes to use their findings to develop interventions that could prevent preterm birth. That would definitely be good news for moms and babies.

Previously: Counseling parents of the earliest-born preemies: A mom and two physicians talk about the challenges, Stanford/VA study finds link between PTSD and premature birth and Maternal obesity linked to earliest premature births, says Stanford study
Photo by bradleyolin

Neuroscience, Research

Exploring the role of prion-like proteins in memory disorders

Exploring the role of prion-like proteins in memory disorders

Over on the Mind the Brain blog, Stanford psychiatrist Shaili Jain, MD, discusses disorders of memory, including post-traumatic stress disorder and Alzheimer’s, with Nobel Laureate Eric Kandel, MD.

Ongoing research conducted by Kandel has helped scientists better understand the basic molecular mechanisms underlying learning and memory. His latest study showed how prion-like proteins, which are similar to the prions behind bovine spongiform encephalopathy and Creutzfeld-Jakob disease, are key for maintaining long-term memories in mice – and likely other mammals.

In Jain’s conversation with Kandel, she asks him how these new findings may translate clinically and impact patients diagnosed with memory disorders. He responds:

We are already there in some areas. We have far to go in other areas, but I will give you an example. We have a pretty good understanding of Alzheimer’s disease. We know the toxicity of beta amyloid. We do not know why the drugs that are directed against beta amyloid do not work, but one possibility that is being seriously entertained is that by the time the patient comes to see a physician, they have had the disease for ten years. That is a very long time and you lose a lot of nerve cells in ten years, and drugs do not bring nerve cells back once they are dead.

We need to diagnose the disease earlier and a major effort now, in Alzheimer’s research, is early diagnosis. Imaging, cerebral spinal fluid, genetic warning signals etc.

The other thing is it has proven possible to define an independent disorder, age related memory loss. Recent work from our lab, and that of Scott Small, has shown there is a separate entity, independent of AD, called Age Related Memory Loss. We have identified the molecular pathways involved in that disorder. We have treatments that work very effectively in animals. I think the time is going to come soon when these will be tried in people.

All of these came out from a basic science and work with experimental animals. So even though we are in the very early stage of understanding the really complex functions of the brain, we are making progress and all of this will hopefully have some therapeutic impact.

Previously: Memory of everyday events may be compromised by sleep apnea, Malfunctioning glia – brain cells that aren’t nerve cells – may contribute big time to ALS and other neurological disorders and The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius

Behavioral Science, Mental Health, NIH, Public Health, Research

Developing certain skills may help you cultivate a positive outlook

34835574_9e61cfe6bb_zMany of us have heard that having a positive outlook on life can improve our mental and physical health. Yet, if you’re like me, you’ve noticed that it can be hard to focus on the bright side of things when you’re feeling anything but positive.

That’s why I was drawn to this article in the National Institutes of Health (NIH) newsletter. It discusses several NIH-funded studies on the topic and explains what it means to have a positive outlook and how a positive mood can affect your health. The really helpful information, from my perspective, is it also explains how developing certain skills, like meditation and self-reflection, can make you can feel more positive more often. From the NIH story:

Having a positive outlook doesn’t mean you never feel negative emotions, such as sadness or anger, says Dr. Barbara L. Fredrickson, a psychologist and expert on emotional wellness at the University of North Carolina, Chapel Hill. “All emotions—whether positive or negative—are adaptive in the right circumstances. The key seems to be finding a balance between the two,” she says.

The research teams used a variety of techniques to learn about the underlying mechanisms of positive and negative emotions and what it is that enables people to bounce back from difficult times.

Among those who appear more resilient and better able to hold on to positive emotions are people who’ve practiced various forms of meditation. In fact, growing evidence suggests that several techniques—including meditation, cognitive therapy (a type of psychotherapy), and self-reflection (thinking about the things you find important)—can help people develop the skills needed to make positive, healthful changes.

“Research points to the importance of certain kinds of training that can alter brain circuits in a way that will promote positive responses,” Davidson says. “It’s led us to conclude that well-being can be considered as a life skill. If you practice, you can actually get better at it.”

Previously: Navigating a rare genetic disorder with a positive attitudePromoting healthy eating and a positive body image on college campusesWhen life gives you lemons: Study suggests the benefits of a positive outlook are context dependent and The power of positive moods in improving cognitive function among older adults
Photo by: premasagar

Behavioral Science, Emergency Medicine, Health Disparities, Pain, Patient Care, Pediatrics, Research

Blacks, Hispanics and low-income kids with stomach aches treated differently in ERs

Blacks, Hispanics and low-income kids with stomach aches treated differently in ERs

crying-613389_1280When a child arrives in the emergency room complaining of a stomach pain, appendicitis is the last thing you want to miss, says KT Park, MD, assistant professor of pediatrics.

“The question is, ‘Does this patient have appendicitis – yes or no?,” he said. It is the most common immediate emergency that could bring a child into the emergency room with abdominal pain. If not treated in a timely manner, the appendix can burst, leading to infection or a host of other serious complications.

But kids arrive in the emergency room complaining of stomach aches all the time; most with perfectly healthy appendices. And what if you’re a doctor who has seen seven kids with more minor stomach problems one day? It might be tricky to spot that first case of appendicitis.

Unfortunately, misdiagnosis happens more often when the pediatric patient is black, Hispanic or low-income, according to a study published today in PLOS ONE led by Park and Stanford medical student Louise Wang.

“Our goal in this study is getting the word out about abdominal pain and appendicitis and the importance of the decisions made in the emergency room,” Wang said.

The researchers analyzed national data from 2 million pediatric visits to emergency rooms between 2004 and 2011 complaining primarily of abdominal pain. They found that blacks, Hispanics and low-income children were less likely to receive imaging that could help their physicians diagnose serious conditions like appendicitis. These patients were also less likely to be admitted to the hospital, but more likely to suffer perforated appendicitis, a clue that perhaps they didn’t receive adequate treatment in time, Park said. For example, low-income blacks were 65 percent more likely to have a perforated appendix compared to other children.

The study was not able to precisely determine why these disparities exist, Wang said. “What is the driving influence of these outcomes? Are these kids being mismanaged in the emergency department, or are they presenting at a later time in a more serious condition?,” she asked.

She and Park have a few ideas, based on other findings and their personal experience. Minorities and low-income families are more likely to use the emergency room as a first-stop for more minor conditions, rather than visiting their primary care doctor or pediatrician.

“This is a very delicate topic,” Park said. “Physicians are humans and there is potentially some intuitive thinking that goes on about the probabilities of various diagnoses more common in certain patient groups, potentially leading to differences in how clinicians perceive the acuity of a patient’s status.”

Appendicitis can be tricky to diagnose, a task made even harder when patients are young and unable to clearly describe their pain, Park said.

“The psychology of physicians is an area needing further evaluation,” Park said. “We have internal biases that we often are not even aware of. We want to be objective, but it’s never a black-and-white decision making tree.”

Previously: A young child, a falling cabinet, and a Life Flight rescue, New test could lead to increase of women diagnosed with heart attack and Exploring how the Affordable Care Act has affected number of young adults visiting the ER
Photo by amandacatherine

Cardiovascular Medicine, Genetics, Research, Stanford News

A cheaper, faster way to find genetic defects in heart patients

A cheaper, faster way to find genetic defects in heart patients

15907993264_87339bc83f_zIn most people, heart disease develops through a lifetime of cigarettes, trans fats or high glycemic foods. For only a minority of patients does the cause lie in their genes. But when such atypical patients show up for treatment, figuring out why their hearts aren’t working has been a huge challenge for their doctors. The process of deciding if a heart patient’s problem is genetic and, if so, which gene defects might be causing the problem can take weeks or months, cost a thousand dollars or more, and, at the end, leave physicians still scratching their heads over a mountain of uncertain data.

A new genetic test being developed by pathologist Kitchener Wilson, MD, PhD and cardiology and radiology professor Joseph Wu, MD, PhD, may be able to accurately pinpoint the likely genetic causes of a heart patient’s elusive condition in just a couple of days.

Wilson and Wu say that for a patient with a heart condition that’s difficult to diagnose, it makes no sense to sequence the entire 22,000-gene human genome. Such whole-genome sequencing is costly, time consuming, and produces data marred by small but important errors.

So, taking a more focused approach, Wilson and Wu’s team designed a streamlined assay, or test, that looks at just the 88 genes known to carry mutations that cause heart problems. Materials for the new assay cost about $100, and results are back within three days.

Their approach — surveying a small subgroup of relevant genes instead of the whole genome — is already used to look for other genetic diseases, such as cystic fibrosis. But cystic fibrosis results from mutations in a single gene. “The heart diseases are more challenging just because there are so many genes to sequence,” says Wilson.

Wilson and Wu’s assay is a variation on “complementary long padlock probes,” or cLPPs, a class of genetic probes developed at the Stanford Genome Technology Center. These simple probes accurately target specific parts of the genome and are easily customized to target genes of interest. Wilson and Wu spearheaded the effort to put cLPPs to work on genes connected with heart problems and reported their work in the journal Circulation Research, with Wu as senior author and Wilson as first author.

If further tests validate the assay, it could shorten the time it takes to diagnose difficult or unusual heart disease cases—like that of basketball player Hank Gathers above — hastening appropriate treatment for atypical cardiac patients.

Previously: At Stanford Cardiovascular Institute’s annual retreat, a glimpse into the future of cardiovascular medicine and Coming soon: A genome test that costs less than a new pair of shoes
Photo by: Liviu Ghemaru

Big data, Cardiovascular Medicine, Chronic Disease, In the News, Research, Stanford News

Using “big data” to improve patient care: Researchers explore a-fib treatments

Using "big data" to improve patient care: Researchers explore a-fib treatments

Turakhia photoA Stanford cardiac electrophysiologist and colleagues have used a unique research method to learn more about atrial fibrillation. Mintu Turakhia, MD, and collaborators at Medtronic and Massachusetts General Hospital, extracted data out of decades of continuously recorded medical information from implanted medical devices – pacemakers and defibrillators — in 10,000 heart patients. Then they linked it to medical records, and analyzed it.

The researchers’ goal was to explore whether patients who experienced sudden attacks of a-fib, an irregular and rapid heart rate caused by spasms of the heart’s upper chambers, should be treated with long-term anticoagulants like those who had permanent a-fib or whether perhaps temporary drug therapy could be considered an option. They wanted to know if a patient’s risk of stroke changes as a-fib comes and goes.

The results, which were published recently in Circulation: Arrhythmia and Electrophysiology, found that patients were at an increased risk of stroke the first seven days after their hearts went into a-fib.

A-fib, which afflicts more than 3 million Americans, is known to increase a patient’s risk of stroke – but exactly when this risk occurs is controversial. Currently, physicians recommend long-term anticoagulation for patients, whether the a-fib occurs in sudden attacks or is continuous. This study indicates that transient use of anticoagulants could be an option for some patients and deserves further investigation. Future treatment plans might explore the idea of some kind of wearable device that shows when a patient goes in and out of a-fib, then taking medications just when needed rather than for a lifetime, said Turakhia.

Turakhia told me the study also provides an important example of how using “big data” research methods can ultimately lead to improved clinical care. In an email, he explained:

This is truly a big data approach where we took raw data from implanted pacemakers and implanted defibrillators and linked it to clinical data. The medical device data comes from home remote monitoring systems that patients have and goes to the cloud. We pulled the raw data off the cloud and linked it to VA (Veterans Affairs) electronic health records, VA claims, Medicare claims, and death records. This is truly a novel approach where we are assembling highly disparate data sources and linking them to gain insight into disease.

Previously: A little help from pharmacists helps a-fib patients adhere to prescriptions, Study highlights increased risk of death among patients with atrial fibrillation who take digoxin and What is big data?
Photo of Turakhia by Norbert von der Groeben

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