Research

Among school-aged children in the United States an estimated one in 50 has been diagnosed with autism spectrum disorder, according to a recent survey (.pdf) from the Centers for Disease Control and Prevention. In addition to raising concerns among researchers and parents about why the number of cases has increased, the findings underscored the need to do more autism research and to provide support and services for families caring for autistic children.

To help parents and others in the local community better understand the growing prevalence of autism and to learn about treatments and research advancements, the Stanford Autism Center at Packard Children’s Hospital will host its sixth annual Autism Spectrum Disorders Update on June 1. The event offers an opportunity for exchange between parents, caregivers and physicians and provides an overview of the center’s clinical services and ongoing autism research at the School of Medicine.

In anticipation of the day-long symposium, we’ve asked Carl Feinstein, MD, director of the center, to respond to your questions about issues related to autism spectrum disorder and to highlight how research is transforming therapies for the condition.

At the Stanford Autism Center, Feinstein works with a multidisciplinary team to develop treatments and strategies for autism spectrum disorders. In providing care and support for individuals with autism and their families, Feinstein and colleagues identify ways of targeting the primary autism symptoms, while also paying attention to associated behavior problems that may hold a child back from school or community involvement or seriously disrupt family life.

Questions can be submitted to Feinstein by either sending a tweet that includes the hashtag #AskSUMed or posting your question in the comments section below. We’ll collect questions until Wednesday (May 15) at 5 PM Pacific Time.

When submitting questions, please abide by the following ground rules:

• Stay on topic
• Be respectful to the person answering your questions
• Be respectful to one another in submitting questions
• Do not monopolize the conversation or post the same question repeatedly
• Kindly ignore disrespectful or off topic comments
• Know that Twitter handles and/or names may be used in the responses

Feinstein will respond to a selection of the questions submitted, but not all of them, in a future entry on Scope.

Finally – and you may have already guessed this – an answer to any question submitted as part of this feature is meant to offer medical information, not medical advice. These answers are not a basis for any action or inaction, and they’re also not meant to replace the evaluation and determination of your doctor, who will address your specific medical needs and can make a diagnosis and give you the appropriate care.

Previously: New public brain-scan database opens autism research frontiers, New autism treatment shows promising results in pilot study, Autism’s effect on family income, Study shows gene mutation in brain cell channel may cause autism-like syndrome, New imaging analysis reveals distinct features of the autistic brain and Research on autism is moving in the right direction
Photo by Wellcome Images

Does it make a difference if a gene – or group of genes – is inherited from your mother or your father?

That’s the question behind the study of genomic imprinting, a phenomenon in which a small percent of genes are thought to be expressed differently depending on which parent they came from. In particular, animal research suggests imprinting may affect aspects of brain development. Researchers wonder if genomic imprinting might explain differences in brain anatomy seen between men and women, such as men’s larger brain volumes.

A new Stanford study, published today in the Journal of Neuroscience, adds to evidence that genomic imprinting is, in fact, happening in humans’ brains. The finding comes from MRI brain scans performed on a group of young girls with Turner syndrome, a chromosomal disorder in which a girl or woman has one missing or malfunctioning X chromosome. Turner syndrome gives an unusual opportunity to study genetic imprinting, because it allows comparisons of individuals who received a single X from Mom to those who got a single X from Dad. (The typical two-X-chromosome female body expresses a mosaic of Mom’s X and Dad’s X, making it impossible to tease apart the effects of the two parents. Males invariably get their single X chromosome from their mothers, so their cells always express the maternal X.)

The Stanford team, led by Allan Reiss, MD, documented several distinctions between the brains of Turner syndrome girls who have only a maternal X, those with only a paternal X, and typical girls with two X chromosomes, such as differences in the thickness and volume of the cortex, and in the surface area of the brain. The work helps clarify murky results from earlier studies of adults with Turner syndrome, the researchers say, because many adult women with Turner syndrome take estrogen supplements, which may have their own effects on brain development. None of the girls in the new study had taken estrogen.

The most tantalizing part of the paper is the scientists’ comment on the implications of their work for our general understanding of genetic imprinting. In part, they say:

By far, the most consistent finding with regard to sex differences in brain anatomy is the larger brain volume found in males compared with females. Although our groups did not differ on most whole-brain measures, our analyses revealed the existence of significant trends on total brain volume, gray matter volume and surface area, where these variables increased linearly from the Xp [paternal X] group being smallest, to the Xm [maternal X] group being largest, with typically developing girls in between. Considering that typically developing males invariably inherit the maternal X chromosome, while typically developing females inherit both and randomly express one of them in each cell, a linear increase in brain volume as seen in the present study is in agreement with what would be expected if imprinted genes located on the X chromosome were involved in brain size determination.

In other words, men may have their mothers to thank for their larger brains.

Karyotype image from a Turner Syndrome patient by S Suttur M, R Mysore S, Krishnamurthy B, B Nallur R - Indian J Hum Genet (2009).

Here’s a developing social media story of interest to scientists, clinicians and the general public. National Institutes of Health Director Francis Collins, MD, PhD, kicked a hornets’ nest on Twitter earlier today with a tweet asking researchers to describe the direct impact of the U.S. budget sequestration, which began in March, on their research and lives. He asked respondents to use the hashtag #NIHSequesterImpact. The responses (some of which I’ve included below) are fascinating and depressing:

“I am no longer encouraging undergraduates to consider graduate school. No future in it.”

“The NIH training grant I’m on was canceled”

“Watching top notch science go unfunded; bright, young investigators forced to close labs, it’s heartbreaking.”

“I know a lot of very smart USA young researchers that are seriously considering China”

“Nothing will impact treating patients more in the long term than poorly funded basic science. Nothing“

Check it out if you’d like to hear a real-time conversation about what it’s like to be a researcher today, and join in if you have anecdotes to share.

Previously: As budget sequester nears, a call for Congress to protect funding for scientific and medical research, Director of NIH discusses accelerating translation of biomedical research into clinical applications and Francis Collins profiled in New Yorker

Not long ago, Stanford computer scientist Debashis Sahoo, PhD, told investigators at the Stanford Institute for Stem Cell Biology and Regenerative Medicine that in a few seconds he could find many of the important stem cell genes that the researchers were used to finding only after spending millions of dollars and years in the lab. “We laughed and said, ‘That’s impossible,’” recalls Irving Weissman, MD, director of the institute, in a recent video. But Weissman went ahead and gave Sahoo information about two key genes - and within a few seconds, Sahoo had used his desktop computer to scour the world’s public gene databases, analyzed that information with the computer algorithm he had designed, and come up with over a dozen genes new genes that were involved in the development of certain kinds of cells. That search, Weissman estimates, saved his team a decade of work and about $2.5 million.

More details are shared in the video above. And as a reminder, big data - and the ways in which people like Sahoo are mining through vast amounts of publicly available information to further research and advance health care - is the focus of a Stanford/Oxford conference being held here later this month.

Previously: Atul Butte discusses why big data is a big deal in biomedicine and Mathematical technique used to identify bladder cancer marker

Having a relative with type-1 diabetes makes you 15 times as likely as other people to get the disease, in which the body inappropriately destroys insulin-producing cells in the pancreas. But unlike the more common form of diabetes, type-2 diabetes, physicians don’t know how to prevent type 1 diabetes from developing in at-risk individuals.

To find out, they’re studying family members of type-1 diabetes patients. The large, multi-center research effort, called Type-1 Diabetes TrialNet, screens these folks for the presence of antibodies that recognize “self” tissues and could act as markers of diabetes vulnerability, and invites individuals who have the autoantibodies to take part in diabetes-prevention research. Stanford and Lucile Packard Children’s Hospital are among the 18 clinical centers participating in TrialNet research.

The big news at TrialNet is that, starting today, the first part of the screening process is moving online. Volunteers used to have to participate in a screening event or come to a trial center to be screened, but many people live far from these centers. At the TrialNet screening website, people can now answer a short set of questions to find out if they’re eligible for TrialNet’s research and give consent to participate in screening. After the online questions are complete, eligible volunteers will receive a kit in the mail that they can take to a local lab for a free screening blood test.

Researchers hope this online process will make it easier for more people to participate in type 1 diabetes research. TrialNet must screen more than 20,000 relatives of people with type 1 diabetes each year to reach its scientific goals, according to an National Institutes of Health press release about the new online screening.

Previously: Beta cell development explored by Stanford researchers, Researchers struggle to explain rise of Type 1 diabetes and A patient perspective on social media

In an unusual collaboration, officials from the health-care and nuclear industries met last July to discuss each field’s similarities and differences between four topic areas, including diagnostic and prognostic technologies and human factors that affect risk and reliability. The Association for the Advancement of Medical Instrumentation recently released a 120-page monograph detailing the lessons learned during the tw0-day workshop.

Today’s issue of Inside Stanford Medicine includes a Q&A with David Gaba, MD, professor of anesthesia and the associate dean for immersive and simulation-based learning at the School of Medicine, discussing his participation in last year’s meeting and what health-care providers can learn from the nuclear industry. He says:

One big one is the need for standard operating procedures, where possible, which also retain flexibility as needed. A major spinoff of this principle, used extensively in nuclear power, is to provide graphically enhanced written protocols for emergency situations. It is long recognized that nuclear power operators cannot remember everything they need to know in managing an adverse event in a nuclear plant — memory is too fallible. Thus, the use of written procedures is a mainstay in this setting. Health care has long depended largely on the individual skill and memory of physicians and nurses. Protocols and checklists or emergency manuals were decried as cheat sheets or cribs. We now know that the best people use these kinds of supports — not because they are stupid but because that is the best way to get the best results in tough situations. My lab and other colleagues at Stanford have been working for some time on written cognitive aids and emergency manuals for anesthesia professionals. These have now been disseminated to all the anesthetizing locations in Stanford’s hospitals and those of its close affiliates. This lesson has clearly come from the nuclear industry and from others such as aviation.

Another lesson from the nuclear industry is the importance of the safety culture in an organization. When the organization favors throughput so heavily that people cut corners on safety, or when personnel are afraid to speak up when they see something unsafe, the risk climbs.

Something near and dear to my heart is the utility of simulation for training of skilled professionals. My lab’s development of simulators and simulation-based curricula in health care was triggered by knowing a little bit about how they are used in aviation and other industries like nuclear power. But I actually had no idea, until this workshop, just how much simulation is required for nuclear power operators. They spend six weeks doing their usual shifts in the control room, and the seventh week is spent in training simulations. All year round, no matter how much prior experience they have. Health care is just scratching the surface in simulation compared to that, but at least we have started our way down a similar road.

Previously: Sully Sullenberger talks about patient safety

We always want what we don’t have. My teenage daughter is tall and beautiful (in my naturally biased and loving view). But she’s always complaining about her thighs. She thinks they’re too big and don’t look good in skinny jeans. What I see is a young girl with a fresh face, beautiful curves and a youthful spring of energy.

As a molecular epidemiologist, I see one more thing. She has a so-called “pear-shaped” body, which means she has larger thighs relative to a smaller waist, with most of her fat deposited in the lower body. In contrast, people who have “apple-shaped” bodies are heavier in the middle and have their body fat accumulated around the waist, closer to the heart, putting them at a higher risk for abdominal obesity. Many studies have shown that abdominal obesity has a more detrimental effect than overall obesity (as measured by body mass index, the metric calculated using height and weight) on a number of diseases, including type II diabetes, cardiovascular disease and certain cancers (such as those of the breast, ovary, gallbladder and kidney). The specific biological mechanisms are not entirely clear, but we do know from recent research that fat (adipose tissue) is an endocrine organ that actively secretes a variety of chemicals, such leptin, adiponectin, estrogen and other hormones, and inflammatory cytokines. These markers have been linked to growth and proliferation of cancer cells.

The Stanford Cancer Institute and its affiliated research partner, the Cancer Prevention Institute of California (CPIC), currently are conducting studies to understand more clearly the molecular mechanisms underlying the adverse effects of abdominal obesity on cancers. A better understanding of how leptin and inflammatory markers associated with abdominal obesity can influence cancer risk at the molecular level will help clarify the specific steps involved in carcinogenesis, which in turn can aid the development of effective preventive strategies to stop or slow down cancer development.

Our genetic makeup determines largely which body type we are born with, pear or apple. But our eating habits, physical activity and weight management can also affect fat distribution and disease susceptibility. Regular exercise (three times a week) helps increase muscle mass, which in turn can enhance metabolism and lower the risk of metabolism-related conditions, including certain cancers. Whether cancer prevention and weight reduction guidelines differ for those with different body types is another important topic for future studies.

My daughter is the apple of my eye. But I’m glad that, unlike me, she’s a pear. She inherited her father’s body type. In theory, her risk of certain hormone-related cancers or metabolic disorders is lower than mine. So next time she complains about her thighs, I’ll share with her my recent work on abdominal obesity and cancer and try to convince her that she’s lucky to have “big” thighs.

Ann Hsing, PhD, MPH, is director of research for the Cancer Prevention Institute of California (CPIC). Part of the Stanford Cancer Institute, the CPIC conducts population-based research to prevent cancer and reduce its burden where it cannot yet be prevented.

Photo by KDL Designs

In a novel combination of biochemical experimentation and data mining, Stanford researchers and postdoctoral scholars Cigall Kadoch, PhD, and Diana Hargreaves, PhD, have identified a large protein complex that appears to be significantly involved in cancer development in humans.

The multisubunit is a member of a family of chromatin-regulatory complexes that keep DNA tightly packed in a cell’s nucleus. Originally thought of as a kind of housekeeping, or maintenance, protein in the cell, it’s now becoming apparent that these complexes are really important in development and cancer.

Kadoch, working in the laboratory of developmental biologist Gerald Crabtree, MD, used biochemical techniques to identify seven previously unidentified members of the complex, which is called BAF (or mSWI/SNF). She and Hargreaves then analyzed 44 pre-existing studies that detailed the DNA sequences of primary human tumors of all types. They calculated the likelihood that any protein component of the large group was mutated. (The approach varies from others that analyze the mutation rates of individual proteins.)

As described in our release:

The results, once the newly discovered members were included, were surprising: 19.6 percent of all human tumors displayed a mutation in at least one of the complex’s subunits. In addition, for some types of cancers (such as synovial sarcoma), every individual tumor sample examined had a mutation in a BAF subunit. The results suggest that the BAF complex, when unmutated, plays an important protective role against the development of cancer in many different tissues.

Crabtree, who is also a Howard Hughes Medical Institute investigator, described his lab’s long-standing interest in BAF and other similar protein complexes:

Somehow these chromatin-regulatory complexes manage to compress nearly two yards of DNA into a nucleus about one one-thousandth the size of a pinhead. And they do this without compromising the ability of the DNA to be replicated and selectively expressed in different tissues - all without tangling. In 1994 we reported that complexes of this type were likely to be tumor suppressors. Here we show that they are mutated in nearly 20 percent of all human malignancies thus far examined.

The work was published yesterday in Nature Genetics. The researchers are now working to understand exactly how the mutations they’ve observed affect the function of the BAF complex.

Previously: Dumb, dumber and dumbest? Stanford biologist suggests humans on a downward slide and New clues arise in pancreatic cancer from Stanford researchers
Photo of (left to right) Cigall Kadoch, Gerald Crabtree and Diana Hargreaves, by Nathaniel Hathaway

Daily text messages may be an effective option to help children with asthma manage their symptoms and reduce doctor visits, according to recent research from the Georgia Institute of Technology.

In the study (.pdf), pediatric patients with asthma were randomly assigned to three programs: one group received text messages on alternate days, another received text messages daily and a third served as the control and did not receive any text messages. Participants ranged in age from 10 to 17 years old, owned a mobile phone and could read at the fifth grade level. The text messages asked patients questions about their symptoms and provided health information about asthma. Futurity reports:

Over four months, the intervention groups received and responded to SMS messages 87 percent of the time, and the average response time was within 22 minutes. After the study, the research team analyzed patients who had follow-up visits with their physician and found that sending at least one text message a day, whether it was a question about symptoms or about asthma in general, improved clinical outcomes.

“The results indicate that both awareness and knowledge are crucial to individuals engaging in proactive behavior to improve their condition,” [said Rosa Arriaga, PhD, who led the study].

The findings are noteworthy in light of past data showing texting is teenagers’ preferred method of communication, they get an average of 3,339 texts a month, and previous research showing they are amenable to receiving health information via text message.

Previously: CDC explores potential of using smartphones to collect public health data, Promoting healthy decisions among teens via text and Craving a cigarette but trying to quit? A supportive text message might help
Photo by Summer Skyes 11

Past research suggests that poor sleep during adolescence can have “lasting consequences” on the brain. Now a new study offers additional insights into the negative health effects of sleep deprivation on teens’ health.

In the study, researchers analyzed data collected from more than 10,000 adolescents as part of the National Comorbidity Survey Adolescent Supplement. As MedPage Today reports, their findings show that prolonged fatigue is associated with mood and anxiety disorders among teens:

In a nationally representative sample of adolescents ages 13 to 18, 3% reported having extreme fatigue lasting at least 3 months and about half of those who did also had mood or anxiety disorders, according to Kathleen Merikangas, PhD, of the National Institute of Mental Health in Bethesda, Md., and colleagues.

Having both prolonged fatigue and a mood or anxiety disorder was associated with poorer physical and mental health and greater use of healthcare services compared with having only one of the disorders, the researchers reported online in the American Journal of Psychiatry.

“This suggests that the presence of fatigue may be used in clinical practice as an indicator of a more severe depressive or anxiety disorder,” Merikangas and colleagues wrote.

Stanford physician Michelle Primeau, MD, recently explored the topic of how teen sleep habits affect mood in a recent Stanford Center for Sleep Sciences and Medicine blog entry on the Huffington Post. In her post, she explains why teens in particular are at risk of chronic partial sleep deprivation:

Teenagers need to sleep about nine hours, and as they get older, they tend to sleep less. This is not because they need less, but because they are busier with school, jobs, extracurricular activities, and friends. Their biology also will often shift so that they tend to fall asleep later and want to sleep in later, an occurrence that may represent delayed sleep phase syndrome. This may explains why your teenager is so hard to wake up on Saturdays. But this shift to a later bedtime, both of social and biologic causes, in combination with fixed early school times, means that many teenagers are walking around sleep deprived.

Previously: Can sleep help prevent sports injuries in teens?, Study shows link between lack of sleep and obesity in teen boys, Study shows lack of sleep during adolescence may have “lasting consequences” on the brain, Teens and sleep: A Q&A, Sleep deprivation may increase young adults’ risk of mental distress, obesity, Districts pushing back bells for the sake of teens’ sleep and Lack of sleep may be harmful to a teen’s well-being
Photo by lunchtimemama