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Genetics, In the News, Research, Science, Stanford News, Technology

Policing the editor: Stanford scientists devise way to monitor CRISPR effectiveness

Policing the editor: Stanford scientists devise way to monitor CRISPR effectiveness

edited paperAs a writer, I think a lot about editing. Will this sentence work here? Maybe I should change this word. Argh – a typo! But I’m not alone. Biologists also appreciate the power of editing, particularly when it comes to modifying genes in cells or organisms.

Recently a powerful new technology has emerged (called CRISPR) that allows researchers to make small, precise and permanent changes in the DNA of animal and human cells. It builds on the concept of genome editing that is key to generating cells, cell lines or even whole animals such as laboratory mice, containing specific genetic changes for study. With CRISPR, however, researchers can generate in days or weeks experimental models that usually take months or years. As a result, they can quickly assess the effect of a particular gene by deleting it entirely, or experiment with repeated, tiny changes to its DNA sequence.

According to a recent New York Times article, scientists roundly agree that CRISPR is revolutionary. At least three companies have been launched in the mere 18 months since the first results were reported by researchers at the University of California, Berkeley and Umea University in Sweden, and more than 100 research papers based on the technique have been published. But, although it’s highly specific, it’s (sadly) not perfect. According to the New York Times piece:

Quick is not always accurate, however. While Crispr is generally precise, it can have off-target effects, cutting DNA at places where the sequence is similar but not identical to that of the guide RNA.

Obviously it’s important to know when (and how frequently) this happens. Unfortunately, that’s been difficult to assess.

Enter researchers in the laboratory of pediatric cancer biologist Matthew Porteus, MD, PhD. Porteus’s lab is interested in (among other things) learning how to a particular type of genome editing called homologous recombination to treat diseases like sickle cell anemia, thalassemia, hemophilia and HIV. They’ve devised a way to monitor the efficiency of genome editing by CRISPR (as well as other more-traditional genome editing technologies) that could be widely helpful to researchers worldwide. Their technique was published today in Cell Reports. As postdoctoral researcher Ayal Hendel, PhD, told me:

We have developed a novel method for quantifying individual genome editing outcomes at any site of interest using single-molecule real-time (also known as SMRT) DNA sequencing. This approach works regardless of the editing technique used, and in any type of cell from any species.

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Health and Fitness, In the News, Obesity, Public Health

In Boston, doctor’s orders may include discounted bike-share memberships

Some Boston docs are delivering a dose of preventive care the old-fashioned way. Encouraging physical exercise under the city’s new “Prescribe-a-Bike” program, physicians at Boston Medical Center can refer low-income patients to a $5 bike-share membership, complete with helmet.

Common Health reports:

“Obesity is a significant and growing health concern for our city, particularly among low-income Boston residents,” BMC President and CEO Kate Walsh said in a statement. “Regular exercise is key to combating this trend, and Prescribe-a-Bike is one important way our caregivers can help patients get the exercise they need to be healthy.”

Previously: A bike helmet that doubles as a stress-o-meter and Modest increases in bike ridership could yield major economic, health benefits

Cardiovascular Medicine, In the News, Stanford News, Surgery

Looking at aortic valve replacement without open-heart surgery

SM heart imageSome patients with aortic stenosis undergo open-heart surgery to replace a constricted heart valve in an attempt to stave off heart failure. But others, such as elderly adults, aren’t candidates for this type of surgery. In 2011, the FDA approved a non-surgical alternative procedure called TAVR, or transcatheter aortic valve replacement, but the new method, as discussed in the New York Times earlier this month, also carries certain risks.

In the current issue of Stanford Medicine magazine, my colleague Tracie White digs into the surgery-or-TAVR debate and follows the story of one aortic stenosis patient who was treated by the newer method. Maryann Casey, at 62, is younger and healthier than the average TAVR candidate, but she had faced an increased risk for complications during open-heart surgery because of radiation treatment for breast cancer decades ago.

From the magazine piece:

Casey was lucky. Her Stanford oncologist, Frank Stockdale, MD, PhD, the Maureen Lyles D’Amrogio Professor of Medicine Emeritus, was well-informed about treatment options for aortic stenosis, a calcification of the heart valve. This new nonsurgical approach to valve replacement involves placing an artificial heart valve, made of cow tissue supported by a stainless steel mesh frame, inside the damaged valve. Referred to as “transcatheter aortic valve replacement” or TAVR, the procedure is designed for patients with severe, symptomatic aortic stenosis who have health conditions that make the preferred treatment, open-heart surgery, very high risk.

On Oct. 16, 2012, Casey became one of the more than 120 patients that year at Stanford to undergo the TAVR procedure. The first catheter-based aortic valve transplant was in 2002 in France. It has been approved for use for the past six years in 40 other countries including most of Europe, with a total of 45,000 procedures conducted worldwide.

In the United States, institutions such as Stanford, the Cleveland Clinic, Columbia University and the University of Pennsylvania have been leaders in introducing the new procedure and determining its effectiveness through the clinical trials.

Careful patient selection is key to the successful use of the procedure, says [D. Craig Miller, MD, the Doelger Professor of Cardiovascular Surgery], and that sometimes means not recommending TAVR for a patient who is too old or too sick with other illnesses to benefit from the device.

“That’s a very sobering point,” says surgeon Miller. For patients who are too old or ill, undergoing the procedure may not increase their quality of life or life expectancy; Miller says that the boundary line between TAVR “utility and futility” is still being defined.

Previously: Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questionsAsk Stanford Med: Answers to your questions about heart health and cardiovascular research and Major advancement for once inoperable ailing heart valves
Art, which originally appeared in Stanford Medicine, by Pixologicstudio

Autism, In the News, Pediatrics, Research, Stanford News

Inspired by his autistic son, a Stanford researcher works to understand the biochemistry of autism

Inspired by his autistic son, a Stanford researcher works to understand the biochemistry of autism

dolmetschIn a Q&A published today in the New York Times, Stanford neurobiologist Ricardo Dolmetsch, PhD, tells reporter Claudia Dreifus that his immediate reaction to learning his son was diagnosed with autism was, “We’re not going to leave any stone unturned to help him.”

Leaving no stone unturned included changing the focus of his research to better understand the biochemistry of autism and leading an effort to create a technique that involves reprogramming skin cells from autistic children into neurons. As reported previously on Scope, this approach allows scientists to better study brain function in children with autism.

Dolmetsch, who is currently on leave from Stanford and working at Novartis, tells Dreifus that his main goal is to develop new pharmaceutical therapies for autism. When she asked him how he identifies patients to participate in his research, he responded:

Through social media. We’re often interested in groups or families who have specific kinds of mutations. Some of them are rare — 5,000 people worldwide.

So we have a committee that decides what’s the next mutation we’re going to work on. Then we find children with it. It used to be we’d spend half of our budget locating people. Now, we go to the families with a Facebook page for people with X, Y, or Z mutation. Then I’ll post a call. Parents will come forward.

The aim is to develop a database of the mutations we think are causative of the neuropsychiatric diseases. If we can get samples through stem-cell-derived neurons and create a library of them, we could change the way the diseases are diagnosed.

Previously: Using stem cells to advance autism research, Stanford Magazine spotlights scientists’ efforts to untangle the root causes of autism and Research on autism is moving in the right direction
Photo by Steve Fisch

Health and Fitness, In the News, Orthopedics, Stanford News

Watching your phone or tablet while working out may diminish form

Watching your phone or tablet while working out may diminish form

skeletonSnow White’s dwarves whistled while they worked. With the advent of the Walkman, runners could listen to music as they ran. Now, some people watch TV or movies on a mobile device while they hit the gym. Though all make a demanding physical task more entertaining, looking down at your smartphone in text-head position could harm your skeletal alignment, as Michael Fredericson, MD, professor of sports medicine at Stanford and team physician for several of the school’s sports teams, recently told the San Francisco Chronicle.

From the article:

Although [Frederickson's] in favor of anything that gets people to exercise more, he warns that running while you look down at a screen is poor form, and the distraction prevents you from focusing on your body.

“When you lean forward, you create an arch and hyperextension in your neck,” he says. “You may get a good cardio workout, but when you get off, you’ll be stiff in your upper body.”

Listening to music while you exercise might be a better option. Unlike TV or streaming video, many studies show that music can benefit a workout by distracting people from fatigue and elevating mood.

Fredericson said he even encourages people in his community running clinic to align their running cadence with songs that have 90 beats per minute. But he adds that the most serious runners, like those he works with on the Stanford track team, don’t train with media distractions. “They’re very focused on their bodies and the experience,” he said. “They have a goal in mind for every workout.”

Previously: Walking-and-texting impairs posture – and walking, and texting
Photo by Jim, the Photographer

In the News, Neuroscience, otolaryngology

Say that again? Tone deafness is inherited, study finds

Say that again? Tone deafness is inherited, study finds

singing2Can’t carry a tune? Don’t spend all your money on music lessons: Turns out tone deafness is an inherited non-talent.

Leonard Bernstein (no, not that one) writes in The Checkup:

Finnish researchers say they have found genes responsible for auditory response and neuro-cognitive processing that partially explain musical aptitude. They note “several genes mostly related to the auditory pathway, not only specifically to inner ear function, but also to neurocognitive processes.”

“Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested,” the researchers note in the study. Using a genome-wide scan, researchers evaluated 767 individuals “for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception.” The study was published in Molecular Psychiatry.

Previously: Music that comes straight from the soul…er, DNA
Photo by Kathleen Tyler Conklin

In the News, Sleep, Technology

Exploring the benefit of sleep apps

Exploring the benefit of sleep apps

man sleeping in bedCan sleep-related apps be of benefit to the bleary-eyed masses? That’s the question explored today by the New York Times’ Molly Young, who sought the advice of one of our sleep experts for her story:

Browse the iTunes store or Google Play and you’ll find them by the dozen: offerings with names like SleepBot and eSleep, represented by icons of placid sheep or glowing moons. The offerings fall into two basic categories. One tracks sleep patterns through the smartphone’s accelerometer (the doodad that recognizes when your phone is upside-down), giving users a blueprint of their time in bed. The second promises to lull users to sleep with music, hypnosis or guided meditation.

If you’re the data-driven type, a sleep-tracking app surely appeals. By placing the phone next to you in bed and tapping a button, you record your movements and a sleep chart is created. But according to Dr. Clete Kushida, the medical director of the Stanford Sleep Medicine Center, these apps are hardly precise.

“Without EEG — brain wave activity — it’s very hard to tell different stages of sleep apart,” Dr. Kushida said. “People can stay still and the device will think the person’s asleep.” Still, “the advantage of these devices is that they can help individuals become more aware of a potential sleep problem,” Dr. Kushida said.

Previously: Why physicians should consider patients’ privacy before recommending health, fitness apps, A look at the “Wild West” of medical apps, Designing the next generation of sleep devices, Exploring the effect of sleep loss on health, Turning to an app to help your health and Stanford sleep expert offers evaluation of science behind one sleep device
Photo by dearoot

In the News, Public Health, Research, Stanford News

When caffeine dependence affects quality of life

When caffeine dependence affects quality of life

coffee3Caffeine use disorder: It’s a thing. Maybe you follow your nose to a $5 cup of artisan coffee or perform a morning home-brew ritual and drink in moderation. Even if your fix comes from a six-pack of Nescafé 3in1, your habit wouldn’t necessarily be considered a medical issue. An article in today’s San Francisco Chronicle discusses what constitutes caffeine use disorder, its estimated rate of occurrence, and the comparatively small amount of research that’s been published on it compared with data on the potential health benefits and risks of the drug.

Among the common side effects associated with caffeine misuse – not necessarily caffeine use disorder – are headaches. Erin Allday writes:

“We’re not talking about cancer here. It’s a quality-of-life issue,” said [Robert Cowan, MD,] director of the Stanford Headache Program.

When he sees patients with chronic headaches, one of the first questions he asks is how much caffeine they consume. The caffeine doesn’t necessarily cause the headaches, but the withdrawal can, and even going a few hours without a cup of coffee can cause some people intense pain.

The piece notes some warning signs that caffeine use could be approaching addiction:

“There are people who have chronic reflux, stomach acid pain, bleeding, hemorrhoids – all because of coffee. They’re suffering a lot,” said Keith Humphreys, [PhD,] a Stanford addiction expert. “But they try and they fail to stop.”

Those people may be addicted to caffeine, he said. But he’s loath to apply that label to most people who regularly use caffeine, even those who are physically dependent on it. For something to be considered an addiction, it needs to truly disruptive – causing problems in personal relationships, for example, or interfering with the ability to work.

Previously: Director of Stanford Headache Clinic answers your questions on migraines and headache disordersAsk Stanford Med: Answers to your questions about heart health and cardiovascular research and For new moms, coffee scores a point: Caffeine doesn’t seem to interfere with baby’s sleep in study
Photo by ibeeckmans

Complementary Medicine, In the News, Mental Health, Pediatrics, Stanford News, Videos

Stanford researchers use yoga to help underserved youth manage stress and gain focus

Stanford researchers use yoga to help underserved youth manage stress and gain focus

A segment on PBS NewsHour yesterday explored how Stanford researchers have brought yoga and mindfulness practices to students who experience post-traumatic stress disorder owing to difficult life circumstances. At Cesar Chavez Academy in East Palo Alto, Calif. – a low-income, high-crime area – a group of seventh-graders worked with Stanford’s Victor Carrion, MD, professor of psychiatry and behavioral sciences, and his team during a 10-week program introducing breathing and movement practices to help students manage their emotions and improve their concentration in school.

The researchers used imaging techniques to understand how children respond to daily stress. “With functional imaging, we actually can see what the brain is doing,” Carrion told PBS. “There is a deficit in the area of the middle frontal cortex in kids that have PTSD,” which, he noted, may discourage learning.

In the piece, seventh-grader Brayan Solorio describes how rolling out his yoga mat at home helps him keep his cool.

Previously: Med students awarded Schweitzer Fellowships lead health-care programs for underserved youthThe remarkable impact of yoga breathing for trauma, The promise of yoga-based treatments to help veterans with PTSD and Stanford and other medical schools to increase training and research for PTSD, combat injuries

In the News, Parenting, Pediatrics, Sleep

Study: Baby sound machines may be too loud for little ears

Study: Baby sound machines may be too loud for little ears

DSC_0293Sound machines that help babies sleep more soundly are a staple on many new parents’  baby registries (I had a little sheep that mimicked the sounds of rainfall and ocean waves). Well, as you may have read about elsewhere today, a new study published in the journal Pediatrics finds those soothing sounds may actually do more harm than good. Researchers from the Hospital for Sick Children in Toronto have found that infant sleep machines can reach sound levels that are hazardous to infant hearing and development. Writer Michelle Healy outlines their findings in an article in USA Today:

When set to their maximum volume:

– All 14 sleep machines [studied] exceeded 50 decibels at 30 cm and 100 cm, the current recommended noise limit for infants in hospital nurseries.

– All but one machine exceeded that recommended noise limit even when placed across the room, 200 centimeters away.

–Three machines produced outputs greater than 85 decibels when placed 30 cm away. If played continuously, as recommended on several parenting websites, infants would be exposed to sound pressure levels that exceed the occupational noise limits for an 8-hour period endorsed by the National Institute for Occupational Safety and Health and the Canadian Centre for Occupational Health and Safety.

It’s important to note that the researchers only tested the maximum output levels produced by the sound machines, and not their direct effect on infants. But Nanci Yuan, MD, tells Healy that the study does raise some important concerns:

​Parents “can feel desperate and want to try anything” when a baby has difficulty sleeping, says Nanci Yuan, pulmonologist and sleep medicine specialist at Lucile Packard Children’s Hospital Stanford.

But this research highlights the potential for a previously “unknown harm that can occur,” Yuan says. “We’re getting more and more concerned about issues related to sound and noise and hearing-loss in children because it’s progressive.”

Photo by Margarita Gallardo

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