A new type of wearable sensor teeming with nanoparticles can help diagnose and treat movement disorders by storing and transmitting motion data and then delivering drugs when appropriate.
Sensors on skin -- which go by a range of names including epidermal electronics, flexible electronics, electronic tattoos) -- have long promised to record physiological measurements to help track health and monitor healing. This new wearable design, however, is multifuncational.
To help perform diagnostic and therapeutic tasks, the thin devices integrates stretchable sensors, memory, and actuators, and they’re all made of nanomaterials: silicon nanomembranes for motion sensing, gold nanoparticles for RAM data storage, and silica nanoparticles loaded with drugs within the thermal actuator, or microheater. All these tiny, tiny parts are layered into a soft patch -- about 4 centimeters long, 2 centimeters wide and 0.003 millimeters thick -- that can stretch and bend with your skin.
Here’s how it works. The system measures and records muscle activity on the human wrist, which helps diagnose motion-related neurological disorders such as Parkinson’s or epilepsy. Then the recorded data trigger the release of therapeutic agents (contained in the silica nanoparticles) by means of the thermal actuator, which allows the drug to diffuse into the skin. To prevent burns to the skin, a temperature sensor (made of the silicon nanomembranes) monitors the skin temperature.
The key is the memory device. But as a trade-off, the whole thing only works if it’s connected to a power supply and data transmitter. While commercially available parts (such as lithium batteries and radio-frequency identification tags) can do the work, they’re too rigid for this soft-as-skin brand of electronic device, study coauthor Nanshu Lu of the University of Texas, Austin, tells Nature. They’ll need to find a way to make them compact and flexible before the device can be used on patients.
The work was published in Nature Nanotechnology this week.
An X-ray shows the neurostimulator implanted in the brain of a patient.CreditNeuroPace
ALEXANDRIA, N.H. — For most of his life, Kevin Ramsey has lived with epileptic seizures that drugs cannot control.
At least once a month, he would collapse, unconscious and shaking violently, sometimes injuring himself. Nighttime seizures left him exhausted at dawn, his tongue a bloody mess. After episodes at work, he struggled to stay employed. Driving became too risky. At 28, he sold his truck and moved into his mother’s spare bedroom.
Cases of intractable epilepsy rarely have happy endings, but today Mr. Ramsey is seizure-free. A novel battery-powered device implanted in his skull, its wires threaded into his brain, tracks its electrical activity and quells impending seizures. At night, he holds a sort of wand to his head and downloads brain data from the device to a laptop for his doctors to review.
“I’m still having seizures on the inside, but my stimulator is stopping all of them,” said Mr. Ramsey, 36, whose hands shake because of one of the three anti-seizure drugs he still must take. “I can do things on my own I couldn’t do before. I can go to the store on my own, and get my groceries. Before, I wouldn’t have been able to drive.”
Just approved by the Food and Drug Administration, the long-awaited device, called the RNS System, aims to reduce seizures and to improve the lives of an estimated 400,000 Americans whose epilepsy cannot be treated with drugs or brain surgery. “This is the first in what I believe is a new generation of therapy for epilepsy,” said Dr. Dileep R. Nair, head of adult epilepsy at the Cleveland Clinic and an investigator in the pivotal trial for NeuroPace’s RNS. “It’s delivering local therapy. It’s not taking tissue out; the brain is left intact. And it’s unlike a drug, which is a shotgun approach.”
“We want this yesterday,” said Dr. Orrin Devinsky, director of theComprehensive Epilepsy Center at NYU Langone Medical Center. Next month, pending insurance approval, the center plans to implant the device in its first patient.
An estimated 2.3 million adults nationwide have epilepsy, and in a third of them, seizures are not controlled by drugs. Brain surgery can relieve seizures completely, but many patients aren’t candidates because their seizures start in parts of the brain that can’t be removed, such as those needed for language or memory.
Without treatment options, people with intractable epilepsy often find it difficult to hold jobs or to find spouses. They can suffer repeated injuries from falls and burns; their mortality rate is two to three times higher than that of the general population. “There are people out there who are just desperate for the next treatment,” said Janice Buelow, the vice president of research for the Epilepsy Foundation.
Until he received a stimulator in 2008, Andrew Stocksdale, 32, of Mansfield, Ohio, experienced up to 20 seizures a day. By contrast, in the past month, he’s had three. He is now married, holds a full-time job, and has a newborn son.
The device, which requires a battery change every two to three years, works only for people whose seizures start in one or two places in their brain. Electrical stimulation delivered through thin wires placed precisely at those places helps prevent an incipient seizure from spreading.
Before the RNS is turned on, a patient’s unique seizure patterns must be detected, a process that takes months and multiple clinic visits. Then comes a period of trial and error, when the intensity of stimulation is increased or decreased, or the number of pulses altered, to see if the patient experiences fewer seizures.
Dr. David M. Labiner, the president of the National Association of Epilepsy Centers, said the “lag time” between diagnosis and referral to a comprehensive center “is still up to 20 years.”
Another hurdle is cost. The RNS, with the equipment required to download data, is up to $40,000. That figure doesn’t include $10,000 to $20,000 for the surgery, or diagnostic testing. Thus far, insurers have paid most of the expenses for five or so cases since F.D.A. approval, including one covered by Medicare. Full Article
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Storm brewing over WHO sugar proposal
Industry backlash expected over suggested cut in intake.
The WHO recommends that adults have less sugar per day than is found in one glass of many soft drinks.
Scientists are gearing up for a battle with the food industry after the World Health Organization (WHO) moved to halve its recommendation on sugar intake.
Nutrition researchers fear a backlash similar to that seen in 2003, when the WHO released its current guidelines stating that no more than 10% of an adult’s daily calories should come from ‘free’ sugars. That covers those added to food, as well as natural sugars in honey, syrups and fruit juice. In 2003, the US Sugar Association, a powerful food-industry lobby group based in Washington DC, pressed the US government to withdraw funding for the WHO if the organization did not modify its recommendations. The WHO did not back down, and has now mooted cutting the level to 5%.
“These are reasonable limits,” says Walter Willett, head of nutrition at the Harvard School of Public Health in Boston, Massachusetts. “Five per cent of calories is just a bit less than in a typical serving of soda, and we have good evidence of increased risk of diabetes with that intake, which of course increases with greater intake.”
But Marion Nestle, a nutrition researcher at New York University, predicts that grocery manufacturers are not going to take the proposal lying down. “If people follow this advice, that would be very bad for business,” she says.
Source: CDC/NCHS, National Health and Nutrition Examination Surveys
The WHO made its recommendations in draft guidelines that were released for public consultation on 5 March. In halving the 10% figure, it cited the need to fight obesity — worldwide incidence reached 11% in 2008 — and to prevent tooth decay. Five per cent of daily calories is equivalent to about 25 grams, or 6 teaspoons, of sugar. Many people around the world consume more than that — young adults in the United States, for example, get more than 14% of their calories from free sugars, according to the US Centers for Disease Control and Prevention in Atlanta, Georgia (see ‘Sugar high’).
Industry submissions to the consultation are likely to be forceful. When the WHO recommended the 10% limit, it faced a ferocious attack on the credibility of its science from several camps — including the administration of then US President George W. Bush. The administration said that the WHO report did not meet US data-quality standards, was not properly peer-reviewed, and failed to separate scientific and policy recommendations.
This time around, the WHO is taking steps to counter excessive lobbying. Anyone who wishes to submit a comment on the draft guidelines must first complete a declaration-of-interest form. And the organization says that it will stand firm against any push-back from the food industry. “If pressure comes to the organization, then we’re very well equipped to resist that type of pressure,” said Francesco Branca, director of the WHO’s Department for Nutrition for Health and Development, at a press conference.
A dangerous new form of a powerful stimulant is hitting markets nationwide, for sale by the vial, the gallon and even the barrel.
The drug is nicotine, in its potent, liquid form — extracted from tobacco and tinctured with a cocktail of flavorings, colorings and assorted chemicals to feed the fast-growing electronic cigarette industry.
These “e-liquids,” the key ingredients in e-cigarettes, are powerful neurotoxins. Tiny amounts, whether ingested or absorbed through the skin, can cause vomiting and seizures and even be lethal. A teaspoon of even highly diluted e-liquid can kill a small child.
But, like e-cigarettes, e-liquids are not regulated by federal authorities. They are mixed on factory floors and in the back rooms of shops, and sold legally in stores and online in small bottles that are kept casually around the house for regular refilling of e-cigarettes.
Evidence of the potential dangers is already emerging. Toxicologists warn that e-liquids pose a significant risk to public health, particularly to children, who may be drawn to their bright colors and fragrant flavorings like cherry, chocolate and bubble gum.
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The liquid stimulant used in e-cigarettes, when ingested or absorbed through the skin, can cause vomiting, seizures or death.CreditFrank Franklin II/Associated Press
“It’s not a matter of if a child will be seriously poisoned or killed,” said Lee Cantrell, director of the San Diego division of the California Poison Control System and a professor of pharmacy at the University of California, San Francisco. “It’s a matter of when.”
Reports of accidental poisonings, notably among children, are soaring. Since 2011, there appears to have been one death in the United States, a suicide by an adult who injected nicotine. But less serious cases have led to a surge in calls to poison control centers. Nationwide, the number of cases linked to e-liquids jumped to 1,351 in 2013, a 300 percent increase from 2012, and the number is on pace to double this year, according to information from the National Poison Data System. Of the cases in 2013, 365 were referred to hospitals, triple the previous year’s number.
In terms of the immediate poison risk, e-liquids are far more dangerous than tobacco, because the liquid is absorbed more quickly, even in diluted concentrations.
“This is one of the most potent naturally occurring toxins we have,” Mr. Cantrell said of nicotine. But e-liquids are now available almost everywhere. “It is sold all over the place. It is ubiquitous in society.”
The surge in poisonings reflects not only the growth of e-cigarettes but also a shift in technology. Initially, many e-cigarettes were disposable devices that looked like conventional cigarettes. Increasingly, however, they are larger, reusable gadgets that can be refilled with liquid, generally a combination of nicotine, flavorings and solvents. In Kentucky, where about 40 percent of cases involved adults, one woman was admitted to the hospital with cardiac problems after her e-cigarette broke in her bed, spilling the e-liquid, which was then absorbed through her skin.
Nicotine solutions at Volt Vapes in Boise, Idaho. The “e-liquid” comes in colors and flavors that experts say may entice children.CreditKatherine Jones/The Idaho Statesman, via Associated Press
The website of Liquid Nicotine Wholesalers. The Food and Drug Administration has yet to impose rules on e-liquids’ sale.
Without proper precautions, like wearing gloves while mixing e-liquids, these products “represents a serious workplace hazard,” he said.
The nicotine levels in e-liquids varies. Most range between 1.8 percent and 2.4 percent, concentrations that can cause sickness, but rarely death, in children. But higher concentrations, like 10 percent or even 7.2 percent, are widely available on the Internet. A lethal dose at such levels would take “less than a tablespoon,” according to Dr. Cantrell, from the poison control system in California. “Not just a kid. One tablespoon could kill an adult,” he said.
Electronic cigarettes deliver nicotine without smoke, but their health advantages have been controversial.
The controversy over electronic cigarettes has been reignited today with the publication of a study claiming that they do not help smokers to quit their habit.
Whether or not ‘e-cigarettes’ are an effective aid in the cessation of smoking has become a major issue for the rapidly growing industry that produces the devices, and for the tobacco researchers struggling to assess their impact. There is widespread agreement that inhaling from an e-cigarette, where a heating element vapourizes a liquid containing nicotine, is not as harmful as smoking a conventional cigarette, and proponents say that the products could save millions of lives. But some researchers and tobacco-control activists fear that the devices could make tobacco use seem socially acceptable again and may not assist people in actually reducing their addiction.
Electronic cigarettes have been investigated to assess their effects on gene expression.
Electronic cigarettes can change gene expression in a similar way to tobacco, according to one of the first studies to investigate the biological effects of the devices.
Presented at the American Association for Cancer Research annual meeting on 6 April in San Diego, California, the research looked at human bronchial cells that contained some mutations found in smokers at risk of lung cancer. The cells were immortalized, grown in culture medium that had been exposed to e-cigarette vapour and their gene expression profiled.
The researchers found that the cells grown in medium exposed to the vapour of e-cigarettes showed a similar pattern of gene expression to those grown in a medium exposed to tobacco smoke (S. J. Park et al. Clin. Cancer Res. 20, B16; 2014).
The changes are not identical, says study researcher Avrum Spira, who works on genomics and lung cancer at Boston University in Massachusetts. But “there are some striking similarities”, he says. The team is now evaluating whether the alterations mean that cells behave more like cancer cells in culture.
The work is at a very early stage and therefore cannot establish that e-cigarettes can cause cancerin vitro, let alone in vivo. “They may be safer [than tobacco], but our preliminary studies suggest that they may not be benign,” says Spira.
E-cigarettes are extremely controversial. Because they vaporize liquid containing nicotine, rather than burning tobacco, some researchers believe that the devices could greatly reduce the damage done to health by smoking; others, however, argue that they are simply ‘renormalizing’ smoking.
