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New Skin Patch Monitors Glucose and Delivers Diabetes Drugs

The wearable sweat monitoring patch on the skin. Image Credit: Hyunjae Lee and Changyeong Song

 
People with diabetes need to closely monitor their blood glucose levels multiple times every day, usually using a device that pricks their finger for a blood test to assess whether they need insulin shots or other drugs. Since blood collection and shots can be painful, not all patients do it as regularly as they need to—which can lead to dangerous fluctuations in their blood glucose levels.

Researchers have worked for years on methods to improve and even automate blood glucose monitoring and insulin/drug delivery. For example, insulin pumps make drug delivery easier, and recently designed artificial pancreas systems offer closed-loop monitoring and drug delivery. Now, researchers in Korea have just developed a wearable, and potentially disposable, glucose monitoring and drug-delivery system that uses sweat, not blood, to determine glucose levels.

The results, published today in Science Advances, suggest it’s a major upgrade. There are several differences between the artificial pancreas and the sweat-based monitoring system, according to lead author Hyunjae Lee, of Seoul National University in the Republic of Korea. While both devices can check blood glucose in real time and deliver necessary drugs, the artificial pancreas’s drug-delivery needles are permanently embedded subcutaneously, and the device itself is made of rigid plastic, which "might cause discomfort," Lee tells mental_floss.

The sweat-based system, on the other hand, is transfer-printed onto a thin silicone skin patch. It’s made of flexible and stretchable electronics, a series of stretchable graphene sensors—humidity, glucose, pH, and temperature—packed as closely as possible. The sensors’ electrodes are made from porous gold nanoparticles, whose structure helps create an electrochemically active surface area in order to analyze what’s in your sweat. Above a heating strip, which helps create humidity and generate sweat more quickly, is a film strip of drug-loaded microneedles, 0.6 inches by 0.8 inches. These are loaded with metformin, a drug used to control glucose in Type 2 diabetes. (At present, the sweat-based patch has not been tested on insulin, whose molecules are too big for delivery through the microneedles, though Lee hopes to work on designing one that can work with insulin in the future.)

Detail of the wearable sweat-analysis sensors. Image Credit: Hyunjae Lee and Changyeong Song

 
Sweat accumulates in the porous sweat-uptake layer of the patch, which also helps screen out negatively charged molecules, including drugs that may interfere with the glucose sensing. A waterproof band helps prevent the patch from peeling away from the skin. When the sweat covers the glucose and pH sensors, the measurements begin. "When blood glucose is high, [the] therapeutic part activates microneedle-based drug delivery," automatically, Lee explains.

Researchers adhered the patch to five healthy human subjects, ages 20 to 60. It takes 10–15 minutes for the device to generate enough sweat to measure glucose levels, though exercise could speed that process up. However, Lee says they took into account that for some people with diabetes, "sweat generation through exercise could be a burden." He adds, "Considering [that] point, we miniaturized sensor design that allows for reliable sweat analysis even with an infinitesimal amount of sweat."

The participants’ blood glucose levels were tested using a commercial glucose meter one hour before and after a meal as a comparison. The researchers found that the sweat-glucose sensor measurements were comparable to those of a commercial blood glucose assay kit.

Human clinical trials are not yet scheduled for the drug-delivery process, so to test this part of the system, Lee’s team turned to mice. They took 16 diabetic mice, 8 to 12 weeks old, and fasted them overnight before the experiment. They attached drug-loaded microneedles to their shaved abdomens, which had been stained with a special blue dye. Then, they used an embedded heating element to activate the microneedles, since the mice can’t produce enough sweat to do so. The microneedles' successful penetration of the skin was made visible by the blue dye.

The experimental groups of mice that received the drug delivery of metformin showed a significant decrease in blood glucose levels compared to the control groups that did not receive the drug. "In the animal experiment, we could confirm that blood glucose was continuously decreased and continued for six hours after microneedle therapy," Lee says.

While the system shows great success, Lee acknowledges there are adjustments to be made. "The sensor should be more sensitive and reliable to enhance accuracy of sweat-based glucose monitoring system," he says. In order to control the amount of drug delivered, they will also need to study "the correlation between sweat and blood glucose levels more thoroughly."

Despite the need for further research, Lee feels their device "can surely contribute to improve the quality of life of diabetic patients."

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Scientific Reports, Fernando Ramirez Rozzi
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Stones, Bones, and Wrecks
Humans Might Have Practiced Brain Surgery on Cows 5000 Years Ago
Scientific Reports, Fernando Ramirez Rozzi
Scientific Reports, Fernando Ramirez Rozzi

In the 1970s, archaeologists discovered a site in France containing hundreds of cow skeletons dating back 5000 to 5400 years. The sheer number wasn't surprising—human agriculture in that part of the world was booming by 3000 BCE. What perplexed scientists was something uncovered there a few decades later: a cow skull bearing a thoughtfully drilled hole. Now, a team of researchers has released evidence that suggests the hole is an early example of animal brain surgery.

Fernando Ramírez Rozzi, a paleontologist with the French National Center for Scientific Research, and Alain Froment, an anthropologist at the Museum of Mankind in Paris, published their findings in the journal Nature Scientific Reports. After comparing the opening to the holes chiseled into the skulls of humans from the same era, they found the bones bore some striking similarities. They didn't show any signs of fracturing from blunt force trauma; rather, the hole in the cow skull, like those in the human skulls, seemed to have been carved out carefully using a tool made for exactly that purpose. That suggests that the hole is evidence of the earliest known veterinary surgery performed by humans.

Trepanation, or the practice of boring holes into human skulls, is one of the oldest forms of surgery. Experts are still unsure why ancient humans did this, but the level of care that went into the procedures suggests that the surgery was likely used to treat sick patients while they were still alive. Why a person would perform this same surgery on a cow, however, is harder to explain.

The authors present a few theories, the first being that these ancient brain surgeons were treating a sick cow the same way they might treat a sick human. If a cow was suffering from a neural disease like epilepsy, perhaps they though that cutting a hole in its head would relieve whatever was agitating the brain. The cow would have needed to be pretty special to warrant such an effort when there were hundreds of healthy cows living on the same plot of land, as evidenced by the skeletons it was found with.

Another possible explanation was that whoever operated on the cow did so as practice to prepare them for drilling into the heads of live humans one day. "Cranial surgery requires great manual dexterity and a complete knowledge of the anatomy of the brain and vessel distribution," the authors write in the study. "It is possible that the mastery of techniques in cranial surgery shown in the Mesolithic and Neolithic periods was acquired through experimentation on animals."

Either way, the bovine patient didn't live to see the results of the procedure: The bone around the hole hadn't healed at all, which suggests the cow either died during surgery or wasn't alive to begin with.

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science
8 Unexpected Activities People Have Done in MRI Scanners for Science
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iStock

In medicine, magnetic resonance imaging (MRI) uses powerful magnetic fields and radio waves to show what's happening inside the body, producing dynamic images of our internal organs. Using similar technology that tracks blood flow, functional magnetic resonance imaging (fMRI) scans can show neuroscientists neural activity, indicating what parts of the brain light up when, for instance, a person thinks of an upsetting memory or starts craving cocaine. Both require staying within a massive MRI machine for the length of the scan.

There's some controversy over how scientists interpret fMRI data in particular—fMRI studies are based on the idea that an increase of blood flow to a region of the brain means more cellular activity there, but that might not be a completely accurate measure, and a 2016 report found that fMRI studies may have stunning rates of false positives.

But we're not here to talk about results. We're here to talk about all the weird, weird things scientists have asked people to do in MRI machines so that they could look at their brains and bodies. From getting naked to going to the bathroom, people have been willing to do some unexpected activities in the name of science. Here are just a few of the oddest things that people have done in scanners at the behest of curious researchers.

1. SING OPERA

Researchers once invited world-famous opera singer Michael Volle to sing inside an MRI at the University of Freiburg in Germany. The baritone sang a piece from Richard Wagner's opera Tannhäuser as part of a 2016 study on how the vocal tract moves during singing at different pitches and while changing volume. The study asked 11 other professional singers with different voice types to participate as well. They found that the larynx rose with a singer's pitch, but got lower as the song got louder, and that certain factors, like how open their lips were, correlated more with how loud the singer was than how high they were singing. The scientists concluded that future research on the larynx and the physical aspects of singing should take loudness into consideration.

That study wasn't the first to take MRI images of singers. In 2015, researchers at the University of Illinois demonstrated their technique for recording dynamic MRI imaging of speech using video of U of I speech specialist Aaron Johnson singing "If I Only Had a Brain" from The Wizard of Oz.

2. REACT TO ROBOT-DINOSAUR ABUSE

Stills of a video in which a robot gets petted or beaten by a human
Stills from the videos participants watched of robot dinosaurs being treated kindly or unkindly.
Rosenthal-von der Pütten et al., Computers in Human Behavior (2014)

To test whether or not humans can feel empathy with robots for a 2013 study, researchers put participants into an fMRI machine and made them watch videos of humans and robotic dinosaurs. The videos either included footage of the human or robot being stroked or tickled, or the subject being beaten and choked. The brain scans showed similar activity for people viewing both videos, suggesting that people might be able to feel similar empathy for robots as for people.

3. PLAY VIDEO GAMES WITH A MEAN-SPIRITED A.I.

Two brain scans
Eisenberger et al., Science (2003)

To see whether the brain responds to emotional pain in similar ways to physical pain, researchers asked participants in a 2003 study to experience social rejection within an fMRI machine. During the scans, participants played a virtual ball-tossing game against two other players—whom they believed to be other study participants in other scanners—by watching a screen through goggles and pressing one of two keys to toss the ball to one of the other players. They were actually playing against a computer that was programmed to eventually exclude the human player. At some point during the game, the computer-controlled players stopped throwing the human player the ball, causing them to feel excluded and ignored. The researchers found that the excluded study subjects showed brain activation in regions similar to the ones seen in studies of physical pain.

4. POOP

Watching people poop through MRI imaging is a surprisingly common medical technique. It's called magnetic resonance defecography. Doctors use it to diagnose issues with rectal function, analyzing how the muscles of the pelvis are working and the cause of bowel issues. The scan involves having ultrasound jelly and a catheter inserted into your butt, donning a diaper, and crawling inside an MRI scanner. Then, on command, you clench your pelvic muscles in various ways as ordered by the doctor, eventually resulting in pooping out the ultrasound jelly and whatever else you might need to evacuate. No pressure.

5. HAVE SEX …

MRI of a woman before, pre-, and after orgasm
MRI images of a woman at rest, in a pre-orgasmic phase, and 20 minutes after orgasm (L–R)
Schultz et al. in BMJ, 1999

Scientists have also recorded MRI body scans of couples having sex. In the late '90s, Dutch researcher Pek Van Andel and his colleagues at the University Hospital Groningen asked eight couples to come into their lab on a Saturday and have sex in the tube of an MRI scanner in order to analyze how genitals fit together during heterosexual intercourse. Despite the surroundings, they apparently had a fine time. "The subjective level of sexual arousal of the participants, men and women, during the experiment was described afterwards as average," the study noted.

Meanwhile, other researchers are trying to capture scientific images of sex in different, sometimes even more awkward ways. For her 2008 book Bonk: The Curious Coupling Of Sex And Science, science writer Mary Roach and her husband had sex in a lab at University College London while a researcher stood next to them and held an ultrasound wand to her abdomen.

6. … AND HAVE ORGASMS

Scan of a woman's brain during orgasm
Wise et al., The Journal of Sexual Medicine (2017)

Scientists still don't know all that much about how orgasms work, so various studies have asked participants to come into the lab, lay down in an fMRI scanner, and stimulate themselves to orgasm. (A reporter at Inside Jersey went to Rutgers to take part in the university's orgasm research herself in 2010. She brought her own sex toy, but the lab was kind enough to provide the lube.)

Over the course of their work, Rutgers researchers have found that when people bring themselves to orgasm within an fMRI machine, it activates more than 30 brain systems, including ones that you wouldn't think would be involved in getting off, like the prefrontal cortex, which is associated with problem solving and judgment.

7. COMPOSE MUSIC

A musical score with just a few notes on it
Lu et al., Scientific Reports (2015)

Singers aren't the only music professionals to get inside an fMRI machine for science. For a study published in 2015, 17 young composers were asked to create a piece of music while Chinese researchers examined their brain activity. While all of them played the piano, they were asked to compose a piece for an instrument none of them know how to play—the zheng, a traditional Chinese string instrument. They were given a musical staff with just a few introductory notes already written as inspiration and asked to come up with something from there. As soon as they exited the scanner, they wrote down the notes they had imagined during the imaging process. The researchers found that the composers' visual and motor cortex showed less activity than usual, the opposite of what researchers have seen in studies of musical improvisation.

8. HAVE AN OUT-OF-BODY EXPERIENCE

Four brain scans with different areas of the brain lit up in red, yellow, and orange
Activated portions of the brain during an out-of-body experience
Smith and Messier, Frontiers in Human Neuroscience (2014)

In a 2014 study, psychologists at the University of Ottawa recruited an undergraduate student who reported that she could have out-of-body experiences at will to do so within the confines of an fMRI scanner.

"She was able to see herself rotating in the air above her body, lying flat, and rolling along with the horizontal plane," the researchers wrote. "She reported sometimes watching herself move from above but remained aware of her unmoving 'real' body."

She entered the scanner six times, reporting out-of-body experiences that included feeling as if she were above her body and spinning or rocking side-to-side. The researchers found that the experience activated regions of her brain associated with kinesthetic imagery, the feeling of visualizing movement (as athletes often do during training and competitions, for instance), and a deactivated the visual cortex.

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