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Scientists Make Breakthrough in Controlling Type 1 Diabetes

For the 1.25 million Americans with type 1 diabetes—in which the immune system attacks the pancreas, and makes it difficult for patients to control blood sugar—daily injections of insulin are a way of life. Now, two breakthrough studies done by researchers from MIT in collaboration with Boston’s Children’s Hospital have found a way to encapsulate healthy pancreatic or “islet” cells and transplant them into diabetic mice without an immune response, essentially curing the mice for the duration of the study. (The studies were published in Nature Biotechnology and Nature Medicine, respectively.) These finds hold great promise for a human cure.

Researchers have been studying ways to replace the damaged islet cells in diabetes for years, and moreover, to figure out a way to protect them so the immune system can’t destroy them. Omid Veiseh, a lead author on both studies and a postdoctoral fellow at MIT, tells mental_floss, “We asked the question, 'What if we could protect these cells in a capsule that is porous, so sugars and proteins can pass through, but immune cells would be unable to interact with the stem cells and kill them off?'”

Part of the challenge of finding the right encapsulating material, says Veiseh, is that “the body recognizes these materials as foreign and starts walling them off and building scar tissue, which is a barrier to nutrients and oxygen, so the cells inside those capsules didn’t survive that long.”

That is, until now: “We’ve developed a new kind of material, a polysaccharide, alginate derived from seaweed, that we make the capsules from," Veiseh says. "It’s exciting because we’ve shown we can put them into even nonhuman primates and the immune cells can still survive and thrive.”

Getting to this version of the alginate capsule required extensive testing. Researchers created a library of nearly 800 alginate derivatives before testing these in mice and nonhuman primates. They ultimately settled on one called triazole-thiomorpholine dioxide (TMTD). “It’s able to function very well, resisting fibrosis in primate models, and so we put them into diabetic mice,” Veisah describes.

The human pancreatic stem cells used in the study were generated using a technique pioneered by Harvard University's Douglas Melton, who is also a co-author on the Nature Medicine study. Then, through a small laparoscopic surgery, they transplanted the encapsulated cells, which are about the size of small caviar fish eggs, into the abdominal cavities of the mice. 

“Being able to cure a diabetic animal for up to six months—and we think we could have gone further if the study was longer—was really impressive, and not something we have been able to achieve before,” Veiseh says. “That it was done with stem cells makes it more viable for clinical translation, because you have a replenishable source.”

In fact, since Melton’s study showed that a patient’s skin cell could be converted to a stem cell, one day islet cells could theoretically be derived from a patient’s own cells.

The team will next study the effect of the encapsulated islet cells on nonhuman primates, and, with funding from JDRF Diabetes Foundation, says Veiseh, “we are looking to ways to get this in the clinic faster.”

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Health
People With Type A Blood Are More Prone to Severe Diarrhea
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Bad news for people with type A blood who also love to eat at buffets: A new study spotted by Science News reveals that people with this particular blood type have a significantly higher risk of contracting severe diarrhea from a common bacterial pathogen.

Researchers at the Washington University School of Medicine discovered that a protein secreted by a strain of Escherichia coli latches onto sugar molecules that are only found within the blood cells and intestinal lining of people with type A blood.

For the study, 106 healthy volunteers drank water that contained a strain of the bacterium E. coli—one of the major causes of infectious diarrhea around the world. Only 56 percent of volunteers with blood types O and B contracted moderate to severe diarrhea, but 81 percent of volunteers with blood types A or AB fell ill. All participants were later given antibiotics.

Researchers say these findings, which were published in the Journal of Clinical Investigation, could aid the development of an effective vaccine. Developing parts of the world are particularly susceptible to E. coli contamination, which causes millions of infections and hundreds of thousands of deaths each year, researchers note.

As anyone who has ever had "Delhi belly" can attest, this is also a concern for people who travel to developing regions. The main causes of E. coli infection are contaminated food and water, so it's wise to regularly wash your hands and avoid eating raw produce and undercooked beef while traveling.

[h/t Science News]

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Essential Science
What Is Death?
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The only thing you can be certain about in life is death. Or is it? Merriam-Webster defines death as "a permanent cessation of all vital functions." The Oxford English dictionary refines that to "the permanent ending of vital processes in a cell or tissue." But determining when someone is dead is surprisingly complicated—the medical definition has changed over the centuries and, in many ways, is still evolving.

DEATH, DEFINED

For most of human history, doctors relied on basic observations to determine whether or not a person had died. (This may be why so many feared being buried alive and went to great lengths to ensure they wouldn't be.) According to Marion Leary, the director of innovation research for the Center for Resuscitation Science at the University of Pennsylvania, "If a person wasn't visibly breathing, if they were cold and bluish in color, for example, they would be considered dead."

As time went on, the markers for death changed. Before the mid-1700s, for example, people were declared dead when their hearts stopped beating—a conclusion drawn from watching traumatic deaths such as decapitations, where the heart seemed to be the last organ to give up. But as our understanding of the human body grew, other organs, like the lungs and brain, were considered metrics of life—or death.

Today, that remains true to some degree; you can still be declared dead when your heart and lungs cease activity. And yet you can also be declared dead if both organs are still working, but your brain is not.

In most countries, being brain dead—meaning the whole brain has stopped working and cannot return to functionality—is the standard for calling death, says neuroscientist James Bernat, of the Geisel School of Medicine at Dartmouth College in New Hampshire. "A doctor has to show that the loss of brain function is irreversible," he tells Mental Floss. In some cases, a person can appear to be brain dead if they have overdosed on certain drugs or have suffered from hypothermia, for example, but the lack of activity is only temporary—these people aren't truly brain dead.

In the U.S., all states follow some form of the Uniform Determination of Death Act, which in 1981 defined a dead person as "an individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem."

But that's not the end of the story. In two states, New York and New Jersey, families can reject the concept of brain death if it goes against their religious beliefs. This makes it possible for someone to be considered alive in some states and dead in others.

A BLURRED LINE

In the past, if one of a person's three vital systems—circulation, respiration, and brain function—failed, the rest would usually stop within minutes of each other, and there was no coming back from that. But today, thanks to technological advances and medical breakthroughs, that's no longer necessarily the case. CPR can be performed to restart a heartbeat; a person who has suffered cardiac arrest can often be resuscitated within a 20- to 30-minute window (in rare cases, people have been revived after several hours). And since the 1950s, machines have been used to take on the role of many of the body's vital functions. People who stop breathing naturally can be hooked up to ventilators to move air in and out of their lungs, for example.

While remarkable, this life-extending technology has blurred the line between life and death. "A person can now have certain characteristics of being alive and others of being dead," Bernat says.

People with severe, irreversible brain damage fall into this mixed category. Many lie in intensive care units where ventilators breathe for them, but because they have minimal reflexes or movements, they're considered alive, especially by their families. Medical professionals, however, may disagree, leading to painful and complex debates about whether someone is alive.

Take the case of Jahi McMath, whose tonsil surgery in 2013, at age 13, went terribly wrong, leaving her brain dead—or so doctors thought. Her family refused to believe she was dead and moved her from Oakland, California, to New Jersey, where she was provided with feeding tubes in addition to her ventilator. After several months, her mother began recording videos that she said were proof that Jahi could move different parts of her body when asked to. Additional brain scans revealed that although some parts of her brain, like her brain stem, were largely destroyed, the structure of large parts of her cerebrum, which is responsible for consciousness, language, and voluntary movements, was intact. Her heart rate also changed when her mother spoke, leading a neurologist to declare last year, after viewing many of her mother's videos, that she is technically alive—nearly four years after she was pronounced brain dead. By her mother's reckoning, Jahi turned 17 on October 24, 2017.

Organ donation adds another layer of complications. Since an organ needs to be transplanted as quickly as possible to avoid damage, doctors want to declare death as soon as they can after a person has been disconnected from a machine. The protocol is usually to wait for five minutes after a donor's heart and breathing have stopped. However, some believe that's not long enough, since the person could still be resuscitated at that point.

Bernat—whose research interests include brain death and the definition of death, consciousness disorders including coma and vegetative states, and ethical and philosophical issues in neurology—disagrees. "I would argue that breathing and circulation has permanently ceased even if it hasn't irreversibly ceased," he says. "It won't restart by itself."

THE FUTURE OF BRINGING PEOPLE BACK TO LIFE

As resuscitation technology improves, scientists may find new ways to reverse death. One promising approach is therapeutic hypothermia. Sometimes used on heart attack patients who have been revived, the therapy uses cooling devices to lower body temperature, usually for about 24 hours. "It improves a patient's chance of recovering from cardiac arrest and the brain injury [from a lack of oxygen] that can result from it," says Leary, who specializes in research and education relating to cardiac arrest, CPR quality, and therapeutic hypothermia.

One more out-there possibility—which had its heyday in the early 2000s but still has its proponents today—is cryonic freezing, in which dead bodies (and in some cases, just people's heads) are preserved in the hope that they can be brought back once technology advances. Just minutes after death, a cryonaut's body is chilled; a chest compression device called a thumper keeps blood flowing through the body, which is then shot up with anticoagulants to prevent blood clots from forming; and finally, the blood is flushed out and replaced with a kind of antifreeze to halt the cell damage that usually occurs from freezing.

The idea is highly controversial. "It makes a good story for a movie, but it seems crazy to me," Bernat says. "I don't think it's the answer." But even if cryogenics is out, Bernat does believe that certain types of brain damage now thought to be permanent could one day be subject to medical intervention. "There is currently a huge effort in many medical centers to study brain resuscitation," he says.

Genetics provides another potential frontier. Scientists recently found that some genes in mice and fish live on after they die. And even more surprisingly, other genes regulating embryonic development, which switch off when an animal is born, turn on again after death. We don't yet know if the same thing happens in humans.

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