Posts Tagged ‘medicine’

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Artificial intelligence (AI) can be an invaluable aid to help lung doctors interpret respiratory symptoms accurately and make a correct diagnosis, according to new research presented yesterday (Wednesday) at the European Respiratory Society International Congress.

Dr Marko Topalovic (PhD), a postdoctoral researcher at the Laboratory for Respiratory Diseases, Catholic University of Leuven (KU Leuven), Belgium, told the meeting that after training an AI computer algorithm using good quality data, it proved to be more consistent and accurate in interpreting respiratory test results and suggesting diagnoses than lung specialists.

“Pulmonary function tests provide an extensive series of numerical outputs and their patterns can be hard for the human eye to perceive and recognise; however, it is easy for computers to manage large quantities of data like these and so we thought AI could be useful for pulmonologists. We explored if this was true with 120 pulmonologists from 16 hospitals. We found that diagnosis by AI was more accurate in twice as many cases as diagnosis by pulmonologists. These results show how AI can serve as a second opinion for pulmonologists when they are assessing and diagnosing their patients,” he said.

Pulmonary function tests (PFT) include: spirometry, which involves the patient breathing through a mouthpiece to measure the amount of air inhaled and exhaled; a body box or plethysmography test, which enables doctors to assess lung volume by measuring the pressure in a booth in which the patient is sitting and breathing through a mouthpiece; and a diffusion capacity test, which tests how well a patient’s lungs are able to transfer oxygen and carbon dioxide to and from the bloodstream by testing the efficiency of the alveoli (small air sacks in the lungs). Results from these tests give doctors important information about the functioning of the lungs, but do not tell them what is wrong with the patient. This requires interpretation of the results in order to reach a diagnosis.

In this study, the researchers used historical data from 1430 patients from 33 Belgian hospitals. The data were assessed by an expert panel of pulmonologists and interpretations were measured against gold standard guidelines from the European Respiratory Society and the American Thoracic Society. The expert panel considered patients’ medical histories, results of all PFTs and any additional tests, before agreeing on the correct interpretation and diagnosis for each patient.

“When training the AI algorithm, the use of good quality data is of utmost importance,” explained Dr Topalovic. “An expert panel examined all the results from the pulmonary function tests, and the other tests and medical information as well. They used these to reach agreement on final diagnoses that the experts were confident were correct. These were then used to develop an algorithm to train the AI, before validating it by incorporating it into real clinical practice at the University Hospital Leuven. The challenging part was making sure the algorithm recognised patterns of up to nine different diseases.”

Then, 120 pulmonologists from 16 European hospitals (from Belgium, France, The Netherlands, Germany and Luxembourg) made 6000 interpretations of PFT data from 50 randomly selected patients. The AI also examined the same data. The results from both were measured against the gold standard guidelines in the same way as during development of the algorithm.

The researchers found that the interpretation of the PFTs by the pulmonologists matched the guidelines in 74% of cases (with a range of 56-88%), but the AI-based software interpretations perfectly matched the guidelines (100%). The doctors were able to correctly diagnose the primary disease in 45% of cases (with a range of 24-62%), while the AI gave a correct diagnosis in 82% of cases.

Dr Topalovic said: “We found that the interpretation of pulmonary function tests and the diagnosis of respiratory disease by pulmonologists is not an easy task. It takes more information and further tests to reach a satisfactory level of accuracy. On the other hand, the AI-based software has superior performance and therefore can provide a powerful decision support tool to improve current clinical practice. Feedback from doctors is very positive, particularly as it helps them to identify difficult patterns of rare diseases.”

Two large Belgian hospitals are already using the AI-based software to improve interpretations and diagnoses. “We firmly believe that we can empower doctors to make their interpretations and diagnoses easier, faster and better. AI will not replace doctors, that is certain, because doctors are able to see a broader perspective than that presented by pulmonary function tests alone. This enables them to make decisions based on a combination of many different factors. However, it is evident that AI will augment our abilities to accomplish more and decrease chances for errors and redundant work. The AI-based software has superior performance and therefore may provide a powerful decision support tool to improve current clinical practice.

“Nowadays, we trust computers to fly our planes, to drive our cars and to survey our security. We can also have confidence in computers to label medical conditions based on specific data. The beauty is that, independent of location or medical coverage, AI can provide the highest standards of PFT interpretation and patients can have the best and affordable diagnostic experience. Whether it will be widely used in future clinical applications is just a matter of time, but will be driven by the acceptance of the medical community,” said Dr Topalovic.

He said the next step would be to get more hospitals to use this technology and investigate transferring the AI technology to primary care, where the data would be captured by general practitioners (GPs) to help them make correct diagnoses and referrals.

Professor Mina Gaga is President of the European Respiratory Society, and Medical Director and Head of the Respiratory Department of Athens Chest Hospital, Greece, and was not involved in the study. She said: “This work shows the exciting possibilities that artificial intelligence offers to doctors to help them provide a better, quicker service to their patients. Over the past 20 to 30 years, the evolution in technology has led to better diagnosis and treatments: a revolution in imaging techniques, in molecular testing and in targeted treatments have make medicine easier and more effective. AI is the new addition! I think it will be invaluable in helping doctors and patients and will be an important aid to their decision-making.”

[1] Abstract no: PA5290, “Artificial intelligence improves experts in reading pulmonary function tests”, by M. Topalovic et al; Poster Discussion “The importance of the pulmonary function test in different clinical settings”, 08.30-10.30 hrs CEST, Wednesday 19 September, Room 7.2D.

The research was funded by Vlaams Agentschap Innoveren & Ondernemen – VLAIO (Belgian government body: Agency for Innovation and Entrepreneurship – VLAIO)




Dr. Leslie Norins is willing to hand over $1 million of his own money to anyone who can clarify something: Is Alzheimer’s disease, the most common form of dementia worldwide, caused by a germ?

By “germ” he means microbes like bacteria, viruses, fungi and parasites. In other words, Norins, a physician turned publisher, wants to know if Alzheimer’s is infectious.

It’s an idea that just a few years ago would’ve seemed to many an easy way to drain your research budget on bunk science. Money has poured into Alzheimer’s research for years, but until very recently not much of it went toward investigating infection in causing dementia.

But this “germ theory” of Alzheimer’s, as Norins calls it, has been fermenting in the literature for decades. Even early 20th century Czech physician Oskar Fischer — who, along with his German contemporary Dr. Alois Alzheimer, was integral in first describing the condition — noted a possible connection between the newly identified dementia and tuberculosis.

If the germ theory gets traction, even in some Alzheimer’s patients, it could trigger a seismic shift in how doctors understand and treat the disease.

For instance, would we see a day when dementia is prevented with a vaccine, or treated with antibiotics and antiviral medications? Norins thinks it’s worth looking into.

Norins received his medical degree from Duke in the early 1960s, and after a stint at the Centers for Disease Control and Prevention he fell into a lucrative career in medical publishing. He eventually settled in an admittedly aged community in Naples, Fla., where he took an interest in dementia and began reading up on the condition.

After scouring the medical literature he noticed a pattern.

“It appeared that many of the reported characteristics of Alzheimer’s disease were compatible with an infectious process,” Norins tells NPR. “I thought for sure this must have already been investigated, because millions and millions of dollars have been spent on Alzheimer’s research.”

But aside from scattered interest through the decades, this wasn’t the case.

In 2017, Norins launched Alzheimer’s Germ Quest Inc., a public benefit corporation he hopes will drive interest into the germ theory of Alzheimer’s, and through which his prize will be distributed. A white paper he penned for the site reads: “From a two-year review of the scientific literature, I believe it’s now clear that just one germ — identity not yet specified, and possibly not yet discovered — causes most AD. I’m calling it the ‘Alzheimer’s Germ.’ ”

Norins is quick to cite sources and studies supporting his claim, among them a 2010 study published in the Journal of Neurosurgery showing that neurosurgeons die from Alzheimer’s at a nearly 2 1/2 times higher rate than they do from other disorders.

Another study from that same year, published in The Journal of the American Geriatric Society, found that people whose spouses have dementia are at a 1.6 times greater risk for the condition themselves.

Contagion does come to mind. And Norins isn’t alone in his thinking.

In 2016, 32 researchers from universities around the world signed an editorial in the Journal of Alzheimer’s Disease calling for “further research on the role of infectious agents in [Alzheimer’s] causation.” Based on much of the same evidence Norins encountered, the authors concluded that clinical trials with antimicrobial drugs in Alzheimer’s are now justified.

NPR reported on an intriguing study published in Neuron in June that suggested that viral infection can influence the progression of Alzheimer’s. Led by Mount Sinai genetics professor Joel Dudley, the work was intended to compare the genomes of healthy brain tissue with that affected by dementia.

But something kept getting in the way: herpes.

Dudley’s team noticed an unexpectedly high level of viral DNA from two human herpes viruses, HHV-6 and HHV-7. The viruses are common and cause a rash called roseola in young children (not the sexually transmitted disease caused by other strains).

Some viruses have the ability to lie dormant in our neurons for decades by incorporating their genomes into our own. The classic example is chickenpox: A childhood viral infection resolves and lurks silently, returning years later as shingles, an excruciating rash. Like it or not, nearly all of us are chimeras with viral DNA speckling our genomes.

But having the herpes viruses alone doesn’t mean inevitable brain decline. After all, up to 75 percent of us may harbor HHV-6 .

But Dudley also noticed that herpes appeared to interact with human genes known to increase Alzheimer’s risk. Perhaps, he says, there is some toxic combination of genetic and infectious influence that results in the disease; a combination that sparks what some feel is the main contributor to the disease, an overactive immune system.

The hallmark pathology of Alzheimer’s is accumulation of a protein called amyloid in the brain. Many researchers have assumed these aggregates, or plaques, are simply a byproduct of some other process at the core of the disease. Other scientists posit that the protein itself contributes to the condition in some way.

The theory that amyloid is the root cause of Alzheimer’s is losing steam. But the protein may still contribute to the disease, even if it winds up being deemed infectious.

Work by Harvard neuroscientist Rudolph Tanzi suggests it might be a bit of both. Along with colleague Robert Moir, Tanzi has shown that amyloid is lethal to viruses and bacteria in the test tube, and also in mice. He now believes the protein is part of our ancient immune system that like antibodies, ramps up its activity to help fend off unwanted bugs.

So does that mean that the microbe is the cause of Alzheimer’s, and amyloid a harmless reaction to it? According to Tanzi it’s not that simple.

Tanzi believes that in many cases of Alzheimer’s, microbes are probably the initial seed that sets off a toxic tumble of molecular dominoes. Early in the disease amyloid protein builds up to fight infection, yet too much of the protein begins to impair function of neurons in the brain. The excess amyloid then causes another protein, called tau, to form tangles, which further harm brain cells.

But as Tanzi explains, the ultimate neurological insult in Alzheimer’s is the body’s reaction to this neurotoxic mess. All the excess protein revs up the immune system, causing inflammation — and it’s this inflammation that does the most damage to the Alzheimer’s-afflicted brain.

So what does this say about the future of treatment? Possibly a lot. Tanzi envisions a day when people are screened at, say, 50 years old. “If their brains are riddled with too much amyloid,” he says, “we knock it down a bit with antiviral medications. It’s just like how you are prescribed preventative drugs if your cholesterol is too high.”

Tanzi feels that microbes are just one possible seed for the complex pathology behind Alzheimer’s. Genetics may also play a role, as certain genes produce a type of amyloid more prone to clumping up. He also feels environmental factors like pollution might contribute.

Dr. James Burke, professor of medicine and psychiatry at Duke University’s Alzheimer’s Disease Research Center, isn’t willing to abandon the amyloid theory altogether, but agrees it’s time for the field to move on. “There may be many roads to developing Alzheimer’s disease and it would be shortsighted to focus just on amyloid and tau,” he says. “A million-dollar prize is attention- getting, but the reward for identifying a treatable target to delay or prevent Alzheimer’s disease is invaluable.”

Any treatment that disrupts the cascade leading to amyloid, tau and inflammation could theoretically benefit an at-risk brain. The vast majority of Alzheimer’s treatment trials have failed, including many targeting amyloid. But it could be that the patients included were too far along in their disease to reap any therapeutic benefit.

If a microbe is responsible for all or some cases of Alzheimer’s, perhaps future treatments or preventive approaches will prevent toxin protein buildup in the first place. Both Tanzi and Norins believe Alzheimer’s vaccines against viruses like herpes might one day become common practice.

In July of this year, in collaboration with Norins, the Infectious Diseases Society of America announced that they plan to offer two $50,000 grants supporting research into a microbial association with Alzheimer’s. According to Norins, this is the first acknowledgement by a leading infectious disease group that Alzheimer’s may be microbial in nature – or at least that it’s worth exploring.

“The important thing is not the amount of the money, which is a pittance compared with the $2 billion NIH spends on amyloid and tau research,” says Norins, “but rather the respectability and more mainstream status the grants confer on investigating of the infectious possibility. Remember when we thought ulcers were caused by stress?”

Ulcers, we now know, are caused by a germ.


An inhaled form of a high blood pressure medication has potential to treat certain types of anxiety as well as pain, according to a new study by the Centre for Addiction and Mental Health (CAMH).

Anxiety disorders are usually treated with different types of medications, such as antidepressants, and psychotherapy. Amiloride is a medication offering a new approach, as a short-acting nasal spray that could be used to prevent an anxiety attack.

“Inhaled amiloride may prove to have benefits for panic disorder, which is typically characterized by spells of shortness of breath and fear, when people feel anxiety levels rising,” says lead author Dr. Marco Battaglia, Associate Chief of Child and Youth Psychiatry and Clinician Scientist in the Campbell Family Mental Health Research Institute at CAMH.

The study was based on understanding the key physiological changes in brain functioning that are linked to anxiety and pain sensitivity. The researchers then tested a molecule, amiloride, which targets this functioning.

Amiloride was inhaled so that it could immediately access the brain. The study showed that it reduced the physical respiratory signs of anxiety and pain in a preclinical model of illness. This therapeutic effect didn’t occur when amiloride was administered in the body, as it didn’t cross the blood-brain barrier and did not reach the brain.

Results were published in the Journal of Psychopharmacology.

The role of early life adversity
The study is based on years of research into how a person’s early life experiences affect their genes, says Dr. Battaglia. Childhood adversity, such as loss or separation from parents, increases the risk of anxiety disorders and pain, among other health issues.

At a molecular level, these negative life experiences are linked to changes in some genes of the ASIC (acid-sensing-ion-channels) family. While the DNA itself doesn’t change, the way it functions is affected.

DNA is converted into working proteins through a process called gene expression. As a result of childhood adversity, some ASIC genes showed increased expression and epigenomic changes. (“Epigenomic” refers to changes in gene regulation that can inherited by children). Overlapping genetic changes were also seen in blood taken from twins who responded to specific tests designed to provoke panic.

These genetic changes are linked to physical symptoms. Breathing can be affected, due to over-sensitivity to higher carbon dioxide levels in the air. In such situations, a person might hyperventilate and experience growing anxiety. Preclinical and human data are strikingly similar in this regard. “As a treatment, amiloride turned out to be very effective preclinically,” says Dr. Battaglia.

The next step in his research is to test whether it eases anxiety symptoms. Dr. Battaglia is now launching a pilot clinical trial, supported through a seed grant from CAMH’s new Discovery Fund. Collaborators at the University of Utah are testing the drug’s safety.

Amiloride has been used as an oral treatment for decades for hypertension, and as an inhaled spray in a few experimental studies of cystic fibrosis, he notes. The researchers are therefore further ahead than if they had to develop and test an entirely new medication.

The discovery sheds new light on the origins of this most common cause of dementia, a hallmark of which is the buildup of tangled tau protein filaments in the brain.

The finding could also lead to new treatments for Alzheimer’s and other diseases that progressively destroy brain tissue, conclude the researchers in a paper about their work that now features in the journal Neuron.

Scientists from Massachusetts General Hospital (MGH) in Charlestown and the Johns Hopkins School of Medicine in Baltimore, MD, led the study, which set out to investigate how tau protein might contribute to brain cell damage.

Alzheimer’s disease does not go away and gets worse over time. It is the sixth most common cause of death in adults in the United States, where an estimated 5.7 million people have the disease.

Exact causes of Alzheimer’s still unknown

Exactly what causes Alzheimer’s and other forms of dementia is still a mystery to science. Evidence suggests that a combination of environment, genes, and lifestyle is involved, with different factors having different amounts of influence in different people.

Most cases of Alzheimer’s do not show symptoms until people are in their 60s and older. The risk of getting the disease rises rapidly with age after this.

Brain studies of people with the disease — together with postmortem analyses of brain tissue — have revealed much about how Alzheimer’s changes and harms the brain.

“Age-related changes” include: inflammation; shrinkage in some brain regions; creation of unstable, short-lived molecules known as free radicals; and disruption of cellular energy production.

The brain of a person with Alzheimer’s disease also has two distinguishing features: plaques of amyloid protein that form between cells, and tangles of tau protein that form inside cells. The recent study concerns the latter.

Changes to tau behavior

Brain cells, or neurons, have internal structures known as microtubules that support the cell and its function. They are highly active cell components that help carry substances from the body of the cell out to the parts that connect it to other cells.

In healthy brain cells, tau protein normally “binds to and stabilizes” the microtubules. Tau behaves differently, however, in Alzheimer’s disease.

Changes in brain chemistry make tau protein molecules come away from the microtubules and stick to each other instead.

Eventually, the detached tau molecules form long filaments, or neurofibrillary tangles, that disrupt the brain cell’s ability to communicate with other cells.

The new study introduces the possibility that, in Alzheimer’s disease, tau disrupts yet another mechanism that involves communication between the nucleus of the brain cell and its body.

Communication with cell nucleus

The cell nucleus communicates with the rest of the cell using structures called nuclear pores, which comprise more than 400 different proteins and control the movement of molecules.

Studies on the causes of amyotrophic lateral sclerosis, frontotemporal, and other types of dementia have suggested that flaws in these nuclear pores are involved somehow.

The recent study reveals that animal and human cells with Alzheimer’s disease have faulty nuclear pores, and that the fault is linked to tau accumulation in the brain cell.

“Under disease conditions,” explains co-senior study author Bradley T. Hyman, the director of the Alzheimer’s Unit at MGH, “it appears that tau interacts with the nuclear pore and changes its properties.”

He and his colleagues discovered that the presence of tau disrupts the orderly structure of nuclear pores containing the major structural protein Nup98. In Alzheimer’s disease cells, there were fewer of these pores and those that were there tended to be stuck to each other.

‘Mislocalized’ Nup98
They also observed another curious change involving Nup98 inside Alzheimer’s disease brain cells. In cells with aggregated tau, the Nup98 was “mislocalized” instead of staying in the nuclear pore.

They revealed that this feature was more exaggerated in brain tissue of people who had died with more extreme forms of Alzheimer’s disease.

Finally, when they added human tau to living cultures of rodent brain cells, the researchers found that it caused mislocalization of Nup98 in the cell body and disrupted the transport of molecules into the nucleus.

This was evidence of a “functional link” between the presence of tau protein and damage to the nuclear transport mechanism.

The authors note, however, that it is not clear whether the Nup98-tau interaction uncovered in the study just occurs because of disease or whether it is a normal mechanism that behaves in an extreme fashion under disease conditions.

They conclude:

“Taken together, our data provide an unconventional mechanism for tau-induced neurodegeneration.”


At this moment, there are 115,000 Americans who will die if they don’t get matched with a donated organ. Twenty of them die every day, according to data collected by the United Network for Organ Sharing (UNOS).

Part of the reason that waiting list is so long is because (surprise) organs don’t fare too well without a warm, gooey body keeping them safe. Both a liver and pancreas, for which the UNOS says 14,000 and 900 people respectively are currently waiting, can only be transplanted within twelve hours of donation. Another 4,000 people are waiting for a new heart, but those only last six hours outside the body before they begin to decay.

The 95,000 people waiting on a kidney donation get a little bit more wiggle room — those can last about 30 hours. But considering all of the logistical hurdles and difficulties of matching, donating, transporting, and, transplanting organs, recipients need to be ready for surgery more or less immediately once one is available.

The simplest way to get more organs to the people who need them, it would seem, is to freeze donated organs until they’re needed, like you might do with a casserole.

It’s such a simple idea that scientists and doctors came up with the idea decades ago, but they encountered two major roadblocks that seemed insurmountable — at least, until very recently.

The doctors, cryobiologists, engineers, and physicists at biotech company Arigos Biomedical may have come up with a way to freeze and store organs for as long as necessary. The company, previously funded by two of Peter Thiel’s science-focused foundations, recently raised just under $1 million in a seed round (participants included a venture firm, an angel investor and a family foundation, they note). Arigos co-founder and CEO Tanya Jones tells Futurism that they hope to begin human experiments as soon as 2020; if that goes well the technique could be used in clinics five to seven years after that.

If their technology works, it could shorten or even eliminate some of the organ transplant waitlists in America and around the world.

To understand the science that makes this possible, we need to look at why cryopreservation hasn’t worked in the past.

The first hurdle that cryobiologists need to overcome happens while the organ is on its way down to -120 degrees Celsius, the temperature at which molecular activity stops and organs can be stored indefinitely. People, you may recall, are mostly water, and when water freezes it expands into solid ice. This fact can cause problems as organs freeze, since congealing ice pulls water from nearby cells that need it and can rupture blood vessels as it expands. This is especially a problem since expansion and freezing happen at different times as organs freeze from the outside in.

The second hurdle comes during the warming process: just like an ice cube thrown into a glass of lukewarm water, organs tended to fracture and pop as they thawed. Not too helpful if you’re trying to replace a leaky lung or heart with a non-leaky one.

Scientists solved the first problem, Jones told Futurism, in the 1970s when they discovered a process called vitrification: pumping a cocktail of organic compounds into the organs pulled out most of the water. The remaining solution — water mixed with the added organic molecules — was so full of ­­stuff that it didn’t form ice. Instead, it froze into a type of solid glass that didn’t damage the organs the way ice did. As a result, organs could be frozen without worrying about harmful ice buildup.

But many solutions used in vitrification ended up being toxic. And the second problem, the fracturing issue, still eluded scientists. Over the following decades, most lost hope and gave up.

Jones says that she and Arigos cofounder Stephen Van Sickle found a new solution when Van Sickle took a trip to the library and realized how many old research papers chronicled the attempts to prevent fracturing.

“He went to a library and uncovered a line of old research in the transplant world that was abandoned,” says Jones.

They found a way to flush out all the arteries and veins of the organ and replace it with gas. In the past, scientists had tried replacing the blood and liquid found in a donated heart with oxygen gas, which gave the organs a little bit of extra support and padding as they grew rigid. The field then shifted towards liquids. These liquid perfusions tended to work a little bit better but left the realm of gas cushions as an unexplored loose end.

Jones and Van Sickle decided gas was worth a shot — helium gas in particular, because it wouldn’t be toxic to the donated organs. “You could use any inert noble gas because rule number one: absolutely no dying [it doesn’t kill organs], and rule number two: no blowing up the lab,” says Jones. In helium, they found a way to uniformly cool an organ and also provide its vasculature with some cushioning so that any stress built up during the cooling process wouldn’t cause a fracture. With helium gas in its veins and arteries, an organ is free to shift as it freezes without shattering, just as skyscrapers are engineered to sway rather than topple in the wind.

When they realized that no one else had tried helium, Arigos was born. And it worked really well. Soon their methods became the only way to successfully freeze and thaw organs from any animal larger than a rabbit.

“We have recovered pig kidneys from temperatures of -120 degrees Celsius, which is basically the glass transition temperature,” Jones says. “We tested on pig hearts, and it worked so well and so quickly that we were unexpectedly unprepared to test the recovery.” To be more prepared in the future, the team is working on automating its processes.

Ideally, the technique could create a universal bank of donated organs so that people could be matched with an organ right when they need it, rather than having to wait their turn in line until a suitable match turns up. Or, at least, it could make it much easier to get organs to the people who need them.

A bank of frozen organs could help solve some of the more banal (but very real) hurdles to transplantation. For example, donors and recipients sometimes have different immune systems. It’s more than just their blood types — before a transplant, doctors need to see how many of the six relevant antigens (molecules that can trigger the immune system into rejecting an organ) match up as well.

With a bank of frozen organs at the ready, doctors would be able to not only save more lives with organ transplants, but they could also more carefully match donated organs and recipients to prevent rejection because a better match could be readily available in the freezer.

But it needs FDA approval to make that happen. The company plans to conduct its first pig transplant in 2019, which it hopes will go well enough to convince the FDA to authorize a human trial in 2020. From there, it will take five to seven years for federal approval.

Others in the organ transplantation community are skeptical that Arigos can achieve everything that it claims to do, especially in the timeframe it set out.

“I would predict it would be longer than that, to actual human trials,” David Klassen, Chief Medical Officer at UNOS, tells Futurism. Normally there needs to be a great deal of animal experimentation before human testing is authorized, Klassen says, and these things take time. “That’s guessing on my part, but I would expect it would be a little longer than two years before human trials.”

But still, Klassen says that that the results coming out of organ freezing research are promising, and that he hopes to see continued interest in freezing organs.

“In broad strokes, I do think it is a top priority and should be. I think from the perspective of clinical transplantation, that whole area is a little underappreciated by people who work in the field day to day,” he says. But in the distant future, he also hopes to see the research community move beyond organ banking and develop ways to 3D print or construct organs from scratch, ultimately eliminating the need for donors in the first place.

But not everyone is convinced that cryopreservation is the future of organ transplantation at all, or that Arigos is the company to do it. Robert Kormos, director of the artificial heart program and co-director of the heart transplantation program at the University of Pittsburgh Medical Center, told Futurism that he’s skeptical of organ freezing technology.

“I went to [Arigos Biomedical’s] website and there’s a lot of claims of what they’re purporting to do and what they want to do, but usually what companies like this do is give you a list of publications so you can look at what’s been published in this area,” Kormos says. The lack of published research, completed by either by Arigos staff or other researchers in the field at large, raised a red flag for Kormos, who adds that he has not seen a lot of progress in organ freezing research, a field that he’s seen slow down over the decades.

“This company may have something, but again I’m eager to see what science they’re bringing to the table,” he says. “I think cryopreservation is an interesting concept, but we’re a ways away from that being reality. Again, I haven’t seen the data.”

Until their technique is approved, Arigos is working with some collaborators to improve the way scientists develop new pharmaceuticals. Right now, it’s difficult to bring new drugs to the market because many compounds that work great in animal studies don’t work the same way in humans. As a result, one in five phase I clinical trials, the first of three types of experiments conducted on humans before a drug can be approved, typically fails.

Arigos is planning to sell some slices of frozen, donated human organs to pharmaceutical researchers. That could help researchers determine whether or not a drug is toxic to people before they try it in a full-fledged experiment.

“We’ve got some collaborators set up who are going to explore that with us once we get access to human hearts, which we don’t quite yet,” says Jones.

But even if Arigos’ human trials are successful, the company won’t be able to store every type of organ that someone might need. Because their technique requires filling blood vessels with helium, it doesn’t work so well on organs that don’t have blood vessels, so they’ve only been able to freeze and store organs such as kidneys, livers, hearts, and lungs.

The military would love to be able to store entire frozen limbs, but that’s not on the table right now. If a soldier were to lose a limb after being caught in an explosion, it would be helpful to be able to freeze that limb until it’s ready to be reattached. That would give the soldier time to recover before undergoing surgery.

Freezing technology can’t help there yet. Bone tissue doesn’t take up the cryoprotectant solution well. And there are so many different tissue and cell types in a whole limb, each of which has a different tolerance level to the somewhat-toxic vitrification solution, that the technique wouldn’t really work. Arigos’ technique also wouldn’t work on transplantable corneas since they also have no vasculature, so scientists will need to develop new techniques if we want a universal bank of donated organs.

This also means, as Jones explained, that Arigos’ technology will not allow (presumably very rich) people to totally freeze their bodies and re-emerge in the distant future, as so many sci-fi stories have assured us will be possible. No, Arigos’ focus is strictly on medical uses for frozen organs.

If things go the way Arigos hopes, people worldwide could benefit. “There some countries in the world that don’t even have transplant technology,” says Jones. Aside from the immediate benefits to Americans stuck on an endless waitlist for the next kidney, frozen organs could be shipped or stored anywhere, bringing aid to countries and regions where there’s no waitlist at all.


A machine learning-based model using data routinely gathered in primary care identified patients with dementia in such settings, according to research recently published in BJGP Open.

“Improving dementia care through increased and timely diagnosis is a priority, yet almost half of those living with dementia do not receive a timely diagnosis,” Emmanuel A. Jammeh, PhD, of the science and engineering department at Plymouth University in the United Kingdom, and colleagues wrote.

“A cost-effective tool that can be used by [primary care providers] to identify patients likely to be living with dementia, based only on routine data would be extremely useful. Such a tool could be used to select high-risk patients who could be invited for targeted screening,” they added.

The researchers used Read codes, a set of clinical terms used in the U.K. to summarize data for general practice, to develop a machine learning-based model to identify patients with dementia. The Read codes were selected based on their significant association with patients with dementia, and included codes for risk factors, symptoms and behaviors that are collected in primary care. To test the model, researchers collected Read-encoded data from 26,483 patients living in England aged 65 years and older.

Jammeh and colleagues found that their machine-based model achieved a sensitivity of 84.47% and a specificity of 86.67% for identifying dementia.

“This is the first demonstration of a machine-learning approach to identifying dementia using routinely collected [National Health Service] data, researchers wrote.

“With the expected growth in dementia prevalence, the number of specialist memory clinics may be insufficient to meet the expected demand for diagnosis. Furthermore, although current ‘gold standards’ in dementia diagnosis may be effective, they involve the use of expensive neuroimaging (for example, positron emission tomography scans) and time-consuming neuropsychological assessments which is not ideal for routine screening of dementia,” they continued.

The model will be evaluated with other datasets, and have its validation tested “more extensively” at general practitioner practices in the future, Jammeh and colleagues added. – by Janel Miller

Diagram of the brain of a person with Alzheimer’s Disease.

In recent years, researchers have largely converged on the role of inflammation in the development and progression of Alzheimer’s disease (AD). Studies over the past decade have revealed unexpected interactions between the brain and the immune system, and metabolic conditions such as obesity and diabetes may activate inflammatory responses that contribute to the development and progression of AD.

The activation of the inflammatory response is controlled by the inflammasome, a multi-protein oligomer that promotes the release of several pro-inflammatory cytokines including interleukin 1β (IL-1β) and interleukin 18 (IL-18). In an earlier study, a group of researchers with the University of Massachusetts Medical School, the University of Tokyo and the University of Bonn reported that mice with a cognate of Alzheimer’s disease that were additionally bred to knock out the NLRP3 gene encoding the inflammasome were completely protected from neurodegenerative effects of the disease. The researchers presumed that this was the result of their inability to produce IL-1β and IL-18.

This finding was quite promising, suggesting that targeting components of the inflammasome might be a path to Alzheimer’s treatments. In their new study, they sought to determine the effect of IL-18 by breeding IL-18 knockout mice. The researchers considered IL-18 to be a promising target, because levels are elevated in the cerebrospinal fluid of AD patients with mild cognitive impairment. Additionally, it is known to increase the production of amyloid peptide.

But the result of the new mouse study was startling, and completely unprecedented in Alzheimer’s research. The IL-18 knockout mice developed a lethal seizure disorder that the researchers attribute to an increase in neuronal network transmission. The authors write, “… the effects of IL-18 deletion were so dramatic that we were unable to identify previous evidence to help understand the phenomena.”

The finding that a proinflammatory cytokine might in some way ameliorate seizure-inducing neural activity seems counterintuitive, since inflammation is theorized to promote neurodegenerative symptoms in AD. The researchers believe that epilepsy is understudied in AD patients, even though it is a common complication; they point out that two-thirds of AD patients experience both motor and non-motor seizures. Additionally, AD patients with epilepsy are more likely to develop memory loss and other cognitive symptoms, and experience a more widespread loss of brain cells than AD patients without epilepsy, according to the researchers.

They theorize that IL-18 may be counteracting seizure-promoting effects of IL-1β, and suppressing IL-18 thus induced seizures in the test mice. “In fact,” they write, “the countereffect of IL-18 and IL-1β has been documented in a mouse model of cerebellar ataxia. Importantly, we found that the acute application of IL-18 protein reduced excitatory synaptic transmission in the hippocampus, providing evidence that IL-18 has a protective function in neuronal excitability. Thus, we speculate that IL-18 directly suppresses these proepileptogenic effects of IL-1β in APP/PS1 mice.”

However, the most important implication of the study may be that, while the inflammasome is a promising therapeutic target for Alzheimer’s, inhibiting specific cytokines could negatively affect people with the disease.

More information: Inflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice. Proceedings of the National Academy of Sciences (2018).

Alzheimer’s disease (AD) is characterized by the progressive destruction and dysfunction of central neurons. AD patients commonly have unprovoked seizures compared with age-matched controls. Amyloid peptide-related inflammation is thought to be an important aspect of AD pathogenesis. We previously reported that NLRP3 inflammasome KO mice, when bred into APPswe/PS1ΔE9 (APP/PS1) mice, are completely protected from amyloid-induced AD-like disease, presumably because they cannot produce mature IL1β or IL18. To test the role of IL18, we bred IL18KO mice with APP/PS1 mice. Surprisingly, IL18KO/APP/PS1 mice developed a lethal seizure disorder that was completely reversed by the anticonvulsant levetiracetam. IL18-deficient AD mice showed a lower threshold in chemically induced seizures and a selective increase in gene expression related to increased neuronal activity. IL18-deficient AD mice exhibited increased excitatory synaptic proteins, spine density, and basal excitatory synaptic transmission that contributed to seizure activity. This study identifies a role for IL18 in suppressing aberrant neuronal transmission in AD.
Journal reference: Proceedings of the National Academy of Sciences