Original image

Common NSAID Used for Period Pain May Reverse Memory Loss in Alzheimer’s

Original image

Alzheimer’s drug research continues to look to the future, toward new drugs that might one day treat the ravaging symptoms of the neurodegenerative disease, such as memory loss and even lead to a cure. However, a research team out of the University of Manchester in the UK, led by neuroimmunologist David Brough, has taken their work in the opposite direction, looking at old drugs that are successfully reversing memory loss in a mouse model. Their findings were published in the journal Nature Communications.

When it comes to understanding what causes the dangerous buildup of amyloid plaques and tau tangles in the brain that are prevalent in Alzheimer’s, “evidence is building for inflammation," neuroimmunologist Jack Rivers-Auty, a co-author on the paper, tells mental_floss. "It’s a bit like when you roll your ankle—you put ice on it to reduce swelling because you’re worried about inflammation causing more damage," he says. "Inflammation is a very complex process made up of many cell types and proteins… many of which may be causing collateral damage in the brain."

He and neuroimmunology colleague Mike Daniels conducted experiments on mice after their lab director theorized that common non-steroidal anti-inflammatory drugs (NSAIDs) might inhibit a key inflammatory pathway in the brain that damages brain cells, called the NLRP3 inflammasome complex. “I screened a number of drugs against the inflammasome with cells in a dish,” Daniels tells mental_floss. He was expecting ibuprofen and other more well-known drugs to be the most potent, but in fact, “they had no effect,” he says.

What did work was a less commonly known NSAID called mefanimic acid, which is mainly used for menstrual pain, he says. It worked because it has a different structure. Classic NSAIDs inhibit a protein called cyclooxygenase, whereas mefanimic acid inhibits the inflammasome complex itself.

Next they tested the drugs in a double-blind, placebo-controlled study on mice that were at an age when memory deficits begin to show up, approximately 15 months old. Rivers-Auty says if they were to translate this into a clinical setting with humans, “we would want to aim for people who have just started Alzheimer’s disease. Alzheimer’s [partly causes] the death of neurons, and it’s hard to grow new neurons.”

They used a range of memory tests on the mice to determine whether their memory was in decline before administering mefanimic acid. The most common among them is called the novel object recognition test. This test is useful because mice, like us, are sensitive to unfamiliar objects. Imagine you enter a parking lot looking for your car. In the lot, you find only two objects: your car and an alien's spaceship. "You would spend more time exploring the spaceship because you hadn’t seen it before,” Rivers-Auty says.

Mice will behave similarly. But what happens if their memory is deficient? To find out, the team gave 10 mice a placebo, while the other 10 were treated with mefanimic acid via a subcutaneous pump for 28 days. The study found that “the mouse with good memory explores the new object, and the mouse with poor memory explores them both,” Rivers-Auty explains. 

At the end of the study, the mice that had been given the mefanimic acid “did not have memory deficits,” he says. The drug had restored memory function to the mice with failing memory.

The results were so surprising to them, Rivers-Auty says, “We were literally hooting and hollering. We couldn’t believe how well it worked. It’s very unusual for groups to reverse memory deficits.”

The team is hopeful that this discovery could bypass as much as 15 years of the usual process to develop a new drug because mefanimic acid is already in use by humans and has been deemed safe. “We can skip the extensive animal testing and the first stage of human trials,” says Rivers-Auty. “This saves a huge amount of time and money.”

However enthusiastic he and his colleagues are about their results, Rivers-Auty is skeptical that the team will find commercial funding sources for the next stage of trials in humans because “pharmaceutical companies who usually fund these studies have no interest in funding a study they can’t make money off,” he says. Instead, this team relies on charities such as the Alzheimer’s Society and Alzheimer’s Research UK, which funded their work.

Original image
iStock // Ekaterina Minaeva
Man Buys Two Metric Tons of LEGO Bricks; Sorts Them Via Machine Learning
Original image
iStock // Ekaterina Minaeva

Jacques Mattheij made a small, but awesome, mistake. He went on eBay one evening and bid on a bunch of bulk LEGO brick auctions, then went to sleep. Upon waking, he discovered that he was the high bidder on many, and was now the proud owner of two tons of LEGO bricks. (This is about 4400 pounds.) He wrote, "[L]esson 1: if you win almost all bids you are bidding too high."

Mattheij had noticed that bulk, unsorted bricks sell for something like €10/kilogram, whereas sets are roughly €40/kg and rare parts go for up to €100/kg. Much of the value of the bricks is in their sorting. If he could reduce the entropy of these bins of unsorted bricks, he could make a tidy profit. While many people do this work by hand, the problem is enormous—just the kind of challenge for a computer. Mattheij writes:

There are 38000+ shapes and there are 100+ possible shades of color (you can roughly tell how old someone is by asking them what lego colors they remember from their youth).

In the following months, Mattheij built a proof-of-concept sorting system using, of course, LEGO. He broke the problem down into a series of sub-problems (including "feeding LEGO reliably from a hopper is surprisingly hard," one of those facts of nature that will stymie even the best system design). After tinkering with the prototype at length, he expanded the system to a surprisingly complex system of conveyer belts (powered by a home treadmill), various pieces of cabinetry, and "copious quantities of crazy glue."

Here's a video showing the current system running at low speed:

The key part of the system was running the bricks past a camera paired with a computer running a neural net-based image classifier. That allows the computer (when sufficiently trained on brick images) to recognize bricks and thus categorize them by color, shape, or other parameters. Remember that as bricks pass by, they can be in any orientation, can be dirty, can even be stuck to other pieces. So having a flexible software system is key to recognizing—in a fraction of a second—what a given brick is, in order to sort it out. When a match is found, a jet of compressed air pops the piece off the conveyer belt and into a waiting bin.

After much experimentation, Mattheij rewrote the software (several times in fact) to accomplish a variety of basic tasks. At its core, the system takes images from a webcam and feeds them to a neural network to do the classification. Of course, the neural net needs to be "trained" by showing it lots of images, and telling it what those images represent. Mattheij's breakthrough was allowing the machine to effectively train itself, with guidance: Running pieces through allows the system to take its own photos, make a guess, and build on that guess. As long as Mattheij corrects the incorrect guesses, he ends up with a decent (and self-reinforcing) corpus of training data. As the machine continues running, it can rack up more training, allowing it to recognize a broad variety of pieces on the fly.

Here's another video, focusing on how the pieces move on conveyer belts (running at slow speed so puny humans can follow). You can also see the air jets in action:

In an email interview, Mattheij told Mental Floss that the system currently sorts LEGO bricks into more than 50 categories. It can also be run in a color-sorting mode to bin the parts across 12 color groups. (Thus at present you'd likely do a two-pass sort on the bricks: once for shape, then a separate pass for color.) He continues to refine the system, with a focus on making its recognition abilities faster. At some point down the line, he plans to make the software portion open source. You're on your own as far as building conveyer belts, bins, and so forth.

Check out Mattheij's writeup in two parts for more information. It starts with an overview of the story, followed up with a deep dive on the software. He's also tweeting about the project (among other things). And if you look around a bit, you'll find bulk LEGO brick auctions online—it's definitely a thing!

Original image
Live Smarter
Working Nights Could Keep Your Body from Healing
Original image

The world we know today relies on millions of people getting up at sundown to go put in a shift on the highway, at the factory, or in the hospital. But the human body was not designed for nocturnal living. Scientists writing in the journal Occupational & Environmental Medicine say working nights could even prevent our bodies from healing damaged DNA.

It’s not as though anybody’s arguing that working in the dark and sleeping during the day is good for us. Previous studies have linked night work and rotating shifts to increased risks for heart disease, diabetes, weight gain, and car accidents. In 2007, the World Health Organization declared night work “probably or possibly carcinogenic.”

So while we know that flipping our natural sleep/wake schedule on its head can be harmful, we don’t completely know why. Some scientists, including the authors of the current paper, think hormones have something to do with it. They’ve been exploring the physiological effects of shift work on the body for years.

For one previous study, they measured workers’ levels of 8-OH-dG, which is a chemical byproduct of the DNA repair process. (All day long, we bruise and ding our DNA. At night, it should fix itself.) They found that people who slept at night had higher levels of 8-OH-dG in their urine than day sleepers, which suggests that their bodies were healing more damage.

The researchers wondered if the differing 8-OH-dG levels could be somehow related to the hormone melatonin, which helps regulate our body clocks. They went back to the archived urine from the first study and identified 50 workers whose melatonin levels differed drastically between night-sleeping and day-sleeping days. They then tested those workers’ samples for 8-OH-dG.

The difference between the two sleeping periods was dramatic. During sleep on the day before working a night shift, workers produced only 20 percent as much 8-OH-dG as they did when sleeping at night.

"This likely reflects a reduced capacity to repair oxidative DNA damage due to insufficient levels of melatonin,” the authors write, “and may result in cells harbouring higher levels of DNA damage."

DNA damage is considered one of the most fundamental causes of cancer.

Lead author Parveen Bhatti says it’s possible that taking melatonin supplements could help, but it’s still too soon to tell. This was a very small study, the participants were all white, and the researchers didn't control for lifestyle-related variables like what the workers ate.

“In the meantime,” Bhatti told Mental Floss, “shift workers should remain vigilant about following current health guidelines, such as not smoking, eating a balanced diet and getting plenty of sleep and exercise.”