An anonymous reader quotes a report from Ars Technica: New data suggests that psychedelics may activate serotonin signaling in a very different way than serotonin itself can, reaching the receptors in parts of the cell that serotonin can't get to. Serotonin signaling is complicated. There are seven classes of receptors in humans; some activate signaling pathways, while others inhibit them. One group of receptors allows ions into a cell in response to serotonin, triggering nerve impulses. The rest interact with proteins inside the cell, triggering longer-term responses to serotonin. Psychedelics such as LSD and mescaline bind to members of this latter group and activate it.

This action produces some rather dramatic changes in how people perceive their surroundings. But there's also some evidence that psychedelics promote changes to nerve cells that allow these cells to alter their connectivity. This occurs by causing the structures that receive input from other nerve cells, called dendrites, to grow and branch, potentially allowing additional or altered inputs. One hypothesis is that this altered connectivity allows cells to escape whatever network configuration has been associated with a medical disorder. The researchers confirmed these results using DMT, a psychedelic found in ayahuasca, and psilocin, the active form of the drug psilocybin, which is typically obtained from mushrooms. Twenty-four hours after mice received one of these drugs, nerve cells in their brains had an increased density of extensions from their dendrites. This growth was accompanied by an increased frequency of activity in individual nerve cells. Running the same tests in mice that lacked the gene for the specific serotonin receptor that these drugs target blocked both of these effects, confirming that serotonin signaling is central to the changes.

The researchers then started testing close chemical relatives of the drugs and saw a clear pattern: Making the drug less likely to interact with water boosted their effects on neurons. This suggested that the ability to cross membranes, which are very water-repellant, might be needed to promote changes in dendrites. To confirm this, the researchers poked holes in the membranes, which boosted the activity of water-friendly drug variants that wouldn't readily cross the membrane. This is all a bit confusing because the serotonin receptors sit inside the membrane and interact with the cell's exterior. They have to -- that's where the serotonin is. So why would anything that interacted with those receptors need to cross a membrane to the cell's interior? The receptors on the cell's surface are definitely key to the cell's response to serotonin. But the receptors don't just magically appear on the cell's surface -- they're made elsewhere in the cell and take a while to be processed and transported to the surface. The researchers found a population of serotonin receptors sitting inside a structure called the Golgi. It's not clear whether this population is simply on its way to the cell surface or whether it's retained there by some specific biological activity. Normally, these receptors wouldn't come into contact with serotonin, so they wouldn't signal from this location. But the researchers modified a protein to make it pump serotonin inside of cells and showed that it had the same effect the psychedelics had, suggesting the receptors could be activated and that this activation was key to altering neural connectivity. The study has been published in the journal Science.

Pollution from livestock farming, pharmaceuticals and healthcare is threatening to destroy a key pillar of modern medicine, as spills of manure and other pollution into waterways are adding to the global rise of superbugs, the UN has warned. From a report: Animal farming is one of the key sources of strains of bacteria that have developed resistance to all forms of antibiotics, through the overuse of the medicines in farming. Pharmaceutical pollution of waterways, from drug manufacturing plants, is also a major contributor, along with the failure to provide sanitation and control sewage around the world, and to tackle waste from healthcare facilities. Resistant superbugs can survive in untreated sewage.

The findings of the new report, published on Tuesday, show that pollution and a lack of sanitation in the developing world can no longer be regarded by the rich world as a faraway and localised problem for poor people. When superbugs emerge, they quickly spread, and threaten the health even of people in well-funded healthcare systems in the rich world. Poor sanitation and healthcare, and a lack of regulation in animal farming, create breeding grounds for resistant bacteria, and threaten global health as a result, the UN Environment Programme found in the report. As many as 10 million people a year could be dying by 2050 as a result of antimicrobial resistance (AMR), according to the UN, making it as big a killer as cancer is today. The rise of superbugs will also take an economic toll, resulting in the loss of about $3.4tn a year by the end of this decade, and pushing 24 million people into extreme poverty.

As farmers in Europe and across the world grapple with increases in the cost of fertilizers, researchers suggest a solution may be closer to home in what people flush down the toilet. From a report: A peer-reviewed paper by scientists in Europe published Monday in the journal Frontiers in Environmental Science found that fertilizer made from human feces and urine is safe to use, and that only extremely tiny quantities of chemicals from medicines or drugs, for example, would get into the food. Governments worldwide are struggling to keep fertilizer costs manageable and increase self-sufficiency after Russia's invasion of Ukraine drove up prices of natural gas, a key feedstock for crop nutrients. European Union authorities are considering ways to speed up development of manure-based fertilizers after the surge in costs spurred anger among the bloc's farmers.

In terms of safety, the researchers screened human waste for 310 chemicals, from pharmaceuticals to insect repellents, and found that only 6.5% of these were above the limit for detection and at low concentrations. "In general, the risk for human health of pharmaceutical compounds entering the food system by means of fecal compost use, seems low," the authors concluded. While they detected two pharmaceutical products in edible parts of cabbages, the painkiller ibuprofen and the anticonvulsant drug carbamazepine, the concentrations were markedly low. This means that more than half a million cabbage heads would need to be eaten to accumulate a dose equivalent to one carbamazepine pill, they said.

New medicines need not be tested in animals to receive U.S. Food and Drug Administration (FDA) approval, according to legislation signed by President Joe Biden in late December 2022. Science Magazine reports: "This is huge," says Tamara Drake, director of research and regulatory policy at the Center for a Humane Economy, a nonprofit animal welfare organization and key driver of the legislation. "It's a win for industry. It's a win for patients in need of cures." In place of the 1938 stipulation that potential drugs be tested for safety and efficacy in animals, the law allows FDA to promote a drug or biologic -- a larger molecule such as an antibody -- to human trials after either animal or nonanimal tests. Drake's group and the nonprofit Animal Wellness Action, among others that pushed for changes, argue that in clearing drugs for human trials the agency should rely more heavily on computer modeling, "organ chips," and other nonanimal methods that have been developed over the past 10 to 15 years.

But pro-research groups are downplaying the law, saying it signals a slow turning of the tide -- not a tsunami that will remake the drug approval process overnight. Jim Newman, communications director at Americans for Medical Progress, which advocates for animal research, argues non-animal technologies are still "in their infancy" and won't be able to replace animal models for "many, many years." FDA still retains tremendous discretion to require animal tests, he notes, and he doesn't expect the agency to change tack anytime soon. In order for a drug to be approved in the United States, FDA typically requires toxicity tests on one rodent species such as a mouse or rat and one nonrodent species such as a monkey or dog. Companies use tens of thousands of animals for such tests each year. Yet more than nine in 10 drugs that enter human clinical trials fail because they are unsafe or ineffective, providing grist to those who argue that animal experiments are a waste of time, money, and lives. [...]

Now, that requirement is gone. In eliminating it, Congress seems to have responded to the emergence of nonanimal methods and growing public sentiment against animal research. Senator Rand Paul (R-KY) and Senator Cory Booker (D-NJ), who both call animal research inefficient and inhumane, introduced the changes, which the Senate passed by unanimous consent in September 2022. In December, Biden signed them into law as part of the Consolidated Appropriations Act, which funds the government through this fiscal year. [...] Still, it remains unclear just how much the new law will change things at FDA. Although the legislation allows the agency to clear a drug for human trials without animal testing, it doesn't require that it do so. What's more, FDA's toxicologists are famously conservative, preferring animal tests in part because they allow examination of a potential drug's toxic effects in every organ after the animal is euthanized.

On Jan. 1, Oregon became the first state in the nation to legalize the adult use of psilocybin, a naturally occurring psychedelic that has shown significant promise for treating severe depression, post-traumatic stress disorder and end-of-life anxiety among the terminally ill, among other mental health conditions. From a report: Although scientists are still working to understand their therapeutic dynamics, psilocybin and other psychedelics are thought to promote neuroplasticity, a rewiring of the brain that gives patients fresh perspectives on longstanding psychiatric problems. One recent study on alcohol-use disorder, for example, found that two doses of psilocybin paired with talk therapy led to an 83 percent decline in heavy drinking among participants, and that nearly half of them had stopped drinking entirely by the end of the eight-month trial. The long-term benefits, however, remain unclear. Measure 109, as it's called, authorized the creation of psilocybin service centers where anyone over 21 can consume the mushrooms in a supervised setting. One key requirement is that a state-certified facilitator must be present during drug-induced journeys, which can last five or six hours.

Longtime Slashdot reader UnanimousCoward writes: Forbes has published a transcript of SBF's planned testimony as well as a synopsis which, of course, will not happen now. At no point does he admit fraudulent behavior and does not address the (multi-)billion dollar loans that helped contribute to the flywheel Ponzi scheme. FTX founder Sam Bankman-Fried was arrested yesterday by the Royal Bahamas Police Force. He was set to testify virtually before the House Financial Services Committee about the exchange's collapse on Tuesday (today).

Here are the key takeaways from SBF's draft testimony, as highlighted by Forbes: - Bankman-Fried is being ghosted by FTX's court-appointed CEO John Ray.
- Bankman-Fried says that FTX.US general counsel and former Sullivan & Cromwell partner, Ryne Miller, put intense pressure on Bankman-Fried and others to rush into filing for Chapter 11.
- Bankman-Fried believes that John Ray and law firms managing the bankruptcy, including Sullivan and Cromwell, are dusting off the Enron playbook in an effort to reap enormous fees from FTX's bankruptcy.
- The Chapter 11 team is not playing nice with foreign regulators.
- Bankman-Fried thinks that John Ray and the U.S. Bankruptcy Court is bullying the Bahamian government and overstepping its rights as the main domicile for FTX International.
- Bankman-Fried devotes seven pages to a section he calls "Misstatements," detailing instances where John Ray and team are disseminating false and inaccurate information about the companies he created.
- FTX did not have a risk management team.
- Bankman-Fried claims that there are signed Letters of Intent (LOIs) from prospective investors that could recapitalize the exchange.
- Binance CEO Changpeng Zhao orchestrated a negative public relations campaign to bring down FTX.
- Having eliminated FTX as its largest global competitor, Binance is now averaging approximately 70% of global cryptocurrency volume.
- Bankman-Fried wants to set the record straight on false reports of hard partying at FTX and on his own drug usage. He says he has never been drunk in his life, and has been on an antidepressant for the last decade.

"After decades in the shadow of the reigning model for Alzheimer's disease, alternative explanations are finally getting the attention they deserve," writes Quanta magazine — in a 10,000-word update on where we are now: Three decades ago, scientists thought they had cracked the medical mystery of what causes Alzheimer's disease with an idea known as the amyloid cascade hypothesis. It accused a protein called amyloid-beta of forming sticky, toxic plaques between neurons, killing them and triggering a series of events that made the brain waste away.... Decades of work and billions of dollars went into funding clinical trials of dozens of drug compounds that targeted amyloid plaques. Yet almost none of the trials showed meaningful benefits to patients with the disease....

A stream of recent findings has made it clear that other mechanisms may be at least as important as the amyloid cascade as causes of Alzheimer's disease.... The emerging new models of the disease are more complex than the amyloid explanation, and because they are still taking shape, it's not clear yet how some of them may eventually translate into therapies. But because they focus on fundamental mechanisms affecting the health of cells, what's being learned about them might someday pay off in new treatments for a wide variety of medical problems, possibly including some key effects of aging.... While these alternate ideas were once hushed and thrown under the rug, now the field has broadened its attention.
The article explores the theory — derived from research on genetically-engineered mice — that neurons bulging with toxic accumulations of proteins and molecules could be mistaken for classic amyloid plaques outside cells. (But in fact "the extracellular amyloid plaques weren't killing the cells — because the cells were already dead.") Scientists are now also investigating lysosomes, cholesterol metabolism, and even the immune system.

To say that the amyloid hypothesis is dead would be overstating it, said Donald Weaver, a co-director of the Krembil Brain Institute in Toronto, but "I would say that the amyloid hypothesis is insufficient...."

By 2017, 146 drug candidates for treating Alzheimer's disease had been deemed unsuccessful. Only four drugs had been approved, and they treated the symptoms of the disease, not its underlying pathology. The results were so disappointing that in 2018, Pfizer pulled out of Alzheimer's research. A 2021 review that compared the results of 14 of the major trials confirmed that reducing extracellular amyloid did not greatly improve cognition....

The hypothesis took another hit last July when a bombshell article in Science revealed that data in the influential 2006 Nature paper linking amyloid plaques to cognitive symptoms of Alzheimer's disease may have been fabricated. The connection claimed by the paper had convinced many researchers to keep pursuing amyloid theories at the time.

An anonymous reader shares a report: At the 1,000-bed not-for-profit Kasturba Hospital in the western Indian state of Maharashtra, doctors are grappling with a rash of antibiotic-resistant "superbug infections." This happens when bacteria change over time and become resistant to drugs that are supposed to defeat them and cure the infections they cause. Such resistance directly caused 1.27 million deaths worldwide in 2019, according to The Lancet, a medical journal. Antibiotics -- which are considered to be the first line of defence against severe infections -- did not work on most of these cases.

India is one of the countries worst hit by what doctors call "antimicrobial resistance" -- antibiotic-resistant neonatal infections alone are responsible for the deaths of nearly 60,000 newborns each year. A new government report paints a startling picture of how things are getting worse. Tests carried out at Kasturba Hospital to find out which antibiotic would be most effective in tackling five main bacterial pathogens have found that a number of key drugs were barely effective.

A new report by Indian Council of Medical Research (ICMR) says that resistance to a powerful class of antibiotics called carbapenems - it defeats a number of pathogens - had risen by up to 10% in just one year alone. The report collects data on antibiotic resistance from up to 30 public and private hospitals every year. "The reason why this is alarming is that it is a great drug to treat sepsis [a life-threatening condition] and sometimes used as a first line of treatment in hospitals for very sick patients in ICUs," says Dr Kamini Walia, a scientist at Indian Council of Medical Research (ICMR) and lead author of the study.

"Scientists have designed compounds that hit the same key receptor that LSD activates without causing hallucinations. A single dose produced powerful antidepressant and antianxiety effects in mice that lasted up to two weeks. The study was recently published in the journal Nature. UC San Francisco reports: The compounds were designed to fit into the 5HT2a receptor, which is the main target of psychedelics like LSD and psilocybin mushrooms. The receptor is also activated by serotonin, a naturally occurring hormone that regulates mood, cognition and many other functions in the body. The 5HT2a receptor is thought to play a role in schizophrenia and other psychotic disorders, as well as anxiety and depression, and a host of antipsychotic and antidepressant drugs block its activity. The new molecules activate it, but in a very different way than psychedelics.

[...] Although it's been known for several decades that 5HT2a receptors activate different signaling pathways in cells, until now there were no compounds selective enough to see what each pathway did. The scientific team discovered the receptors could set off two different pathways, a hallucinatory pathway and an antidepressant/antianxiety one. LSD activates the first one more, while the new compounds activate the second one more. "The receptors are like antennae," said Brian Shoichet, PhD, professor of pharmaceutical chemistry in the UCSF School of Pharmacy. "They pick up a chemical signal, and downstream a bunch of things get activated in a cell."

The compounds had been selected from a computational library of 75 million candidates. Jonathan Ellman, PhD, the Eugene Higgins Professor of Chemistry, and professor of pharmacology at Yale, synthesized them. And the UCSF, UNC, Yale team worked for more than a year to optimize them. "The final molecules were 100 times more potent than what we started with," Shoichet said, although they were still not nearly as strong as LSD. "In the animals they are very potent, much more potent than Prozac." The team expanded to test the designer molecules in mice, adding William Wetsel, PhD, who directs the Mouse Behavioral and Neuroendocrine Analysis Core Facility at Duke. His lab looked for head twitch responses that are the tell-tale signs of psychedelic activity in mice. But the mice hardly twitched. Wetsel's lab ran the mice through a battery of tests to see if the molecules could ameliorate symptoms analogous to human anxiety and depression. And they were highly effective. After many years, what had begun as a science experiment arrived at a discovery with great clinical promise. "The team's next project will be optimizing the compounds, making them selective enough to be used in clinical trials," adds the report.

"A key issue will be making molecules that have no affinity for 5HT2b. Drugs that hit this receptor, like the banned diet drug fen-phen, can cause valvular heart disease when taken chronically. That receptor is also hit by psychedelics, particularly LSD."

A new treatment for amyotrophic lateral sclerosis, or ALS, has been approved by the US Food and Drug Administration. CNN reports: The FDA announced approval of Relyvrio, developed by Amylyx Pharmaceuticals, on Thursday. The oral medication works as a standalone therapy or when added to other treatments, according to the company, and it has been shown to slow disease progression. Patients and some advocacy groups had urged the FDA to approve the drug, as there are limited treatments available for ALS, and the agency granted priority review in December.

In November, Amylyx submitted a drug application to the FDA for the medication, then called AMX0035, as an oral ALS treatment, seeking approval based on a Phase 2 trial that included 137 people with ALS who received either the drug or a placebo for 24 weeks. The study was funded in part by a grant from the ALS Ice Bucket Challenge, the viral social media campaign that started in 2014 involving people dumping buckets of ice water over themselves to raise awareness and money around ALS. The trial also showed that the drug was generally well-tolerated, but there was a greater frequency of gastrointestinal events in the group getting the medication. Amylyx is now continuing to study its safety and efficacy in a Phase 3 trial. In March, the Peripheral and Central Nervous System Drugs Advisory Committee voted 6-4 that a single Phase 2 trial did not establish the conclusion that the drug is effective in treating ALS.

One key difference between the FDA advisory committee's March and September meetings is that in the later meeting, Amylyx indicated that if the drug was approved but its Phase 3 trial results fail to confirm the drug's benefits, the company would consider withdrawing the drug from the market, Lynch said. She added, however, that the company didn't say specifically what it would view as a failure. "So at the vote, the advisory committee members switched, and most of them said, 'Yes, we are now convinced that this product should be approved.' And when they were asked why they changed their minds, some of them said, 'Well, the company said they would withdraw,'" she said. "And they were also convinced by patients' testimonies that they very much want to try this drug." But overall, the FDA's approval was based on Phase 2 trial data, which, Lynch said, may send a message to other pharmaceutical companies that they don't need robust Phase 3 trial data to get products on the market. Although people with ALS want access to this promising drug, there are concerns that such a message could open the door more broadly to the approval of medications that have not been proved to work, says Holly Fernandez Lynch, an assistant professor of medical ethics and health policy at the University of Pennsylvania. "The FDA could later withdraw those products if needed, she said, but doing so without voluntary company agreement is 'a huge pain' and often requires a very lengthy process," reports CNN.

The pharmaceutical companies Biogen and Eisai said this week that a drug they are developing for Alzheimer's disease had slowed the rate of cognitive decline in a large late-stage clinical trial. From a report: The strong results boost the drug's chances of winning approval and offer renewed hope for a class of Alzheimer's drugs that have repeatedly failed or generated mixed results. The positive data also offer Biogen a second chance after the company's disastrous rollout of another Alzheimer's drug, Aduhelm. That medication won regulatory approval last year despite little evidence that it could slow cognitive decline, received only sharply limited coverage by Medicare and has proved to be a commercial failure.

The results appear stronger for the new medication, lecanemab. Cognitive decline in the group of volunteers who received lecanemab was reduced by 27 percent compared with the group who received a placebo in the clinical trial, which enrolled nearly 1,800 participants with mild cognitive impairment or mild Alzheimer's disease, the companies said. The trial of lecanemab, which is administered via intravenous infusion, was the largest to date to test whether clearing the brain of plaques formed by the accumulation of a protein called amyloid could slow the progression of Alzheimer's disease. Aduhelm is designed to work in a similar way.

An anonymous reader quotes a report from NPR: It's well known that weightlifting can strengthen our biceps and quads. Now, there's accumulating evidence that strengthening the muscles we use to breathe is beneficial too. New research shows that a daily dose of muscle training for the diaphragm and other breathing muscles helps promote heart health and reduces high blood pressure. "The muscles we use to breathe atrophy, just like the rest of our muscles tend to do as we get older," explains researcher Daniel Craighead, an integrative physiologist at the University of Colorado Boulder. To test what happens when these muscles are given a good workout, he and his colleagues recruited healthy volunteers ages 18 to 82 to try a daily five-minute technique using a resistance-breathing training device called PowerBreathe. The hand-held machine -- one of several on the market -- looks like an inhaler. When people breathe into it, the device provides resistance, making it harder to inhale.

"We found that doing 30 breaths per day for six weeks lowers systolic blood pressure by about 9 millimeters of mercury," Craighead says. And those reductions are about what could be expected with conventional aerobic exercise, he says -- such as walking, running or cycling. A normal blood pressure reading is less than about 120/80 mmHg, according to the Centers for Disease Control and Prevention. These days, some health care professionals diagnose patients with high blood pressure if their average reading is consistently 130/80 mmHg or higher, the CDC notes. The impact of a sustained 9 mmHg reduction in systolic blood pressure (the first number in the ratio) is significant, says Michael Joyner, a physician at the Mayo Clinic who studies how the nervous system regulates blood pressure. "That's the type of reduction you see with a blood pressure drug," Joyner says. Research has shown many common blood pressure medications lead to about a 9 mmHg reduction. The reductions are higher when people combine multiple medications, but a 10 mmHg reduction correlates with a 35% drop in the risk of stroke and a 25% drop in the risk of heart disease.

So, how exactly does breath training lower blood pressure? Craighead points to the role of endothelial cells, which line our blood vessels and promote the production of nitric oxide -- a key compound that protects the heart. Nitric oxide helps widen our blood vessels, promoting good blood flow, which prevents the buildup of plaque in arteries. "What we found was that six weeks of IMST [inspiratory-muscle strength training] will increase endothelial function by about 45%," Craighead explains. [...] There may also be benefits for elite cyclists, runners and other endurance athletes, he says, citing data that six weeks of IMST increased aerobic exercise tolerance by 12% in middle-aged and older adults. "So we suspect that IMST consisting of only 30 breaths per day would be very helpful in endurance exercise events," Craighead says. It's a technique that athletes could add to their training regimens. Craighead, whose personal marathon best is 2 hours, 21 minutes, says he has incorporated IMST as part of his own training.

Sociologist Ashley Mears know the secret to making viral videos on Facebook. "It's like a magic trick," one creator explains. Literally.

"Many of the most successful people in the content-creation game on Facebook are magicians," Mears explains in a video. "I think that that's not such a surprise, because magicians are extremely skilled in manipulating people's attention, which is basically what the viral video economy does."

Mears recently visited the "new creative elites," a group of creators regularly getting 100 million to 200 million views, which includes former jazz singer Anna Rothfuss and her magician boyfriend Justin Flom: Rothfuss and Flom are among the 180 video-makers (or "creators" in the industry's jargon) working with a Las Vegas magician called Rick Lax. They produce short videos timed to last the precise number of seconds that Facebook requires a clip to run to be eligible for an ad (this used to be three minutes but recently went down to one). Though the clips usually look like authentic user-generated material, all are scripted. Most fall into genres: diy, crafts, hazards, adultery and proposals. Lax manages his network like a cross between a Hollywood agent and a schoolteacher. He takes a slice of the ad revenue that creators earn. In exchange, he gives them online tutorials about how to make viral content: everything from how to hold the camera to which metrics matter to Facebook. He releases new instructions every time the algorithm changes substantially, and offers feedback on people's videos. He also posts his creators' videos on his own Facebook page, which has 14m followers....

A friend was making videos for Rick Lax, and invited Rothfuss to join in 2019. A year later she bought her first mansion. Entering the viral-content game involves a certain surrendering of artistic aspirations, but Rothfuss says she doesn't care. "I do not want to be famous," she says. "I love being low-key and flying under the radar, and just getting rich...."

Lax realised that appetite for these videos was insatiable: the only obstacle to earning more money was how many clips he could make in a day.... Lax wouldn't go into details of his profit-sharing arrangement but his creators are clearly flourishing. Many told me they felt like they were taking part in a 21st-century gold rush. "This doesn't happen to that many people," says Amy Boiss, a one-time Uber driver whose magician boyfriend introduced her to Lax's network. "To make more money than neurosurgeons...." Lax and his friends got rich without anyone knowing who they are....

It's perhaps no coincidence that the two most-viewed Facebook creators in 2021, Lax and Julius Dein, both started out as magicians (as did many of their affiliates). Their videos aren't magic performances as such, but they're informed by the art of magic. "Magicians start by looking for blind spots, edges, vulnerabilities and limits of people's perception," wrote a former Google employee (and amateur magician) in an essay published on Medium in 2017, "How technology hijacks your mind". Social-media companies, wrote the author, "influence what people do without them even realising it", just as magicians do: "Once you know how to push people's buttons you can play them like a piano."
Ironically, the creators end up driven by "the same dopamine rush they were exploiting in us," the article points out. "If you're looking at the data, you can actually see your earnings go up as people watch your work: making viral videos can be just as addictive as watching them."

One of the magicians in Lax's network even says point-blank that "It feels like a drug."

An anonymous reader quotes a report from the BBC: In 2020 [EndeavorRx] became the first such game to be approved by the US Food and Drug Administration (FDA) for use in the treatment of ADHD in children. Currently only available on prescription from doctors in the US, EndeavorRx at first glance looks very similar to countless other games. You control a little alien that races on a spaceship through different worlds having to collect things. But the app-based game was developed in conjunction with neuroscientists, and is designed to stimulate and improve areas of the brain that play a key role in attention function. The idea is that it trains a child with ADHD to both better multitask and ignore distractions, with a computer algorithm measuring his or her performance and customizing the difficulty of the game in real time. When doctors prescribe it, the child's parents get sent an activation link that is needed before the game will play.

Eddie Martucci, chief executive of Akili, the Boston-based tech firm behind EndeavorRx, says the game has been designed to boost cognitive progressing. "It is something that's very difficult to get through molecular means, like taking a pill. But it turns out that sensory stimuli can actually directly stimulate parts of the brain controlling cognitive function." His company now plans to launch the game in Europe in the next few years. Akili is one of only a handful of companies with clearance to offer a digital therapeutic as a prescription for medical conditions. Late last year, the FDA approved a virtual reality-based treatment for children with the visual disorder amblyopia, or lazy eye.

A retracted paper highlights chemistry's history of trying to avoid the expensive, toxic -- but necessary -- catalyst. From a report: It's hard to find a place on Earth untouched by palladium. The silvery-white metal is a key part of catalytic converters in the world's 1.4 billion cars, which spew specks of palladium into the atmosphere. Mining and other sources add to this pollution. As a result, traces of palladium show up in some of the most remote spots on Earth, from Antarctica to the top of the Greenland ice sheet. Palladium is also practically indispensable for making drugs. That's because catalysts with palladium atoms at their core have an unmatched ability to help stitch together carbon --carbon bonds. This kind of chemical reaction is key to building organic molecules, especially those used in medications.

"Every pharmaceutical we produce at some point or another has a palladium-catalysed step in it," says Per-Ola Norrby, a pharmaceutical researcher at drug giant AstraZeneca in Gothenburg, Sweden. Palladium-catalysed reactions are so valuable that, in 2010, their discoverers shared a Nobel prize. But despite its versatility, chemists are trying to move away from palladium. The metal is more expensive than gold, and molecules that contain palladium can also be extremely toxic to humans and wildlife. Chemical manufacturers have to separate out all traces of palladium from their products and carefully dispose of the hazardous waste, which adds extra expense. Thomas Fuchb, a medicinal chemist at the life-sciences company Merck in Darmstadt, Germany, gives the example of a reaction to make 3 kilograms of a drug molecule for which the ingredients cost US$250,000. The palladium catalyst alone adds $100,000; purifying it out of the product another $30,000.

Finding less-toxic alternatives to the metal could help to reduce environmental harm from palladium waste and move the chemicals industry towards 'greener' reactions, says Tianning Diao, an organometallic chemist at New York University. Researchers hope to swap palladium for more common metals, such as iron and nickel, or invent metal-free catalysts that sidestep the issue altogether. Several times in the past two decades, researchers have reported finding palladium-free catalysts. But in what has become a recurring pattern for the field, each heralded discovery turned out to be a mistake.

Scientists from the University of Michigan have "fabricated a nanoparticle to deliver an inhibitor to brain tumor in mouse models, where the drug successfully turned on the immune system to eliminate the cancer," reports ScienceDaily. "The process also triggered immune memory so that a reintroduced tumor was eliminated -- a sign that this potential new approach could not only treat brain tumors but prevent or delay recurrences." From the report: The small molecule inhibitor AMD3100 was developed to block the action of CXCR12, a cytokine released by the glioma cells that builds up a shield around the immune system, preventing it from firing up against the invading tumor. Researchers showed in mouse models of glioma that AMD3100 prevented CXCR12 from binding with immune-suppressive myeloid cells. By disarming these cells, the immune system remains intact and can attack the tumor cells. But AMD3100 was having trouble getting to the tumor. The drug did not travel well through the bloodstream, and it did not pass the blood brain barrier, a key issue with getting drugs into the brain.

The Castro-Lowenstein lab collaborated with Joerg Lahann, Ph.D., Wolfgang Pauli Collegiate Professor of Chemical Engineering at the U-M College of Engineering, to create protein-based nanoparticles to encapsulate the inhibitor, in the hopes of helping it pass through the bloodstream. Castro also connected with Anuska V. Andjelkovic, M.D., Ph.D., professor of pathology and research professor of neurosurgery at Michigan Medicine, whose research focuses on the blood brain barrier. They noted that glioma tumors create abnormal blood vessels, interfering with normal blood flow.

The researchers injected AMD3100-loaded nanoparticles into mice with gliomas. The nanoparticles contained a peptide on the surface that binds to a protein found mostly on the brain tumor cells. As the nanoparticles traveled through the bloodstream toward the tumor, they released AMD3100, which restored the integrity of the blood vessels. The nanoparticles could then reach their target, where they released the drug, thus blocking the entry of the immune-suppressive myeloid cells into the tumor mass. This allowed the immune cells to kill the tumor and delay its progression. [...] Among the mice whose tumors were eliminated, the researchers then reintroduced the tumor, simulating a recurrence. Without any additional therapy, 60% of mice remained cancer-free. The research has been published in the journal ACS Nano.

To attack tumors, the Guardian reports, "scientists are developing magnetically guided microscopic projectiles that can be injected into patients' blood." The project — led by researchers at Sheffield University — builds on progress in two key medical fields. The first involves viruses that specifically attack tumours.... After infection with an oncolytic virus, a cancer cell will burst open and die. The US Food and Drug Administration has already approved the use of T-Vec, a modified herpes simplex virus that infects and kills tumour cells and is now being used to treat people with certain types of melanoma, a skin cancer.
Unfortunately, the viruses soon get attacked by the body's immune system. So the scientists want to coat the viruses with magnetic particles, so that magnets (outside a patient's body) can quickly guide those viruses where they're needed.

And to accomplish this they're using a soil bacteria which is known to make magnets to align with Earth's own magnetic field. "The essence of this approach is straightforward," one of the project's leaders explains to the Guardian. "We are using bugs as drugs.... we have found bacteria do a better job of manufacturing them than we could." Having developed the technology, the Sheffield team is now working to ensure they can manufacture sufficient supplies so that clinical trials on humans can begin soon. To date, trials have focused on animal models. "These early tests have been very encouraging and we now need to take the next steps to bring this technique to a state where it can be administered to humans — hopefully in a few years' time."

Thanks to Slashdot reader Falconhell for sharing the article!

An anonymous reader quotes a report from International Business Times: US scientists have developed a new form of drug that promotes the regeneration of cells and reversed paralysis in mice with spinal injuries, allowing them to walk again within four weeks of treatment. The research was published in the journal Science on Thursday, and the team of Northwestern University scientists behind it hope to approach the Food and Drug Administration as early as next year to propose human trials. [Northwestern's Samuel Stupp, who led the study, and his team] used nanofibers to mimic the architecture of the "extracellular matrix" -- a naturally occurring network of molecules surrounding tissue that is responsible for supporting cells. Each fiber is about 10,000 times narrower than a human hair, and they are made up of hundreds of thousands of bioactive molecules called peptides that transmit signals to promote nerve regeneration. The therapy was injected as a gel into tissue surrounding the spinal cords of lab mice 24 hours after an incision was made in their spines.

The team decided to wait a day because humans who receive devastating spinal injuries from car accidents, gunshots and so on also experience delays in getting treatment. Four weeks later, mice who received the treatment regained their ability to walk almost as well as before the injury. Those left untreated did not. The mice were then put down to examine the impacts of the therapy on the cellular level, and the team found dramatic improvements to the spinal cords. The severed extensions of neurons called axons regenerated, and scar tissue that can act as a physical barrier to regeneration was significantly diminished. What's more, an insulating layer of axons called myelin that is important in transmitting electric signals had reformed, blood vessels that deliver nutrients to injured cells had formed, and more motor neurons survived.

A key discovery by the team was that creating a certain mutation in the molecules intensified their collective motion and heightened their efficacy. This is because receptors in neurons are naturally in constant motion, Stupp explained, and increasing the motion of the therapeutic molecules within the nanofibers helps connect them more effectively with their moving targets. The researchers in fact tested two versions of the treatment -- one with the mutation and one without -- and found that mice that received the modified version regained more function. The gel developed by the scientists is the first of its kind, but could usher in a new generation of medicines known as "supramolecular drugs," because the therapy is an assembly of many molecules rather than a single molecule, said Stupp. According to the team, it is safe because the materials biodegrade within a matter of weeks and become nutrients for cells. Stupp said he hopes to rapidly move direct to human studies next without the need for further animal testing, such as on primates.

Pfizer's oral antiviral drug was found to reduce the risk of hospitalization or death from COVID-19 by 89%, according to interim results from a mid-to-late-stage study announced by the company on Friday. From a report: Antiviral drugs can be a key pandemic-fighting tool, as not everyone will get vaccinated against the virus and it may take years to fully inoculate people in certain countries -- particularly given current gaps in global vaccine supplies. Pfizer CEO Albert Bourla said in a statement that these findings from the phase 2/3 study marked "a real game-changer in the global efforts to halt the devastation of this pandemic." Pfizer's antiviral pill, PAXLOVID (PF-07321332), was developed specifically to treat COVID-19, by blocking activity of the main enzyme the virus needs to multiply. This was co-administered with a low dose of ritonavir, which is widely used in combination treatments for HIV infection.

A key Centers for Disease Control and Prevention advisory group unanimously voted Thursday to recommend distributing Pfizer and BioNTech's Covid-19 booster shots to older Americans and nursing home residents, clearing the way for the agency to give the final OK as early as this evening. CNBC reports: The agency's Advisory Committee on Immunization Practices specifically endorsed giving third Pfizer shots to people 65 and older in the first of four votes. The panel will also vote on whether to recommend the shots for adults with medical conditions that put them at risk of severe disease and those who are more frequently exposed to the virus -- possibly including people in nursing homes and prisons, teachers, front-line health employees and other essential workers. The elderly were among the first groups to get the initial shots in December and January.

The vote is seen as mostly a win for President Joe Biden, whose administration has said it wants to give booster shots to all eligible Americans 16 and older as early as this week. While the CDC panel's recommendation doesn't give the Biden administration everything it wanted, boosters will still be on the way for millions of Americans. The endorsement comes a day after the Food and Drug Administration granted emergency use authorization to administer third Pfizer shots to many Americans six months after they complete their first two doses. While the CDC's panel's recommendation isn't binding, Director Dr. Rochelle Walensky is expected to accept the panel's endorsement shortly.