Isegoria

Acetaminophen, also known as paracetamol and sold widely under the brand names Tylenol and Panadol, also increases risk-taking:

In a series of experiments involving over 500 university students as participants, Way and his team measured how a single 1,000 mg dose of acetaminophen (the recommended maximum adult single dosage) randomly assigned to participants affected their risk-taking behaviour, compared against placebos randomly given to a control group.

In each of the experiments, participants had to pump up an uninflated balloon on a computer screen, with each single pump earning imaginary money. Their instructions were to earn as much imaginary money as possible by pumping the balloon as much as possible, but to make sure not to pop the balloon, in which case they would lose the money.

The results showed that the students who took acetaminophen engaged in significantly more risk-taking during the exercise, relative to the more cautious and conservative placebo group. On the whole, those on acetaminophen pumped (and burst) their balloons more than the controls.

For Lars Peter Nielsen, it all began with the mysterious disappearance of hydrogen sulfide.

The microbiologist had collected black, stinky mud from the bottom of Aarhus Harbor in Denmark, dropped it into big glass beakers, and inserted custom microsensors that detected changes in the mud’s chemistry. At the start of the experiment, the muck was saturated with hydrogen sulfide—the source of the sediment’s stink and color. But 30 days later, one band of mud had become paler, suggesting some hydrogen sulphide had gone missing. Eventually, the microsensors indicated that all of the compound had disappeared. Given what scientists knew about the biogeochemistry of mud, recalls Nielsen, who works at Aarhus University, “This didn’t make sense at all.”

The first explanation, he says, was that the sensors were wrong. But the cause turned out to be far stranger: bacteria that join cells end to end to build electrical cables able to carry current up to 5 centimeters through mud. The adaptation, never seen before in a microbe, allows these so-called cable bacteria to overcome a major challenge facing many organisms that live in mud: a lack of oxygen. Its absence would normally keep bacteria from metabolizing compounds, such as hydrogen sulfide, as food. But the cables, by linking the microbes to sediments richer in oxygen, allow them to carry out the reaction long distance.

[...]

Most cells thrive by robbing electrons from one molecule, a process called oxidation, and donating them to another molecule, usually oxygen—so-called reduction. Energy harvested from these reactions drives the other processes of life. In eukaryotic cells, including our own, such “redox” reactions take place on the inner membrane of the mitochondria, and the distances involved are tiny—just micrometers. That is why so many researchers were skeptical of Nielsen’s claim that cable bacteria were moving electrons across a span of mud equivalent to the width of a golf ball.

The vanishing hydrogen sulfide was key to proving it. Bacteria produce the compound in mud by breaking down plant debris and other organic material; in deeper sediments, hydrogen sulfide builds up because there is little oxygen to help other bacteria break it down. Yet, in Nielsen’s laboratory beakers, the hydrogen sulfide was disappearing anyway. Moreover, a rusty hue appeared on the mud’s surface, indicating that an iron oxide had formed.

(Hat tip to Hans G. Schantz.)

The immune system is very complicated, Ed Yong notes, but it works, roughly, like this:

The first of three phases involves detecting a threat, summoning help, and launching the counterattack. It begins as soon as a virus drifts into your airways, and infiltrates the cells that line them.

When cells sense molecules common to pathogens and uncommon to humans, they produce proteins called cytokines. Some act like alarms, summoning and activating a diverse squad of white blood cells that go to town on the intruding viruses — swallowing and digesting them, bombarding them with destructive chemicals, and releasing yet more cytokines. Some also directly prevent viruses from reproducing (and are delightfully called interferons). These aggressive acts lead to inflammation. Redness, heat, swelling, soreness — these are all signs of the immune system working as intended.

This initial set of events is part of what’s called the innate immune system. It’s quick, occurring within minutes of the virus’s entry. It’s ancient, using components that are shared among most animals. It’s generic, acting in much the same way in everyone. And it’s broad, lashing out at anything that seems both nonhuman and dangerous, without much caring about which specific pathogen is afoot. What the innate immune system lacks in precision, it makes up for in speed. Its job is to shut down an infection as soon as possible. Failing that, it buys time for the second phase of the immune response: bringing in the specialists.

Amid all the fighting in your airways, messenger cells grab small fragments of virus and carry these to the lymph nodes, where highly specialized white blood cells — T-cells — are waiting. The T-cells are selective and preprogrammed defenders. Each is built a little differently, and comes ready-made to attack just a few of the zillion pathogens that could possibly exist. For any new virus, you probably have a T-cell somewhere that could theoretically fight it. Your body just has to find and mobilize that cell. Picture the lymph nodes as bars full of grizzled T-cell mercenaries, each of which has just one type of target they’re prepared to fight. The messenger cell bursts in with a grainy photo, showing it to each mercenary in turn, asking: Is this your guy? When a match is found, the relevant merc arms up and clones itself into an entire battalion, which marches off to the airways.

Some T-cells are killers, which blow up the infected respiratory cells in which viruses are hiding. Others are helpers, which boost the rest of the immune system. Among their beneficiaries, these helper T-cells activate the B-cells that produce antibodies — small molecules that can neutralize viruses by gumming up the structures they use to latch on to their hosts. Roughly speaking — and this will be important later — antibodies mop up the viruses that are floating around outside our cells, while T-cells kill the ones that have already worked their way inside. T-cells do demolition; antibodies do cleanup.

Both T-cells and antibodies are part of the adaptive immune system. This branch is more precise than the innate branch, but much slower: Finding and activating the right cells can take several days. It’s also long-lasting: Unlike the innate branch of the immune system, the adaptive one has memory.

After the virus is cleared, most of the mobilized T-cell and B-cell forces stand down and die off. But a small fraction remain on retainer — veterans of the COVID-19 war of 2020, bunkered within your organs and patrolling your bloodstream. This is the third and final phase of the immune response: Keep a few of the specialists on tap. If the same virus attacks again, these “memory cells” can spring into action and launch the adaptive branch of the immune system without the usual days-long delay. Memory is the basis of immunity as we colloquially know it — a lasting defense against whatever has previously ailed us.

In general, the immune system’s reaction to SARS-CoV-2 is what you would expect:

Still, “any virus that can make people sick has to have at least one good trick for evading the immune system,” [Shane Crotty from the La Jolla Institute of Immunology] says. The new coronavirus seems to rely on early stealth, somehow delaying the launch of the innate immune system, and inhibiting the production of interferons — those molecules that initially block viral replication. “I believe this [delay] is really the key in determining good versus bad outcomes,” says Akiko Iwasaki, an immunologist at Yale. It creates a brief time window in which the virus can replicate unnoticed before the alarm bells start sounding. Those delays cascade: If the innate branch is slow to mobilize, the adaptive branch will also lag.

[...]

Immune responses are inherently violent. Cells are destroyed. Harmful chemicals are unleashed. Ideally, that violence is targeted and restrained; as Metcalf puts it, “Half of the immune system is designed to turn the other half off.” But if an infection is allowed to run amok, the immune system might do the same, causing a lot of collateral damage in its prolonged and flailing attempts to control the virus.

This is apparently what happens in severe cases of COVID-19. “If you can’t clear the virus quickly enough, you’re susceptible to damage from the virus and the immune system,” says Donna Farber, a microbiologist at Columbia. Many people in intensive-care units seem to succumb to the ravages of their own immune cells, even if they eventually beat the virus. Others suffer from lasting lung and heart problems, long after they are discharged. Such immune overreactions also happen in extreme cases of influenza, but they wreak greater damage in COVID-19.

There’s a further twist. Normally, the immune system mobilizes different groups of cells and molecules when fighting three broad groups of pathogens: viruses and microbes that invade cells, bacteria and fungi that stay outside cells, and parasitic worms. Only the first of these programs should activate during a viral infection. But Iwasaki’s team recently showed that all three activate in severe COVID-19 cases. “It seems completely random,” she says. In the worst cases, “the immune system almost seems confused as to what it’s supposed to be making.”

Zach Weinersmith (the cartoonist behind Saturday Morning Breakfast Cereal and Soonish) illustrates the ideas in Stuart Ritchie’s new book, Science Fictions: How Fraud, Bias, Negligence and Hype Undermine the Search for Truth.

(Ritchie’s previous book was Intelligence: All that Matters.)

Here are a few of my favorite panels:

Your brain handles a perceived threat differently depending on how close it is to you;

“Clinically, people who develop PTSD are more likely to have experienced threats that invaded their personal space, assaults or rapes or witnessing a crime at a close distance. They’re the people that tend to develop this long-lasting threat memory,” said Kevin LaBar, a professor of psychology and neuroscience at Duke University who is the senior author on a paper appearing this week in the Proceedings of the National Academy of Sciences.

“We’ve never been able to study that in the lab because you have a fixed distance to the computer screen,” LaBar said.

But Duke graduate student Leonard Faul and postdoc Daniel Stjepanovic figured out a way to do it, using a 3D television, a mirror and some MRI-safe 3D glasses.

“It’s like an IMAX experience,” LaBar said. “The threatening characters popped out of the screen and would either invade your personal space as you’re navigating this virtual world, or they were farther away.”

The VR simulation put 49 study subjects into a first-person view that had them moving down either a dark alley or a brighter, tree-lined street as they lay in the MRI tube having their brains scanned. Ambient sound and visual backgrounds were altered to provide some context for the threat versus safe memories.

On the first day of testing, subjects received a mild shock when the “threat avatar” appeared, either two feet away or 10 feet away, but not when they saw the safe avatar at the same distances.

The data from the first day showed that near threats were more frightening and they engaged limbic and mid-brain “survival circuitry,” in a way that the farther threats did not.

The following day, subjects encountered the same scenarios again but only a few shocks were given initially to remind them of the threatening context. Once again, the subjects showed a greater behavioral response to near threats than to distant threats.

“On the second day, we got fear reinstatement, both near and far threats, but it was stronger for the near threat,” LaBar said.

Tellingly, the nearby threats that engaged the survival circuits also proved harder to extinguish after they no longer produced shocks. The farther threats that engaged more higher-order thinking in the cortex were easier to extinguish. The near threats engaged the cerebellum, and the persistence of this signal predicted how much fear was reinstated the next day, LaBar said. “It’s the evolutionarily older cortex.”

The more distant threats showed greater connectivity between the amygdala, hippocampus and ventral medial prefrontal cortex and the areas of the cortex related to complex planning and visual processing, areas the researchers said are more related to thinking one’s way out of a situation and coping.

(Hat tip to Greg Ellifritz.)

Covid-19 kills from around 0.3% to 1.5% of people infected:

Most studies put the rate between 0.5% and 1.0%, meaning that for every 1,000 people who get infected, from five to 10 would die on average.

More than 14.7 million people have been infected with SARS-CoV-2 across the globe, and over 609,000 people have died, with nearly a quarter of the fatalities in the U.S., according to data compiled by Johns Hopkins University. That means that among confirmed global cases, roughly 4.2% of those people died.

The percentage of deaths among people with confirmed infections is higher than the percentage of deaths among infections overall, researchers say, because so many milder and asymptomatic Covid-19 cases go missed.

The U.S. Centers for Disease Control and Prevention has estimated that for every known case of Covid-19, roughly 10 more went unrecorded through the beginning of May. From March to early May, the total number of infections was likely six to 24 times greater than the number of reported cases depending on the state, the agency said Tuesday in a paper published in the journal JAMA Internal Medicine.

[...]

An analysis of 26 different studies estimating the infection-fatality rate in different parts of the globe found an aggregate estimate of about 0.68%, with a range of 0.53% to 0.82%, according to a report posted in July on the preprint server medRxiv, which hasn’t yet been reviewed by other researchers.

A study conducted by professor Yaakov Nahmias at Hebrew University in Israel has found that an existing cholesterol drug, fenofibrate, could ‘downgrade’ Covid-19 threat level to that of a common cold:

According to the research, the virus leads to deposits of lipids in the lungs. Nahmias partnered with Mount Sinai Medical Center researcher Dr Benjamin tenOever to gain better insights into SARS-CoV-2 mechanism of attack on the human body.

The researchers observed that the virus changes lipid metabolism in human lungs. They believe that halting this process could help prevent the onset of problems that increase the severity of the disease.

While SARS-CoV-2 hinders the ability of the body to break down fat, fenofibrate starts this process by binding and activating the DNA site that is blocked by the virus.

Countries in the Southern Hemisphere are reporting far lower numbers of influenza and other seasonal respiratory viral infections this year, due to measures meant to corral the coronavirus, like mask use and restrictions on air travel:

“We keep checking for the other viruses, but all we’re seeing is Covid,” said Dr. Cortés, the Chilean doctor. Of roughly 1,300 Covid-19 patients she has treated since late March, only a handful had the flu. “We were surprised by the decline in the other viruses like influenza. We never dreamed it would practically disappear,” she said.

Chile has recorded only 1,134 seasonal respiratory infections so far this year, compared with 20,949 during the same period last year. In the first two weeks of July—the equivalent to early January in the Northern Hemisphere and the height of the local flu season—the country reported no new confirmed influenza cases.