I’m too lazy to think of a new headline

The (antidepressant) pathway not taken (yet)

New antidepressants come out every so often, but they tend to be variations on the SSRI/SNRI theme. Ketamine, though, works differently — it leads to an increase in IGF-1, which has antidepressant effects. And Japanese researchers confirmed that yes, this is an entirely different kind of antidepressant pathway.

The researchers hypothesized that the single dose of ketamine increases the level of IGF-1 in the brain, persistently changing prefrontal cortex nerves and causing them to increase their number of stable connections.

So what does this mean? It means “IGF-1 presents a brand-new direction for future studies investigating antidepressants.”

We did improvise — next is adapt and overcome

In February 2021, the White House directed the HHS: Find out how vulnerable the country’s drug supply is, and identify the weak spots.

Well, the report is out, and it found plenty of weak spots, from lack of communication and data sharing, to purchasing practices that choose price over resiliency, to “[l]ack of clearly defined roles for federal agencies,” and even the lack of a plan for when shortages occur.

(The good news is that this is less of a “Everything’s Horrible and We’re All Gonna Die” report, and more of a “Here’s What We Can Do to Fix It” report — there are no recommendations out of the realm of possibility.)

The new age of drug discovery

Lock and key, bacteria-style

Nanoengineers at the University of Michigan, they’ve developed computer models that can predict how nanoparticles will fit into various proteins like puzzle pieces.

Instead of just looking for chemical reactions, they’re screening for molecules with a specific shape — one that can “attack bacteria and viruses in ways that they choose, taking advantage of the “lock-and-key” mechanisms that dominate interactions between biological molecules.”

Learning from bacteria

Some bacteria can kill other bacteria, but teasing out the exact mechanism hasn’t been easy. But now Rockefeller University genetic engineers have developed a way to read the genes of “stubborn bacteria that are tricky or impossible to study in the lab” and have a computer figure out what kinds of compounds they encode for.

[M]odern algorithms can predict the structure of the antibiotic like compounds that a bacterium with these sequences would produce. Organic chemists can then take that data and synthesize the predicted structure in the lab.

Then they test that structure to see if it can kill resistant bacteria. And now they have a first potential drug: A compound named cilagicin that “employs a novel mechanism to attack MRSA, C. diff, and several other deadly pathogens.”

A downside to caffeine

As hard as it may be to believe, it’s possible that having too much caffeine could make you less of a man — whether or not you stick out your pinkie when drinking tea.

A study out of Emory University (with a little help from colleagues at Stanford and Italy’s Rome University) found that six of the metabolic products of caffeine “are associated with” lower testosterone and indeed lower biochemical androgens in general. Of course associated with doesn’t necessarily mean causes — but it’s a path they think worth exploring.

Remind me: Why do we have laws?

What happens if you make a rule but don’t enforce it? Hospitals, it seems, just ignore it.

Hospitals are required by federal mandate (via CMS) to make their prices transparent — among other disclosures, they’re supposed to make the cash price and maximum and minimum negotiated prices for some services. But a new report out of Rice University found that “Many of the nation’s most prominent hospitals are blatantly violating” that mandate.

[H]ospitals justify flouting the transparency rules by arguing that the mandates put them at a competitive disadvantage, and that collecting and posting the data is burdensome.

The translation sounds like a whiny teenager: “It’s not faaaaair! And I don’t wanna do all that work!”

The Long Read: Viral Disruption edition

Measures to prevent the spread of Covid-19 also (obviously) stopped the spread of other viruses — think about the last two mild flu seasons. But it’s never that simple; our response to Covid has scrambled the usual patterns of illness.

Today’s non-pharma, cool science story

Most residents of Pompeii fled the city as Vesuvius began erupting, but not everyone. A genetic study of the remains of two victims (the first of its kind) revealed why they may have stayed behind:

[T]he man’s skeleton contained DNA from tuberculosis-causing bacteria, suggesting he might have had the disease prior to his death.

The woman has osteoporosis, which may have made it hard to move, or she may have stayed behind with the man (who was 15 years her junior).