English Language & Usage: Multi-Layered Discourse Room

CowperKettle

12:02 AM

I think I can have this condition

Lesbian Initiation

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Is there life on other planets? (1962) | RetroFocus

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That accent at 00:27.

I had to listen thrice

Michael Rybkin

12:21 AM

Hi, guys. What would be the correct plural form of expressions such as "a potter's wheel", "a turner's wheel", etc?

Cerberus

12:32 AM

@MichaelRybkin Simply potter's wheels.

Michael Rybkin

@Cerberus Thank you

Cerberus

What do you need it for?

Michael Rybkin

Exactly for that, to figure our which one is the correct plural form. Need to make a note in my notebook

CowperKettle

@alphabet Julian Ropcke also wrote that one strong attack was sucessfully repelled by the Russian army, with the Ukrainian side losing 11 armored vehicles/tanks. He usually double-checks everything.

He wrote that the UKR side failed to properly investigate the terrain and advanced through a minefield in a dense formation.

Girkin praises the work of some senior RUS army officer who was charged with closely inspecting all defences and fixing all issues. This coming from the usually-galled Girkin, seems believable to me.

Cerberus

@MichaelRybkin Notebooks are nice.

Michael Rybkin

12:38 AM

yep

Got to go. See you later, guys.

CowperKettle

See ya!

alphabet

12:53 AM

ISW agrees that the counteroffensive is off to a rocky start: iswresearch.org/2023/06/…

It does seem that Ukraine is only committing a small fraction of its forces at this point. But they've already lost a fair amount of Western equipment. As expected, the front line will shift very, very slowly.

It's hard to say which of these are fixing or probing attacks. The main effort appears to be in the south, but Russia knows that & has heavily fortified that section of the front.

Cerberus

Ukraine isn't very experienced in great offensives, I suppose.

alphabet

Russia is sending its best attack fish: twitter.com/EuromaidanPress/status/1666913237940736000#m

Importantly: newly-constituted Ukrainian units are almost completely untested. We have no idea how competent or incompetent they will prove to be.

Cerberus

1:11 AM

There is that, too.

@alphabet Yum.

alphabet

If Igor Girkin gets into a pickle, does he become Igor Gherkin?

Cerberus

1:25 AM

Hah.

alphabet

I will henceforth be referring to him as "blogger, alleged war criminal, and former cucumber Igor Gherkin"

Cerberus

Henceforth or thenceforth?

alphabet

@Cerberus I think "henceforth" is correct there, no?

Cerberus

Wouldn't that imply he was in a pickle now?

alphabet

@Cerberus No, I'm just going to start saying that because it sounds funny

War crimes are fun!

Cerberus

1:38 AM

I see.

So the policy condition "if Igor Girkin gets into a pickle" has been rescinded, I see.

War crimes are the funnest.

alphabet

@Cerberus Yes. Be gay, do crimes. Be straight, do war crimes.

Cerberus

Hmm.

Under the influence of what are you, Mister?

Ugaritic?

alphabet

Apparently the phrase is "be gay, do crime." My apologies.

@Cerberus Tylenol

Cerberus

I do not know phrases.

I can't remember what Tylenol was.

alphabet

It's an Internet thing

@Cerberus Acetaminophen aka paracetamol. (Hence my "under the influence of" joke.)

Cerberus

1:47 AM

Ahh paracetamol.

I suspected something like that.

alphabet

Yep. The favorite drug of serial killers

Cerberus

1:58 AM

@alphabet Interesting.

Do people still buy it in capsule in your country, or is that something from the eighties?

And is it sold in bottles, rather than those strips you press?

Few medicines in drug stores are sold in bottles here.

tchrist

Mitch

@Cerberus in the US, both.

Or rather most pain relievers (aspirin, paracetamol, ibuprofen, naproxen come in blister packs and in bottles.

tchrist

@Cerberus You pay your $10 and then you have your choice of whatever delivery mechanism you please or vice versa, ranging from a dozen little stickups to some eyedropper dispenser of a fluid to a couple strips of push throughs to a bottle of 50 or of 200 or of 500 or of 1000. Your choice.

Cerberus

@tchrist Looks like strips?

Mitch

I'm not sure if the Tylenol brand in particular has or has not the bottle.

tchrist

2:04 AM

The less you buy the more you pay.

@Mitch Seriously? Haven't you been to grocery store?

Cerberus

I believe the (attempted) suicide rate went down in England after they banned bottles.

Mitch

Some of the bottles are obnoxiously large

200 pills?

Like maybe it's for a restaurant where a lot of customers want it.

tchrist

Mitch

@tchrist I'm just being honest about my state of knowledge

Cerberus

Bottles are more convenient, but they help the suicidal, in addition to not protecting the pills against humidity/oxygen as well.

tchrist

2:06 AM

Mitch

Nice!

tchrist

@Cerberus People don't do that on purpose here.

Cerberus

Do what?

Mitch

I suddenly feel like investing in whatever company makes Tylenol

tchrist

Kill themselves with it.

It's an accident because they're stupid.

Cerberus

2:07 AM

I'm pretty sure they do?

Surely is the same around the world, or at least amongst similar cultures?

tchrist

@Cerberus Mirror mirror on the wall, who's the fairest of the mall?

Mitch

You are very pretty that is true but isn't that a bit conceited of you to state so plainly?

Cerberus

Ugh I'm so tired.

Mitch

Haha

Cerberus

In addition to conceited.

Mitch

2:09 AM

Your only flaw is being too honest

Cerberus

If only...

Mitch

There are some things you just can't say

Because of the accent

tchrist

There are MANY, MANY HUNDREDS of medications that contain acetaminophen both at your nearest Kum N' Go and via a physician's prescription.

The people who get into trouble with it are the stupid ones.

They do it accidentally.

Mitch

Pain relief is one of the miracles of modern medicine

Everything before was just charlatanry

-or- tree bark chewing, which while science based is still chewing bark

tchrist

Some people died of Tylenol back in the 80s, but that was because of a serial killer sneaking deadly poison into the bottles at the grocery store. Now they're all tamper-evident because of this.

Mitch

2:11 AM

Progress

Also I can't open the bottle

Maybe I had a headache before but now I really do

Wow the 1980's were so long ago, but I still remember them

Music really started to go downhill then

tchrist

Over a decade, 1,500 Americans lost their lives to acetaminophen.

All those were accidental deaths.

Mitch

I mean who doesn't like Taylor Swift but is she really the Beatles of our time?

Cerberus

> In September 1998, Britain changed the packaging for paracetamol, the active ingredient in Tylenol, to require blister packs for packages of 16 pills when sold over the counter in places like convenience stores, and for packages of 32 pills in pharmacies. The result: a study by Oxford University researchers showed that over the subsequent 11 or so years, suicide deaths from Tylenol overdoses declined by 43 percent, and a similar decline was found in accidental deaths from medication poisonings. In addition, there was a 61 percent reduction in liver transplants attributed to Tylenol toxici…

archive.nytimes.com/opinionator.blogs.nytimes.com/2013/06/02/…

Mitch

@tchrist I thought they put an emetic in them so if you take too many you throw up before the killing part happens

Cerberus

Good idea.

Mitch

2:16 AM

@Cerberus the early 2000's was also a lifetime ago. But I still remember things from them

Like...

Like... um...

I'm sure there's something memorable from then

tchrist

ncbi.nlm.nih.gov/pmc/articles/PMC111182

Mitch

Hm...does it say how many tablets roughly are needed to cause death? And is the death only from liver failure? I'm reading but it's a lot to read

Cerberus

I think I read several packages of 16 each.

But a single package will probably already cause serious pain and damage.

tchrist

theatlantic.com/national/archive/2013/09/…

@Cerberus I have any number of bottles in my medicine cabinet the bottoms-up consumption of whose contents would easily kill me were I to do that.

Mitch

@Cerberus memory is faulty...but I thought Tylenol wasn't -that- toxic. Anyway now I know

Cerberus

2:24 AM

@tchrist But this is about the number of pills.

tchrist

@Mitch Of course this is why people die of it accidentally all the time. More likely, in fact, by accident than by intent.

Cerberus

@Mitch I think it isn't if you don't take a silly amount.

Mitch

Also like with all @CowperKettle's articles I'm learning new words

Cerberus

> je kunt al leverschade krijgen als je 6 gram paracetamol slikt. Dat zijn twaalf tabletten van 500 mg.

Dutch suicide hotline's website.

Mitch

Like 'parasuicidal' (= ... They said it much better than I can remember... Not with lethal intent? They didn't say 'for attention' which is uncool to say

tchrist

2:26 AM

> What makes acetaminophen especially dangerous, though, is the worryingly small gap between the recommended dose and the dose that can harm or even kill consumers. As one FDA report put it, that gap puts "a large fraction of users close to a toxic dose in the ordinary course of use."

> You're more likely to die from acetaminophen poisoning if you overdose by accident than if you commit suicide.
This was one finding by a Dallas doctor named Will Lee, who spent decades studying acetaminophen toxicity. It sounds preposterous, but makes sense given how long it take for acetaminophen poisoning to kick in.

Mitch

@tchrist the paper said of 93 deaths, 80 were suicide attempts, so quite a small percentage accidental

tchrist

> Consider: those who attempt suicide often regret the decision almost
instantly, so in this case they'd take McNeil's poison antidote,
which is likely to work if taken within eight hours of the overdose.
That's reassuring. But more worrisome is the fact that those who
poison themselves by accident are not likely to take the antidote
at all because they don't realize anything is wrong (and, in large
part, because the dose that can hurt or kill is so close to the
recommended dose). Hence, ProPublica reports, those patients symptoms

Mitch

And they hinted that the accidental deaths were mostly in chronic alcoholics (with already much lessened hepatic performance

tchrist

I certainly don't take it as often as once a month. And I never take it accidentally mixed into something else.

Mitch

Yes I know I'm mixing my tech language but I'm only learning

@Cerberus twelve doesn't seem like a lot

Cerberus

2:28 AM

It doesn't.

Mitch

But that's a lot of water

To drink

You know to get it down

Cerberus

I suppose so.

Mitch

They should make all medicines as milk shakes

Cerberus

Nice and bitter?

Mitch

Or lotions

Cerberus

2:30 AM

My mother used to give us paracetamol dissolved in water.

Horribly bitter.

Mitch

@Cerberus haha no but with chocolate or whatever to mask the taste

Cerberus

Would be difficult to mask that bitterness?

tchrist

I take it only when I am sick with actual fever and I'm alternating overlapping doses of ibuprofen and acetaminophen so that each overs the other for the fever and pain. It takes me two or three years to go through a bottle, and I never take more than 2 grams spread over a 24-hour period.

I much prefer ibuprofen for aches and pains. Acetaminophen has no antiïnflammatory properties, so it doesn't do as much as the NSAIDs do. But it is reasonably ok with fever.

Cerberus

I believe paracetamol is very safe as long as you keep to the recommended doses.

Whereas ibuprofen is never quite so harmless.

At least that's what I've heard.

tchrist

I don't think that's true. You should never take any of these every day.

Any of them taken every day can do lasting damage.

Mitch

2:33 AM

@tchrist that's the way to do it

tchrist

Never take them with alcohol.

Mitch

@Cerberus if only @M.A.R. would set us straight with professional advice

tchrist

Unless it's in the prescription cough medicine you're given that has codeine and acetaminophen in it.

Cerberus

I read that even with alcohol, that's not a huuuge deal.

As long as the dose is low.

Mitch

@tchrist so complicated. I want the tricorder wand you wave over somebody and it 3d prints a patch with just the right amount of quadrotetracetamol

tchrist

2:36 AM

I have close friends and family who are cardiac patients who are under special instructions about these, including one who takes a full-strength aspirin daily on his cardiologist's orders because although that it is risky, for him not taking it is riskier. And I know others who've unwittingly done themselves permanent harm and must never take another no matter what.

Mitch

@Cerberus and you don't have ETOH cirrhosis

Or any kind of cirrhosis I guess

tchrist

People with chronic pain can do very stupid things.

Mitch

You can't think with that pain

You're trying so hard with all your mental faculties to stop the pain

As though that might actually work

@tchrist wow. And for something as presumably innocuous

It's not like it's fentanyl or heroin

It's me. -I- can't think with any pain. And I think if I concentrate hard enough it will go away

Swearing helps a lot

tchrist

@Cerberus Yes, that's the thing. I believe you're supposed to reduce the daily max from like 4 g to 3 if you imbibe. Others recommend not mixing at all. And there may be interactions with other meds.

Cerberus

@Mitch No, indeed!

@tchrist Right, but 3 grams isn't just two pills before bed.

@tchrist I can certainly imagine that the risk will be quite different those with relevant medical conditions.

What do you know about those who have done themselves harm unwittingly?

Mitch

2:47 AM

I mean is heroin that bad?

Cerberus

How much did they take, for how long?

Did they have underlying conditions?

Mitch

(fentanyl surely is)

tchrist

@Cerberus 2.4 g ibuprofen daily for six to eight months, with alcohol at night.

Normal OTC dose is 200 or 400 mg.

A doctor will for very specific circumstances up that to 600 or even 800 mg a dose, and go up to 2400 per day. But only for a VERY short period of time. I have never seen them call for that even for a full week. Months is suicide.

1800 to 2400 a day is not unusual in a hospital setting.

But only for an acute situation.

And there they usually have viable alternatives.

Cerberus

@tchrist Thanks.

Just one or two glasses of alcohol, or more?

And was it liver damage?

tchrist

That I don't know for sure.

Yes, it was.

Cerberus

2:52 AM

OK.

I've never taken anything like that for a longer time.

Mitch

Your liver self repairs if you stop doing the bad thing

Cerberus

But probably not always?

Mitch

Well probably no guarantee

Cerberus

I have some liver values checked quarterly anyway.

Mitch

The self repair thing...I'm not sure...check with your local doctor

Cerberus

3:05 AM

I know the liver can do such things, even regrow. But I'm sure there will be various limits.

Especially if you have other medical issues.

Mitch

I just vaguely remember that liver tissue is different from other tissues in that it is possible to regrow but I don't know the limits

> In a hearing, a lawyer who relied on A.I. to craft a motion full of made-up case law said he “did not comprehend” that the chat bot could lead him astray.

Cerberus

3:24 AM

Now he does.

CowperKettle

Israeli scientists gave an artificial molecule they invented to 30 mice suffering from Alzheimer’s — and found that all of them recovered, regaining full cognitive abilities. translationalneurodegeneration.biomedcentral.com/articles/…

Neuroscientists are in full competition with AI scientists, so it's unclear what will destroy humanity sooner: a super-AI or a bunch of super-smart mice from an Israeli lab.

Cerberus

3:40 AM

Not some biological virus?

MetaEd

Wordle 720 4/6

⬛⬛🟨⬛⬛
⬛🟨⬛⬛🟨
🟩⬛⬛⬛⬛
🟩🟩🟩🟩🟩

mein crag

Cerberus

Wordle 720 4/6

🟨⬜⬜⬜🟨
🟨🟩⬜⬜🟩
⬜🟩🟨⬜🟩
🟩🟩🟩🟩🟩

Crag?

Mitch

@Cerberus possibly still not. But at least he feels bad?

MetaEd

me caring

Cerberus

me not understanding

MetaEd

3:50 AM

manic reg

@Cerberus it's the Thurber word game

Cerberus

Thurber?

Mitch

Creaming?

CowperKettle

A pro-Russian military blogger estimates the current losses coefficient as 1:3 (killed/wounded), which is not bad, but quite low compared even with US losses in pitched battles of the Vietnam War, which was about 1:5. He says that 1:3 is "closer to WWII data", which is poor, considering that today's soldiers have improved lightweight individual armor and (theoretically) modern improved drugs t.me/s/RostislavDDD

He gives a link to a 2003 description of a wound given to a US soldier, who managed to survive it.

> " After shredding my spleen (which had to be removed), puncturing and collapsing my left lung, lacerating my stomach and left kidney, severing my aorta and blowing out a large chunk of my vertebrae, the bullet severed my spinal cord at the T12/L1 level, which instantly and completely paralyzed me from the waist down."

swatmag.com/article/…

I wonder if any Russian soldier could survive this. So many organs affected, and an aorta severed.

Mitch

And I think post WWI, the deaths of soldiers due to sickness outside of combat is probably negligible

(penicillin)

MetaEd

name a crime era: anger, rage, cain cinema, iceman race cager, enigma in a grim carmine game.

@Cerberus James Thurber, author

@Mitch yes but also:

Mitch

4:09 AM

What's the original word?

Robusto

Germanic

@MetaEd racine gem, me racing, cane grime, creaming, gin cream, mic anger ...

@MetaEd I thought the Thurber word game was Superghosts.

MetaEd

@Robusto this is the blood game, or here come the tigers

Mitch

@Robusto oh

MetaEd

Russian is also pregnant with meaning

Robusto

Sinsaur

@MetaEd Thurber didn't invent anagrams.

MetaEd

4:11 AM

I'm finding: sarin airs, ursa, anus, sins, rains, i, ruins, sinus, urn, us, run

Mitch

Ass ruin

Robusto

Nor did he invent ars magna.

MetaEd

sarin airs ...

Robusto

saurins

sun airs

Mitch

@MetaEd redolent with the perfume of ... burnt toast?

Robusto

4:14 AM

@Mitch No, Elvis Presley's back-up singers, only poisonous.

CowperKettle

5:31 AM

Xanne

5:59 AM

Karen Khachanov

Karen Abgarovich Khachanov (Каре́н Абга́рович Хача́нов; born 21 May 1996) is a Russian professional tennis player. Khachanov has won four ATP Tour singles titles, including a Masters 1000 title at the 2018 Paris Masters, has claimed an Olympic silver medal at the 2020 Tokyo Olympics, and has reached two major semifinals at the 2022 US Open and 2023 Australian Open. He has also won one doubles title, a Masters 1000 title at the 2023 Madrid Open partnering Andrey Rublev. He achieved his career-high singles ranking of world No. 8 on 15 July 2019. == Early life and background == Khachanov sta...

Probably not part of the SSA data base.

Xanne

7:06 AM

Wordle 720 5/6

🟨🟨⬜⬜⬜
⬜⬜⬜⬜🟨
🟨⬜⬜⬜⬜
🟩🟩🟩⬜🟨
🟩🟩🟩🟩🟩

jlliagre

9:15 AM

Wordle 720 5/6

⬜⬜⬜⬜⬜
🟩⬜⬜🟨⬜
🟨⬜⬜⬜⬜
🟩🟨🟨🟩⬜
🟩🟩🟩🟩🟩

alphabet

9:59 AM

@tchrist IMHO naproxen is much better. Lasts about 12 hours and seems to be stronger than ibuprofen.

CowperKettle

10:51 AM

Quantum computer is 180 million times faster on AI tasks: paper

I'm feeling so obsolete.

Compared with AI engines that will exist in 2030, I'll look like a slightly upgraded cockroach, in terms of intelligence.

Nice weather.

Still trying to memorize this.

Have reached up to "Back-o-Bourke"

The latest from Girkin's pulpit t.me/s/strelkovii

Robusto

12:23 PM

#Worldle #504 1/6 (100%)
🟩🟩🟩🟩🟩🎉
⭐⭐🏙️🪙
https://worldle.teuteuf.fr

@jlliagre If I were to use a different starter now it would throw off all the understanding of distances between one country and another. Better not to chase the long shot and stick with what I know.

🌎 Jun 9, 2023 🌍
🔥 28 | Avg. Guesses: 4.5
🟧🟥🟥🟩 = 4

globle-game.com
#globle

CowperKettle

Word of the day: sepulka

Sepulka

Sepulkas (also sepulcas or scrupts in English translation), are fictional objects found in works The Star Diaries and Observation on the Spot, Stanisław Lem. A fictional encyclopedia lists them as "objects used for sepuling". == In-universe sepulkas == Sepulkas were first mentioned by Lem's interstellar traveller Ijon Tichy during his fourteenth voyage. Lem never explains what they are and what their use is. The Encyclopaedia Cosmica gives the following definitions: Sepulka – pl.: sepulkas, a prominent element of the civilization of Ardrites from the planet of Enteropia; see "Sepulkaria"...

jlliagre

@Robusto That makes sense. Yesterday's Globle was tricky because there are three other microstates around the same distance from the principauté.

Robusto

Wordle 720 5/6

🟨⬛⬛⬛⬛
🟨⬛⬛⬛⬛
⬛🟨🟨🟩⬛
⬛🟩🟩🟩🟩
🟩🟩🟩🟩🟩

@jlliagre I forget what that one was now.

I remember the Worldle, though, because I got it wrong on the first try.

jlliagre

@Robusto Monaco-Germany

Robusto

Ah, yes.

Easy-peasy.

jlliagre

12:33 PM

I hesitated with the Vatican, San Marino and Andorra.

No, not San Marino, Liechtenstein.

Robusto

@jlliagre Liechtenstein used to be my starter, so I have a pretty good idea of the shape.

But in deference to you I play Monaco now.

jlliagre

Yes, but there are no shapes with Globle. Je suis flatté ;-)

Robusto

When the first measure comes up over 16000 km I know it's a Pacific island and then it's Katie-bar-the-door and I just start rattling off names of the island groups I know.

@jlliagre Yes. But it showed up in Worldle yesterday, in the bordering countries.

jlliagre

Switzerland is the kind of country I recognize even with my eyes closed ;-)

CowperKettle

hosh geldiniz!

M.A.R.

12:40 PM

Sagh ol

CowperKettle

> Cognate with Kazakh қош келдіңіз (qoş keldıñız), Azerbaijani xoş gəldiniz, Kyrgyz кош келипсиз (koş kelipsiz), etc. Literally: “you have come well”.

Possibly a partial loan translation of Persian خوش آمدید‎ (xoš âmadid, “welcome”).

My friend who is moving to Kazakhstan must have already memorized it.

M.A.R.

@Mitch there's a lot to unpack here, depending on how many of the questions in the transcript you want answered. So here goes: Dr. M.A.R., or how I learned to stop worrying and love the NSAID cc @Cerb

@tchrist is right on all points, because of course he is. But first off, should you take painkillers every day and what happens if you do?

Painkillers are designed for acute pain, not chronic. The ideal situation is that they should relieve pain until you can discontinue them, unless you have some chronic debilitating pain that will return. But relieve they should, and if they don't you need to switch drugs or drug classes until they do.

For headache, if you use painkillers every day, you will easily get Medication Overuse Headache. It's commonly seen with both NSAIDs and triptans (i.e. sumatriptan) for migraine headache. If your headache persists, either you are underdosing, or your headache is misdiagnosed and not treated properly. The most common people with MOH are people who have migraines and take NSAIDs, which are only marginally effective.

So, for example, no more than two sumatriptan pills are allowed per day, each 100 mg.

The underlying mechanism is probably sensitization of whatever pain mechanisms.

Next, acetaminophen: Max allowable dose is 4 g/d. In alcoholic patients, it's 2 g/d. In individuals otherwise susceptible, liver toxicity can occur at 3.25 g/d dose. Here, each pill ranges from 325 mg to 500 mg acetaminophen. Meaning, 8 pills can cause serious liver damage.

How does toxicity occur? The liver normally metabolizes acetaminophen by binding it to a molecule of glucose, making it more polar and excreble in urine. A high dose saturates this pathway easily, so the liver instead chooses to change the acetaminophen molecule to make it more polar. The resulting compound is an electrophile, meaning, it's an organic molecule that likes binding to functional groups that have electrons. Proteins and DNA are full of those functional groups.

Thus, electrophiles are always toxic because they bind DNA and proteins, rendering them dysfunctional. Many carcinogens are electrophiles, for example. Many anticancer drugs are electrophiles. Acetaminophen's transformed metabolite is also an electrophile.

The drug is easily accessible, increasing the likelihood of using it for suicide attempts. BUT liver failure is extremely painful and rarely lethal because they're discovered and treated for toxicity promptly, so there are much less painful and surer methods to commit suicide using drugs.

TCh is also right that toxicity happens accidentally, because combination painkillers tend to have some acetaminophen, and so do cold pills. Someone taking several of these at once is getting acetaminophen from multiple sources.

Robusto

1:09 PM

@jlliagre That's because it's close to you. I go by shapes in Worldle.

M.A.R.

Nevertheless, my go-to drug for mild pain is acetaminophen. Take 1 pill, and if it doesn't help, take another, and then 1 every 6 ours until the pain subsides. No chronic complications, and very effective, unless there's an inflammatory component to the pain.

Robusto

@M.A.R. I take meloxicam for arthritis every day. It has helped wonderfully, way better than any ibuprofen or naproxen sodium ever did.

CowperKettle

Meloxicam

Meloxicam, sold under the brand name Mobic among others, is a nonsteroidal anti-inflammatory medication (NSAID) used to treat pain and inflammation in rheumatic diseases and osteoarthritis. It is used by mouth or by injection into a vein. It is recommended that it be used for as short a period as possible and at a low dose.Common side effects include abdominal pain, dizziness, swelling, headache, and a rash. Serious side effects may include heart disease, stroke, kidney problems, and stomach ulcers. Use is not recommended in the third trimester of pregnancy. It blocks cyclooxygenase-2 (COX-2) more...

M.A.R.

Now, the NSAIDs: They all, with the exception of celecoxib, inhibit both cyclooxygenase 1 (COX1) and cyclooxygenase 2 (COX2), though to varying extent, preventing the production of pain mediators called prostaglandins.

To my knowledge, there's no consistent difference in efficacy, but response is rather individualized: Cowp could benefit the most from ibuprofen, Cerb from naproxen, and Rob from meloxicam, and nobody can say why. So we instead focus on the adverse effects of acute and chronic use when choosing one, and then changing dose or drug based on response.

Based on increasing COX1 inhibition activity, you can sort NSAIDs like this: Celecoxib (no COX1 inhibition), meloxicam, naproxen, diclofenac, ibuprofen, ketorolac, indomethacin (a lot of COX1 inhibition). So why is this important?

COX1 is constitutively expressed. It's ever present in many cells, and produces prostalglandins all the time. PGs induce secretion of the protective mucosa in the stomach: So NSAIDs that inhibit COX1 a lot damage the gastric mucus a lot.

Robusto

I think about getting off meloxicam, but when I do for a week or so I find it difficult to ride my bike enough. Wrist pain, knee pain, back pain—all from osteoarthritis.

M.A.R.

1:22 PM

COX1 is also responsible for making prostaglandins that cause the dilation of renal arterioles: Thus, NSAIDs that inhibit COX1 a lot cause a lot of kidney damage in the long run. A huge reason drugs like ibuprofen shouldn't be used chronically unless we can't help it

NSAIDs can also cause acute kidney injury by other mechanisms, but it's fairly rare. Ibuprofen does it more than others.

Robusto

Daily Quordle 501
9️⃣8️⃣
5️⃣6️⃣
m-w.com/games/quordle/

Weak.

M.A.R.

COX2 is inducible, not constitutive. It doesn't normally secrete prostalglandins, but does so during inflammation. Unfortunately, it also has a protective role for the heart, severely limiting the use of NSAIDs: Mefenamic acid must not be used for more than 7 days. Ketorolac must not be used more than 5.

Meloxicam and diclofenac have a maximum allowable daily dose of two pills only.

All NSAIDs block COX2. All NSAIDs have been associated with worsening heart problems.

Though overall they say the safest NSAID in heart failure is naproxen.

@Robusto all about risk vs. benefit. Being pain-free is a huge benefit itself: Being in a state of pain is generally harmful to the body, and we don't even abstain from drugs of abuse if it would mean pain relief for someone

CowperKettle

It's amazing that they all sprang up very recently, these drugs. Only in the 1980s.

Robusto

I definitely feel better when I can get enough riding in. I would think this ought to be good for my heart.

CowperKettle

Poor medics won't be able to remember even the basics about drugs soon. A deluge of new drugs.

alphabet

1:37 PM

@CowperKettle There's something comical about Igor Girkin's posts. An odd combination of petulance and paranoia. I wish someone translated his posts into English; WarTranslated has some of them.

CowperKettle

Are there some radical drugs like special-tailored antibodies for osteoarthritis?

Robusto

Daily Octordle #501
5️⃣🕚
3️⃣7️⃣
🕛🔟
8️⃣🕐
Score: 69
Another lackluster performance.

jlliagre

Daily Quordle 501
8️⃣6️⃣
7️⃣5️⃣
m-w.com/games/quordle/
I could have done better if an anagram hadn't thwarted my progression.

CowperKettle

@alphabet I watched a video with him, and from time to time, some cracks appear and you can feel some anti-Semitism and some doom-expectation. He quoted from a Russian survivalist doom future novel, in which the whole global civilization goes kaput due to lack of resources.

alphabet

He seems to think that Russia's problems can be solved by just trying harder.

If you donate to a group funding Ukraine's war effort you can now get a "Crimea Beach Party 2023" patch: help99.co/wartranslated-2

M.A.R.

1:42 PM

@CowperKettle not for osteoarthritis, but for rheumatoid arthritis, you already have several monoclonal antibodies in routine care, such as adalimumab

Robusto

@alphabet This is every idiot's plan when something doesn't work: stick to the same plan but do it harder.

CowperKettle

I got the feeling that he believes that the civilization may soon fail. In order for Russia and other Slavic nations to survive, they should group together, and maybe slide back to some harsher style of rule. At the same time, he is kind of pro-democracy. It's hard to get him.

M.A.R.

Infliximab

Robusto

@CowperKettle Yes. Big Brother will save you.

CowperKettle

He thinks that Judeo-Freemasons and the UK conspired to bring down the Romanov dynasty

Or something like this.

jlliagre

1:45 PM

Daily Octordle #501
7️⃣6️⃣
3️⃣5️⃣
9️⃣🟥
🕐8️⃣
Score: 65

CowperKettle

It's the reason he isn't afraid to write truth. He has crazy grandiose ideas, while others only pretend to have them, and in reality just grab money and climb up the ruling ladder.

alphabet

(They also have an "adopt a drone" program.)

Robusto

Cerberus

3:19 PM

@M.A.R. Thank your for the explanations, quite interesting.

200 mg a day of Ibuprofen chronically, that is probably already harmful, isn't it?

I should really get off that, but it's the only thing that seems to prevent aphthae, it's such a miracle drug hehe.

M.A.R.

3:33 PM

@Cerberus you'd need a proton pump inhibitor to go with that to mitigate the risk of GI ulcer. Even so it'd still be a concern

alphabet

@M.A.R. I prefer naproxen, but only because it lasts longer. In particular, it lasts long enough that you can get a full night of sleep if you have some sort of pain.

(I currently have some nasty cold/flu type of thing--tested negative for Covid, thankfully--so this is on my mind.)

CowperKettle

3:59 PM

Erenumab

Erenumab, sold under the brand name Aimovig, is a medication which targets the calcitonin gene-related peptide receptor (CGRPR) for the prevention of migraine. It is administered by subcutaneous injection.Erenumab, which was developed by Amgen and Novartis, was approved in May 2018, and was the first CGRPR antagonist to be approved by the U.S. Food and Drug Administration. In 2020, it was the 234th most commonly prescribed medication in the United States, with more than 1 million prescriptions. == Medical uses == Erenumab is indicated for the prevention of migraine in adults. == Side effects... ==

Monoclonal antibody against migraines

> How does Ghengis Khan establish an empire?
One steppe at a time.

I don't get this one

Etymology of the eve: to explode -- First recorded around 1538, from the Latin verb explōdere (“drive out or off by clapping”). The meaning was originally theatrical, "to drive an actor off the stage by making noise," hence meaning to "to drive out" or "to reject". From ex- (“out”) + plaudere (“to clap; to applaud”). The sense of "bursting with destructive force" is first recorded around 1882.

Robusto

4:16 PM

@CowperKettle Drab, flat Kansas is no substitute for the magic of Oz.

Laurel

@CowperKettle It references the end of the Planet of the Apes (the first one???). Pretty iconic

CowperKettle

@Laurel Ah!

Dr Zeus Dr Zeus - Simpsons

►

Robusto

@Laurel Oh, right. I didn't notice the Statue of Liberty except as a meaningless fantasy. Which perhaps it is these days.

MetaEd

4:33 PM

@Robusto Thurber actually made no claim of invention -- he described a game, well actually several variations: given a word, find as many words in it as you can. given a word, find as many words as you can that have that word in it. given a word, write a sentence that conveys the word's mood and tone. "Here Come the Tigers" is more about the third variation than anything

Robusto

4:55 PM

@MetaEd OK.

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