Contramuffin

Nine sols. A metroidvania with parry-based combat and insanely good plot.

My understanding is that there was a scene where a young girl rides a naked man/woman around. Apparently it has since been changed to make the child older, but... I can perfectly understand why anyone would be hesitant to accept such a game based on that description alone. Even if it's not intended to be sexual, the developers were certainly pushing the line

7 is a soft reboot and it's really good, I think it's a good starting point. 8 continues from 7, and neither games mention anything from the first 6 games. The only returning character is Chris Redfield, and only as a side character that you see 1% of the time

Thanks, we had that issue but I think we just solved it by downclocking

Although, that would assume that companies don't already trend towards doing so

Pro tip: don't. It'll make you feel worse than if you just isolated yourself.

The incentive structure of dating apps is completely twisted and makes you feel like every part of yourself is getting commodified and ranked.

Find some social groups or clubs and go hang out there. You'll have a much better time. Many people don't mind if you aren't comfortable with communicating, just being present is a positive in their book.

That makes sense, but unfortunately in a frustratingly unhelpful way. NF-kB is the central mediator of cellular immunity. What that means is that everything that needs an immune response triggers NF-kB and everything immunity-related gets activated due to NF-kB. Likewise, TNFa is the prototypical pro-inflammatory cytokine. It's remarkably good at triggering immune responses in a wide variety of cells, and every immune response that I know involves TNFa in some way.

In other words, having inflammatory symptoms be caused by NF-kB>TNFa is less of a "that's an interesting pathway" and more of a "yeah, of course NF-kB and TNFa would be involved, what's new?"

The concern is that we don't really know what's activating NF-kB in the first place, and so as a result you can't really fix the core problem. And because NF-kB and TNFa are involved in basically every immune process, it's hard to tell if these proteins are the ones actually responsible for causing your symptoms. You'd be operating on a hunch, essentially. Though I will say that your unusually nondescript and broad symptoms do seem roughly in line with what I would expect from TNFa signaling.

All that to say, I'm not a doctor and I have no experience with translating knowledge into practicable therapies, so definitely talk to a doctor about it. But TNFa is very easy to detect in your blood, and if TNFa is causing your symptoms, then it's really easy to just check to see if you've got high TNFa in your blood when you're taking the antibiotics vs. when you're not. If you had the money, you could even buy a test kit yourself and get an answer in a single day, assuming you know how to use the kit

I'm not familiar with COVID, but it does sound to me like you've got long COVID. I've got no advice on that front - frankly, I don't think anybody really knows what's up with that. I get the impression that that's why the advice that you've received so far are primarily focused on treating symptoms.

If your hypothesis is correct that your antibiotic is helping through its immunomodulatory effects, then it looks like it's acting primarily through inhibiting cytokine production. Messing with cytokines will certainly affect your ability to fight off infections, since that's how your body signals to immune cells that there's something wrong. Of course, immunity is all about balance, and you don't need to block cytokine signaling completely in order to decrease it to manageable levels... A brief search shows that there are inhibitors for TNFa, which based on your links seem to be what you're leaning towards as the molecular mediator.

Have you considered bringing this up to your doctor? I'm not sure how feasible it would be to do a "trial run" with one of these inhibitors to see if it helps your symptoms. However, it may be simple enough to ask for a blood test to measure the amounts of different cytokines in your blood. My understanding (don't trust me on this - I'm not a clinician) is that standard blood tests don't typically measure cytokines, which is potentially why your blood tests so far haven't been able to pick anything up out of the ordinary. That would at least help rule in/out any possible causes.

I will also point out an alternative hypothesis that might be worth considering - it could be that the antibiotic is depleting your microbiome, which would reduce the same cellular pathways that your antibiotic is said to inhibit due to your cells being in less contact with bacteria. Have you tried other antibiotics, and did they have a similar effect?

Immunologist here: what you're describing seems vague. Inflammation is honestly just an umbrella term that generally refers to any time when the immune system is doing something (hence the seemingly conflicting advice). As a result, it's not entirely clear to me what specifically you're referring to.

Remember that no pathogen will just sit there and let themselves be destroyed. Many will actively exploit the immune system to cause disease, and in those cases, having a stronger immune response is actually bad for you. As well, I'm not sure what you mean by having higher "baseline inflammation," because again, inflammation isn't a singular thing

I was taught in my Micro course that lichen is actually a symbiosis between 3 organisms: fungi, algae, and cyanobacteria. The cyanobacteria produces energy, but more importantly fixes nitrogen into a more biologically available form, which would not be otherwise accessible in the environments that lichen grows in

Scientists don't wait for mice to get cancer, then cure the cancer. That would be inefficient. They just force the mouse to get cancer instead. And cures are tested based on how quickly the mice die to the cancer with or without the drug