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I'd prefer that they call it something other than "fatigue". There are so many different interpretations of "fatigue" that one study's measurements will likely be misapplied for someone else's interpretation of "fatigue". If a study--using questionnaires--is measuring some factor reproducibly...

Were they measuring true fatigue, or were they just measuring something that appeared to be fatigue from a certain viewpoint? They might be able to reproduce results in different groups of people, but maybe that's an artifact of the questionnaires, but not actually measuring whatever mechanism...

I think there's a good chance that many of the studies are measuring things other than actual PEM. Someone should probably do a study measuring various factors of PEM that is triggered in different ways. For example, PEM from socializing, emotional stress, strenuous physical exertion, and less...

My guess is that sloppiness is more likely to occur when it results in convenient conclusions. If the data looks good, "Hey, it must be correct! No need to double-check."

My temporary remissions didn't last only minutes; they tended to last "until the next morning". I can't recall now whether any switched off during a day, but I think it did. The time from full ME to full non-ME, and from full non-ME to full ME again were IIRC just a few minutes. My PEM, and...

Other people have reported them. It's like flipping a switch. That tells me that ME (at least my ME) rules out a bunch of theories that involve slow-changing processes. A mechanism involving brain cells fits, and even better--one that involves a small region of the brain (hypothalamus or...

Do you have any theories that would explain how ME symptoms can completely switch off over a period of minutes, and then switch back to full on again over a similar period? That's how my temporary remissions were, and I use that to judge any ME theories. I think it's not unreasonable for glial...

Is "inflammation" required for glial cells to affect neural functions? Do the cells have to be in a visibly altered state? Cells are pretty complex, so it seems reasonable to me that an astrocyte (which is part of the BBB), for example, might respond in some way to a circulating cytokine...

https://pubmed.ncbi.nlm.nih.gov/8963753/ "One mechanism by which blood-borne cytokines might affect the function of the central nervous system (CNS) is by crossing the blood-brain barrier (BBB) for direct interaction with CNS tissue. Saturable transport systems from blood to the CNS have been...

I never even questioned that. I came across numerous papers claiming that glial cells activated in response to immune activation in the body, so I assumed that was standard knowledge. Other similar claims are that most of the "flu symptoms" are due to glial cells responding to cytokines from...

Not necessarily, but I believe that any activation of the immune system(s) can trigger ME. Whether the cytokines are the result of viral infection or muscle damage, IL-6 is IL-6. I also believe that glial cells activating in response to cytokines is part of the ME trigger. Once triggered, a...

I like that they're studying miRNAs related to brain function. I do wonder how well the serum level correlates with the levels in the brain. Do miRNAs pass the BBB with no loss? Are they not bound or broken down before reaching the blood? Do those characteristics vary (eg. miRNA 123 has a...

FADE is composed of three symptoms that are not simply unquantifiable, but also very poorly defined. It doesn't apply to my ME, since I never considered "depression" as a symptom for me. Brainfog, yes. My weakness is perceived weakness (lack of will to exert myself). I suppose if your...

I was thinking more about this. How complete is your set of inputs and outputs when PWME respond so differently to inputs? Supplement x makes person A feel better, person B feel worse, and other people notice no effect. Also the system isn't just ME's core dysfunction; all the other systems...

Yes, but the important word there is "complete". For an electrical circuit, the model might match the real-life device perfectly with inputs ranging from 0 to 12V, but provide completely unexpected results outside that range. We don't know the range of inputs for ME. We don't even know what...

I once walked into a natural health store, and there was a group of people there holding electrodes connected to some device (made electric pulses I think). One person with a blissful look on his face told the rest of the group "I can feel my cancer melting away!" I regard that incident as the...

One reason for glial (astrocytes and others might be involved too) activation to be a more likely cause is that those other possibilities are much easier to study and already much better studied, and don't show a clear sign of being involved. The brain is much less understood, so there's...

Do you notice any difference from the type of physical activity? Physical activity does involve some cognitive exertion, so a mindless task might result in longer delay or lesser symptoms than playing basketball or some other activity requiring concentration.

Yes. My cognitively-induced PEM had a short and fairly variable delay (15-60+ minutes). My physically-induced PEM had a consistent 24 hr delay, which matches the rise in IFN-g following exertion. It seems reasonable that the delayed rise in cytokines or other messengers triggered glial cells...

That's my view too, that even normal levels of cytokines can be worsening ME symptoms. I don't think that microglial hypersensitivity is the root cause of ME, but it's something that adds to the severity. I also think other glial cells might be involved; there are some highly specialized and...