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I don't know much about this receptor. It sounds like a broad spectrum inflammatory target. In the absence of inflammation in ME I am not sure it would have potential but maybe the pathway is relevant.

I don't think you will find a physio-affective phenome in any of those much!

Like Hutan, I agree with you that there are two aspects here, mechanisms and manifestations. The problem is that, with my rheumatoid hat on, I don't see any likelihood of there being 'an underlying mechanism'. Things are going to be more complex. Diseases involving misbehaviour of regulation...

The irony is that for lack of effect you don't really need to worry about risk of bias because bias will usually be towards increasing positivity. You do sometimes get people trying to prove things don't wrk but they tend to do things thoroughly!

The most egregious fact seems to be that the claim that PWME show a different 'effort preference' is at best a weak statistical thing and would not be there if the authors had not excluded one of the normal control results as being 'aberrant'. In other words, a disinterested sensible...

I think again that this is trying to be too clever and is unlikely ever to pan out to an established effect. They do not report purifying an Ig fraction that actually has the activity proposed - which would be the acid test. That last step is always the most difficult but if you don't do it the...

And that is what I would disagree with and warn may be a slippery road to go down. You are suggesting not so much correlation as identity. The same thing. Exertion (rather than exercise, as members have often reminded me) intolerance is not being able to tolerate exertion because of feeling...

Yes, happy to review a draft with a view to joining authorship.

But what is a 'cardinal marker'? Does cardinal mean the best available, or definitive, or always the case, or what? Does marker mean correlate or something in a causal relation? Generally marker means correlate, and that is the issue. As @EndME implies, the second day COET result might reflect...

Edit: This may just repeat Hutan's immediately prior post but I wrote it anyway! I am not sure what your rhetorical statement is intended to imply, @Mark Vink. I agree with Hutan that the 2 day CPET is not actually a measure of PEM and I am not sure it helps that much to say it documents 'PEM...

My guess is that you have to have symptoms first. If you feel bad on standing and that is associated with a 30bpm rise and no blood pressure fall then it gets called POT. If blood pressure falls it is called orthostatic hypotension. This may seem unjustified but there are other examples of...

I do not know the literature but I have seen it commented that a rise of 30bpm is not necessarily abnormal.

Blood flow to an organ depends only on average blood pressure and vessel calibre. There is no obvious reason why people with POTS should constrict brain vessels on standing so the only relevant change would be change in arterial pressure. Brain venous pressure would go down on standing which...

One thing do not understand is that people with 'POTS' are supposed to be at risk of low cerebral blood flow. Yet, if the BP is maintained (as it is by definition in POTS) and the heart rate goes up there is no reason why the brain should get less perfusion. It might get more.