Search results

Absolutely, I think everyone is agreed on that. But if rare variants are really rare it is hard to get statistical data on relative prevalence. i think people are just arguing about how much weight one can give to rare variants that look a bit like what you were expecting to find when we cannoot...

I think we probably have individual threads for all those studies, or at least nearly all. The analysis is usually fairly penetrating! There are lots of papers on mitochondrial function but that probably just reflects a presupposition that mitochondria are relevant (which mitochondrial experts...

Fringe describes people who pursue ideas away from the academic a nd clinical consensus. The great majority have no clue what they are doing. There may be physicians on the fringe with brilliant new ideas so no they need not necessarily be the opponent. Opponent seems an unhelpful term here. The...

I have explained this in detail on relevant threads here but in brief: The original criteria required clear evidence of monogenic Mendelian inheritance for the EDS cluster. The way hEDS is used now does not. A monogenic process is worthy of being a 'syndrome' because it tends to be homogeneous...

But Chris made a point of saying that the variant seemed to be in the wrong direction for implicating a mitochondrial metabolic defect. Things might be more complicated but I do think that if one tries to model things on the basis of multiple alternative key pathways the opportunities for...

In general I don't think these criteria make sense as ways to identify a particular pathological entity. Like the ICC ME/CFS criteria they include preconceptions and interpretations that will bias clinicians. They also appear to be a scattershot set of abnormalities that are quite likely each...

I am completely confused by all this . Are we supposed to look at criteria X or Y? Is one of them consensus 2?

I would agree with @Utsikt for several of those points. Peripheral neuropathy is not a known feature of ME/CFS. Nor is rhabdomyolysis. (There is one report which is at odds with a very long history of relevant negative data.) We don't have any evidence for mitochondrial malfunction being...

It really is remarkably bad. When one sees stuff as bad as this I think it is legitimate to develop just a little bit of 'negative prejudice' when reading authors' names?

Agreed.

I am not sure that anyone is disputing the logic here. My thought is that if a rare gene variant has very strong evidence for pathogenicity - as in a multicase family with a Mendelian disease expression - or points very strongly to a very specific testable model, then it may take us a step...

It acknowledges a medical involvement but not much sign of continued medical assessment long term - just initial labelling. The sentence about facilitating triage is pretty obscure but probably means trying to reduce the number of time-wasting patients that get referred to secondary care. The...

I know very little about epigenetics methodology of this sort. The question comes up in my mind as to whether this would be upstream or downstream of the disease. Maybe the controls should be equally disabled and disheartened people with some other disease like Parkinsonism or diabetes.

Yes, I think your basic point is right here @butter. An ME/CFS diagnosis precludes there being another explanation for symptoms. But if three different gene variants are found in people diagnosed with ME/CFS on the basis of current knowledge and it then becomes convincing that each of the three...

In fact that seems to be yet another B12: HLA-B12, which is a tissue type antigen.

Lymphoid tissues are tricky. Throat 'inflammation' is probably often mostly activity in the lymphoid ring around the pharynx. Lymphoid tissue is normally full of white blood cells and when activated is not really 'inflamed' (you do not see neutrophils coming for instance), although similar...

What would be the consequences of upregulating the NLRP3 pathway? Would there be more interferons or something like that? Would T cell costimuation be affected?

I think we are agreed that rare gene variants could be key to unpicking ME/CFS, just as homozygous C1q deficiency gives us the key to lupus. And I agree that upstream pathways to PEM may vary quite a lot but they somehow have to feed in to a common step. If that step is muscle weakness it is...

I think autoimmunity (my life work!) may be a slightly misleading analogy. ME/CFS has a very dist9nct clinical presentation. Autoimmunity does not. It is a category for a wide range of parallel but in many cases causally unrelated errors of B cell regulation that all involve production of...

In the model I am envisaging glymphatic channels would be an important part of maximising an oncotically driven diffusion process to maintain low brain ECF 'oncolarity'. Cortical grey matter is bathed directly in low protein CSF. Deep grey matter is fed by the ventricular CSF but arterial...