Yeah, Hanson's presentation I reckon pretty much covers the status on the "something in the blood" finding. To paraphrase it shortly, they have looked into extracellular vesicles (EVs), of which exosomes is one group. They found no change in average size or total concentration of EVs between healthy and ME/CFS groups and neither in individual cytokine levels in EVs. They found, however, that correlations between different cytokines were different in ME/CFS group and healthy controls both in EVs and plasma.
To me it seems this energy metabolism and "something in the blood" research is leading the researchers back to the immune system and abnormal cytokines. If this is the case, I'm not very optimistic it will lead to any major discoveries anytime soon, as cytokines and immune system in ME/CFS has been studied for decades. If it really comes down to the metabolic issues being caused by cytokine signaling, then this isn't the root cause of the disease.
The way I see it, the only finding of OMF that so far comes close at a root cause would be the metabolic trap model. If the trap can be demonstrated to exist in vivo, then great, at least there is a cause found. If not, I'm not sure where they'd go from there. Hanson went on to talk about ME/CFS outbreaks and how a hit-and-run virus could possibly trigger the disease. IMO it would be an absolute key to understand at least if a subgroup of patients have active infections. The research regarding viruses and ME/CFS seems to move along slowly, like in the past 20 years, but I understand it's probably financial limitations again at play for the most part.
I've only scanned your post. I think Maureen Hanson found an increase in the numbers of the smallest size - not sure if that's the smallest of exosomes or extracellular vesicles (exosomes?). I intend to try to watch the videos when they are posted online.
It's far from clear what is causing the switch in cellular energy production e.g. cytokines, microRNA's ---. The link to exosomes is simply that they are the correct size i.e. filter out that size category then the effect disappears. Possibly, if Maureen has found a size category which is increased then that might help to identify the signalling compound/parent cells (the cells which produce the exosomes).
I understand that those who know a lot more than I do are cautious about the something in the blood - it needs to be tested by others.
My view is that exosomes --- something in the blood -- are downstream consequence. Robert Phair describes himself as a top down scientist rather than a bottom up --. It would be good to find what is causing something in the blood; but Robert's approach may get there more quickly.
The nano-needle may be a way of identifying drugs/treatments which improve the quality of people lives i.e. as well as diagnosis -- seems reasonable to me. It might get some people to treatments relatively quickly.
I've seen stuff recently on a bug hiding in the system causing Alzheimer's (gingivilas - gum disease). So yes bugs, and virus's, are a possibility in my view. The interest in other diseases (Alzheimer's etc.) may help to develop a model for this latent bug/virus (causing immune activation) theory. I think Bhupresh Pust's work also relies on some post infection effect. Bear in mind Ron Davis's view (talk after Bhupresh's at NIH Conference April 2019) that there's no RNA/DNA i.e. genetic fingerprint to support latent bug/virus theory.
Re funding:
Dr Vicky Whittemore (NIH) at Invest in ME Conference (2019):
"advocacy groups --- that's what makes the difference -
- when they [
elected representatives] hear that, from people with the disease -
- advocates -- telling them [
elected representatives] what's needed is really what makes the difference"