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Mitochondrial and Energy Metabolism Dysfunction in ME/CFS — Myhill, Booth and McLaren-Howard Papers

nandixon

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At this point I am not sure, but it does place a question mark over the Acumen Lab test.
Yes, I would really like to see blinded samples of patients and healthy controls sent to the Acumen people to see if they can correctly discriminate between the two just to make sure there's not some hidden little detail that Acumen does that Karl Morten's group isn't aware of that actually makes the Acumen test work right and be valid. The Acumen people should be making that offer if they stand behind their test.
 

boolybooly

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Dr Myhill has previously responded.

FYI:)

https://drmyhill.co.uk/wiki/Response_to_the_paper_'Assessing_cellular_energy_dysfunction_in_CFS/ME_using_a_commercially_available_laboratory_test'_by_Cara_Tomas_et_al

Why does the Tomas Paper fail to replicate our findings?
Dr Norman Booth suggested that before the Tomas group proceeded with their test, they should do paired samples to compare with the Acumen test. The idea was that Dr Myhill would take blood from one patient and send samples to both laboratories to be tested on the next day. Dr Myhill offered to fund the cost of such a comparison. This offer was never taken up. What this means is that we can have little confidence in the ability of the Tomas group to replicate the Acumen test.
 

nandixon

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"The idea was that Dr Myhill would take blood from one patient and send samples to both laboratories to be tested on the next day. Dr Myhill offered to fund the cost of such a comparison."

A single patient analyzed by the two groups is not good enough. Blinded amples need to come from multiple patients and multiple healthy controls and Myhill needs to show that the Acumen test can differentiate between the patients and healthy controls without knowing which is which.
 

grapes

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Just for everyone's reference, the mitochondria dysfunction ME/CFS patient subtypes that Myhill et al discovered are these:

ME/CFS Patient Mitochondria Dysfunction Subtype Groups:

Group A Patients — oxidative phosphorylation running normally. Group A then divides into two subgroups:
  • Group A1 Patients ('no HIs') — These are Group A patients who have normal or sub-normal TL IN values (and 87% of these patients also have sub-normal TL OUT values).
  • Group A2 Patients ('HI TL IN') — Group A patients who have super-normal TL IN value.
Group B Patients ('HI Blk') — oxidative phosphorylation partially blocked and running at low efficiency.
  • All of the Group B patients were found have sub-normal TL IN values (ie, they have reduced translocator protein transfer of ATP from mitochondria to the cytosol of the cell). And 78% of the Group B patients have sub-normal values of TL OUT (decreased translocator protein ferrying of ADP from the cell to the mitochondria).

Group A patients try to compensate for the mitochondrial ATP shortage by increasing glycolysis to make ATP.

Group B patients try to compensate for the shortfall in mitochondrial ATP most likely by using the adenylate kinase reaction to make ATP.
Does TL refer to the translocator protein transfer of ATP from mitochondria to the cytosol of the cell?
 

Hip

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Does TL refer to the translocator protein transfer of ATP from mitochondria to the cytosol of the cell?
The translocator protein (TL) has two functions and is a two-way street: it carries fresh ATP from the mitochondria into the rest of the cell (this Myhill calls TL IN), and also carries the spent ATP (it becomes ADP once spent) back out from the cell into the mitochondria for recycling (TL OUT).
 

grapes

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The Lactic Acid Build-Up Problem in PEM

PEM is compounded and exacerbated by the problem of lactic acid build-up in the muscles, in ME/CFS patients who rely on anaerobic glycolysis to make up for the shortfall of energy (a shortfall originally resulting from dysfunctional mitochondria). This because anaerobic glycolysis produces lactic acid as a by-product.

This lactic acid build-up then further compounds the energy shortage problem of PEM, because to clear lactic acid by converting it back to glucose, it requires considerably more energy than was originally gained from the conversion of glucose to lactic acid.
Hip, in my process of reading everything, I haven't yet found this. Do problems in ANY of the five energy processes excess high lactic acid? Because the lactic acid issues seems to be mentioned more in (3) Oxidative Phosphorylation.
 

Hip

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Hip, in my process of reading everything, I haven't yet found this. Do problems in ANY of the five energy processes excess high lactic acid? Because the lactic acid issues seems to be mentioned more in (3) Oxidative Phosphorylation.
According to the Myhill theory, lactic acid build up is a problem in Group A patients. It's not such an issue in the Group B patients (Group B have more severe ME/CFS than Group A).
 

godlovesatrier

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It would be brilliant if someone could be funded to do a genetic mapping (WGS) and ATP test as these studies did, replicate the ATP tests and then perform the genetic mapping to single out high incidence of gene mutations correlated as a trend in the same way the ATP mitochondrial performance correlates depending on severity of symptoms. That would at least rule out genetic issues, including genes we may not even have fully understood yet.