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Obvious Hypotheses may not be Correct

Wishful

Senior Member
Messages
5,684
Location
Alberta
I just had a good non-medical example. My Kobo Clara was at about half charge. I put it to sleep, then a couple hours later I woke it up and it said 1% charge. I recharged it partially, and next time I woke it, same thing. The two obvious hypotheses are that the battery failed and no longer holds a charge, or that the sleep setting wasn't working properly and that it was doing something that drained the battery quickly. I reset to factory defaults, and not only did the problem go away, but the battery went from showing a few % charge to fully charged. So, the correct answer was that a software error was misreading or miscomputing the charge level.

In terms of ME, there are some hypotheses that seem obvious. "I feel low in energy, therefore ME obviously mitochondrial dysfunction." "It started with a viral infection, therefore ME is obviously a viral infection that's still there."

The proper way to treat hypotheses is to devise a test, do the test, and accept the results. The improper way is to have faith in the hypothesis and keep coming up with inventive excuses for any data that doesn't support it, because, after all, it's obviously correct. So, if your hypothesis is that ME is due to mitochondrial dysfunction, propose some tests, such as "95% of PWME should show low ATP" or "<drug that increases ATP production> should effectively treat ME". If the results show that only 23% of PWME have low ATP, or that only a few people report partial improvement from the ATP boosting drug, then mark the hypothesis as 'false' and move on to a new one. Likewise, if a large percentage of PWME don't have a viral infection, and only a minority show improvement from antiviral treatments, write that one off too. No point in wasting resources on failed hypotheses.

I'd start a thread about 'outside the box' hypotheses, but I expect that most of us here lack the biological knowledge to come up with ones that might actually be true. I just posted a link about a specific protein that subtly reduces microglial activity. I certainly don't know enough about all the various proteins and how they might affect cells to come up with such a hypothesis.

Right now, I think resources should go towards finding reliable markers for ME. The obvious hypotheses have failed their tests, so we need more data to base new hypotheses on.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
The proper way to treat hypotheses is to devise a test, do the test, and accept the results. The improper way is to have faith in the hypothesis and keep coming up with inventive excuses for any data that doesn't support it, because, after all, it's obviously correct.

I have an idea for a ME model. Set up a mouse study. Infect mice with EBV and surpress immune function to simulate stress. Then co-infect them with HHV6. Should give instant ME.
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
Set up a mouse study. Infect mice with EBV and surpress immune function to simulate stress. Then co-infect them with HHV6. Should give instant ME.

That sounds like a reasonable test of that hypothesis. However, if it doesn't result in ME in nearly 100% of the mice, would you accept that ME is not a viral disease? That was the point of my minor rant: that we (and researchers and fund managers) should accept negative results and move on to other hypotheses, rather than inventing an endless stream of ex post facto excuses for why the test they agreed to was not valid, so we should keep funding the hypothesis.

My mailbox had something from the OMF about a researcher getting funding for studying PEM in skeletal muscles. I see that as a waste of funding, since my PEM wasn't in my skeletal muscles. There should first be a test of the hypothesis that PEM is located in skeletal muscles. If a reasonable percentage of the test subjects don't show any sign of PEM being located in their skeletal muscles, scratch that hypothesis.
 

sometexan84

Senior Member
Messages
1,229
@Wishful
There is no correct hypothesis because ME/CFS isn't a real thing. ME/CFS (the term) only exists as a label for those w/ certain symptoms, that have yet to be diagnosed w/ what's really causing the problem.

All of us on this forum are way more different than everyone thinks. A lot of our symptoms like PEM and fatigue are similar. But we also have a TON of completely different symptoms (and infections).

Quoting my post from another thread:

The term ME/CFS is going to disappear. ME/CFS means "we don't know why you're tired". In a few yrs, ME/CFS will have been split out into a lot of specific diseases, most of which will be autoimmune. They're still discovering new auto-antibodies, and then labeling with a specific condition, a new name to say this is the illness you have. This is what's going to be happening.​
Like HSP-60 (Heat Shock Protein 60). There is literally no commercial test available for this. It's only for research at this point. 1 or 2 yrs from now, there might be a name for those with auto-antibodies to HSP60. You'll be able to test for it at Quest and LabCorp. If you're positive, then you have HSP Encephalitis, or something like that.​
Post-exertional malaise is not unique to ME/CFS. Nothing is. They can't find consistent overlapping symptoms or infections. It's because ME/CFS is not really a thing.​
We're just a bunch of people with undiagnosed Lyme, Sjögren's syndrome, autonomic neuropathies, hypothyroidism, POTS, cancer, anemia, lambert-eaton myasthenic syndrome, antiphospholipid syndrome or thrombocytopenia, pure autonomic failure and orthostatic hypotension, multiple system atrophy, amyloidosis, small fiber polyneuropathy, multiple sclerosis, diabetes, celiac, lupus, arthritis, and a bunch of "syndromes" that don't exist yet on paper. Most of which are auto-immune related.​
Mitochondrial dysfunction is just getting researchers sidetracked. It's definitely a player in symptoms, but it's only a small part of the overall picture. Most people on this forum haven't even considered the autoimmune aspect, and haven't been tested.

Why do WE have re-activated EBV??? WHY is it that everyone else takes care of Enterovirus B like it's nothing, where we have it as a persistent infection?? WHY do people w/ ME/CFS seem to have multiple infections?

Our immune system is out of whack. Most here are genetically susceptible to this. This is part of the reason why ME/CFS is rare. You have to have the perfect set of unfortunate circumstances AND have a genetic predisposition.

Autoimmunity hardly ever gets talked about in this forum. So I know people aren't normally testing for this stuff. But it's this that keeps our bodies from killing off infections. And the auto-antibodies are driving inflammation, and fatigue by attacking our thyroid gland, attacking key receptors, attacking our cells, heart and blood vessels, attacking nerves, etc.

It's not the infections that are the problem, it's our immune response to them. Now that is something we all share.

And yes, most people here do have an active infection of some sort. Doesn't have to be EBV, it could be a hundred different things.

There is no correct hypothesis for CFS, because it doesn't exist.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
However, if it doesn't result in ME in nearly 100% of the mice, would you accept that ME is not a viral disease?

No because ME is only occurring in a small percentage of the population (2%). We need to analyze the genomes of the ME mice and see if a genetic predisposition (ie. autoimmune disease genes) is causing to develop ME after exposure to concurrent viruses and then see if you do it to only those mice whether it shows high causation.
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
We need to analyze the genomes of the ME mice and see if a genetic predisposition (ie. autoimmune disease genes) is causing to develop ME after exposure to concurrent viruses and then see if you do it to only those mice whether it shows high causation.

To me that sounds like you're saying that ME is a genetic problem, of which viral infections are a common trigger, but not the actual cause of ME. It may be hard to prove that some PWME didn't trigger on a virus, but if we identify some people who had a non-viral trigger, that would kill that hypothesis.

Some virus strains may be particularly good at triggering ME, but that still wouldn't make them a cause of ME.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
To me that sounds like you're saying that ME is a genetic problem, of which viral infections are a common trigger, but not the actual cause of ME. It may be hard to prove that some PWME didn't trigger on a virus, but if we identify some people who had a non-viral trigger, that would kill that hypothesis.

Some virus strains may be particularly good at triggering ME, but that still wouldn't make them a cause of ME.

I don't think so myself because of the presentation. If viruses were triggering ME then why do we see symptoms of active viral infections: Sith1 depression from HHV6, mitochondral inhibition (Nf-kb activation), chronic inflammation. These things need a constant viral stimulus. I don't see a mechanism for a one time viral trigger. I think that coinfection is much more likely. Also, why does the symptom severity keep increasing? That suggests viral spread.
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
If viruses were triggering ME then why do we see symptoms of active viral infections:

I don't seem to show symptoms of active viral infections. I've had a couple of viral infections during my ME, and they caused normal viral symptoms and worsened ME symptoms, but then the viral symptoms passed and ME symptoms returned to baseline.

I don't see a mechanism for a one time viral trigger.

Researchers are still discovering new organs and particles in the body, so I wouldn't be surprised that they haven't yet discovered a mechanism that can switch state from a viral infection or other immune system activation event.

Also, why does the symptom severity keep increasing?

It hasn't for me. My ME has varied a bit since 2001, but it hasn't increased. In fact, I've lost several symptoms and sensitivities. Why might ME symptoms increase over time for other people? I can think of several mechanisms offhand: accumulation or depletion of something; cell alterations due to the abnormal conditions; changes to DNA or RNA transcription. Viral replication wouldn't be at the top of my list of reasons.
 

Rufous McKinney

Senior Member
Messages
13,249
why does the symptom severity keep increasing? That suggests viral spread.

possibly: also collagen loss over time.

And western medicine will entirely ignore for now, the implications of our connective tissue- containing collagen...being weakened and not transmitting signals properly. (why acupuncture communicates thru the body, potentially).

on symptoms becoming more severe over time- what about the toxin build up? If our brains aren't being cleansed properly (washed in CSF nightly)...and if our lymph systems are stagnent (slow) and then the lack of exercise furthers that stagnation....toxins build up. this could be contributing to worsening severeity/ combined with other worsening factors.
 

sometexan84

Senior Member
Messages
1,229
To me that sounds like you're saying that ME is a genetic problem, of which viral infections are a common trigger, but not the actual cause of ME. It may be hard to prove that some PWME didn't trigger on a virus, but if we identify some people who had a non-viral trigger, that would kill that hypothesis.

Some virus strains may be particularly good at triggering ME, but that still wouldn't make them a cause of ME.
Ya know, I feel like the best studies on ME/CFS and infections, are the prospective cohort studies, where they follow those w/ acute infection to see if they develop ME/CFS.

I think research has all but delivered the final blow, in proving the ME/CFS infections association.

They just can't find which infection. Like Wishful says, some infections are more likely to cause autoimmunity and ME/CFS. But there are a TON of infections and co-infections that can be involved.

A solid 2006 study following those w/ acute Epstein-Barr virus, Coxiella burnetii (Q fever), or Ross River virus. (no clue why there haven't been more studies like this...)
https://www.bmj.com/content/333/7568/575

28 of 253 (11%) went on to develop CFS.

5 w/ EBV
3 w/ Q fever
13 w/ Ross River virus
8 w/ unconfirmed infection

It's all over the place
 

Rufous McKinney

Senior Member
Messages
13,249
There should first be a test of the hypothesis that PEM is located in skeletal muscles.

Somewhere in this swirl, another aspect of evaluating any of this may also include PEM itself. What is PEM? That would need to be pretty specifically defined, and be measurable and quantifiable, in order to then correlate it with other variables.

For me, decades in the making, a lifetime of- issues with this....I'll never be able to really know if I experienced PEM per se, during the decades I had whatever this is, mild version. Able to keep working version. What would happen would be- flares of like a low grade fever and swollen lymph, rundown and tired. But I don't believe it was like the way we now view PEM. It might happen a couple of times a year, not Every Thursday, or after major exertion. During these decades, I consider myself to have some type of post viral chronic Eppstein Barr. I've always viewed this as the Virus got me some how on an ongoing and permanent basis.

Then because of doing chinese herbs, there is clearly a genetic component associated with, well in my case red hair. Very yin deficient.

And I will also still contend that some other toxin/poison/major stressor was also required to fulfill our algorhythm.
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
Somewhere in this swirl, another aspect of evaluating any of this may also include PEM itself. What is PEM?

Yes, to me that's a better target for funding than studying 'PEM in skeletal muscles'. At this point we don't know what PEM is or whether it has anything to do with muscles. Since PEM can be triggered by cerebral exertion, with a shorter delay, to me it seems that PEM is neurological, and that neurological response can also be triggered by physical exertion, but isn't actually caused by the muscles themselves. I wouldn't be surprised if injecting certain cytokines would trigger PEM. Is there the cytokine equivalent of a multivitamin tablet? :)
 

Rufous McKinney

Senior Member
Messages
13,249
I'd start a thread about 'outside the box' hypotheses, but I expect that most of us here lack the biological knowledge to come up with ones that might actually be true

For whatever reason- FLOURIDE....I"m wondering about it. It does't get discussed around here much. Flouride is very toxic, I have health expert friends who swear its literally being diverted from hazardous landfills to our toothpaste and water supply.

Its such a now nearly universally distributed substance....I try not to buy flouride toothpastes myself.

There is some evidence it can disrupt the gut, biofilms, etc. I'm just saying- so many variables assault us daily.

This discusssion includes mass quantities of references I've not had time to look into ...just wondering.

https://mybiohack.com/blog/toxic-fluoride-not-just-a-problem-for-the-eye