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A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

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Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#61

Post by mnw21cam »

tomrod wrote: post #42
pja wrote: post #16

Earlier quoted context omitted.

23andme looks for specific single nucleotide polymorphisms (SNPs) so it’s completely unsuitable for looking for this kind of DNA alteration that could be anywhere in the genome.

Thank you for the correction. How would you look for DNA alteration, generally?

Whole genome sequencing of some kind, preferably one of the newfangled long-read technologies such as Oxford Nanopore or Pacbio, would be best for looking for novel insertions into the genome.

However, this is likely to be a fool's errand in this case, because this kind of sequencing normally assumes that we can take a sample of many cells from the body, and that all those cells have the exact same DNA changes. If you have a mutation that is induced in a parent or the single-figure-cell stage of embryo development then that will be true, but for DNA modification by a virus in an adult it will not be. Each cell will have a different insertion. Now, there are some techniques that can sequence the DNA from a single cell, but they don't give quite as good quality data, and because you'd be wanting to sample a good number of cells to see what the distribution of insertions is, it will likely also be very expensive.

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#62

Post by hotdogscout »

maxehmookau wrote: post #56
PaulKeeble wrote: post #52

Earlier quoted context omitted.

The name ME comes from the observation in the 1950s that the brain stem was inflamed as shown on CT scans run in the Royal free hospital in London (what is now called St Thomas' hospital). In the 1980s they found numerous immune and metabolic dysfunctions in sufferers as well and the list of physiological things wrong has steady increased since. Yet mostly doctors have treated patients with psychology and tried to fo…

Your comment kinda casts doctors as the boogiemen though and I struggle to understand the motive for them to act in this way. Doctors, generally, want the best outcome for their patients. I find it hard to believe that they're doing something actively harmful that's against accepted best practices, informed by scientific literature, because... they hate their patients? If there truely were thousands of papers showing…

Unwillingness to admit they don't know what's happening, memes, resentment of criticism after malpractices.

Any illness with primarily neurological symptoms have a history of medical malpractice and gaslighting.

As early as 1944, an author in the Journal of Nervous and Mental Disease remarked: "The history of prefrontal lobotomy has been brief and stormy. Its course has been dotted with both violent opposition and with slavish, unquestioning acceptance."

The last recorded lobotomy in the United States was performed by Dr. Walter Freeman in 1967 and ended in the death of the person on whom it was performed.

https://en.m.wikipedia.org/wiki/Lobotomy

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#63

Post by soudiere »

GordonS wrote: post #34
krisoft wrote: post #29

Earlier quoted context omitted.

> If it turns out that ME/CFS doesn't has a physical marker, then what? The problem is that ME/CFS is similar in presentation to other conditions such as for example certain kinds of depression. The difference is that exercise is thought to help with those conditions and exacerbates ME/CFS. Thus there are two different groups of people, one who you are helping by encouraging them to exercise and one who you are harmi…

PEM (post-exertional malaise) is a core symptom of ME/CFS, but I've never heard of it being a symptom of depression. IME it's more correct to say that depression can be a symptom of ME/CFS - having your life blow up can do that.

Post-exertional malaise is a poor diagnostic indicator, the sensitivity and specificity are quite low.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988339/

First problem, I do not have ME/CFS, let's use the Maes et al (2012) scale. 0-5 scale, 5 being the worst.

"1 means mild exacerbations of fatigue/pain/neurocognitive symptoms following exercise (either cognitive or physical)" Yep, after a longer, harder than normal bike ride I'm quite fatigued, in quite a bit of pain (bad back, knee, shoulder), and can't think particularly well.

"2 means moderate exacerbations of symptoms following exercise; 3 means severe, incapacitating exacerbations lasting less than 24 hours;" Accurately describes what happens when I do HIIT style intervals that exceed my work capacity, or what it's extremely hot outside. Dreadfully exhausted, usually have to nap, or lay on the couch, every muscle hurts, extremely sore, difficult & painful to move for 24-72 hours.

I'm not saying ME/CFS does not exist, this is just a terrible indicator.

The worst part is making it so specific obscures the large body of existing research that would provide tools for treatment protocols here, eg work capacity in athletes.

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#64

Post by InSteady »

aestetix wrote: post #47
maxehmookau wrote: post #46

Earlier quoted context omitted.

> Consider the example of Physics Girl (I linked the video in another comment). The video shows her before COVID, and after COVID. It's obvious that her COVID infection did something to cause her to go from being an amateur astronaut to being bed-bound. I didn't really make an argument to "not make sense". Right now, ME/CFS may just be a collection of symptoms rather than a specific _thing_ that can be tracked, measu…

Ah, I see what you're saying. I think a more logical approach (for me) would be to say that there might be multiple biomarkers which could present ME/CFS type symptoms in different ways. Dr. Bhupesh Prusty has recently given some lectures on his discoveries related to Fibernectin, for example. That could be a massive breakthrough, but we need more studies on it. One other data point that might interest you: apparentl…

The viral angle is fascinating to me.

From the article:

>Viruses can trigger ER [endoplasmic reticulum] stress, perhaps explaining why ME/CFS and related conditions often arise after infection.

Since you mention herpes, I'll bring up what I've read about Epstein-Barr (EBV) (which belongs to the herpes family of viruses). It's estimated that 90% of the global population will contract EBV in their lifetime. In most people, EBV goes dormant for after the initial infection is cleared and more or less stays that way for life. But in some people, for unknown reasons, it can chronically reactivate, triggered by stress, other illnesses, immune dysfunction episodes, etc. Apparently it loves to hang out in the spleen, although I believe it has been found to reside in other organs as well in these cases of chronic reactivation.

I would be shocked if this were the only virus to do so, but at present it seems to be the most studied, perhaps because EBV is fairly strongly correlated with a bunch of cancers, auto-immune disorders, and chronic conditions (including MS as recently demonstrated in a huge study by the VA, n=10,000,000). Very interesting and important stuff. I look forward to further research into these mysterious long-term effects of viral infection.

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#65

Post by mnw21cam »

rocqua wrote: post #45
treprinum wrote: post #10

Earlier quoted context omitted.

Did you try antihistamines? This could be some form of acquired allergy or auto-immune reaction.

Is there a plausible mechanism for histamine to affect gut-health? I thought histamine was just an airway thing.

Histamine is a general inflammation-inducing chemical. That pain and rash you get when you touch a stinging nettle - that's caused by the stinging nettle literally injecting histamine into your skin.

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#66

Post by r2_pilot »

rocqua wrote: post #45
treprinum wrote: post #10

Earlier quoted context omitted.

Did you try antihistamines? This could be some form of acquired allergy or auto-immune reaction.

Is there a plausible mechanism for histamine to affect gut-health? I thought histamine was just an airway thing.

Histamines affect a broad spectrum of body systems. One time I was really stressed about work, went to bed and started itching unbearably and had welts. Apparently I had broken out into hives, which I didn't recognize at first, then I took an antihistamine and within half an hour everything was back to normal.

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#67

Post by soudiere »

PaulKeeble wrote: post #52
maxehmookau wrote: post #25

Earlier quoted context omitted.

> doctors dismiss patients as crazy or "making it up." I don't think that's true, at least not in my experience anyway. People (myself included) are too quick to conflate "all in your head" with "making it up". Things "in your head" can and do have real, physical, life-limiting, effects. If it turns out that ME/CFS doesn't has a physical marker, then what? There may never be a way to verifiably test for it other than…

The name ME comes from the observation in the 1950s that the brain stem was inflamed as shown on CT scans run in the Royal free hospital in London (what is now called St Thomas' hospital). In the 1980s they found numerous immune and metabolic dysfunctions in sufferers as well and the list of physiological things wrong has steady increased since. Yet mostly doctors have treated patients with psychology and tried to fo…

"Tried to force them to exercise ... ignores all the science and evidence"

This is a baseless claim, there's a Cochrane review showing exercise is beneficial. Pacing appears to be a common strategy, and it's exercise in of itself.

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#68

Post by maxehmookau »

hotdogscout wrote: post #62
maxehmookau wrote: post #56

Earlier quoted context omitted.

Your comment kinda casts doctors as the boogiemen though and I struggle to understand the motive for them to act in this way. Doctors, generally, want the best outcome for their patients. I find it hard to believe that they're doing something actively harmful that's against accepted best practices, informed by scientific literature, because... they hate their patients? If there truely were thousands of papers showing…

Unwillingness to admit they don't know what's happening, memes, resentment of criticism after malpractices. Any illness with primarily neurological symptoms have a history of medical malpractice and gaslighting. As early as 1944, an author in the Journal of Nervous and Mental Disease remarked: "The history of prefrontal lobotomy has been brief and stormy. Its course has been dotted with both violent opposition and wi…

> Unwillingness to admit they don't know what's happening, memes, resentment of criticism after malpractices.

Let's assume that all doctors fit your description. (I don't agree, but let's go with it.)

What's the alternative? I just can't accept that the vast majority of medical professionals are ignoring a potential cure or refusing to accept that one for ME may exist because it might hurt their egos.

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#69

Post by hgomersall »

circlefavshape wrote: post #28
aestetix wrote: post #14

There needs to be more research into this horrible disease. There are no yet confirmed biomarkers for it, so doctors dismiss patients as crazy or "making it up." Once there is a biomarker, perhaps like this protein, we can actually start testing treatments to see what works. The scary thing is that there seems to be a vicious path, of COVID->long COVID->ME/CFS. We're not sure what makes COVID evolve into long COVID,…

> doctors dismiss patients as crazy or "making it up" It's very easy to frame what doctors say like this, but in my experience at least that's not really what they're doing. A doctor is a classification machine - they take your symptoms as inputs and output a disease or a syndrome, hopefully with mitigation measures associated with it. When my wife had long covid for 3 years and doctors couldn't find anything wrong w…

The problem really is the stigma associated with mental illness as opposed to other kinds of illness. There are clearly mechanisms through which psychiatric effects manifest as real physical symptoms. If there's no obvious physiological cause to symptoms, working with it having a psychiatric basis seems perfectly reasonable. That doesn't mean we shouldn't try to understand more about it though.

Re: A protein that disrupts cells’ energy centers may be a culprit in CFS/ME

#70

Post by alphazard »

rocqua wrote: post #40
londons_explore wrote: post #15

Earlier quoted context omitted.

One potential mechanism for fatigue: * Virus' have a high failure rate - many infected cells never go on to multiply. * However, those infected cells may also not still perform correctly. * If you have a good chunk of your cells in your body no longer performing their function, yet not dying and making way for replacements either, everything isn't going to work as well. That would explain why it is a wide range of vi…

That seems like a plausible hypthosis, but hard to test for. In this hypothesis, what would be a solution? Best I can think of is Chemo-therapy, to kill of the bad cells. But that feels incredibly heavy handed, as well as liable to do more damage.

Two sibling comments mentioned fasting. Adding more to that.

Prolonged fasting is known to clear away senescent cells. So that is the intervention which seems most promising here. Intermittent fasting can help the gut by giving it time to rest between meals, and it can improve insulin sensitivity because the body spends more time in a low insulin state. Maybe there are longer chains of mechanism there, but at first glance, they don't seem quite as relevant.

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