Profile of circulating microRNAs in Myalgic Encephalomyelitis......(2020)Moreau et al

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ScottTriGuy

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Google translated:

The Canadian Press
MONTREAL - A new test developed by Montreal researchers is expected to improve the diagnosis and treatment of patients with myalgic encephalomyelitis (ME), a condition better known as chronic fatigue syndrome.


L'EM is currently diagnosed primarily by elimination, as doctors put aside other possible causes of the patient's symptoms.

Researchers from the University of Montreal and the CHU Sainte-Justine led by Professor Alain Moreau have now put their finger on a blood biomarker that can identify patients with ME.

https://translate.google.com/transl...4d40157913a8afda06d910546&prev=search&pto=aue
 
Needs a much larger replication.
MiRNAs were extracted from plasma samples obtained from ME/CFS patients (n = 11), and matched healthy controls (n = 8)
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Post-exertional stress challenge
The participants were exposed to a stress-test to provoke PEM using an ABR therapeutic massager device developed by Panacis Medical Ltd. (Ottawa, Ontario, Canada). The ABR method includes an inflatable cuff that is applied to the arm of each participant. The cuff dynamically exerts pulsatile compressions producing a pressure of variable amplitude from 0–4 psi at 0.006 Hz. All participants were mechanically stimulated for 90 min (T90) to induce PEM and evaluate changes in the miRNA expression profile in response to this mechanical stimulation.

Blood specimen collection
Peripheral blood samples of participants were collected at two time-points (baseline, T0 and after the stress-test, T90) in EDTA-treated tubes, and centrifuged at 11,000×g for 10 min. Derived plasma samples were aliquoted and kept frozen at − 80 °C until analysis.
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So samples were taken just before, and just after, the arm cuff test. Because of that, it looks like they are, potentially, measuring fatigueability, rather then PEM to me. To be more sure of measuring PEM then I would have thought that they would need to take samples at longer time periods.
 
In conclusion, we developed a post-exertional stress challenge that provokes PEM in ME/CFS patients.

Measurement of the differential expression of circulating miRNAs in severely affected ME/CFS patients led to the discovery and validation of eleven miRNAs associated with ME/CFS.

Based on these different miRNA signatures, machine learning algorithm led to the classification of ME/CFS patients into four clusters associated with symptom severity.

These findings may provide a foundation for the development of a new non-invasive test to diagnose ME/CFS patients.

These miRNA signatures and clusters could eventually be used to predict responses to pharmacological treatments for ME/CFS, and may even allow clinicians to identify individuals to whom such treatments could be beneficial.

In addition, we present possible mechanisms that still need to be validated, by which each of the miRNAs could play a role in the pathogenesis and etiology of ME/CFS.
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Andy said:
Needs a much larger replication.
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That was just the discovery cohort

For the discovery cohort, thirty-eight plasma samples (Table 1) were obtained from 11 ME/CFS patients (9 women and 2 men) and 8 matched healthy controls (5 women and 3 men). For the replication cohort, ninety-eight plasma samples (Table 1) were obtained from 32 ME/CFS patients (18 women and 14 men) and 17 matched controls (11 women and 6 men).
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I may be wrong here but an increase or decrease in mi-RNAs following a post exertional challenge may still be the cause of PEM. It probably takes some time for these miRNAs to influence gene expression and then go on to cause symptoms. So testing them for longer than 90 minutes as they did in this study may not be necessary. But I don’t know how long these mi-RNAs need to be altered for, for them to cause symptoms if that makes sense. I guess having more time points would allow you to see how long they are altered for at least.

They said they tested housebound patients but was the test conducted in their homes? Otherwise getting to the university in itself would surely cause a change in mi-RNAs. Although they did measure these at baseline and found a difference between ME/CFS vs controls and after 90 minutes and also ME/CFS compared to themselves at baseline and again at 90 minutes.
 
https://globalnews.ca/news/7457827/montreal-chronic-fatigue-syndrome-breakthrough/
A discovery by Montreal researchers is expected to improve the diagnosis and treatment of patients with myalgic encephalomyelitis (ME), better known as chronic fatigue syndrome.

In most instances, ME is currently diagnosed by elimination, as doctors put aside other possible causes of the patient’s symptoms.

But researchers from the University of Montreal and the CHU Sainte-Justine, led by Professor Alain Moreau, have found a blood biomarker that can help identify patients with ME.

Their findings could lead to better treatment for the disease, including early detection.
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https://montreal.ctvnews.ca/montrea...o-diagnose-chronic-fatigue-syndrome-1.5185761
MONTREAL -- A new test developed by Montreal researchers is expected to improve the diagnosis and treatment of patients with myalgic encephalomyelitis (ME), a condition better known as chronic fatigue syndrome.

ME is currently diagnosed primarily by a process of elimination, as doctors check off other possible causes of the patient's symptoms.

Researchers from the University of Montreal and the CHU Sainte-Justine led by Professor Alain Moreau have now put their finger on a blood biomarker that can identify patients with ME.
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"Simulated discomfort

Some patients with myalgic encephalomyelitis will be confined to their bed for several days simply after daring to walk to the corner store or fill out a questionnaire. In such a context, it became problematic for Mr. Moreau to reproduce in his volunteers the "discomfort after effort" that they feel, without at the same time putting them on the floor for a long period of time.

The researchers therefore used an inflatable cuff, like the one used during therapeutic massages, to safely induce this discomfort.

“This mechanical stimulation creates a certain effort, a response, while the participant is simply seated in a comfortable chair,” explained Mr. Moreau. We do this stimulation for 90 minutes. "

A blood sample taken at the start of the test provides the starting value. The differences measured at the end of the test provide an accurate molecular signature.

It then becomes possible to differentiate “blind”, with 90% accuracy, between participants with ME and normal subjects or those suffering from related diseases, such as fibromyalgia."



How do we know that this effort ( the inflatable cuff) truly creates the exertion that induces pem/pese? I use a machine to create a sort of therapeutic massage for another medical condition but it does not create pem/pese.
 
Andy said:
Fair enough but my point still stands, it needs replicating on a larger scale, and at longer time points.
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I've re-read the paper and while the patients report suffering from PEM after the use of the cuff, I still have my doubts about whether the study proves that what they are measuring is necessarily what causes PEM. It could be, there is nothing that proves that it isn't, but I don't see the evidence to be able to say definitely it is. So, as is often the case, I think there is a bit too much hype about this.

Looking back, https://www.s4me.info/threads/dr-al...ess-protocol-for-provoking-pem-thoughts.6329/, I see my thoughts on this method aren't exactly new.
 
I think before putting any particular interpretation on this we need to see the difference between a group of PWME before and after cuff massage, and a group of PWME before and after a similar period of no massage plus a dose range in between so that there is a dose response curve indicating what aspect of the procedure is producing an effect.

I worry a bit that they think they are 'stressing' people. It is easy to induce a physiologic stress response just by putting people in a room and saying something of importance is going to happen. The problem is that the stress response for patients and healthy volunteers are likely to be very different because volunteers are just having a day off being guinea pigs.

If there is a consistent dose-dependent effect in PWME then this looks quite interesting, but I would like to be sure.
 
Wonko said:
Surely asking the people who've been subject to it, a few days later, would gain that information.
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It might but I am still not sure what would be being measured. On using my therapeutic massage machine initially, I did have an unpleasant response (nausea type but not the draining exhaustion of pem) such that I stopped using it for a while but on starting it again, I seemed to learn to tolerate it even at significantly increased pressures without any unpleasant after effects. The initial effects were similar to those sometimes induced by manual lymphatic drainage given by a therapist.

I still feel unsure that what is being measured actually equates to pem.
 
Jonathan Edwards said:
I think before putting any particular interpretation on this we need to see the difference between a group of PWME before and after cuff massage, and a group of PWME before and after a similar period of no massage plus a dose range in between so that there is a dose response curve indicating what aspect of the procedure is producing an effect.

I worry a bit that they think they are 'stressing' people. It is easy to induce a physiologic stress response just by putting people in a room and saying something of importance is going to happen. The problem is that the stress response for patients and healthy volunteers are likely to be very different because volunteers are just having a day off being guinea pigs.

If there is a consistent dose-dependent effect in PWME then this looks quite interesting, but I would like to be sure.
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The "stress" of the device is minimal. Frankly going there and talking for an hour was more demanding than the cuff. Really going with trying to get the minimal exertion that can be measured, but more useful results would probably come from trying different levels to find the sweet spot that doesn't cause flares, and limiting the test to home, which is a serious issue. The milder/moderate patients, like me, went to the hospital, the more severe ones were seen at home, but that severely limits the number of participants.

But I have no issues about potential side-effects, it's so mild that going there is still most of the exertion. I would definitely be curious about differences between patients who went to the facility and those who were visited at home.

(I was probably not part of that cohort but I went twice before, last time about 3 years ago, I think)
 
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