A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

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New PNAS paper from Ron Davis and team released ahead of print (not open access).

https://www.pnas.org/content/early/2019/04/24/1901274116

ABSTRACT. There is not currently a well-established, if any, biological test to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The molecular aberrations observed in numerous studies of ME/CFS blood cells offer the opportunity to develop a diagnostic assay from blood samples. Here we developed a nanoelectronics assay designed as an ultrasensitive assay capable of directly measuring biomolecular interactions in real time, at low cost, and in a multiplex format. To pursue the goal of developing a reliable biomarker for ME/CFS and to demonstrate the utility of our platform for point-of-care diagnostics, we validated the array by testing patients with moderate to severe ME/CFS patients and healthy controls. The ME/CFS samples’ response to the hyperosmotic stressor observed as a unique characteristic of the impedance pattern and dramatically different from the response observed among the control samples. We believe the observed robust impedance modulation difference of the samples in response to hyperosmotic stress can potentially provide us with a unique indicator of ME/CFS. Moreover, using supervised machine learning algorithms, we developed a classifier for ME/CFS patients capable of identifying new patients, required for a robust diagnostic tool.
 

Ben H

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Hey guys,

Exciting stuff :)


New OMF-funded Research Publication: A Nanoelectronics-blood-based diagnostic biomarker for ME/CFS

Dr. Ron Davis, OMF Scientific Advisory Board Director, explains the PNAS publication on the nanoneedle (April 29, 2019)

A paper describing the nanoneedle was published in the Proceedings of the National Academy of Sciences. Ronald W. Davis, Ph.D. is the senior author. Rahim Esfandyarpour, Ph.D. is the lead author. The nanoneedle is a test that measures changes in immune cells with their blood plasma as a result of salt stress. Inside the nanoneedle, the immune cells interfere with a small electric current. The change in electrical activity is directly correlated with the health of the sample. The test, which is still in a pilot phase, is based on how a person’s immune cells respond to stress. With blood samples from 40 people — 20 with ME/CFS and 20 without — the test yielded precise results, accurately flagging all patients and none of the healthy individuals.



Click here to watch the video.

Click here to read the abstract and full publication on PNAS.

Click here to read the Stanford announcement.


B
 

Countrygirl

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https://www.telegraph.co.uk/science...-syndrome-may-picking-symptoms-not-condition/

Test for chronic fatigue syndrome may be picking up symptoms not condition, warn experts



UK 'scientists' refute the findings and Wessely is critical and disputes the use of the Stanford's work, The test could merely be picking up the patient's anxiety apparent. Well, there is a surprise! :xeyes:


But experts in Britain said the test may be picking up symptoms of fatigue or anxiety rather than the disease itself, and could not be used as proof the condition is real.
Prof John Martin, Professor of Cardiovascular Medicine, University College London (UCL), said: “If a test is to have meaning it has to be able to be applied to a population of patients who can be defined clinically.

“The patients described had a variety of symptoms that could have arisen from a variety of causes.

“Further the authors do not relate the cellular finding in the test to a possible cause of the disease. CFS/ME is probably not a disease but a syndrome.

“The authors should consider whether their test is related to an effect of symptoms and not related to the cause.”
Prof Sir Simon Wessely, President of the Royal Society of Medicine, said: “There have been many previous attempts to find a specific biomarker for CFS. The problem is not differentiating patients with CFS from healthy controls. The issue is can any biomarker distinguish CFS patients from those with other fatiguing illnesses?
“And second, is it measuring the cause, and not the consequence, of illness? This study does not provide any evidence that either has finally been achieved.”
The Stanford team has also been using their test to see if drugs can dampen down the electrical response of cells under stress. They have already discovered that one medication in common use does, and hope to start clinical trials soon.

The research was published in the Proceedings of the National Academy of Sciences.
 

Navid

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The Stanford team has also been using their test to see if drugs can dampen down the electrical response of cells under stress. They have already discovered that one medication in common use does, and hope to start clinical trials soon.

What is it?????
 
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This section from the paper describes their investigations into why the impedance changes.

1. it could be exosomes or other stuff in the blood

"to identify the mechanisms and components involved at the cellular and molecular levels, we have started to investigate the plasma components (e.g., proteins, exosomes, and lipids) and individual cell types (e.g., T cells) separately. This investigation forms part of on-going studies that require further investigation before mechanisms may be suggested with a good degree of certainty"

and/or

2. adding salt may make the cells produce cytokines.

"a number of reports in the literature indicate that the addition of salts or other osmotic agents to the cell environment may induce the production of inflammatory cytokines (20, 39–44). These studies indicate that the development of inflammation as a consequence of osmotic stress may be a general phenomenon affecting PBMCs (44, 45) and a number of other cell types (46–50). Both lower (20 mM to 41 mM) (48) and higher (100 mM to135 mM) (47) concentrations of NaCl than the amount tested inthe present study (65 mM) have been investigated. In a study on the effect of osmotic stress on human bronchial epithelial cells, IL-8 production was stimulated by additional NaCl (ranging from 50 mM to 150 mM) in a time- and dose-dependent manner"
 
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One good thing about the paper is they provide a lot of info about how the nano-needle was made and used, to make it easier for other labs to try to replicate this study. Replication is going to be very important.

A note of caution:

It is important to retain some doubt and skepticism about this finding until it is replicated. To be honest, I have a slight fear these findings are too good to be true - total separation between control and patient like that is extremely rare. You never know what kind of errors might be involved. Perhaps some junior person knows Ron desperately wants results and is giving him what they think he wants. Perhaps samples from patients and controls were treated differently in a way nobody noticed. Or something else. It could be anything. I think the most likely situation is that the results are true and replicable. But there's a small chance they're not and we should be ready for that.
 

msf

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https://www.telegraph.co.uk/science...-syndrome-may-picking-symptoms-not-condition/

Test for chronic fatigue syndrome may be picking up symptoms not condition, warn experts

UK 'scientists' refute the findings and Wessely is critical and disputes the use of the Stanford's work, The test could merely be picking up the patient's anxiety apparent. Well, there is a surprise! :xeyes:

But experts in Britain said the test may be picking up symptoms of fatigue or anxiety rather than the disease itself, and could not be used as proof the condition is real.

Prof John Martin, Professor of Cardiovascular Medicine, University College London (UCL), said: “If a test is to have meaning it has to be able to be applied to a population of patients who can be defined clinically.

“The patients described had a variety of symptoms that could have arisen from a variety of causes.

“Further the authors do not relate the cellular finding in the test to a possible cause of the disease. CFS/ME is probably not a disease but a syndrome.

“The authors should consider whether their test is related to an effect of symptoms and not related to the cause.”
Prof Sir Simon Wessely, President of the Royal Society of Medicine, said: “There have been many previous attempts to find a specific biomarker for CFS. The problem is not differentiating patients with CFS from healthy controls. The issue is can any biomarker distinguish CFS patients from those with other fatiguing illnesses?

“And second, is it measuring the cause, and not the consequence, of illness? This study does not provide any evidence that either has finally been achieved.”

The Stanford team has also been using their test to see if drugs can dampen down the electrical response of cells under stress. They have already discovered that one medication in common use does, and hope to start clinical trials soon.

The research was published in the Proceedings of the National Academy of Sciences.
Wessely is that most dangerous of creatures, a person that thinks he is much smarter than he is. In fact, I think he is the highest level of charlatan, in that he probably thinks that he is right, purely because he is too dumb and arrogant to perceive his own stupidity and credulity. If he had any sense he would shut up when scientists and logical, rational thinkers enter the arena. Instead he insists on making a fool of himself.

Just as one example, if no biomarker can distinguish CFS from other fatiguing illnesses (not true, but whatever, I will take it as an article of faith that Wessely is as poorly read as he is dumb), then how can you be sure that ME is a psychosomatic illness and that the other fatiguing illnesses aren't? By using your magic psychosomatic divining rod? What a cretin.
 
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By using your magic psychosomatic divining rod? What a cretin.
Wessely is that most dangerous of creatures,
I was working on anxiety reduction today then this shows up. The link seems to lead to an incomplete article??

So UK is so disinterested they don't even bother to report directly on the Davis research and instead: move immediately to refute it? And produce this type of biased, incomplete, distorted AWFUL commentary and call that science reporting? One sided baseless opinion.

Troll? Who pays this guy: follow the Money.
 
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To me this looks like the most interesting and exciting news that I've seen in quite some time. It will be interesting to see if they can replicate these results with the same high levels of accuracy.

For those of you who are much more scientifically minded than I am, I am curious: does this test give us any new or better understanding into the causes and/or effects of ME/CFS?
 

Jackb23

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@msf “Wessely is that most dangerous of creatures, a person that thinks he is much smarter than he is. In fact, I think he is the highest level of charlatan, in that he probably thinks that he is right, purely because he is too dumb and arrogant to perceive his own stupidity and credulity. If he had any sense he would shut up when scientists and logical, rational thinkers enter the arena. Instead he insists on making a fool of himself.“

Precisely the Dunning-Kruger Effect.

These guys have to be sitting on some serious coin or some other personal incentive. The excessive punctuality of their rebuttal reeks of insecurity.
 

Countrygirl

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Wessely is that most dangerous of creatures, a person that thinks he is much smarter than he is. In fact, I think he is the highest level of charlatan, in that he probably thinks that he is right, purely because he is too dumb and arrogant to perceive his own stupidity and credulity. If he had any sense he would shut up when scientists and logical, rational thinkers enter the arena. Instead he insists on making a fool of himself.

Just as one example, if no biomarker can distinguish CFS from other fatiguing illnesses (not true, but whatever, I will take it as an article of faith that Wessely is as poorly read as he is dumb), then how can you be sure that ME is a psychosomatic illness and that the other fatiguing illnesses aren't? By using your magic psychosomatic divining rod? What a cretin.
Well, I did read in a court transcript where Wessely was called as an expert witness (of what?) that he told the court that what he knew about the immune system you could write on a postage stamp. Most people with any sense given his lack of knowledge would know better than to try to undermine the work of someone who is actually an expert in his field. I don't t think he is a cretin though, more of a clever devil. It is more entertaining anyway to work out which are the Personality Disorders this man exhibits. Perhaps @Janet Dafoe (Rose49) could take this poor afflicted tortured soul on as a patient and help iron him out .
 
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