A nanoelectronics-blood-based diagnostic biomarker for ME/CFS (2019) Esfandyarpour, Davis et al

[anciendaze]

Interesting how the ME/CFS characteristic seems to be a greatly exaggerated version of the controls. From time zero the impedance drops initially, then steadily rises again. For ME/CFS, the drop is much more dramatic and for longer, before then rising far more significantly. Also presumably significant that when not stressed, the impedance is the same for both.

View attachment 7057

This difference in the graph is what we've been looking for, a major difference in response to cellular stress, and I don't mean psychological stress. We've all been reporting variations on such problems since we fell ill, and being misunderstood. This time someone has tried to find a physiological response that mirrors patient reports. I'll admit I don't understand the details of the test set up very well. This is the kind of thing where you would probably need to visit the laboratory and ask questions rather than just read a short write up. It is clear they tried a number of approaches, and we know very little about the ones that were discarded. This often tells you a great deal more than reported successes.

What struck me is that they didn't start out to use this the way they ended up. It sounds a lot like a common pattern in research discoveries where "the control becomes the new experiment." People who plow on ahead without paying attention to distractions they had not predicted will miss these opportunities.

My favorite example has to do with an obscure physicist who berated his assistant for storing photographic plates that were ruined next to a Crookes tube. He remains obscure, while Wilhelm Röntgen became famous for discovering X-rays. (A Ukrainian named Ivan Puluj should share some honors.)

Compare this with the PACE study where they might say "we started off with the idea such-and-such might cure patients, and we persevered to reach that conclusion even though the patients and data fought back vigorously."

Ignoring academic honors, which group sounds like it is doing real research?

 

[wigglethemouse]

Another suggestion for an experiment.

Could cell membrane potential be measured before and after 2-3 hours of salt solution? Patch Clamps can measure membrane potential. The change in impedance observed could be related to the change in potential.........

Seems like there are several different Patch Clamp methods. This is one company that offers a range.
https://www.moleculardevices.com/applications/patch-clamp-electrophysiology

@Chris Ponting @Jonathan Edwards @Simon M appreciate your thoughts and if it could be relevant do you know anyone you can run this idea by?

 

[mango]

Did your tweets actually appear under the #mecfs hashtag listing though when you used this hashtag in your tweets?

I see other familiar ME/CFS patients' tweets appear in the #mecfs listing, but my tweets never do.

Perhaps I'm some sort of persona non grata on Twitter!

Are you aware that there are several different tabs on Twitter for the hashtag searches? The link you gave now to the hashtag listing goes to Top Tweets (most popular tweets). Have you checked under Latest? The latest tweets listing is less filtered.

 

[Londinium]

Sodium potassium pumps are sexually dimorphic and if the controls are not matched then you would have an overrepresentation of females in the CFS population leading to altered impedance.

This would be a bigger concern if there had been a statistically significant difference between the groups but some overlap in results. As it is, there was no overlap in results so it cannot be an artefact of control/patient matching. That suggests it’s either:

1) a genuine result, with a difference between patients and HCs (with the caveats around that not necessarily meaning it’ll distinguish between ME/CFS patients and other conditions); or
2) some kind of handling error in which patients’ blood was collected/stored/tested differently to that of HCs.

If the serum swap results mentioned but not yet published turn out to verify, that would seem to rule out (2) to some extent.

 

[beverlyhills]

I have pointed those out, and the K/ATPase gender differential would be subject to scaling effects as the sample size widens. Anyways, it is wholly irrelevant.

Give patients with CFS and healthy active controls 100 g dextrose and attach a clamp and measure their blood sugar levels over hundreds of time points. The CFS patients will have more postprandial insulin resistance then their comparators. If you have enough time points you can isolate a single aperture in which 100% of CFS patients have a slower rate of glucose disposal than their healthy counterparts. Do this multiple times, and then triangulate a specific time window in which this is likely to occur.

 

[wigglethemouse]

I have pointed those out, and the K/ATPase gender differential would be subject to scaling effects as the sample size widens. Anyways, it is wholly irrelevant.

Give patients with CFS and healthy active controls 100 g dextrose and attach a clamp and measure their blood sugar levels over hundreds of time points. The CFS patients will have more postprandial insulin resistance then their comparators. If you have enough time points you can isolate a single aperture in which 100% of CFS patients have a slower rate of glucose disposal than their healthy counterparts. Do this multiple times, and then triangulate a specific time window in which this is likely to occur.

Did you watch Neil McGregors recent talk - you might find it interesting as he retrospectively subtyped 777 patients by Glucose response and came up with 3 subtypes based on response 1. Flat (7%). 2. Truncated (83%). 3. Normal (10%)
Link : https://mecfsconference.org.au/videos/neil-mcgregor/

 

[Hip]

Are you aware that there are several different tabs on Twitter for the hashtag searches? The link you gave now to the hashtag listing goes to Top Tweets (most popular tweets). Have you checked under Latest? The latest tweets listing is less filtered.

Thanks mango, I did not notice that there were Top tweets and Latest tweets tabs. I think that explains why I did not see my tweets, as I was looking at Top tweets. They do seem to appear under Latest tweets.

Looks like under the Latest tweets tab there are hundred of tweets a day on #MECFS, so I guess unless you get into the Top tweets, the tweet is not likely to be noticed much.

 

[TiredSam]

At the risk of getting no likes, am I alone in thinking that SW comments were surprisingly sensible and even quite helpful? I sincerely hope that this test may be able to differentiate between ME or CFS patients and patients with other sorts of fatiguing illnesses or incapacities but, as far as I can see, we have no evidence to suggest that it can – and it feels appropriate and necessary to make that point loud and clear, lest people start to get carried away.

Mixing whatever line of bullshit you want to sell with a few statements of the bleedin' obvious and some sensible and helpful comments is not without precedent, in fact it is a technique straight out of the charletan's handbook. Trying to work out what SW believes is a fairly pointless exercise in my opinion, he is without values or beliefs. To misquote Groucho Marx - These are my beliefs. If I find it suits my interests, I have others.

 

[Wonko]

Mirror man

 

[hixxy]

Has anything been said about the potential viability of this test for use in regular pathology labs rather than expensive specialty labs?

 

[TigerLilea]

Has anything been said about the potential viability of this test for use in regular pathology labs rather than expensive specialty labs?

Didn't Ron Davis say that his goal was to have every doctor have a nanoneedle in their office so that they could do testing right away?

 

[wigglethemouse]

Looks like under the Latest tweets tab there are hundred of tweets a day on #MECFS, so I guess unless you get into the Top tweets, the tweet is not likely to be noticed much.

@Hip Here is a recent tweet on hashtag popularity

 

[Sean]

Gotta love Vogt's accusation of "overselling" this finding. Projection much?

Requiring a biomarker to match clinical assessments, when different schools of thought have trouble agreeing, is a recipe for stagnation.

It is a truly bizarre demand from the critics, and might indicate how desperate they are getting.

 

[Barry]

This difference in the graph is what we've been looking for, a major difference in response to cellular stress, and I don't mean psychological stress. We've all been reporting variations on such problems since we fell ill, and being misunderstood. This time someone has tried to find a physiological response that mirrors patient reports.

Yes, I understand and appreciate that. My concern is that until the cellular stress differences can be proven due to something other than deconditioning, then team PACE can still just say they have never disagreed there is something physically wrong with pwME - just that they believe it is deconditioning. I would think (and sincerely hope) it a high probability the cellular stress difference will be proven to be something other than deconditioning, but until it is proven, not just hypothesised, I'm not sure this gives us much more to argue at the PACE advocates. In terms of pure science of course (which is what this should ideally all be about), then Ron Davis' team are doing some great work.

 

[James Morris-Lent]

Yes, I understand and appreciate that. My concern is that until the cellular stress differences can be proven due to something other than deconditioning, then team PACE can still just say they have never disagreed there is something physically wrong with pwME - just that they believe it is deconditioning. I would think (and sincerely hope) it a high probability the cellular stress difference will be proven to be something other than deconditioning, but until it is proven, not just hypothesised, I'm not sure this gives us much more to argue at the PACE advocates. In terms of pure science of course (which is what this should ideally all be about), then Ron Davis' team are doing some great work.

I'd be curious to see results for the so-called mild patients such as myself, who are plainly not 'deconditioned' (in the way the word is used in this context) but still have profound deficits in stamina and vigor (not to mention all the other shit...).

 

[Barry]

I'd be curious to see results for the so-called mild patients such as myself, who are plainly not 'deconditioned' (in the way the word is used in this context) but still have profound deficits in stamina and vigor (not to mention all the other shit...).

Absolutely. I think of my wife as mild/moderate, and no way is she deconditioned. When she is able (which is quite often) she gets on with quite a lot, pacing herself as she does. But then, at various times during the day, has to "collapse in a heap", in a way she never used to have to do, and no fit person has to. I do believe that research into mild/moderate people might help benefit all, especially the severe in fact, because mild/moderate pwME especially will not have the confounding factor of deconditioning to confuse results, whereas severe pwME unavoidably will have.

 

[Andy]

Comment on the coverage of this paper from Steve Topple
https://mrtopple.com/2019/04/30/the...-ill-and-disabled-people-just-went-up-a-gear/

 

[Adrian]

I have no idea if this is relevant but there are quite a few research papers using similar kind of test looking at calcium.

"Real-time cellular impedance measurements detect Ca2+ channel-dependent oscillations"
"Calcium Signaling Is Dispensable for Receptor Regulation of Endothelial Barrier Function"
https://www.sciencedirect.com/science/article/pii/S0167488911000243
http://www.jbc.org/content/291/44/22894.full

and this
"Simultaneous impedance spectroscopy and fluorescence microscopy for the real-time monitoring of the response of cells to drugs"
https://pubs.rsc.org/en/content/articlehtml/2017/sc/c6sc05159f

I haven't read the details of Ron Davis work (as I wouldn't understand it anyway) but could there be any relation between the 'mystery molecule' in the serum, and the nanoneedle impedence testing?

There does seem to be quite a lot of work on impedance spectroscopy and its use in micro fluidics devices most of it seems to be applied to looking at different chemicals or flows of stuff rather than biological analysis. So I assume there is a solid background behind what Ron is doing with his Nanoneedle but I've not looked in any detail.

There is a review of some of impedance flow analysis here which may have useful background in terms of impedance analysis of cells.
https://www.mdpi.com/1422-0067/16/5/9804

This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for single-cell electrical property characterization; (2) microfluidic impedance flow cytometry with enhanced sensitivity; (3) microfluidic impedance and optical flow cytometry for single-cell analysis and (4) integrated point of care system based on microfluidic impedance flow cytometry. We examine the advantages and limitations of each technique and discuss future research opportunities from the perspectives of both technical innovation and clinical applications.

 

[S-VV]

Did your tweets actually appear under the #mecfs hashtag listing though when you used this hashtag in your tweets?

I see other familiar ME/CFS patients' tweets appear in the #mecfs listing, but my tweets never do.

Perhaps I'm some sort of persona non grata on Twitter!

@Hip
You appear to be "shadowbanned", a fate usually reserved for people Twitter deems are wrongthinkers.

Edit: it seems you are not shadowbanned
https://shadowban.eu/Hip_III

 

[jamari]

Not sure if it's been shared or seen by any of you, but Ron Davis has summarized where they are, regarding the topic of this thread.