A message from Ron Davis

[Ben H]

A Message from Ron Davis

Dear all:
I’m excited to announce that we have added two eminent Stanford engineering researchers to expand our red blood cell deformability project.

Eric Shaqfeh, PhD, is famous for his computational modeling of microfluidic flow. His past work has been modeling air flow over aircraft wings to increase fuel efficiency. He has done extensive work with the Department of Defense and has access to their powerful computer facilities. He has just completed his chairmanship of Stanford’s Chemical Engineering Department and is excited to start a new project.

Juan Santiago, PhD, is a mechanical engineering professor, world-famous for his ingenious designs of small, low cost devices, many of which are used in medicine. We have worked with him for many years and I’ve been very impressed with his design skills. He often comes up with very simple and robust designs that transform a field. When he heard about our project on red blood cell deformability, which now requires a blood draw and expensive equipment and complex image analysis with considerable computational time, not suitable for a doctor’s office, he was excited to take up the challenge to apply his skills and develop a device that will be simple and cheap to use.

Dr. Shaqfeh and Dr. Santiago plan to work together, along with Mohsen Nemat-Gorgani, PhD, Biochemist at the Stanford Genome Technology Center, and Anand Ramasubramanian, PhD, Biomedical, Chemical, and Materials Engineer, San Jose State University, to develop this technology into a diagnostic tool for ME/CFS. I was so pleased that all four of these outstanding scientists attended the recent 3-day Working Group meeting at Stanford, along with their students. It was wonderful to watch their enthusiasm grow as they collaborated and made plans for their research during the breaks!

Due to the dedication and hard work of OMF, the different aspects of this project have been funded and are now in progress. I’d like to express my gratitude to these creative scientists and to OMF for enabling this work to proceed.

Below is a description of their research, as well as one additional outstanding project that the Scientific Advisory Board has approved for OMF funding. Jonas Bergquist, PhD, is unique in his ability to use cerebral spinal fluid to investigate molecular components that might be used as a diagnostic biomarker as well as giving us new insight into the neurological aspects of ME/CFS. Dr. Bergquist was also an enthusiastic participant in the 3-day Working Group meeting, and his great sense of humor made it especially fun to have him there! Be sure to watch his Community Symposium talk on YouTube to discover a traditional Swedish food.

We are continuing to work day and night to find a treatment and cure as fast as possible.
Sincerely,

Ronald W. Davis, PhD
Director, OMF Scientific Advisory Board
Director, Stanford Genome Technology Center

OMF Funds Four Additional Research Projects for a Total of $241,670

Red blood cells (RBCs) transport oxygen from the lungs to the cells of your body and then carry carbon dioxide from your cells to your lungs. For RBCs to get to all these cells, they need to be able to flow through small blood vessels with minimal friction. Ultimately, this requires RBCs to be smooth, rounded, and elastic. Alterations in these properties of RBCs can occur during chronic inflammatory diseases like sepsis, and we have found that this deformability is also occurring in ME/CFS. For more information on RBC deformability, click here.

These observations along with new technology available for measuring RBC deformability prompted engineers from Stanford and their collaborators at San Jose State University to examine RBC deformability in ME/CFS. The following three projects will develop and evaluate a device to rapidly determine the ‘deformability’ of RBCs as a potential biomarker for ME/CFS.

1. Eric Shaqfeh, PhD, Department of Chemical Engineering, Stanford University -
Computer Simulation of the Effect of Membrane Rigidity on the Micro-Flows of Red Blood Cells to Create a Diagnostic for ME/CFS
The Shaqfeh group at Stanford University will produce computer 3D simulations of RBCs through a set of channels that resemble a blood circulation system. Using these simulations, the Shaqfeh group will determine how to characterize the properties of RBCs by the way they flow through these channels.

2. Anand Ramasubramanian, PhD, Biomedical, Chemical & Materials Engineering, San José State University - Erythrocyte Biomechanics in ME/CFS
The computer simulations described above will be conducted in close collaboration with the Ramasubramanian group at San Jose State University, where they are producing a microfluidics chip to estimate the properties of RBCs. A microfluidic chip is a set of tiny channels etched into a piece of material like glass or plastic and is around the size of a SIM card. Designing the microfluidic chip will require ongoing RBC simulations by the Shaqfeh group to determine the optimal set of channels to distinguish ME/CFS RBCs from normal RBCs. The microfluidic devices suggested from the simulations will be tested at San Jose State with the ultimate goal being the creation of a sensitive diagnostic device.

3. Juan G. Santiago, PhD, Department of Mechanical Engineering, Stanford University - Computer Simulation of the Effect of Membrane Rigidity on the Micro-Flows of Red Blood Cells to Create a Diagnostic for ME/CFS

A key part of determining RBC properties in these channels will be the development of a state-of-the-art image analysis tool that can automatically identify and track the position and shape of thousands of RBCs under relaxed and stressed conditions. The Santiago group will develop this visualization technology at Stanford University.

The visualization technology developed by the Santiago group will be applied to develop a microfluidics device in conjunction with the Ramasubramanian and Shaqfeh groups.

The longer-term goal of this collaborative effort between these three groups is to produce a low-cost, disposable device to determine the rapid quantitation of deformability of the cells in a single drop of blood.

4. OMF has granted Scientific Advisory Board member, Jonas Bergquist, MD, PhD,Uppsala University (Sweden), additional funds to expand his work on targeted proteomics for neuroinflammatory markers in cerebrospinal fluid (CSF) in ME/CFS patients.

Continuing with his ongoing study of CSF from ME/CFS patients, Dr. Bergquist has recently acquired a piece of technology that significantly enhances the detection of inflammation markers. This technology has yet to be used on CSF, so this will be the world’s first test case for ME/CFS samples. Using this technology, Bergquist's team is going to selectively test for a set of over 900 markers of neuroinflammation.



www.omf.ngo


Triple Tuesday OMF now through November 27.





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Exciting stuff


B

@Janet Dafoe (Rose49) @AshleyHalcyoneH @marilynbsg

 

[Moof]

Fab news! Things like this keep us all going on the really tough days.

 

[Neunistiva]

As someone who is severely ill I usually only focus on a treatment or a cure, because I'm worried how much longer I can last, but recent threads on craniocervical instability reminded me why it's so important to have proper diagnostic device for ME/CFS.

It's amazing this red blood cell deformability collaboration was organized so quickly after the Symposium, it's great that everyone understands how urgent the situation is.

Thank you all for your hard work.

 

[ljimbo423]

Alterations in these properties of RBCs can occur during chronic inflammatory diseases like sepsis, and we have found that this deformability is also occurring in ME/CFS.

This observation ties in nicely with ME/CFS researcher Chris Armstrong's view, that a slow, chronic sepsis is what causes PEM. This is a quote from a post Chris made here at Phoenix Rising-

Well we all experience a bacteremia when we exercise. The type of bacteria that enter your bloodstream are usually quite controllable by your immune system,

but if your gut is further compromised they may release more bacteria into your blood or more pathogenic species or your immune system may already be depleted.

This is the concept for the chronic sepsis or SIRS and this is what I think may be behind PEM.

Link to his post

 

[Gemini]

This observation ties in nicely with ME/CFS researcher Chris Armstrong's view, that a slow, chronic sepsis is what causes PEM.

@ljimbo423 wonder if the new computational tool "Strain Sifter," that recently caught NIH Director Collins' eye, could id gut bacteria translocation to the blood in ME/CFS as per Armstrong?

Developed in Bhatt's Stanford lab:

https://directorsblog.nih.gov/2018/...infections-traced-to-patients-own-microbiome/

www.ncbi.nlm.nih.gov/pubmed/?term=30323331

 

[ljimbo423]

@ljimbo423 wonder if the new computational tool "Strain Sifter," that recently caught NIH Director Collins' eye, could id gut bacteria translocation to the blood in ME/CFS as per Armstrong?

The Strain sifter is a pretty neat tool. I don't see why it wouldn't identify DNA from gut bacteria translocated to the blood in ME/CFS.

I have 5-6 studies that I have saved, that show elevated blood levels of lipopolysaccharides in ME/CFS verses controls. From my point of view, I am very confident that there is ongoing translocation of LPS into the bloodstream.

Below is a screenshot from one of the papers I have saved. The median level of LPS in the blood of controls was 74.74 pg/ml. In the ME/CFS group it was 119.43 pg/ml !!

Clearly the blood level of bacterial LPS in the ME/CFS group is much higher.

link to paper

 

[cigana]

The Strain sifter is a pretty neat tool. I don't see why it wouldn't identify DNA from gut bacteria translocated to the blood in ME/CFS.

I have 5-6 studies that I have saved, that show elevated blood levels of lipopolysaccharides in ME/CFS verses controls. From my point of view, I am very confident that there is ongoing translocation of LPS into the bloodstream.

Below is a screenshot from one of the papers I have saved. The median level of LPS in the blood of controls was 74.74 pg/ml. In the ME/CFS group it was 119.43 pg/ml !!

Clearly the blood level of bacterial LPS in the ME/CFS group is much higher.

View attachment 30148


link to paper

Thanks for posting that study. Chronic immune activation by LPS is still my number 1 root cause. It seems so many of the successful treatments fall into the category of immune regulation.

 

[ljimbo423]

Thanks for posting that study. Chronic immune activation by LPS is still my number 1 root cause.

Mine too!

It seems so many of the successful treatments fall into the category of immune regulation.

Excellent point!

 

[nandixon]

I have 5-6 studies that I have saved, that show elevated blood levels of lipopolysaccharides in ME/CFS verses controls. From my point of view, I am very confident that there is ongoing translocation of LPS into the bloodstream.

I think I remember that there are some that show normal levels as well, but I think it is likely that LPS exacerbates symptoms in ME/CFS, although I don't see it as the primary driver of the disease but rather more of a case of adding fuel to an underlying inflammatory fire.

Don't know if you saw it, but I recently used a study as a reference that provides a link been LPS and the IDO2 (and potentially IDO1) enzyme that Dr Phair is interested in as part of his metabolic trap hypothesis:

https://forums.phoenixrising.me/ind...ic-trap-for-me-cfs.58606/page-18#post-1012430

 

[ljimbo423]

I think I remember that there are some that show normal levels as well, but I think it is likely that LPS exacerbates symptoms in ME/CFS, although I don't see it as the primary driver of the disease but rather more of a case of adding fuel to an underlying inflammatory fire.

I think there probably are studies that show normal blood levels of LPS in ME/CFS.

I apologize if my view offends you or anyone that thinks the tryp/trap is the cause of ME/CFS. I know all to well how much I and others can invest in these things.

I just think the tryp/trap or dysregulation, is a downstream effect from the immune activation from LPS.

 

[nandixon]

I think there probably are studies that show normal blood levels of LPS in ME/CFS.

I apologize if my view offends you or anyone that thinks the tryp/trap is the cause of ME/CFS. I know all to well how much I and others can invest in these things.

I just think the tryp/trap or dysregulation, is a downstream effect from the immune activation from LPS.

@ljimbo423
I'm in agreement with you. I use the new study showing the link between LPS and IDO2 to show that the metabolic trap hypothesis is less likely to be correct, and that rather than a nonfunctional IDO2 meaning there's not a backup for IDO1, as that hypothesis requires, that instead a nonfunctional IDO2 may simply be causing less IDO1 to be present in the first place (due to IDO2’s immunomodulatory abilities).

And yes, under the latter scenario the lower rate of consumption of tryptophan that Phair found would presumably be a downstream effect of an underlying inflammatory process, with LPS contributing to that. Although it might possibly help to ameliorate the effects of a nonfunctional IDO2, and I suggest the possible use of tocilizumab in that regard in the link I gave.

 

[alex3619]

I just think the tryp/trap or dysregulation, is a downstream effect from the immune activation from LPS.

Presuming the tryp-trap is correct, something still has to set it off. Chronic sepsis or rising LPS are two things that need to be investigated, though also for other reasons.

 

[Research 1st]

As Ron alluded to in his Stanford OMF talk it won't surprise any of us to see a link between ME, POTS, Lyme, EDS, MS, MCAS, Autism etc as they may share a critical common component.

Think what the psyche lobby will do if MS is ME + factor Y, and Chronic Lyme is ME + factor Z etc. A great day that would be, and as Ron alluded to, this would provide an end to the political block on funding this disease, because the 'real' diseases would ostensibly be hybrid versions of us. Imagine that, imagine the shame and humiliation CFS psychiatry would be inescapably immersed in. A heart warming imagery emerges...the serial abusers finally cut loose from defacing Science.

 

[FMMM1]

As Ron alluded to in his Stanford OMF talk it won't surprise any of us to see a link between ME, POTS, Lyme, EDS, MS, MCAS, Autism etc as they may share a critical common component.
---
A great day that would be, and as Ron alluded to, this would provide an end to the political block on funding this disease, because the 'real' diseases would ostensibly be hybrid versions of us.

Very interesting i.e. that ME/CFS may be similar to those diseases. I think @Vassie had noticed this as well. As you point out this may help to access funding for ME/CFS research. Must re-watch Ron's presentation; if you have the reference time then that would be useful (if not - don't worry about it).


Consider writing to your elected representative i.e. to request funding for ME/CFS research including the development of a diagnostic test.
I've written to the European Union Committee on the Environment, Public Health and Food Safety (ENVI) requesting that they lobby for funding for research into ME/CFS including the development of a diagnostic test [https://forums.phoenixrising.me/ind...ch-theyre-working-for-you.61516/#post-1003111].
Currently the ENVI Committee is lobbying for increased funding for research into Lyme disease and the development of a diagnostic test.
In 2016 the European Commission [European Union civil service] said [regarding Lyme disease] that "Both basic research and the development of new diagnostics, treatments and vaccines for Lyme borreliosis are funded by EU research and innovation framework programmes. The total EU contribution to such projects since 2007 amounts to EUR 33.9 million [US dollars]" [http://www.europarl.europa.eu/doceo/document/E-8-2016-008631-ASW_EN.html].

ME/CFS received no funding from the European Union [http://www.europarl.europa.eu/doceo/document/E-8-2017-006901-ASW_EN.html].