Thesis Develop Microfluidic-based Diagnostic Approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2024, Guo

Dolphin

Dolphin

Senior Member (Voting Rights)
This item is not available for download from eScholarship

Develop Microfluidic-based Diagnostic Approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
2024

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a global health concern,impacting millions of individuals, yet diagnosis remains a challenge due to the absence of consistent laboratory testing methods.

Currently, diagnosis is solely dependent on doctors’ experience and in depth understanding on patients’ medical histories.

This thesis aims to develop an accessible, rapid, and cost-effective laboratory-based diagnostic method for ME/CFS, while also exploring potential applications in treatment monitoring and evaluation using microfluidic approaches.

We achieved this by creating a microfluidic platform to measure capillary velocity of red blood cells (RBCs) at controlled oxygen tensions (PO2).

Our research revealed that RBCs from ME/CFS patients exhibit impaired responses to changes in PO2, as compared to healthy controls.

Such PO2 - regulated RBC capillary velocity was thus used for ME/CFS diagnosis and exhibited an approximately 80% accuracy using machine learning methods.

Additionally, our investigation identified two potential drug candidates, Salmeterol Xinafoate and Xanomeline, which showed promise in improving PO2 - regulated capillary velocity of RBCs from ME/CFS patients.

Moreover, we found that a simple phosphate buffered saline (PBS) wash can recover RBC’s sensitivity to deoxygenation, implying that RBC-cytokine interaction in ME/CFS contributes to PO2 - regulated RBC capillary velocity.

In conclusion, we have developed a diagnostic platform for ME/CFS using a combination of microfluidic techniques and machine learning, offering a cost-effective and simple approach to ME/CFS diagnosis.

It also opens doors for in-depth exploration of the underlying mechanisms of the condition.

This item is under embargo until May 15, 2026.

https://twitter.com/user/status/1794356850617696439
Click to expand...
 
Dolphin said:
Moreover, we found that a simple phosphate buffered saline (PBS) wash can recover RBC’s sensitivity to deoxygenation, implying that RBC-cytokine interaction in ME/CFS contributes to PO2 - regulated RBC capillary velocity.
Click to expand...

This reminds me of the late Dr Paul Cheney's observations and theories re: poor oxygen desaturation in the blood of PWME which he ascribed to a pH imbalance created by intracellular proton production in atypical respiration metabolism causing blood alkalosis as the body's homeostatic systems respond by providing bicarbonate ions to mop up the acidic overproduction from cells.

The observation that normal RBC desaturation is restored by changing the medium pH to nearer normal with a phosphate buffered saline (PBS) wash is consistent with Dr Cheney's hypothesis.

It might be worth exploring this hypothesis and the biochemical root cause of poor desaturation.

Velocity is not necessarily the only thing impairing oxygen transfer.
 
This is the reason why I think that the control for ME/CFS should be not only similarly sedentary, but also similarly sick. We don't know if whatever they found here is also present in people who are sick with, say, flu. Biomarkers in particular needs to be present in, and in nothing else other than, ME/CFS.
 
boolybooly said:
This reminds me of the late Dr Paul Cheney's observations and theories re: poor oxygen desaturation in the blood of PWME which he ascribed to a pH imbalance created by intracellular proton production in atypical respiration metabolism causing blood alkalosis as the body's homeostatic systems respond by providing bicarbonate ions to mop up the acidic overproduction from cells.

The observation that normal RBC desaturation is restored by changing the medium pH to nearer normal with a phosphate buffered saline (PBS) wash is consistent with Dr Cheney's hypothesis.

It might be worth exploring this hypothesis and the biochemical root cause of poor desaturation.

Velocity is not necessarily the only thing impairing oxygen transfer.
Click to expand...

In relation to this, an article on bicarb supplementation by athletes caught my eye, as the purpose of this is aligned with Dr Cheney's premise that cellular proton production in metabolism is buffered by blood bicarbonate.

From baking cakes to breaking records: the rise of sodium bicarbonate in sport.
https://www.chemistryworld.com/news...odium-bicarbonate-supplements/4019967.article

There is not yet an agreed consensus on exactly how sodium bicarbonate enhances performance, but it is likely that the mechanism lies in its role in supporting extracellular buffering capacity.

Blood bicarbonate (HCO3-) is part of the acid–base buffer system that helps to regulate blood pH concentrations and supporting metabolic functions. If blood pH is too alkaline a proton dissolves from carbonic acid (H2CO3) forming HCO3-.

If the blood pH is too acidic, HCO3- binds a proton to form H2CO3, which then dissociates into water and carbon dioxide (CO2). This leads to increased breathing rate in order to release more CO2 and restore the acid–base balance.

The additional buffering capacity provided by a bicarbonate supplement has been found to increase blood lactate after exercise, which is suspected to be due to a greater flow of hydrogen ions out of muscle tissue. This reduces the build-up of lactic acid in the muscles and overall fatigue.
Click to expand...

Interesting since this is Dr Cheney's premise with the added observation that too much bicarb in the blood of PWME seems to prevent oxygen desaturation at tissues. Meanwhile excess lactic acid production in the CNS has been measured in PWME.

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/nbm.2772 Shungu et al
Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology

The article refers to papers such as the following.
https://pubmed.ncbi.nlm.nih.gov/34687438/ de Oliveira et al
Extracellular Buffering Supplements to Improve Exercise Capacity and Performance: A Comprehensive Systematic Review and Meta-analysis
 
Last edited:
You must log in or register to reply here.
Back
Top Bottom