Season's Greetings NanoVoltOhmMeter- New CFS Diagnostic Quantitative marker for fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome Figure C

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Joseph Arabasz MD

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Dec 7, 2021, 11:03:37 PM12/7/21
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Subject- NanoVoltOhmMeter- New CFS Diagnostic Quantitative marker for fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome Figure C

Dear Topica et al,
                                                                                                                                                                   I hope this note finds You well

FYI- regarding CFS (chronic fatigue syndrome) etiology problem at Na+/K+ ATPase sites on cellular walls

     Some are of the opinion there isn't much difference between the CFS (chronic fatigue syndrome) and PTSD

Now, there is this Quantitative measurement which occurs at the Na+/K+ ATPase Pump Cellular level which is found in CFS Patients, but wasn't seen in the non-CFS population

     Basically, the Nano-electrode measures immense rise of impedance at the Na+/K+ ATPase site

Subtitled- Researchers find objective, Quantitative, measurable entity found with CFS Patients

"A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)" 
R. Esfandyarpoura,1, A. Kashib , M. Nemat-Gorganib,c, J. Wilhelmyc , and R. W. Davisb,c,1 
a Department of Electrical Engineering and Computer Science, University of California, Irvine, CA 92697; 
b Stanford Genome Technology Center, Stanford University, Stanford, CA 94304; and 
c Department of Biochemistry, School of Medicine, Stanford University, Stanford, CA 94304 Contributed by R. W. Davis, March 26, 2019
(sent for review February 5, 2019; reviewed by Javad Gatabi and David R. Hillyard
Published 2019
Proceedings of the National Academy of Science Journal

"several studies have shown that inducing a biological stressor on peripheral blood mononuclear cells (PBMCs) in the form of hyperosmotic stress forces the cells to consume ATP, a key metabolite, which is hypothesized to be deficient in ME/CFS patients" (BUT ELEVATED UNKNOWN REQUIREMENTS FOR ATP WHEN NOT STRESSED MIGHT BE ANOTHER POSSIBILITY)

"Results and Discussion
Initial Motivation. The main feature of ME/CFS is considered
to be a worsening of symptoms postexertion known as 
postexertional malaise. To mimic this condition on a cellular
level, we introduced a stressor into the patient’s clinical samples,
composed of isolated PBMCs incubated in their own plasma. We
initially hypothesized that stressing PBMCs (in a hyperosmotic environment)
would result in extensive consumption and potential
depletion of ATP, a high-energy metabolite.

-hyperosmotic stress is a commonly applied stress model
in studies on various types of cells such as plant, yeast, bacteria,
mice, and human (26–32). To stimulate hyperosmotic stress in our
study, we increased the plasma’s NaCl concentration to 200 mmol/L.
NaCl is a typical stimulator of the osmotic response, which acts
in essentially the same way as many other agents, such as sugars
(33). However, as shown in Fig. 1C, the promising experimental
findings produced by the use of our assay led us to the conclusion
that the significantly different impedance response of the hyperosmotic
stressed PBMCs we identified constitutes a reliable method of 
differentiating CFS patients from healthy controls, which is the main focus of this work


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

Figure C

Fig. 1.

Fig. 1.

(A) Schematic of a single nanoelectronic sensor (not to scale). (B) Circuit model of a sensor−solution interface, where Zm-s is media−sensor surface interactions, Zc-c is cell−cell interactions, Zc-s is cell−sensor surface adhesion, Zc is a cell impedance (membrane capacitance Cm, and cytoplasm conductivity of the cells, σcp), and Rs is resistance of the solution. (C) The experimentally obtained impedance versus time curves illustrating the electrical response of hyperosmotic-stressed samples of a bed-bound ME/CFS patient and a healthy control in real time. A gray region is defined experimentally and its top and bottom borders are shown with orange and green lines, respectively (for further details see Trial Population and Statistical Analysis). (D) Array of nanoneedle sensors fabricated on a 4-in wafer. (E and F) SEM images of a nanoelectronic sensor tips, (E) top view and (F) from the microfluidics channel side.


     Rumor is that resolving the CFS/PTSD spectrum of diseases has as much to do with terminating the sociopathy of the perps that would use toxins, etc to cause such events, as the wars

     Basically, fatigue:depression::dementia:psychosis

     Severe deficiency of some Essential B Vitamines cause the fatigue/dementia spectrum of diseases, often misdiagnosed as depression/psychosis, which makes for an expensive medical misadventure

     Previous terminology for PTSD expressed other descriptive terms- battle fatigue, etc which was used for Qualitative Diagnostic Criteria for PTSD
Early Literature descriptions of PTSD- 1597

     "has proposed that Lady Percy's soliloquy in the William Shakespeare play Henry IV, Part 1 (act 2, scene 3, lines 40–62[252]), written about 1597, represents an unusually accurate description of the symptom constellation of PTSD.[253]"

Lady

O, my good lord, why are you thus alone?For what offence have I this fortnight beenA banish’d woman from thy bed?Tell me, sweet lord, what is’t that takes from theeThy stomach, pleasure and thy golden sleep?Why dost thou bend thine eyes upon the earth,And start so often when thou sit’st alone?Why hast thou lost the fresh blood in thy cheeks;And given my treasures and my rights of theeTo thick-eyed musing and cursed melancholy?In thy faint slumbers I by thee have watch’d,And heard thee murmur tales of iron wars;Speak terms of manage to thy bounding steed;Cry “Courage! to the field!” And thou hast talk’dOf sallies and retires, of trenches, tents,Of palisadoes, frontiers, parapets,Of basilisks, of cannon, culverin,Of prisoners’ ransom and of soldiers slain,And all the currents of a heady fight.Thy spirit within thee hath been so at warAnd thus hath so bestirr’d thee in thy sleep,That beads of sweat have stood upon thy brow,Like bubbles in a late-disturbed stream;And in thy face strange motions have appear’d,Such as we see when men restrain their breathOn some great sudden hest. O, what portents are these?Some heavy business hath my lord in hand


FYI- regarding CFS (chronic fatigue syndrome) etiology, problem at Na+/K+ ATPase sites on cellular wall

Pictures of atoms forming compounds-

Would be nice to see the functioning of the Na+/K+ ATPase areas of cell wall as they open and close, with sequential Pictures
     Obstruction might be why the impedance elevates, eg toxin etc
     Their function is to expel Na+ and acquire K+ through the cellular wall
Reportedly, as a triplet of Na+ atoms exit the cell, a pair of K+ atoms enter at a cost of 1 ATP


Ye et al, 2011
"The Na/K-ATPase is ubiquitously expressed in the plasma membrane of almost all eukaryotic cells. It belongs to the type II class of P-type ATPases, hydrolyzing ATP to transport 3 Na+ out and 2 K+ into the cell against their electrochemical gradients. 
(THAT APPARENTLY OCCURS AT THE COST OF 1 ATP MOLECULE)
By establishing gradient differences of Na+ and K+ across the plasma membrane, the Na/K-ATPase maintains a steady-state cellular milieu, provides the driving force for Na+-coupled cotransporters on the apical membrane of the epithelium, and reestablishes the electrical potential in excitable tissues" 

-----------------------------

Attached ATP CELLRESPIRATION pdf-
     Production of 30 ATP from 1 molecule of Glucose with Aerobic Metabolism

    Production of only 2 ATP from 1 molecule of Glucose with anaerobic metabolism

ATP is the main source of cellular Energy
     Think of it as placing a plug onto a wall outlet which is supposed to provide 30 Volts with Aerobic Metabolism, but only has 2, under anaerobic respiration metabolism conditions, eg sleep apnea

----------------------------

     Cells are ~10 microns, viruses about 1 micron but both are variable
Atoms and simple compounds are a few or several Angstrom  (1x 10−10 m)

https://www.lsu.edu/science/soar/files/how_big_is_a_cell.pdf

Best wishes always

Thank you for your assistance with this matter

Cordially,

Joseph W Arabasz MD
S/P USAF, Top Secret 1964-69
University of Colorado at Boulder 1972, CU School of Medicine '75, '77, '83
Past Division Chairman, Anesthesiology, Cook County Hospital, Chicago, Illinois
Past Chairman, Respiratory Therapy, Cook County Hospital, Chicago
Diplomate ABA
Mensa
Sigma Xi, The Professional Science Research Society
PO Box 6939
Denver, CO 80206
USA
http://www.topica.com/lists/joseph...@topica.com (2001-2014 site closed/open)

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https://www.pnas.org/content/116/21/10250 

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

PNAS May 21, 2019 116 (21) 10250-10257; first published April 29, 2019; https://doi.org/10.1073/pnas.1901274116 

Article Figures & SI Info & Metrics PDF
Significance
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease which afflicts  millions people in the United States and many more around the globe. A combination of factors might trigger ME/CFS, and there is currently no well-established blood-based biomarker to diagnose it. Taking advantage of advancements in micro/nanofabrication, direct electrical detection of cellular and molecular properties, microfluidics, and artificial intelligence techniques, we developed a nanoelectronics blood-based assay that can potentially establish a diagnostic biomarker and a drug-screening platform for ME/CFS. Given the significance of this assay, we envision it has the potential to be widely employed in research laboratories and clinics in the future as an aid to physicians as well as to our colleagues in the ME/CFS research community.

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

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