Welcome to the 84th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles.

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Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients

Authors: Bertinat R, Villalobos-Labra R, Hofmann L, Blauensteiner J, Sepúlveda N, Westermeier F (FH Joanneum University of Applied Sciences, Austria)
Publication: Vascular Pharmacology
Link: https://www.sciencedirect.com/science/article/pii/S1537189122000027?via%3Dihub

Previous studies have found that a subset of ME/CFS patients have endothelial dysfunction (ED) and altered ED-related microRNAs in plasma. A major cause of ED is inadequate nitric oxide (NO), primarily produced by the endothelial isoform of nitric oxide synthase (eNOS) in endothelial cells. This study aimed to identify whether the plasma from ME/CFS patients induces eNOS-related ED in vitro.

Plasma samples from 11 ME/CFS patients (Canadian Consensus Criteria and/or Fukuda Criteria) and 12 healthy controls were included in this study. Samples were randomly selected from a pool of 58 ME/CFS and 29 healthy control samples, that these authors had used in a previous study. Human umbilical vein endothelial cells were cultured in the presence of plasma from either the ME/CFS patients or healthy controls. NO production was measured in the presence and absence of tyrosine kinase and G protein-coupled receptor agonists (known eNOS activators).

The authors found that human umbilical vein endothelial cells that were incubated with ME/CFS plasma produced less NO both in the absence and presence of eNOS activators compared to healthy control plasma. It was also found that NO production elicited by G protein-coupled receptor agonists was more affected than production triggered by insulin. Finally, inhibitory eNOS phosphorylation was higher in treated ME/CFS plasma than in treated healthy control plasma.

The authors acknowledged that their study is limited by a small sample size and that their in vitro approach represents a simplification of what is occurring in vivo. However, the authors conclude that the observed in vitro decrease in NO production in plasma from ME/CFS patients in comparison to healthy controls, may indicate a previously unreported role of eNOS in the pathophysiology of ME/CFS. The authors anticipate these results to provide a new perspective on the study of endothelial function in ME/CFS, with the eventual translation of findings into clinical settings to assist in the diagnosis of ME/CFS patient subsets.

                                                       
Figure. Effects on NO production in endothelial cells exposed to plasma from healthy controls and ME/CFS patients in the absence and presence of receptor agonists.

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Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome

Authors: Germain A, Giloteaux L, Moore GE, Levine SM, Chia JK, Keller BA, … Hanson MR (Cornell University, USA)
Publication: JCI Insight 
Link: https://insight.jci.org/articles/view/157621
 
Plasma metabolomic changes have been found after acute physical activity in healthy people. While the metabolome of patients with ME/CFS has been researched, the authors argue that no studies have examined metabolic changes before and after maximal exercise designed to induce PEM. This study aimed to characterise temporal metabolic changes in ME/CFS patients before and after exercise.

Plasma samples from 60 patients with ME/CFS (Canadian Consensus Criteria) and 45 sedentary healthy controls were collected 15-20 minutes before and after two maximal-effort cardiopulmonary exercise tests (CPET), yielding four samples per participant in total. The two CPETs were separated by a 24-hour recovery period. Samples were analysed via liquid chromatography-mass spectrometry resulting in relative concentrations of plasma metabolites.

There were significant differences in the metabolomes of patients and healthy controls at baseline. The number of metabolites that were significantly different between ME/CFS patients and healthy controls increased as the study proceeded; indicating that the metabolome of patients became more and more different from that of healthy controls when the CPETs were performed. However, this effect was driven by the female participants only, as a slight decrease in the number of significantly different metabolites after exercise was found in the male participants. The significantly different metabolites were predominantly lower in patients.

Pathway analyses of the baseline metabolites found that pathways related to vitamin B, energy and sugars, and lipids were significantly different between the two groups. Pathway analysis comparing the differences between the effect of exercise on day 1 and day 2 in female participants found no significant differences in healthy controls, suggesting that the consequences of exercise on day one and day two were similar for healthy controls. By contrast, the influence of day 1 exercise and day 2 exercise on the ME/CFS plasma metabolome was markedly distinct. The recovery process was also found to be highly disrupted in patients with ME/CFS.

The results of this study highlight the importance of researching ME/CFS not only at baseline but also in response to exercise. Moreover, given the clear sex differences found in this study, the authors recommend including a sufficient number of participants of both sexes, to have enough power to detect these discrepancies. Pathways that were identified in this study include fatty acid and amino acid metabolism, many of which are dependent on glutamate metabolism.

Figure. Plasma metabolome of Myalgic encephalomyelitis/Chronic fatigue syndrome 

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Long Covid at the crossroads: Comparisons and lessons from the treatment of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Authors: Hunt J, Blease C, Geraghty KJ (University of Manchester, UK)
Publication: Journal of Health Psychology
Link: https://journals.sagepub.com/doi/pdf/10.1177/13591053221084494
 
Many studies have found that ME/CFS patients experience negative attitudes and/or mistreatment from health professionals, some of whom question the existence of the condition. Given the similarities between ME/CFS and Long COVID, these authors explore factors that have contributed to this treatment of ME/CFS patients, the risks of Long COVID patients receiving similar treatment, and make recommendations to prevent such injustices.

The authors identified four reasons why ME/CFS patients have received such poor treatment:

1.   Prevalence

The high rates of new Long COVID cases provide a buffer against negative stereotyping and help lead to a tipping point of public awareness of the condition which ME/CFS has not experienced.

2.   Aetiology

While it is unclear why some people develop Long COVID following infection with the SARS-CoV-2 virus, it is nonetheless clear that the virus is the trigger for the condition. Even though many ME/CFS patients also have an infectious trigger, the predominance of the biopsychosocial model of the condition has de-emphasised the importance of this origin.

3.   Biological markers

Both Long COVID and ME/CFS patients experience a wide range of symptoms, many of which lack objective biomarkers. However, many Long COVID patients also experience organ damage that can be objectively measured, and which lends credibility to the condition. It has also resulted in the full medical investigation of these patients being recommended, whereas this is discouraged in ME/CFS patients.

4.   Socio-political dimensions of illness

A driver of the psychologisation of ME/CFS may be political forces that choose to downplay the severity of the condition, especially in the context of the impact of long term disability on the welfare systems and economy, and instead have adopted a model whereby rehabilitation is effective and recovery is possible. While it is early days for Long COVID, advocates are already concerned that a large influx of new patients seeking disability support may lead to a similar downplaying of the seriousness of Long COVID and a push to “return to normal” for the sake of the economy.

 
The authors argued that, while Long COVID has been protected from the worst experiences of ME/CFS patients, it is at a crossroads as more patients seek long term support. They suggest that the approach to both conditions includes lessons for the other which can benefit patients. In particular, they recommend that the inclusion and valuing of Long COVID patients’ lived experience in research, should be extended to ME/CFS.

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I'm one of thousands of Australians with chronic fatigue syndrome but I'm lucky: I've become a human experiment

Author: Rumble A
Publication: ABC News  
Link:  https://www.abc.net.au/news/2022-05-14/australians-with-me-chronic-fatigue-syndrome-human-experiment/101059572
 
Disabled writer and ME/CFS advocate, Alice Rumble, describes her choice to become a human experiment, working with her specialist to trial different medications in the hope of finding some benefit to her health.
 
“ME has no treatment or cure. Millions of people are joining this cohort via long COVID, which shares striking similarities with ME. Both patients and doctors are in a murky world of unknowns.
 
But I am one of the lucky ones: I've become a human experiment.
 
If there's a chance a treatment could increase my capacity so I can work, or drive, or socialise independently again, I will try it. When you're trapped with a debilitating illness, any different feeling can be a welcome relief.”

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