Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by medically unexplained debilitating fatigue with suggested altered immunological state. Our study aimed to explore peripheral blood mononuclear cells (PBMCs) for microRNAs (miRNAs) expression in ME/CFS subjects under an exercise challenge. The findings highlight the immune response and inflammation links to differential miRNA expression in ME/CFS.

The present study is particularly important in being the first to uncover the differences that exist in miRNA expression patterns in males and females with ME/CFS in response to exercise. This provides new evidence for the understanding of differential miRNA expression patterns and post-exertional malaise in ME/CFS.

We also report miRNA expression pattern differences associating with the nutritional status in individuals with ME/CFS, highlighting the effect of subjects’ metabolic state on molecular changes to be considered in clinical research within the NINDS/CDC ME/CFS Common Data Elements.

The identification of gender-based miRNAs importantly provides new insights into gender-specific ME/CFS susceptibility and demands exploration of sex-suited ME/CFS therapeutics.

© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Source: Cheema AK, Sarria L, Bekheit M, Collado F, Almenar-Pérez E, Martín-Martínez E, Alegre J, Castro-Marrero J, Fletcher MA, Klimas NG, Oltra E, Nathanson L. Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS. J Cell Mol Med. 2020 Apr 14. doi: 10.1111/jcmm.15260. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32291908

Maximal handgrip strength can predict maximal physical performance in patients with chronic fatigue

Abstract:

BACKGROUND: Maximal handgrip strength is used to predict exercise performance in healthy older subjects and in patients with chronic obstructive pulmonary disease, breast cancer or cirrhosis. Our objective was to evaluate the ability of maximal handgrip strength to predict maximal exercise performance in patients with chronic fatigue.

METHODS: Sixty-six patients with myalgic encephalomyelitis/chronic fatigue syndrome and 32 patients with chronic fatigue but no diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were included. The maximal physical performance was measured on a cycle ergometer to measure the peak oxygen uptake and the maximal work rate. We searched for linear regressions between maximal handgrip strength and maximal performances.

FINDINGS: No significant differences in slopes and ordinates of regression lines were noted between patients with or without a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, allowing to pool the data. Maximal handgrip strength was significantly and positively correlated with peak oxygen uptake and maximal work rate in all patients with chronic fatigue.

INTERPRETATION: We conclude that handgrip strength can predict maximal exercise performance in patients with chronic fatigue.

Source: Jammes Y, Stavris C, Charpin C, Rebaudet S, Lagrange G, Retornaz F. Maximal handgrip strength can predict maximal physical performance in patients with chronic fatigue. Clin Biomech (Bristol, Avon). 2020 Jan 9;73:162-165. doi: 10.1016/j.clinbiomech.2020.01.003. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31986462

Results of the feasibility phase of the managed activity graded exercise in teenagers and pre-adolescents (MAGENTA) randomised controlled trial of treatments for chronic fatigue syndrome/myalgic encephalomyelitis

Editor’s Comment: Graded exercise therapy (GET) has been widely discredited as a treatment for ME/CFS. It has caused permanent damage in some patients. Exercise of any type is not recommended for severely ill patients, as it can cause significant harm. No exercise program should be undertaken that employs a structured incremental increase in exercise for patients at any level of illness. ME/CFS is a highly variable disease that can fluctuate unpredictably between exacerbations and remissions, which prohibits a goal-oriented exercise regimen.

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis (ME) is relatively common in young people and causes significant disability. Graded exercise therapy (GET) and activity management are recommended by the National Institute for Health and Care Excellence (NICE) despite a limited evidence-base for either treatment in paediatric CFS/ME. This paper reports on feasibility and acceptability measures from the feasibility phase of the ongoing MAGENTA randomised controlled trial (RCT) investigating GET versus activity management for young people with CFS/ME.

METHODS: Setting: Three specialist secondary care National Health Service (NHS) Paediatric CFS/ME services (Bath, Cambridge and Newcastle).Participants: Young people aged 8-17 years with a diagnosis of mild to moderate CFS/ME. Young people were excluded if they were severely affected, referred to cognitive behavioural therapy (CBT) at initial assessment or unable to attend clinical sessions.Interventions: GET and activity management delivered by physiotherapists, occupational therapists, nurses and psychologists. Families and clinicians decided the number (typically 8-12) and frequency of appointments (typically every 2-6 weeks).Outcome Measures: Recruitment and follow-up statistics. We used integrated qualitative methodology to explore the feasibility and acceptability of the trial processes and the interventions.

RESULTS: 80/161 (49.7%) of eligible young people were recruited at two sites between September 2015 and August 2016, indicating recruitment to the trial was feasible. Most recruitment (78/80; 97.5%) took place at one centre. Recruitment consultations, online consent and interventions were acceptable, with less than 10% in each arm discontinuing trial treatment. Response rate to the primary outcome (the SF36-PFS at 6 months) was 91.4%. Recruitment, treatment and data collection were not feasible at one centre. The site was withdrawn from the study.In response to data collected, we optimised trial processes including using Skype for recruitment discussions; adapting recruiter training to improve recruitment discussions; amending the accelerometer information leaflets; shortening the resource use questionnaires; and offering interventions via Skype. These amendments have been incorporated into the full trial protocol.

CONCLUSIONS: Conducting an RCT investigating GET versus activity management is feasible and acceptable for young people with CFS/ME.

TRIAL REGISTRATION: ISRCTN23962803 10.1186/ISRCTN23962803, date of registration: 03 September 2015.

© The Author(s). 2019.

Source: Brigden A, Beasant L, Gaunt D, Hollingworth W, Mills N, Solomon-Moore E, Jago R, Metcalfe C, Garfield K, Wray C, Trist A, Vilenchik V, Grayson C, Crawley E. Results of the feasibility phase of the managed activity graded exercise in teenagers and pre-adolescents (MAGENTA) randomised controlled trial of treatments for chronic fatigue syndrome/myalgic encephalomyelitis. Pilot Feasibility Stud. 2019 Dec 19;5:151. doi: 10.1186/s40814-019-0525-3. eCollection 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924066/ (Full article)

The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients

[Editor’s Note: The dropout rate for this study was 50%. After false discovery rate (FDR) correction, none the results achieved statistical significance.]

Abstract:

BACKGROUND: Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined.

METHODS: Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times) and Choice Reaction Time (CRT) measurements, a Visual Attention Test (VAT) and a Delayed Matching to Sample (DMS) assessment.

RESULTS: Statistically significant improvement was noted in the third attempt to SRT in reaction time for correct answers, p = 0.045, r = 0.24. Moreover, significant improvement was noted in VAT reaction time, number of correct answers and errors committed, p = 0.02, omega = 0.03, p = 0.007, r = 0.34 and p = 0.004, r = 0.35, respectively. Non-significant changes were noted in other cognitive tests.

CONCLUSIONS: A substantial number of participants were unwilling or unable to complete the exercise programme. ME/CFS patients able to complete the SEP showed improved visual attention both in terms of reaction time and correctness of responses and processing speed of simple visual stimuli.

Source: Zalewski P1, Kujawski S1, Tudorowska M2, Morten K3, Tafil-Klawe M4, Klawe JJ1, Strong J3, Estévez-López F5, Murovska M6, Newton JL7, The European Network On Me/Cfs Euromene. The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients. Brain Sci. 2019 Dec 19;10(1). pii: E4. doi: 10.3390/brainsci10010004. https://www.mdpi.com/2076-3425/10/1/4 (Full study)

Understanding neuromuscular disorders in chronic fatigue syndrome

Abstract:

Muscle failure has been demonstrated in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Neurophysiological tools demonstrate the existence of both central and peripheral fatigue in these patients. Central fatigue is deduced from the reduced amplitude of myopotentials evoked by transcranial magnetic stimulation of the motor cortex as well as by the muscle response to interpolated twitches during sustained fatiguing efforts. An impaired muscle membrane conduction velocity assessed by the reduced amplitude and lengthened duration of myopotentials evoked by direct muscle stimulation is the defining feature of peripheral fatigue.

Some patients with ME/CFS show an increased oxidative stress response to exercise. The formation of lipid hydroperoxides in the sarcolemma, which alters ionic fluxes, could explain the reduction of muscle membrane excitability and potassium outflow often measured in these patients. In patients with ME/CFS, the formation of heat shock proteins (HSPs) is also reduced. Because HSPs protect muscle cells against the deleterious effects of reactive oxygen species, the lack of their production could explain the augmented oxidative stress and the consecutive alterations of myopotentials which could open a way for future treatment of ME/CFS.

Copyright: © 2019 Jammes Y and Retornaz F.

Source: Jammes Y, Retornaz F. Understanding neuromuscular disorders in chronic fatigue syndrome.F1000Res. 2019 Nov 28;8. pii: F1000 Faculty Rev-2020. doi: 10.12688/f1000research.18660.1. eCollection 2019. https://www.ncbi.nlm.nih.gov/pubmed/31814961

Exercise therapy for chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy.

OBJECTIVES: The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout.

SEARCH METHODS: We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy.

DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, ‘Risk of bias’ assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE.

MAIN RESULTS: We included eight RCTs with data from 1518 participants.Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks.

Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study).Most studies had a low risk of selection bias. All had a high risk of performance and detection bias.

Exercise therapy compared with ‘passive’ control. Exercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33).

We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants).Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty.

Exercise therapy compared with CBT. Exercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence).

We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants).The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty.

Exercise therapy compared with adaptive pacing. Exercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence).

We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence).The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain.Exercise therapy compared with antidepressants. We are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results.

AUTHORS’ CONCLUSIONS: Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.

Source: Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2019 Oct 2;10:CD003200. doi: 10.1002/14651858.CD003200.pub8. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31577366

Unexplained exertional intolerance associated with impaired systemic oxygen extraction

Abstract:

PURPOSE: The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE).

METHODS: We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO2)/[Hb] ≤ 0.8 and VO2max < 80% predicted in the absence of a cardiac or pulmonary mechanical limit. Those with peak (Ca-vO2)/[Hb] > 0.8, VO2max ≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO2 < [1.5 × HCO3 + 6].

RESULTS: Prevalence of impaired SOE as the sole cause of exertional intolerance was 12.5% (32/257). At peak exercise, poor SOE and HV had less acidemic arterial blood compared to NL (pHa = 7.39 ± 0.05 vs. 7.38 ± 0.05 vs. 7.32 ± 0.02, p < 0.001), which was explained by relative hypocapnia (PaCO2 = 29.9 ± 5.4 mmHg vs. 31.6 ± 5.4 vs. 37.5 ± 3.4, p < 0.001). For a subset of poor SOE, this relative alkalemia, also seen in mixed venous blood, was associated with a normal PvO2 nadir (28 ± 2 mmHg vs. 26 ± 4, p = 0.627) but increased SvO2 at peak exercise (44.1 ± 5.2% vs. 31.4 ± 7.0, p < 0.001).

CONCLUSIONS: We identified a cohort of patients whose exercise limitation is due only to systemic oxygen extraction, due to either an intrinsic abnormality of skeletal muscle mitochondrion, limb muscle microcirculatory dysregulation, or hyperventilation and left shift the oxyhemoglobin dissociation curve.

Source: Melamed KH, Santos M, Oliveira RKF, Urbina MF, Felsenstein D, Opotowsky AR, Waxman AB, Systrom DM. Unexplained exertional intolerance associated with impaired systemic oxygen extraction. Eur J Appl Physiol. 2019 Sep 6. doi: 10.1007/s00421-019-04222-6. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31493035

Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases

Abstract:

Post-exertional malaise (PEM) is a cardinal predictive symptom in the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). If the cases overexert themselves they have what is termed “payback” resulting in a worsening of symptoms or relapse which can last for days, weeks or even months. The aim was to assess the changes in biochemistry associated with the cases self-reported PEM scores over a 7-day period and the frequency of reporting over a 12-month period.

Forty-seven ME/CFS cases and age/sex-matched controls had a clinical examination, completed questionnaires; were subjected to standard serum biochemistry; had their serum and urine metabolomes analyzed in an observational study. Thirty-five of the 46 ME/CFS cases reported PEM in the last 7-days and these were allocated to the PEM group.

The principal biochemical change related to the 7-day severity of PEM was the fall in the purine metabolite, hypoxanthine. This decrease correlated with alterations in the glucose:lactate ratio highly suggestive of a glycolytic anomaly. Increased excretion of urine metabolites within the 7-day response period indicated a hypermetabolic event was occurring. Increases in urine excretion of methylhistidine (muscle protein degradation), mannitol (intestinal barrier deregulation) and acetate were noted with the hypermetabolic event.

These data indicate hypoacetylation was occurring, which may also be related to deregulation of multiple cytoplasmic enzymes and DNA histone regulation. These findings suggest the primary events associated with PEM were due to hypoacetylation and metabolite loss during the acute PEM response.

Source: Neil R. McGregor, Christopher W. Armstrong , Donald P. Lewis and Paul R. Gooley. Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases. Diagnostics 2019, 9(3), 70; https://doi.org/10.3390/diagnostics9030070 https://www.mdpi.com/2075-4418/9/3/70/htm (Full article)

Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Post-exertional malaise and delayed recovery are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Studies on repeated cardiopulmonary exercise testing (CPET) show that previous exercise negatively affects oxygen uptake (VO2 ) and power output (PO) in ME/CFS. Whether this affects arterial lactate concentrations ([Laa ]) is unknown.

We studied 18 female patients (18-50 years) fulfilling the Canadian Consensus Criteria for ME/CFS and 15 healthy females (18-50 years) who underwent repeated CPETs 24 h apart (CPET1 and CPET2 ) with [Laa ] measured every 30th second. VO2 at peak exercise (VO2 peak) was lower in patients than in controls on CPET1 (P < 0.001) and decreased in patients on CPET2 (P < 0.001).

However, the difference in VO2peak between CPETs did not differ significantly between groups. [Laa ] per PO was higher in patients during both CPETs (Pinteraction < 0.001), but increased in patients and decreased in controls from CPET1 to CPET2 (Pinteraction < 0.001). Patients had lower VO2 (P = 0.02) and PO (P = 0.002) at the gas exchange threshold (GET, the point where CO2 production increases relative to VO2 ), but relative intensity (%VO2peak ) and [Laa ] at GET did not differ significantly from controls on CPET1 .

Patients had a reduction in VO2 (P = 0.02) and PO (P = 0.01) at GET on CPET2 , but no significant differences in %VO2peak and [Laa ] at GET between CPETs. Controls had no significant differences in VO2 , PO or %VO2peak at GET between CPETs, but [Laa ] at GET was reduced on CPET2 (P = 0.008).

In conclusion, previous exercise deteriorates physical performance and increases [Laa ] during exercise in patients with ME/CFS while it lowers [Laa ] in healthy subjects.

© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Source: Lien K, Johansen B, Veierød MB, Haslestad AS, Bøhn SK, Melsom MN, Kardel KR, Iversen PO. Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome. Physiol Rep. 2019 Jun;7(11):e14138. doi: 10.14814/phy2.14138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546966/ (Full article)

Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing

Abstract:

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes.

ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption ([Formula: see text]) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points.

None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.

Source: Bouquet J, Li T, Gardy JL, Kang X, Stevens S, Stevens J, VanNess M, Snell C, Potts J, Miller RR, Morshed M, McCabe M, Parker S, Uyaguari M, Tang P, Steiner T, Chan WS, De Souza AM, Mattman A, Patrick DM, Chiu CY. Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing. PLoS One. 2019 Mar 21;14(3):e0212193. doi: 10.1371/journal.pone.0212193. eCollection 2019. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212193 (Full article)
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