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1

Denman, AM. "AIDS and CFS/ME." Clinical Medicine 3, no. 2 (March 1, 2003): 188.2–188. http://dx.doi.org/10.7861/clinmedicine.3-2-188a.

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2

SHEPHERD, C. "Research Update Note on ME (ME/CFS)." British Journal of Social Work 27, no. 5 (October 1, 1997): 755–60. http://dx.doi.org/10.1093/oxfordjournals.bjsw.a011264.

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3

Taylor, Anna K., Maria Loades, Amberly LC Brigden, Simon M. Collin, and Esther Crawley. "‘It’s personal to me’: A qualitative study of depression in young people with CFS/ME." Clinical Child Psychology and Psychiatry 22, no. 2 (October 14, 2016): 326–40. http://dx.doi.org/10.1177/1359104516672507.

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Background: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has a prevalence of 0.4–2.4% and is defined as ‘generalised disabling fatigue persisting after routine tests and investigations have failed to identify an obvious underlying cause’. One-third of young people with CFS/ME have probable depression. Little is known about why depression develops, the relationship between depression and CFS/ME, or what treatment might be helpful. Methods: We conducted nine semi-structured interviews with young people with CFS/ME (aged 13–17 years, 8/9 female) and probable depression, covering perceived causes of depression, the relationship between CFS/ME and depression, and treatment strategies. Results: Most thought CFS/ME caused depression. Many discussed a cyclical relationship: low mood made CFS/ME worse. A sense of loss was common. CFS/ME restricted activities participants valued and changed systemic structures, causing depression. There was no single helpful treatment approach. Individualised approaches using combinations of cognitive behavioural therapy (CBT), medication, activity management and other strategies were described. Conclusion: This study suggests that depression may be secondary to CFS/ME in young people because of the impact of CFS/ME on quality of life. Clinicians treating young people with CFS/ME need to consider strategies to prevent development of depression, and research is needed into approaches that are effective in treating CFS/ME with co-morbid depression.
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4

Josev, Elisha K., Rebecca C. Cole, Adam Scheinberg, Katherine Rowe, Lionel Lubitz, and Sarah J. Knight. "Health, Wellbeing, and Prognosis of Australian Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case-Controlled Follow-Up Study." Journal of Clinical Medicine 10, no. 16 (August 16, 2021): 3603. http://dx.doi.org/10.3390/jcm10163603.

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Background: The purpose of this study was to follow-up an Australian cohort of adolescents newly-diagnosed with ME/CFS at a tertiary paediatric ME/CFS clinic and healthy controls over a mean period of two years (range 1–5 years) from diagnosis. Objectives were to (a) examine changes over time in health and psychological wellbeing, (b) track ME/CFS symptomatology and fulfillment of paediatric ME/CFS diagnostic criteria over time, and (c) determine baseline predictors of ME/CFS criteria fulfilment at follow-up. Methods: 34 participants aged 13–18 years (25 ME/CFS, 23 controls) completed standardised questionnaires at diagnosis (baseline) and follow-up assessing fatigue, sleep quality and hygiene, pain, anxiety, depression, and health-related quality of life. ME/CFS symptomatology and diagnostic criteria fulfilment was also recorded. Results: ME/CFS patients showed significant improvement in most health and psychological wellbeing domains over time, compared with controls who remained relatively stable. However, fatigue, pain, and health-related quality of life remained significantly poorer amongst ME/CFS patients compared with controls at follow-up. Sixty-five percent of ME/CFS patients at baseline continued to fulfil ME/CFS diagnostic criteria at follow-up, with pain the most frequently experienced symptom. Eighty-two percent of patients at follow-up self-reported that they still had ME/CFS, with 79% of these patients fulfilling criteria. No significant baseline predictors of ME/CFS criteria fulfilment at follow-up were observed, although pain experienced at baseline was significantly associated with criteria fulfilment at follow-up (R = 0.6, p = 0.02). Conclusions: The majority of Australian adolescents with ME/CFS continue to fulfil diagnostic criteria at follow-up, with fatigue, pain, and health-related quality of life representing domains particularly relevant to perpetuation of ME/CFS symptoms in the early years following diagnosis. This has direct clinical impact for treating clinicians in providing a more realistic prognosis and highlighting the need for intervention with young people with ME/CFS at the initial diagnosis and start of treatment.
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5

Jason, Leonard A., Suzanna So, Meredyth Evans, Abigail Brown, Madison Sunnquist, Young Im, and Charles Schafer. "An Overview of Operationalizing Criteria for ME, ME/CFS, and CFS Case Definitions." Journal of Prevention & Intervention in the Community 43, no. 1 (January 2, 2015): 1–4. http://dx.doi.org/10.1080/10852352.2014.973237.

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6

Ryabkova, Varvara A., Natalia Y. Gavrilova, Tamara V. Fedotkina, Leonid P. Churilov, and Yehuda Shoenfeld. "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground?" Diagnostics 13, no. 1 (December 26, 2022): 66. http://dx.doi.org/10.3390/diagnostics13010066.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown etiology, sharing a similar clinical presentation with the increasingly recognized post-COVID syndrome. We performed the first cross-sectional study of ME/CFS in a community population in Russia. Then we described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves as suffering from ME/CFS, 56 were diagnosed with ME/CFS by clinicians according to ≥1 of the four most commonly used case definitions. Of the cohort of 14 individuals with post-COVID-19 syndrome, 14 met the diagnostic criteria for ME/CFS. The severity of anxiety/depressive symptoms did not correlate with the severity of fatigue either in ME/CFS or in post-COVID ME/CFS. Still, a positive correlation was found between the severity of fatigue and 20 other symptoms of ME/CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, “dysfunction of the autonomic nervous system”, “neurological sensory/motor disorders” and “pain syndromes”. Immunological abnormalities were identified in 12/12 patients with ME/CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed in the active orthostatic test amounted to 37.5% in ME/CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02). There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified laser doppler flowmetry pattern corresponded to the hyperemic form of microcirculation disorders usually observed in acute inflammatory response or in case of systemic vasoconstriction failure.
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7

Mandarano, Alexandra H., Ludovic Giloteaux, Betsy A. Keller, Susan M. Levine, and Maureen R. Hanson. "Eukaryotes in the gut microbiota in myalgic encephalomyelitis/chronic fatigue syndrome." PeerJ 6 (January 22, 2018): e4282. http://dx.doi.org/10.7717/peerj.4282.

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Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often suffer from gastrointestinal symptoms and many are diagnosed with irritable bowel syndrome (IBS). Previous studies, including from our laboratory, have demonstrated that the ME/CFS gut bacterial composition is altered and less diverse when compared to healthy individuals. Patients have increased biomarkers of inflammation and leaky gut syndrome. To further investigate dysbiosis in the ME/CFS gut microbiome, we sought to characterize the eukaryotes present in the gut of 49 individuals with ME/CFS and 39 healthy controls. Using 18S rRNA sequencing, we have identified eukaryotes in stool samples of 17 healthy individuals and 17 ME/CFS patients. Our analysis demonstrates a small, nonsignificant decrease in eukaryotic diversity in ME/CFS patients compared to healthy individuals. In addition, ME/CFS patients show a nonsignificant increase in the ratio of fungal phyla Basidiomycota to Ascomycota, which is consistent with ongoing inflammation in ME/CFS. We did not identify specific eukaryotic taxa that are associated with ME/CFS disease status.
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8

Jahanbani, Fereshteh, Rajan D. Maynard, Justin Cyril Sing, Shaghayegh Jahanbani, John J. Perrino, Damek V. Spacek, Ronald W. Davis, and Michael P. Snyder. "Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study." PLOS ONE 17, no. 8 (August 9, 2022): e0272703. http://dx.doi.org/10.1371/journal.pone.0272703.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic multi-systemic disease characterized by extreme fatigue that is not improved by rest, and worsens after exertion, whether physical or mental. Previous studies have shown ME/CFS-associated alterations in the immune system and mitochondria. We used transmission electron microscopy (TEM) to investigate the morphology and ultrastructure of unstimulated and stimulated ME/CFS immune cells and their intracellular organelles, including mitochondria. PBMCs from four participants were studied: a pair of identical twins discordant for moderate ME/CFS, as well as two age- and gender- matched unrelated subjects—one with an extremely severe form of ME/CFS and the other healthy. TEM analysis of CD3/CD28-stimulated T cells suggested a significant increase in the levels of apoptotic and necrotic cell death in T cells from ME/CFS patients (over 2-fold). Stimulated Tcells of ME/CFS patients also had higher numbers of swollen mitochondria. We also found a large increase in intracellular giant lipid droplet-like organelles in the stimulated PBMCs from the extremely severe ME/CFS patient potentially indicative of a lipid storage disorder. Lastly, we observed a slight increase in platelet aggregation in stimulated cells, suggestive of a possible role of platelet activity in ME/CFS pathophysiology and disease severity. These results indicate extensive morphological alterations in the cellular and mitochondrial phenotypes of ME/CFS patients’ immune cells and suggest new insights into ME/CFS biology.
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9

Shimosako, Nana, and Jonathan R. Kerr. "Use of single-nucleotide polymorphisms (SNPs) to distinguish gene expression subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)." Journal of Clinical Pathology 67, no. 12 (September 19, 2014): 1078–83. http://dx.doi.org/10.1136/jclinpath-2014-202597.

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AimsWe have reported gene expression changes in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and the fact that such gene expression data can be used to identify subtypes of CFS/ME with distinct clinical phenotypes. Due to the difficulties in using a comparative gene expression method as an aid to CFS/ME disease and subtype-specific diagnosis, we have attempted to develop such a method based on single-nucleotide polymorphism (SNP) analysis.MethodsTo identify SNP allele associations with CFS/ME and CFS/ME subtypes, we tested genomic DNA of patients with CFS/ME (n=108), patients with endogenous depression (n=17) and normal blood donors (n=68) for 504 human SNP alleles located within 88 CFS-associated human genes using the SNP Genotyping GoldenGate Assay (Illumina, San Diego, California, USA). 360 ancestry informative markers (AIM) were also examined.Results21 SNPs were significantly associated with CFS/ME compared with depression and normal groups. 148 SNP alleles had a significant association with one or more CFS/ME subtypes. For each subtype, associated SNPs tended to be grouped together within particular genes. AIM SNPs indicated that 4 subjects were of Asian origin while the remainder were Caucasian. Hierarchical clustering of AIM data revealed the relatedness between 2 couples of patients with CFS only and confirmed the overall heterogeneity of all subjects.ConclusionsThis study provides evidence that human SNPs located within CFS/ME associated genes are associated with particular genomic subtypes of CFS/ME. Further work is required to develop this into a clinically useful subtype-specific diagnostic test.
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10

Vyas, Jui, Nina Muirhead, Ravinder Singh, Rachel Ephgrave, and Andrew Y. Finlay. "Impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the quality of life of people with ME/CFS and their partners and family members: an online cross-sectional survey." BMJ Open 12, no. 5 (May 2022): e058128. http://dx.doi.org/10.1136/bmjopen-2021-058128.

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ObjectivesThe aim of this study was to assess the impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the quality of life (QoL) of people with ME/CFS and their relative or partner (family member).DesignA patient-partner, multinational, subject-initiated, cross-sectional online survey.SettingInternational survey using ME/CFS charities, support groups and social media.ParticipantsParticipants were self-selected with recruitment via social media. Inclusion criteria were aged 18 years or over and reported diagnosis of ME/CFS by health professional. 1418 people with ME/CFS and their 1418 family members from 30 countries participated in the survey. Participants with ME/CFS had a mean age of 45.8 years (range 18–81) and were predominantly women (1214 (85.6%) of 1418). Family members had a mean age of 51.9 years (range 18–87) and were predominantly men (women: 504 (35.5%) of 1418). 991 (70%) family members were partners of the people with ME/CFS.InterventionsEuroQoL-5 Dimension (EQ-5D-3L), completed by people with ME/CFS, and Family Reported Outcome Measure (FROM-16) questionnaire, completed by family members.ResultsThe mean overall health status on a Visual Analogue Scale for people with ME/CFS was 33.8 (0=worst, 100=best). People with ME/CFS were most affected by ability to perform usual activities, pain, mobility, self-care and least impacted by anxiety. For family members, the overall mean FROM-16 score was 17.9 (0=no impact, 32=worst impact), demonstrating a major impact on QoL. Impact on QoL was significantly correlated between the person with ME/CFS and their family member (p<0.0001). Family members were most impacted emotionally by worry, frustration and sadness and personally by family activities, holidays, sex life and finances.ConclusionsTo the best of our knowledge, this is the largest study on the impact of the QoL of persons with ME/CFS and their family members. While open participation surveys are limited by selection bias, this research has revealed a significant worldwide burden of ME/CFS on the QoL of people with ME/CFS and their family members.
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11

Tokumasu, Kazuki, Hiroyuki Honda, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Koichiro Yamamoto, Yasuhiro Nakano, et al. "Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID." Medicina 58, no. 7 (June 25, 2022): 850. http://dx.doi.org/10.3390/medicina58070850.

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Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusion: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.
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12

Perrin, R. N. "Chronic fatigue syndrome/myalgic encephalomyelitis: diagnosis from an osteopathic perspective." Russian Osteopathic Journal, no. 1-2 (August 8, 2018): 19–27. http://dx.doi.org/10.32885/2220-0975-2018-1-2-19-27.

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Introduction. To date, there have existed different sets of symptoms of CFS/ME. Scientifi c ideas about the clinical manifestation of this disease continue to appear.Goal of research - to justify osteopathic approach in diagnostics of CFS/ME.Materials and methods. Analysis of approaches to the diagnostics of CFS/ME, osteopathic diagnostics.Results. The author describes the possible pathogenesis of CFS/ME, which may be related to the neurolymphatic changes connected with the alteration of the drainage. All of this leads to dysfunctions of the sympathetic system. Medical history of patients with CFS/ME often contains indications on spinal trauma or congenital developmental disorders of the cranium and vertebral column, which may alter the function of the lymphatic system and lead to the further central neurotoxicity through perivascular spaces. The article presents a protocol of physical signs, typical for patients with CFS/ME, and the results of diagnostics of 94 patients: 52 patients with CFS/ME and 42 non-CFS/ME controls.Conclusion. The research concluded that examining for physical signs is both quick and simple for the practitioner and may be used as an effi cient screening tool for CFS/ME.
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Krumina, Angelika, Katrine Vecvagare, Simons Svirskis, Sabine Gravelsina, Zaiga Nora-Krukle, Sandra Gintere, and Modra Murovska. "Clinical Profile and Aspects of Differential Diagnosis in Patients with ME/CFS from Latvia." Medicina 57, no. 9 (September 11, 2021): 958. http://dx.doi.org/10.3390/medicina57090958.

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Background and objectives: There is still an uncertainty regarding the clinical symptomatology and the diagnostic criteria in terms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), as different diagnostic criteria exist. Our aim is to identify the core symptoms of ME/CFS in the outpatient setting in Riga; to distinguish symptoms in patients with ME/CFS and those with symptoms of fatigue; and to investigate patient thoughts on the onset, symptoms, treatment and effect of ME/CFS. Materials and methods: Total of 65 Caucasian patients from an ambulatory care setting were included in the study. Questionnaires, specialist evaluation of the patients and visual analogue scale (VAS) measurements were used to objectify the findings. Results: The study showed that ME/CFS with comorbidities is associated with a more severe disease. A negative correlation was found regarding an increase in age and number of current symptoms, as well as an increase in VAS score and the duration of fatigue and age in the ME/CFS without comorbidities group. Conclusions: Comorbidities tend to present with a more severe course of ME/CFS. Fatigue, myalgia, arthralgia and sleep disturbances tend to be more prevalent in the ME/CFS patients compared to the non-ME/CFS patients. VAS score has a tendency to decrease with age and duration of fatigue. Nonsteroidal anti-inflammatory drugs are the most commonly used pharmacological drug class that reduces ME/CFS symptoms.
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14

Wu, Ting Yu, Taura Khorramshahi, Lindsey A. Taylor, Nikita S. Bansal, Betsy Rodriguez, and Irma R. Rey. "Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients." International Journal of Environmental Research and Public Health 19, no. 4 (February 12, 2022): 2052. http://dx.doi.org/10.3390/ijerph19042052.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a known complex, multi-organ system disorder with a sudden or subacute onset. ME/CFS occurs most commonly among women between 30 and 50 years of age. The current diagnostic criteria of ME/CFS, as defined by the Centers for Disease Control and Prevention, includes: profound fatigue and post-exertional malaise (>6 mo) unrelieved by rest, persistent cognitive impairment or orthostatic intolerance, and chronic unrefreshing sleep. Despite reported associations between ME/CFS onset and exposure to infectious agents (viral, bacterial, or fungal), the pathophysiology of ME/CFS remains unknown. In this prevalence study, we investigated the rates of Aspergillus-derived toxin levels, Aflatoxin (AF), Ochratoxin A (OTA), and Gliotoxin (GT), in the urinalysis of 236 ME/CFS patients with a history of chronic exposure to mold (i.e., from water-damaged buildings). Among ME/CFS patients reporting chronic exposure to mold, we found evidence of exposure in 92.4 percent of patients, with OTA being the most prevalent mycotoxin. Mold distributions (OTA, AF, and GT) in the urinalysis all demonstrated right skewness, while the distribution of age of ME/CFS patients diagnosed showed no deviation from normality. This study aims to provide preliminary, epidemiological evidence among ME/CFS patients who were diagnosed in South Florida with a history of exposure to mycotoxins. Based on these findings, we proposed how future control studies should approach investigating the association between chronic mold exposure and the diagnosis of ME/CFS.
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15

Ali, HM. "Chronic Fatigue Syndrome (CFS/ME)." Physiotherapy 87, no. 1 (January 2001): 52. http://dx.doi.org/10.1016/s0031-9406(05)61201-1.

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16

Karfakis, Nikos. "The biopolitics of CFS/ME." Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences 70 (August 2018): 20–28. http://dx.doi.org/10.1016/j.shpsc.2018.05.009.

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17

Nijs, Jo. "Current Papers in ME/CFS." Journal of Chronic Fatigue Syndrome 11, no. 2 (January 2003): 121–28. http://dx.doi.org/10.1300/j092v11n02_09.

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18

Cornes, O. "Commentary: Living with CFS/ME." BMJ 342, jun22 1 (June 22, 2011): d3836. http://dx.doi.org/10.1136/bmj.d3836.

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Jason, Leonard A., and Joseph A. Dorri. "ME/CFS and Post-Exertional Malaise among Patients with Long COVID." Neurology International 15, no. 1 (December 20, 2022): 1–11. http://dx.doi.org/10.3390/neurolint15010001.

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This study sought to ascertain the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) among a sample of 465 patients with Long COVID. The participants completed three questionnaires: (1) a new questionnaire measuring both the frequency and severity of 38 common symptoms of COVID and Long COVID, (2) a validated short form questionnaire assessing ME/CFS, and (3) a validated questionnaire measuring post-exertional malaise. The population was predominantly white, female, and living in North America. The mean duration since the onset of COVID-19 symptoms was 70.5 weeks. Among the 465 participants, 58% met a ME/CFS case definition. Of respondents who reported that they had ME/CFS only 70.57% met criteria for ME/CFS and of those who did not report they had ME/CFS, 29.43% nevertheless did meet criteria for the disease: both over-diagnosis and under-diagnosis were evident on self-report. This study supports prior findings that ME/CFS occurs with high prevalence among those who have persistent COVID-19 symptoms.
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Van Oosterwijck, Jessica, Uros Marusic, Inge De Wandele, Mira Meeus, Lorna Paul, Luc Lambrecht, Greta Moorkens, Lieven Danneels, and Jo Nijs. "Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome." Journal of Clinical Medicine 10, no. 19 (September 30, 2021): 4527. http://dx.doi.org/10.3390/jcm10194527.

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Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people. Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout. At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS. This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population.
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Nacul, de Barros, Kingdon, Cliff, Clark, Mudie, Dockrell, and Lacerda. "Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study." Diagnostics 9, no. 2 (April 10, 2019): 41. http://dx.doi.org/10.3390/diagnostics9020041.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease presenting with extreme fatigue, post-exertional malaise, and other symptoms. In the absence of a diagnostic biomarker, ME/CFS is diagnosed clinically, although laboratory tests are routinely used to exclude alternative diagnoses. In this analytical cross-sectional study, we aimed to explore potential haematological and biochemical markers for ME/CFS, and disease severity. We reviewed laboratory test results from 272 people with ME/CFS and 136 healthy controls participating in the UK ME/CFS Biobank (UKMEB). After corrections for multiple comparisons, most results were within the normal range, but people with severe ME/CFS presented with lower median values (p < 0.001) of serum creatine kinase (CK; median = 54 U/L), compared to healthy controls (HCs; median = 101.5 U/L) and non-severe ME/CFS (median = 84 U/L). The differences in CK concentrations persisted after adjusting for sex, age, body mass index, muscle mass, disease duration, and activity levels (odds ratio (OR) for being a severe case = 0.05 (95% confidence interval (CI) = 0.02–0.15) compared to controls, and OR = 0.16 (95% CI = 0.07–0.40), compared to mild cases). This is the first report that serum CK concentrations are markedly reduced in severe ME/CFS, and these results suggest that serum CK merits further investigation as a biomarker for severe ME/CFS.
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Froehlich, Laura, Daniel B. R. Hattesohl, Leonard A. Jason, Carmen Scheibenbogen, Uta Behrends, and Manuel Thoma. "Medical Care Situation of People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Germany." Medicina 57, no. 7 (June 23, 2021): 646. http://dx.doi.org/10.3390/medicina57070646.

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Background and Objective: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe illness with the hallmark symptom of Post-Exertional Malaise (PEM). Currently, no biomarkers or established diagnostic tests for ME/CFS exist. In Germany, it is estimated that over 300,000 people are affected by ME/CFS. Research from the United States and the UK shows that patients with ME/CFS are medically underserved, as they face barriers to medical care access and are dissatisfied with medical care. The first aim of the current research was to investigate whether patients with ME/CFS are medically underserved in Germany in terms of access to and satisfaction with medical care. Second, we aimed at providing a German-language version of the DePaul Symptom Questionnaire Short Form (DSQ-SF) as a tool for ME/CFS diagnostics and research in German-speaking countries. Materials and Methods: The current research conducted an online questionnaire study in Germany investigating the medical care situation of patients with ME/CFS. The questionnaire was completed by 499 participants who fulfilled the Canadian Consensus Criteria and reported PEM of 14 h or longer. Results: Participants frequently reported geographic and financial reasons for not using the available medical services. Furthermore, they reported low satisfaction with medical care by the physician they most frequently visited due to ME/CFS. The German version of the DSQ-SF showed good reliability, a one-factorial structure and construct validity, demonstrated by correlations with the SF-36 as a measure of functional status. Conclusions: Findings provide evidence that patients with ME/CFS in Germany are medically underserved. The German-language translation of the DSQ-SF provides a brief, reliable and valid instrument to assess ME/CFS symptoms to be used for research and clinical practice in German-speaking countries. Pathways to improve the medical care of patients with ME/CFS are discussed.
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23

Capdevila, Lluis, Jesús Castro-Marrero, José Alegre, Juan Ramos-Castro, and Rosa M. Escorihuela. "Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology." Sensors 21, no. 11 (May 28, 2021): 3746. http://dx.doi.org/10.3390/s21113746.

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In a previous study using mobile-health technology (mHealth), we reported a robust association between chronic fatigue symptoms and heart rate variability (HRV) in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study explores HRV analysis as an objective, non-invasive and easy-to-apply marker of ME/CFS using mHealth technology, and evaluates differential gender effects on HRV and ME/CFS core symptoms. In our methodology, participants included 77 ME/CFS patients (32 men and 45 women) and 44 age-matched healthy controls (19 men and 25 women), all self-reporting subjective scores for fatigue, sleep quality, anxiety, and depression, and neurovegetative symptoms of autonomic dysfunction. The inter-beat cardiac intervals are continuously monitored/recorded over three 5-min periods, and HRV is analyzed using a custom-made application (iOS) on a mobile device connected via Bluetooth to a wearable cardiac chest band. Male ME/CFS patients show increased scores compared with control men in all symptoms and scores of fatigue, and autonomic dysfunction, as with women in the first study. No differences in any HRV parameter appear between male ME/CFS patients and controls, in contrast to our findings in women. However, we have found negative correlations of ME/CFS symptomatology with cardiac variability (SDNN, RMSSD, pNN50, LF) in men. We have also found a significant relationship between fatigue symptomatology and HRV parameters in ME/CFS patients, but not in healthy control men. Gender effects appear in HF, LF/HF, and HFnu HRV parameters. A MANOVA analysis shows differential gender effects depending on the experimental condition in autonomic dysfunction symptoms and HF and HFnu HRV parameters. A decreased HRV pattern in ME/CFS women compared to ME/CFS men may reflect a sex-related cardiac autonomic dysfunction in ME/CFS illness that could be used as a predictive marker of disease progression. In conclusion, we show that HRV analysis using mHealth technology is an objective, non-invasive tool that can be useful for clinical prediction of fatigue severity, especially in women with ME/CFS.
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Muirhead, Nina, John Muirhead, Grace Lavery, and Ben Marsh. "Medical School Education on Myalgic Encephalomyelitis." Medicina 57, no. 6 (May 28, 2021): 542. http://dx.doi.org/10.3390/medicina57060542.

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Background and objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex multi-system disease with a significant impact on the quality of life of patients and their families, yet the majority of ME/CFS patients go unrecognised or undiagnosed. For two decades, the medical education establishment in the UK has been challenged to remedy these failings, but little has changed. Meanwhile, there has been an exponential increase in biomedical research and an international paradigm shift in the literature, which defines ME/CFS as a multisystem disease, replacing the psychogenic narrative. This study was designed to explore the current UK medical school education on ME/CFS and to identify challenges and opportunities relating to future ME/CFS medical education. Materials and methods: A questionnaire, developed under the guidance of the Medical Schools Council, was sent to all 34 UK medical schools to collect data for the academic year 2018–2019. Results: Responses were provided by 22 out of a total of 34 medical schools (65%); of these 13/22 (59%) taught ME/CFS, and teaching was led by lecturers from ten medical specialties. Teaching delivery was usually by lecture; discussion, case studies and e-learning were also used. Questions on ME/CFS were included by seven schools in their examinations and three schools reported likely clinical exposure to ME/CFS patients. Two-thirds of respondents were interested in receiving further teaching aids in ME/CFS. None of the schools shared details of their teaching syllabus, so it was not possible to ascertain what the students were being taught. Conclusions: This exploratory study reveals inadequacies in medical school teaching on ME/CFS. Many medical schools (64% of respondents) acknowledge the need to update ME/CFS education by expressing an appetite for further educational materials. The General Medical Council (GMC) and Medical Schools Council (MSC) are called upon to use their considerable influence to bring about the appropriate changes to medical school curricula so future doctors can recognise, diagnose and treat ME/CFS. The GMC is urged to consider creating a registered specialty encompassing ME/CFS, post-viral fatigue and long Covid.
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Yamano, Emi, Yasuyoshi Watanabe, and Yosky Kataoka. "Insights into Metabolite Diagnostic Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome." International Journal of Molecular Sciences 22, no. 7 (March 26, 2021): 3423. http://dx.doi.org/10.3390/ijms22073423.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, and with a minimum duration of 6 consecutive months. Its pathogenesis is not fully understood. There are no firmly established diagnostic biomarkers or treatment, due to incomplete understanding of the etiology of ME/CFS and diagnostic uncertainty. Establishing a biomarker for the objective diagnosis is urgently needed to treat a lot of patients. Recently, research on ME/CFS using metabolome analysis methods has been increasing. Here, we overview recent findings concerning the metabolic features in patients with ME/CFS and the animal models which contribute to the development of diagnostic biomarkers for ME/CFS and its treatment. In addition, we discuss future perspectives of studies on ME/CFS.
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Harvey, S. B., M. Wadsworth, S. Wessely, and M. Hotopf. "The relationship between prior psychiatric disorder and chronic fatigue: evidence from a national birth cohort study." Psychological Medicine 38, no. 7 (November 2, 2007): 933–40. http://dx.doi.org/10.1017/s0033291707001900.

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BackgroundIncreased rates of psychiatric disorder have previously been reported in those diagnosed with chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME), although the direction of causation in this relationship has not been established. We aimed to test the hypothesis that individuals with self-reported CFS/ME have increased levels of psychiatric disorder prior to the onset of their fatigue symptoms.MethodA total of 5362 participants were prospectively followed with various measures of personality, psychiatric disorder and fatigue levels collected over the first 43 years of their life. CFS/ME was identified through self-report during a semi-structured interview at age 53 years.ResultsThirty-four (1.1%) of the 3035 subjects assessed at age 53 years reported a diagnosis of CFS/ME. CFS/ME was more common among females, but there was no association between CFS/ME and either social class, social mobility or educational level. Those with psychiatric illness between the ages of 15 and 36 years were more likely to report CFS/ME later in life with an odds ratio (OR, adjusted for sex) of 2.65 [95% confidence interval (CI) 1.26–5.57, p=0.01]. Increased levels of psychiatric illness, in particular depression and anxiety, were present prior to the occurrence of fatigue symptoms. There was a dose–response relationship between the severity of psychiatric symptoms and the likelihood of later CFS/ME. Personality factors were not associated with a self-reported diagnosis of CFS/ME.ConclusionsThis temporal, dose–response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have an aetiological role in some cases of CFS/ME.
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Szrajda, Justyna. "ME/CFS in Adolescents — Study Review." Journal of Neurological and Neurosurgical Nursing 9, no. 2 (June 2020): 76–79. http://dx.doi.org/10.15225/pnn.2020.9.2.5.

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Chronic Fatigue Syndrome (CFS), also called myalgic encephalomyelitis (ME), is a condition characterized by long-term fatigue that is not significantly alleviated during rest and is not caused by previous medical conditions or continuous exercise. Symptoms are quite diverse, but not specific to this disease entity. The most common are: concentration and memory problems, sore throat, swollen lymph nodes, joint pain, sleep disturbances, headache. Moreover, autonomic nervous system functioning and post-exertional malaise examination is considered to be important in diagnosis of adolescent patients with ME/CFS. The presented analysis of research shows that adolescents with ME/CFS urge to be understood and believed regarding an illness that few understood. Continuing education and remaining the social activity in young ME/CFS patients seems to be crucial in maintaining quality of life. ME/ CFS in adolescents might lead to significant problems related to the school absenteeism, poorer quality of life at school, school and academic achievement compared to healthy adolescents. Anxiety might co-occur with ME/CFS in adolescents. Supportive therapy for comorbidities could be considered, if needed. However, there is no established effective treatment for ME/CFS, for which there is urgent need. (JNNN 2020;9(2):76–79) Key Words: ME/CFS, adolescents, Chronic Fatigue Syndrome
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Smith, Lucie, Esther Crawley, Madeleine Riley, Megan McManus, and Maria Elizabeth Loades. "Exploring anhedonia in adolescents with Chronic Fatigue Syndrome (CFS): A mixed-methods study." Clinical Child Psychology and Psychiatry 26, no. 3 (April 16, 2021): 855–69. http://dx.doi.org/10.1177/13591045211005515.

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Background: Chronic Fatigue Syndrome (CFS/ME) may get in the way of enjoying activities. A substantial minority of adolescents with CFS/ME are depressed. Anhedonia is a core symptom of depression. Anhedonia in adolescents with CFS/ME has not been previously investigated. Method: One hundred and sixty-four adolescents, age 12 to 18, with CFS/ME completed a diagnostic interview (K-SADS) and questionnaires (HADS, RCADS). We used a mixed-methods approach to explore the experience of anhedonia and examine how common it is, comparing those with clinically significant anhedonia to those without. Results: Forty-two percent of adolescents with CFS/ME reported subclinical or clinical levels of anhedonia. Fifteen percent had clinically significant anhedonia. Thematic analysis generated two themes: (1) stopping activities that they previously enjoyed and (2) CFS/ME obstructs enjoyment. Most (72%) of those who reported clinically significant anhedonia met the depression diagnostic criteria. Those who were depressed used more negative language to describe their experience of activities than in those who were not depressed, although the themes were broadly similar. Conclusions: Experiencing pleasure from activities may be affected in CFS/ME, particularly in those who are depressed. Anhedonia may get in the way of behavioural strategies used within CFS/ME treatments.
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Baraniuk, James N., Alison Amar, Haris Pepermitwala, and Stuart D. Washington. "Differential Effects of Exercise on fMRI of the Midbrain Ascending Arousal Network Nuclei in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) in a Model of Postexertional Malaise (PEM)." Brain Sciences 12, no. 1 (January 5, 2022): 78. http://dx.doi.org/10.3390/brainsci12010078.

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Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and control subjects underwent fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction. Methods: Activated midbrain nuclei were inferred by a re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI subjects showed greater activation during cognition than ME/CFS in the left pedunculotegmental nucleus. Post exercise, ME/CFS subjects showed greater activation than GWI ones for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI, indicating reciprocal patterns of activation. The controls had no changes. Conclusions: Exercise caused the opposite effects with increased activation in ME/CFS but decreased activation in GWI, indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.
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Sweetman, Noble, Edgar, Mackay, Helliwell, Vallings, Ryan, and Tate. "Current Research Provides Insight into the Biological Basis and Diagnostic Potential for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)." Diagnostics 9, no. 3 (July 10, 2019): 73. http://dx.doi.org/10.3390/diagnostics9030073.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe fatigue illness that occurs most commonly following a viral infection, but other physiological triggers are also implicated. It has a profound long-term impact on the life of the affected person. ME/CFS is diagnosed primarily by the exclusion of other fatigue illnesses, but the availability of multiple case definitions for ME/CFS has complicated diagnosis for clinicians. There has been ongoing controversy over the nature of ME/CFS, but a recent detailed report from the Institute of Medicine (Academy of Sciences, USA) concluded that ME/CFS is a medical, not psychiatric illness. Importantly, aspects of the biological basis of the ongoing disease have been revealed over the last 2–3 years that promise new leads towards an effective clinical diagnostic test that may have a general application. Our detailed molecular studies with a preclinical study of ME/CFS patients, along with the complementary research of others, have reported an elevation of inflammatory and immune processes, ongoing neuro-inflammation, and decreases in general metabolism and mitochondrial function for energy production in ME/CFS, which contribute to the ongoing remitting/relapsing etiology of the illness. These biological changes have generated potential molecular biomarkers for use in diagnostic ME/CFS testing.
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Davenport, Todd E., Staci R. Stevens, Mark J. VanNess, Christopher R. Snell, and Tamara Little. "Conceptual Model for Physical Therapist Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis." Physical Therapy 90, no. 4 (April 1, 2010): 602–14. http://dx.doi.org/10.2522/ptj.20090047.

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Fatigue is one of the most common reasons why people consult health care providers. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is one cause of clinically debilitating fatigue. The underdiagnosis of CFS/ME, along with the spectrum of symptoms that represent multiple reasons for entry into physical therapy settings, places physical therapists in a unique position to identify this health condition and direct its appropriate management. The diagnosis and clinical correlates of CFS/ME are becoming better understood, although the optimal clinical management of this condition remains controversial. The 4 aims of this perspective article are: (1) to summarize the diagnosis of CFS/ME with the goal of promoting the optimal recognition of this condition by physical therapists; (2) to discuss aerobic system and cognitive deficits that may lead to the clinical presentation of CFS/ME; (3) to review the evidence for graded exercise with the goal of addressing limitations in body structures and functions, activity, and participation in people with CFS/ME; and (4) to present a conceptual model for the clinical management of CFS/ME by physical therapists.
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Reid, Victoria Alice, and Nina Muirhead. "Investigating undergraduate medical education on myalgic encephalomyelitis/chronic fatigue syndrome." British Student Doctor Journal 6, no. 1 (December 1, 2022): 35–40. http://dx.doi.org/10.18573/bsdj.308.

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Background and Objectives: ME/CFS is a poorly understood, highly stigmatised condition which significantly reduces patients’ quality of life. ME/CFS had been identified as a gap in many health professionals’ knowledge, therefore this research aims to explore the understanding of ME/CFS amongst UK medical students. Methods: An online survey developed using Redcap was distributed to participants who were recruited via social media or via medical societies' emails. The participants were undergraduate UK medical students. Results: 94 students completed the survey from more than 16 medical schools. 35% of the students did not know what ME/CFS is and 88% say that the disease has not been covered in their course so far. 89% of participants would like to learn more about ME/CFS, specifically through elearning and videos. Discussion: Participants were generally unaware of ME/CFS and its symptoms and had not received relevant teaching or exposure to the disease. Education on ME/CFS within undergraduate UK medical schools is currently inadequate and the interest expressed by students in this survey demonstrates a new teaching opportunity for UK medical schools.
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Krishnakumar, Priya, Camila Jaramillo, Shawn Kurian, Wendy Levy, Cara Milman, Nadine Mikati, Fatma Huffman, Maria Abreu, and Amanpreet Cheema. "Intracellular Nutritional Biomarker Differences in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subjects and Healthy Controls." Current Developments in Nutrition 6, Supplement_1 (June 2022): 745. http://dx.doi.org/10.1093/cdn/nzac062.014.

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Abstract Objectives A comparison of the nutritional biomarkers between ME/CFS subjects and healthy controls (HC) was undertaken on secondary data collected from an IRB approved cross-sectional study in ME/CFS patients. Methods ME/CFS participants were recruited per the 2018 revised Canadian Clinical Case Definition for ME/CFS along with age matched HCs. Self-reported information on demographics and supplement use was collected, and body mass index calculated. HEI was calculated from Willet FFQ and multiple day 24-hour recall data, and severity of fatigue measured by Multidimensional Fatigue Inventory (MFI). Lymphocyte transformation assay by SpectraCell Lab (Houston, TX) was employed for intracellular micronutrient status. A series of two-tailed Mann-Whitney U tests (ɑ = 0.05) were performed for the non-parametric data expressed as mean ± standard error of the mean. All statistical analyses were conducted in IBM SPSS Statistics version 25 (Armonk, NY). Results Out of the 21 participants (11 ME/CFS and 10 HC), 82% of ME/CFS and 50% of HC were female. Higher fatigue scores were observed in ME/CFS (16.64 ± 1.36) than HC (10.78 ± 2.14). ME/CFS had better HEI scores (63.36 ± 13.44) than the HC (38.55 ± 12.29). However, despite better diet quality and supplementation, ME/CFS group showed lower intracellular Vitamin B3 and manganese (Mn) (86.3 ± 2.42 and 53.6 ± 2.81 respectively) but higher calcium (Ca) (57.5 ± 3.55) as compared to HC (97.2 ± 2.31, 64.5 ± 1.87 and 46.5 ± 0.96 respectively). Conclusions The results align with the current literature on indications of mitochondrial dysfunction in ME/CFS. Reduced intracellular vit B3 provides suboptimal production of the NAD(P)(H)-cofactor family, thus affecting mitochondrial function and consequently energy production. The aberration in energy metabolism is compounded by other factors, such as reduced Mn but higher Ca intracellular levels seen in this study indicating disruptions in oxidative stress pathways, resulting in debilitating fatigue experienced by individuals with ME/CFS. Funding Sources NSU Presidential Faculty Research and Development Grant.
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Varesi, Angelica, Undine-Sophie Deumer, Sanjana Ananth, and Giovanni Ricevuti. "The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications." Journal of Clinical Medicine 10, no. 21 (October 29, 2021): 5077. http://dx.doi.org/10.3390/jcm10215077.

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The well-known symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are chronic pain, cognitive dysfunction, post-exertional malaise and severe fatigue. Another class of symptoms commonly reported in the context of ME/CFS are gastrointestinal (GI) problems. These may occur due to comorbidities such as Crohn’s disease or irritable bowel syndrome (IBS), or as a symptom of ME/CFS itself due to an interruption of the complex interplay between the gut microbiota (GM) and the host GI tract. An altered composition and overall decrease in diversity of GM has been observed in ME/CFS cases compared to controls. In this review, we reflect on genetics, infections, and other influences that may factor into the alterations seen in the GM of ME/CFS individuals, we discuss consequences arising from these changes, and we contemplate the therapeutic potential of treating the gut to alleviate ME/CFS symptoms holistically.
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Burley, Lucy, Diane L. Cox, and Leslie J. Findley. "Severe Chronic Fatigue Syndrome (CFS/ME): Recovery is Possible." British Journal of Occupational Therapy 70, no. 8 (August 2007): 339–44. http://dx.doi.org/10.1177/030802260707000803.

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The recovery of individuals with very severe chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) is possible with successful multidisciplinary management. This case vignette aims to highlight the beneficial outcome of using occupational therapy lifestyle management and the Canadian Occupational Performance Measure to identify perceived problems in occupational performance and indicate change. The current management strategies in CFS/ME are discussed briefly and the challenges of the management of severe CFS/ME are described, indicating a need for a supportive team and specialist inpatient services. In 2003, the Department of Health released funds in England to develop more widely accessible CFS/ME services. This case study illustrates a positive outcome for one individual with severe CFS/ME, following admission to a specialist inpatient facility. It is hoped that it may aid other therapists working with and developing services for people with severe presentations of CFS/ME.
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Silvestre, Isabel Barao, Raul Y. Dagda, Ruben K. Dagda, and Victor Darley-Usmar. "Mitochondrial alterations in NK lymphocytes from ME/CFS patients." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 126.39. http://dx.doi.org/10.4049/jimmunol.202.supp.126.39.

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Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by profound fatigue, flu-like symptoms, trouble concentrating, and autonomic problems, all of which worsen after exertion. ME/CFS patients have impaired natural killer (NK) cell activity. NK lymphocytes are a critical first defense against viruses and cancer. ME/CFS patients have difficulties controlling viral infections and many develop non-Hodgkin’s lymphoma. Mitochondrial metabolism is crucial for immune cell function. Mitochondria dysfunction has been previously reported in ME/CFS, but it is not known whether the NK cells of these patients have altered mitochondrial metabolism that affect their activity and contribute to ME/CFS pathogenesis. More importantly, there is currently no efficient method to diagnose ME/CFS or assess efficacy of therapeutic interventions. The Bioenergetic Health Index (BHI) has been developed as promising and reliable surrogate readout of human health by measuring the bioenergetic status of immune cells. Variations in bioenergetic function in patient’s immune cells can reflect both metabolic stress and the mutable role of these cells in ME/CFS immunity and pathogenesis. In our study, we observed that the two main energy-generating mitochondrial pathways, oxidative phosphorylation and glycolysis (bioenergetics parameters), are deregulated in ME/CFS NK cells and in PBMCs. Moreover, we observed alterations in the morphology and membrane potential of the mitochondria of NK cells. These mitochondrial features can affect NK cell function and contribute to the severity of disease. To date, this is the first metabolism assessment of NK cells in ME/CFS and as potential new diagnostic tool for the disease.
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Dafoe, Whitney. "Extremely Severe ME/CFS—A Personal Account." Healthcare 9, no. 5 (April 27, 2021): 504. http://dx.doi.org/10.3390/healthcare9050504.

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A personal account from an Extremely Severe Bedridden ME/CFS patient about the experience of living with extremely severe ME/CFS. Illness progression, medical history, description of various aspects of extremely severe ME/CFS and various essays on specific experiences are included.
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Lutz, Lena, Johanna Rohrhofer, Sonja Zehetmayer, Michael Stingl, and Eva Untersmayr. "Evaluation of Immune Dysregulation in an Austrian Patient Cohort Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome." Biomolecules 11, no. 9 (September 14, 2021): 1359. http://dx.doi.org/10.3390/biom11091359.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multi-systemic disease characterized by debilitating fatigue that is not relieved by rest. The causes of the disease are still largely unexplained, and no causative treatment is currently available. Changes in the immune response are considered as fundamental in the development of ME/CFS. Thus, we aimed to evaluate the immunological profile of ME/CFS patients in a retrospective data analysis. As part of the routine workup for ME/CFS patients, a differential blood count, leukocyte subtyping, and quantification of immunoglobulins and IgG subclasses, as well as a complement analysis, was performed. Out of 262 ME/CFS patients, 64.9% had a reduction or deficiency in at least one of the listed immune parameters. In contrast, 26.3% showed signs of immune activation or inflammation. A total of 17.6% of the ME/CFS patients had an unclassified antibody deficiency, with IgG3 and IgG4 subclass deficiencies as the most common phenotypes. Reduced MBL (mannose-binding lectin) levels were found in 32% of ME/CFS patients, and MBL deficiency in 7%. In summary, the present results confirmed the relevance of immune dysfunction in ME/CFS patients underlining the involvement of a dysfunctional immune response in the disease. Thus, immune parameters are relevant disease biomarkers, which might lead to targeted therapeutic approaches in the future.
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Jason, Leonard A., and Chelsea Torres. "Differences in Symptoms among Black and White Patients with ME/CFS." Journal of Clinical Medicine 11, no. 22 (November 12, 2022): 6708. http://dx.doi.org/10.3390/jcm11226708.

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Study samples of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have primarily involved White subjects, so the literature on ethnic differences is sparse. The current study identified a sample of 19 Black patients diagnosed with ME/CFS and compared them with White patients with ME/CFS, as well as with healthy controls. The studies used a similar psychometrically sound assessment tool to assess symptoms in all subjects. Findings indicated there were significant differences between patients with ME/CFS versus controls, but few differences between patients who identified as Black or White. The results suggest there might be few symptom differences between patients with ME/CFS in these two ethnic groups. The implications of these findings are discussed.
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Araja, Diana, Uldis Berkis, Asja Lunga, and Modra Murovska. "Shadow Burden of Undiagnosed Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) on Society: Retrospective and Prospective—In Light of COVID-19." Journal of Clinical Medicine 10, no. 14 (July 6, 2021): 3017. http://dx.doi.org/10.3390/jcm10143017.

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Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood, complex, multisystem disorder, with severe fatigue not alleviated by rest, and other symptoms, which lead to substantial reductions in functional activity and quality of life. Due to the unclear aetiology, treatment of patients is complicated, but one of the initial problems is the insufficient diagnostic process. The increase in the number of undiagnosed ME/CFS patients became specifically relevant in the light of the COVID-19 pandemic. The aim of this research was to investigate the issues of undiagnosed potential ME/CFS patients, with a hypothetical forecast of the expansion of post-viral CFS as a consequence of COVID-19 and its burden on society. Methods: The theoretical research was founded on the estimation of classic factors presumably affecting the diagnostic scope of ME/CFS and their ascription to Latvian circumstances, as well as a literature review to assess the potential interaction between ME/CFS and COVID-19 as a new contributing agent. The empirical study design consisted of two parts: The first part was dedicated to a comparison of the self-reported data of ME/CFS patients with those of persons experiencing symptoms similar to ME/CFS, but without a diagnosis. This part envisaged the creation of an assumption of the ME/CFS shadow burden “status quo”, not addressing the impact of COVID-19. The second part aimed to investigate data from former COVID-19 patients’ surveys on the presence of ME/CFS symptoms, 6 months after being affected by COVID-19. Descriptive and analytical statistical methods were used to analyse the obtained data. Results: The received data assumed that the previously obtained data on the ME/CFS prevalence of 0.8% in the Latvian population are appropriate, and the literature review reports a prevalence of 0.2–1.0% in developed countries. Regarding the reciprocity of ME/CFS and COVID-19, the literature review showed a lack of research in this field. The empirical results show quite similar self-esteem among ME/CFS patients and undiagnosed patients with longstanding disease experience, while former COVID-19 patients show a significantly lower severity of these problems. Notably, “psychological distress (anxiety)” and “episodic fatigue” are significantly predominant symptoms reported by former COVID-19 patients in comparison with ME/CFS patients and undiagnosed patients prior to the COVID-19 pandemic. The results of our analysis predict that the total amount of direct medical costs for undiagnosed patients (out-of-pocket payments) is more than EUR 15 million p.a. (in Latvia), and this may increase by at least 15% due to the consequences of COVID-19. Conclusions: ME/CFS creates a significant shadow burden on society, even considering only the direct medical costs of undiagnosed patients—the number of whom in Latvia is probably at least five times higher than the number of discerned patients. Simultaneously, COVID-19 can induce long-lasting complications and chronic conditions, such as post-viral CFS, and increase this burden. The Latvian research data assume that ME/CFS patients are not a high-risk group for COVID-19; however, COVID-19 causes ME/CFS-relevant symptoms in patients. This increases the need for monitoring of patients for even longer after recovering from COVID-19′s symptoms, in order to prevent complications and the progression of chronic diseases. In the context of further epidemiological uncertainty, and the possibility of severe post-viral consequences, preventive measures are becoming significantly more important; an integrated diagnostic approach and appropriate treatment could reduce this burden in the future.
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Che, Xiaoyu, Christopher R. Brydges, Yuanzhi Yu, Adam Price, Shreyas Joshi, Ayan Roy, Bohyun Lee, et al. "Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome." International Journal of Molecular Sciences 23, no. 14 (July 18, 2022): 7906. http://dx.doi.org/10.3390/ijms23147906.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.
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Esfandyarpour, R., A. Kashi, M. Nemat-Gorgani, J. Wilhelmy, and R. W. Davis. "A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)." Proceedings of the National Academy of Sciences 116, no. 21 (April 29, 2019): 10250–57. http://dx.doi.org/10.1073/pnas.1901274116.

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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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43

Peterson, D., E. W. Brenu, G. Gottschalk, S. Ramos, T. Nguyen, D. Staines, and S. Marshall-Gradisnik. "Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis." Mediators of Inflammation 2015 (2015): 1–4. http://dx.doi.org/10.1155/2015/929720.

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Objectives. Previous research has provided evidence for dysregulation in peripheral cytokines in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To date only one study has examined cytokines in cerebrospinal fluid (CSF) samples of CFS/ME patients. The purpose of this pilot study was to examine the role of cytokines in CSF of CFS/ME patients.Methods. CSF was collected from 18 CFS/ME patients and 5 healthy controls. The CSF samples were examined for the expression of 27 cytokines (interleukin- (IL-) 1β, IL-1ra, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF) using the Bio-Plex Human Cytokine 27-plex Assay.Results. Of the 27 cytokines examined, only IL-10 was significantly reduced in the CFS/ME patients in comparison to the controls.Conclusions. This preliminary investigation suggests that perturbations in inflammatory cytokines in the CSF of CFS/ME patients may contribute to the neurological discrepancies observed in CFS/ME.
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44

van Campen, C. (Linda) M. C., Peter C. Rowe, and Frans C. Visser. "Two-Day Cardiopulmonary Exercise Testing in Females with a Severe Grade of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison with Patients with Mild and Moderate Disease." Healthcare 8, no. 3 (June 30, 2020): 192. http://dx.doi.org/10.3390/healthcare8030192.

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Introduction: Effort intolerance along with a prolonged recovery from exercise and post-exertional exacerbation of symptoms are characteristic features of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The gold standard to measure the degree of physical activity intolerance is cardiopulmonary exercise testing (CPET). Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients, and that a 2-day CPET protocol further discriminates between ME/CFS patients and sedentary controls. Limited information is present on ME/CFS patients with a severe form of the disease. Therefore, the aim of this study was to compare the effects of a 2-day CPET protocol in female ME/CFS patients with a severe grade of the disease to mildly and moderately affected ME/CFS patients. Methods and results: We studied 82 female patients who had undergone a 2-day CPET protocol. Measures of oxygen consumption (VO2), heart rate (HR) and workload both at peak exercise and at the ventilatory threshold (VT) were collected. ME/CFS disease severity was graded according to the International Consensus Criteria. Thirty-one patients were clinically graded as having mild disease, 31 with moderate and 20 with severe disease. Baseline characteristics did not differ between the 3 groups. Within each severity group, all analyzed CPET parameters (peak VO2, VO2 at VT, peak workload and the workload at VT) decreased significantly from day-1 to day-2 (p-Value between 0.003 and <0.0001). The magnitude of the change in CPET parameters from day-1 to day-2 was similar between mild, moderate, and severe groups, except for the difference in peak workload between mild and severe patients (p = 0.019). The peak workload decreases from day-1 to day-2 was largest in the severe ME/CFS group (−19 (11) %). Conclusion: This relatively large 2-day CPET protocol study confirms previous findings of the reduction of various exercise variables in ME/CFS patients on day-2 testing. This is the first study to demonstrate that disease severity negatively influences exercise capacity in female ME/CFS patients. Finally, this study shows that the deterioration in peak workload from day-1 to day-2 is largest in the severe ME/CFS patient group.
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Cook, Dane B., Stephanie VanRiper, Ryan J. Dougherty, Jacob B. Lindheimer, Michael J. Falvo, Yang Chen, Jin-Mann S. Lin, and Elizabeth R. Unger. "Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study." PLOS ONE 17, no. 3 (March 15, 2022): e0265315. http://dx.doi.org/10.1371/journal.pone.0265315.

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Background Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear. Purpose To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness. Methods As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent (V˙E/V˙O2, V˙E/V˙CO2), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges’ g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20–100% peak V˙O2). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak V˙O2 (~1 ml/kg/min-1). Results Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20–100% peak V˙O2) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for V˙E/V˙O2, V˙E/V˙CO2 and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, V˙E/V˙O2, V˙E/V˙CO2, and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., V˙E/V˙CO2nadir) were generally reflective of those seen throughout exercise (i.e., 20–100%). Conclusion Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.
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46

Danilenko, Olga V., Natalia Y. Gavrilova, and Leonid P. Churilov. "Chronic Fatigue Exhibits Heterogeneous Autoimmunity Characteristics Which Reflect Etiology." Pathophysiology 29, no. 2 (May 25, 2022): 187–99. http://dx.doi.org/10.3390/pathophysiology29020016.

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Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is considered to be associated with post-viral complications and mental stress, but the role of autoimmunity also remains promising. A comparison of autoimmune profiles in chronic fatigue of different origin may bring insights on the pathogenesis of this disease. Thirty-three patients with CFS/ME were divided into three subgroups. The first group included Herpesviridae carriers (group V), the second group included stress-related causes of chronic fatigue (distress, group D), and the third group included idiopathic CFS/ME (group I). Were evaluated thirty-six neural and visceral autoantigens with the ELISA ELI-test (Biomarker, Russia) and compared to 20 healthy donors, either without any fatigue (group H), or “healthy but tired” (group HTd) with episodes of fatigue related to job burnout not fitting the CFS/ME criteria. β2-glycoprotein-I autoantibodies were increased in CFS/ME patients, but not in healthy participants, that alludes the link between CFS/ME and antiphospholipid syndrome (APS) earlier suspected by Berg et al. (1999). In CFS/ME patients, an increase in levels of autoantibodies towards the non-specific components of tissue debris (double-stranded DNA, collagen) was shown. Both CFS and HTd subgroups had elevated level of autoantibodies against serotonin receptors, glial fibrillary acidic protein and protein S100. Only group V showed an elevation in the autoantibodies towards voltage-gated calcium channels, and only group D had elevated levels of dopamine-, glutamate- and GABA-receptor autoantibodies, as well as NF200-protein autoantibodies. Therefore, increased autoimmune reactions to the multiple neural antigens and to adrenal medullar antigen, but not to other tissue-specific somatic ones were revealed. An increase in autoantibody levels towards some neural and non-tissue-specific antigens strongly correlated with a CFS/ME diagnosis. Autoimmune reactions were described in all subtypes of the clinically significant chronic fatigue. Visceral complaints in CFS/ME patients may be secondary to the neuroendocrine involvement and autoimmune dysautonomia. CFS may be closely interrelated with antiphospholipid syndrome, that requires further study.
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47

Dibble, Joshua J., Simon J. McGrath, and Chris P. Ponting. "Genetic risk factors of ME/CFS: a critical review." Human Molecular Genetics 29, R1 (August 3, 2020): R117—R124. http://dx.doi.org/10.1093/hmg/ddaa169.

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Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem illness that lacks effective therapy and a biomedical understanding of its causes. Despite a prevalence of ∼0.2–0.4% and its high public health burden, and evidence that it has a heritable component, ME/CFS has not yet benefited from the advances in technology and analytical tools that have improved our understanding of many other complex diseases. Here we critically review existing evidence that genetic factors alter ME/CFS risk before concluding that most ME/CFS candidate gene associations are not replicated by the larger CFS cohort within the UK Biobank. Multiple genome-wide association studies of this cohort also have not yielded consistently significant associations. Ahead of upcoming larger genome-wide association studies, we discuss how these could generate new lines of enquiry into the DNA variants, genes and cell types that are causally involved in ME/CFS disease.
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Nunes, Jean M., Arneaux Kruger, Amy Proal, Douglas B. Kell, and Etheresia Pretorius. "The Occurrence of Hyperactivated Platelets and Fibrinaloid Microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)." Pharmaceuticals 15, no. 8 (July 27, 2022): 931. http://dx.doi.org/10.3390/ph15080931.

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We have previously demonstrated that platelet-poor plasma (PPP) obtained from patients with Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is characterized by a hypercoagulable state and contains hyperactivated platelets and considerable numbers of already-formed amyloid fibrin(ogen) or fibrinaloid microclots. Due to the substantial overlap in symptoms and etiology between Long COVID/PASC and ME/CFS, we investigated whether coagulopathies reflected in Long COVID/PASC—hypercoagulability, platelet hyperactivation, and fibrinaloid microclot formation—were present in individuals with ME/CFS and gender- and age-matched healthy controls. ME/CFS samples showed significant hypercoagulability as judged by thromboelastography of both whole blood and platelet-poor plasma. The area of plasma images containing fibrinaloid microclots was commonly more than 10-fold greater in untreated PPP from individuals with ME/CFS than in that of healthy controls. A similar difference was found when the plasma samples were treated with thrombin. Using fluorescently labelled PAC-1, which recognizes glycoprotein IIb/IIIa, and CD62P, which binds P-selectin, we observed hyperactivation of platelets in ME/CFS hematocrit samples. Using a quantitative scoring system, the ME/CFS platelets were found to have a mean spreading score of 2.72 ± 1.24 vs. 1.00 (activation with pseudopodia formation) for healthy controls. We conclude that ME/CFS is accompanied by substantial and measurable changes in coagulability, platelet hyperactivation, and fibrinaloid microclot formation. However, the fibrinaloid microclot load was not as great as was previously noted in Long COVID/PASC. Fibrinaloid microclots, in particular, may contribute to many ME/CFS symptoms, such as fatigue, seen in patients with ME/CFS, via the (temporary) blockage of microcapillaries and hence ischemia. Furthermore, fibrinaloid microclots might damage the endothelium. The discovery of these biomarkers represents an important development in ME/CFS research. It also points to possible uses for treatment strategies using known drugs and/or nutraceuticals that target systemic vascular pathology and endothelial inflammation.
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49

van Campen, C. (Linda) M. C., and Frans C. Visser. "Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol." Healthcare 9, no. 6 (June 5, 2021): 683. http://dx.doi.org/10.3390/healthcare9060683.

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(1) Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS )patients, using the gold standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls. No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfill the ME/CFS criteria in a male population and hypothesized a different pattern of response would be present during the 2nd day CPET. (2) Methods: We compared 25 male patients with ICF who had completed a 2-day CPET protocol to an age-/gender-matched group of 26 male ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities. (3) Results: Baseline characteristics for both groups were similar for age, body mass index (BMI), body surface area, (BSA), and disease duration. A significant difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs. zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001). ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload. (4) Conclusion: This study confirms that male ME/CFS patients have a reduction in exercise capacity in response to a second-day CPET. These results are similar to published results in male ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls.
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van Campen, C. (Linda) M. C., and Frans C. Visser. "Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol." Healthcare 9, no. 6 (June 5, 2021): 682. http://dx.doi.org/10.3390/healthcare9060682.

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Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients, using the golden standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls. No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfil the ME/CFS criteria in a male population and hypothesized a different pattern of response would be present during the 2nd day CPET. Methods: Fifty-one female patients with ICF completed a 2-day CPET protocol and were compared to an age/sex-matched group of 50 female ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities. Results: Baseline characteristics for both groups were similar for age, BMI, BSA, and disease duration. A significance difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001). ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload. Conclusion: This study confirms that female ME/CFS patients have a reduction in exercise capacity in response to a second day CPET. These results are similar to published results in female ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls.
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