User:In Vitro Infidelium/sandbox

CBT edit

Previously CBT has been considered as moderately effective for treating chronic fatigue syndrome. however a National Institutes of Health Pathways to Prevention Workshop stated that in respect of improving treatment options for ME/CFS that the modest benefit from cognitive behavioral therapy should be studied as an adjunct to other methods. The Centres for Disease Control advice on the treatment of ME/CFS [1] makes no reference to CBT while the National Institute for Health and Care Excellence [2] states that cognitive behavioural therapy (CBT) has sometimes been assumed to be a cure for ME/CFS, however, it should only be offered to support people who live with ME/CFS to manage their symptoms, improve their functioning and reduce the distress associated with having a chronic illness."

References in Pathophysiology sub article meeting MEDRS

Hempel S, Chambers D, Bagnall AM, Forbes C (July 2008). "Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies". Psychol Med 38 (7): 915–26. doi:10.1017/S0033291707001602. PMID 17892624.

• Reference not listed in IOM Report
• Reference used in Main article in Section: Risk Factors
• Sub Article text

The pathophysiology of chronic fatigue syndrome is unknown. Several potential causes for the development of chronic fatigue syndrome have been proposed, including neurological factors, psychological or psychosocial factors or influences, infections, immunological factors, endocrinal factors and genetic factors. Other, less-common theories have also been articulated. No clinically meaningful risk factor has been identified.[1]

A systematic scoping review included one retrospective study which reported that childhood trauma was significantly associated with the development of adult CFS, one prospective study which reported that genetics and self-reported stress sensitivity could contribute to CFS-like illness 25 years later, and one prospective study on fatigued employees which took measurements of current psychological distress and recent "shocking life events" (within last 12 months) at baseline and 12/24 month followup but did not find these to predict CFS-like caseness at 44 month followup.[1]

______________________________________________________

Goldstein DS, Robertson D, Esler M, Straus SE, Eisenhofer G (2002). "Dysautonomias: clinical disorders of the autonomic nervous system". Annals of Internal Medicine 137 (9): 753–63. doi:10.7326/0003-4819-137-9-200211050-00011. PMID 12416949.

• Reference not listed in IOM Report
• Reference used in Main article in Section: Pathophysiology
• Sub Article text

Dysautonomia is the disruption of the function of the autonomic nervous system (ANS) which controls many aspects of homeostasis. In CFS this is mostly orthostatic intolerance - the inability to stand up without feeling dizzy, faint, or nauseated.[10] ______________________________________________________

Margutti P, Delunardo F, Ortona E (2006). "Autoantibodies associated with psychiatric disorders". Curr Neurovasc Res 3 (2): 149–57. doi:10.2174/156720206776875894. PMID 16719797.

• Reference not listed in IOM Report
• Reference not used in Main article: CFS reference is speculative only
• Sub Article text

The brain and immune system influence each other, especially in the HPA axis and sympathetic nervous system. Mental stress causes suppression of the immune system by hormones such as cortisol and epinepherine. Release of stress hormones, caused by diseases outside the brain, can result in neurological symptoms due to the influence of stress hormones on neurotransmitters. Neuropsychiatric disorders present in CFS may be related to autoantibodies to neuronal or endothelial (interior surface of blood vessels) targets,[17]

______________________________________________________

Cho HJ, Hotopf M, Wessely S (2005). "The placebo response in the treatment of chronic fatigue syndrome: A systematic review and meta-analysis". Psychosom Med 67 (2): 301–13. doi:10.1097/01.psy.0000156969.76986.e0. PMID 15784798. Retrieved 2008-12-12. http://journals.lww.com/psychosomaticmedicine/Abstract/2005/03000/The_Placebo_Response_in_the_Treatment_of_Chronic.21.aspx

• Reference not listed in IOM Report
• Reference used in Main article in Section: Management
• Sub Article text

Some individuals with CFS firmly reject any psychological involvement and believe strongly that their condition has a physical cause.[22] ______________________________________________________

Prins JB, van der Meer JW, Bleijenberg G (2006). "Chronic fatigue syndrome". Lancet 367 (9507): 346–55. doi:10.1016/S0140-6736(06)68073-2. PMID 16443043. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)68073-2/fulltext

• Reference not listed in IOM Report
• Reference used in Main article in Section: Management
• Sub Article text

Neuroticism and introversion have previously been reported as risk factors for developing CFS.[26]

Some research suggests that CFS may be perpetuated when patients fixate on a physical cause for their symptoms or when exercise is avoided.[26][30

A lack of support, or the reinforcement of illness behavior by social networks, may be associated with delayed recovery for some patients.[26] ______________________________________________________

van Geelen SM, Sinnema G, Hermans HJ, Kuis W (January 2007). "Personality and chronic fatigue syndrome: Methodological and conceptual issues" (PDF). Clin Psychol Rev 27 (8): 885–903. doi:10.1016/j.cpr.2007.01.010. PMID 17350740.

• Reference not listed in IOM Report
• Reference not used in Main article: Not used main article - self negating
• Sub Article text

Although personality seems to play a role in CFS, it is difficult to draw general conclusions on the relation between personality and CFS. A systematic review of personality and CFS found an association with neuroticism, but stated that it was often accounted for by co-morbid depression and levels were similar to those in patients with other chronic diseases. It found no firm evidence for introversion.[27]

______________________________________________________

Natelson BH, Lange G (2002). "A status report on chronic fatigue syndrome". Environ. Health Perspect. 110 Suppl 4 (Suppl 4): 673–7. doi:10.1289/ehp.02110s4673. PMC 1241224. PMID 12194905.

• Reference not listed in IOM Report
• Reference used in Main article in Section: Pathophysiology
• Sub Article text

In response to a version of the cognitive behavioural model described in the book "Chronic Fatigue and Its Syndromes", the authors of a status report on CFS state, "Although this model may explain continued illness in some CFS patients, it certainly does not pertain to all CFS patients and is thus not too satisfactory."[29] -

However, although symptoms of CFS can occur after severe infection, strong data do not yet exist to support an infectious process in disease maintenance.[29 but they may not represent the entire picture[99] and some CFS experts doubt they are responsible.[29] ______________________________________________________

Deary V, Chalder T, Sharpe M (October 2007). "The cognitive behavioural model of medically unexplained symptoms: a theoretical and empirical review". Clin Psychol Rev 27 (7): 781–97. doi:10.1016/j.cpr.2007.07.002. PMID 17822818.

• Reference not listed in IOM Report
• Reference not used in Main article: Not used main article - not pathology, speculative and argumentative with stronger sources.

Sub Article text

Some research suggests that CFS may be perpetuated when patients fixate on a physical cause for their symptoms or when exercise is avoided.[26][30] ______________________________________________________

Whitehead WE, Palsson O, Jones KR (2002). "Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?". Gastroenterology 122 (4): 1140–56. doi:10.1053/gast.2002.32392. PMID 11910364.

• Reference not listed in IOM Report
• Reference not used in Main article: - not pathology, speculative and argumentative with stronger sources

Sub Article text

The presence of multiple comorbid disorders could be a marker for psychological influences on etiology.[33] ______________________________________________________

Klimas NG, Koneru AO (December 2007). "Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions". Curr Rheumatol Rep 9 (6): 482–7. doi:10.1007/s11926-007-0078-y. PMID 18177602.

• Reference not listed in IOM Report
• Reference not used in Main article: - speculative and argumentative with stronger sources

Sub Article text

or a factor in reactivation.[64]

______________________________________________________

Appel S, Chapman J, Shoenfeld Y (2007). "Infection and vaccination in chronic fatigue syndrome: myth or reality?". Autoimmunity 40 (1): 48–53. doi:10.1080/08916930701197273. PMID 17364497.

Reference not listed in IOM Report

• Reference used in Main article in Section: Pathophysiology
• Sub Article text

Immunological factors including a chronic activation or suppression of the immune system may contribute to symptoms of CFS,[98

High levels of Th2-type cytokines and the cells that make them are also found in CFS.

______________________________________________________

Cho HJ, Skowera A, Cleare A, Wessely S (2006). "Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology". Current Opinion in Psychiatry 19 (1): 67–73. doi:10.1097/01.yco.0000194370.40062.b0. PMID 16612182.

• Reference not listed in IOM Report
• Reference used in Main article in Section: Pathophysiology
• Sub Article text

Immunological factors including a chronic activation or suppression of the immune system may contribute to symptoms of CFS,[98] but they may not represent the entire picture[99]

A 2006 update in the journal Current Opinion in Psychiatry stated, "Recent advances in understanding the pathophysiology of chronic fatigue syndrome continue to demonstrate the involvement of the central nervous system. Hyperserotonergic state and hypoactivity of the hypothalamic-pituitary-adrenal axis (HPA axis) constitute other findings, but the question of whether these alterations are a cause or consequence of chronic fatigue syndrome still remains unanswered."[99] ______________________________________________________

Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G (February 2009). "Immunological aspects of chronic fatigue syndrome". Autoimmun Rev 8 (4): 287–91. doi:10.1016/j.autrev.2008.08.003. PMID 18801465.

• Reference not listed in IOM Report
• Reference used in Main article in Section: Pathophysiology
• Sub Article text

A 2009 review into the immunological aspects of CFS reported that patients do seem to have a specific immune dysfunction profile involving an enhanced baseline activation of lymphoid subsets but a suppression of certain immune responses, particularly Th1-driven ones such as the anti-viral and anti-tumour responses. Reported findings from various studies include an alteration in cytokine profile (high level of pro-inflammatory cytokines and dysregulation of anti-inflammatory cytokines), decreased function of natural killer (NK) cells, the presence of autoantibodies, reduced responses of T cells and abnormal activation of T lymphocyte subsets. The authors note that the immune alteration pattern of CFS "has a striking resemblance to the one caused by developmental immune toxicology", perhaps due to a combination of factors such as xenobiotics, infections and stress.[100] ______________________________________________________

Nijs J, Nees A, Paul L, De Kooning M, Ickmans K, Meeus M, Van Oosterwijck J (2014). "Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review" (PDF). Exerc Immunol Rev 20: 94–116. PMID 24974723. Retrieved 2015-06-19.

• Reference is listed in IOM Report
• Reference used in Main article in Section: Pathophysiology
• Sub Article text

A systematic literature review published in 2014 concluded persons diagnosed with the illness have an abnormal immune response to exercise. Specifically, complement products are increased, larger oxidative stress is generated along with reduced anti-oxidant immune response, and larger interleukin-10 and toll-like receptor 4 gene expression are seen verses healthy controls. Many of these immune responses correlate with the symptom of post-exertional malaise.[101] ______________________________________________________

Patarca-Montero R, Antoni M, Fletcher MA, Klimas NG (2001). "Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors". Appl Neuropsychol 8 (1): 51–64. doi:10.1207/S15324826AN0801_7. PMID 11388124.

• Reference not listed in IOM Report
• Reference not used in Main article: - covered by more recent resources via IOM refs

• Sub Article text

High levels of Th2-type cytokines and the cells that make them are also found in CFS. [104 Therapeutic alterations of cytokine expression patterns are being investigated.[104] In contrast, immunodeficiency disorders characterized by abnormal T-cell subset ratios, levels of immunoglobulins, and hypoallergic responses on the French Multitest have been reported in CFS.[104]

______________________________________________________

Papadopoulos, Andrew S.; Cleare, Anthony J. (27 September 2011). "Hypothalamic–pituitary–adrenal axis dysfunction in chronic fatigue syndrome". Nature Reviews Endocrinology 8 (1): 22–32. doi:10.1038/nrendo.2011.153. PMID 21946893.

• Reference not listed in IOM Report
• Reference used in Main article in Section: Pathophysiology
• Sub Article text

The hypothalamic-pituitary-adrenal axis (HPA axis) controls levels of hormones such as cortisol and is activated in a circadian rhythm and modulated by factors such as stress, digestion or illness. It is important in regulating energy metabolism, the immune system, stress responses and inflammation in the body.

A substantial body of evidence points to the following findings in CFS patients: mild hypocortisolism, an attenuated diurnal variation in cortisol, enhanced cortisol negative feedback, and a blunted HPA axis responsiveness. Women are more likely to exhibit hypocortisolism than men, as well as those who are depressed, inactive or not taking medication. The findings are similar to those seen in atypical depression. Glucocorticoid and mineralocorticoid receptor hypersensitivity appears to be the most probable explanation for the enhanced HPA axis negative feedback. Patients who undergo treatment such as CBT show reversal of the HPA axis changes. Steroid replacement therapy is not recommended due to lack of evidence and possible adverse effects.[108] ______________________________________________________

Cleare AJ (April 2003). "The neuroendocrinology of chronic fatigue syndrome.". Endocr Rev 24 (2): 236–52. PMID 12700181.

• Reference not listed in IOM Report
• Reference not used in Main article: - negated by more recent resources via IOM refs
• Sub Article text

It has been debated whether these disturbances would play a primary role in the pathogenesis of CFS, but prospective evidence suggests that the HPA axis is not an important factor during the early stages of CFS, although it has been hypothesized that it might play a role in exacerbating or perpetuating symptoms later on in the course of the illness .[109][110][111]

______________________________________________________

Van Den Eede F, Moorkens G, Van Houdenhove B, Cosyns P, Claes SJ (2007). "Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome." (PDF). Neuropsychobiology 55 (2): 112–20. doi:10.1159/000104468. PMID 17596739.

• Reference not listed in IOM Report – although 2014 article by these authors is.
• Reference used in Main article in Section: Pathophysiology
• Sub Article text

It has been debated whether these disturbances would play a primary role in the pathogenesis of CFS, but prospective evidence suggests that the HPA axis is not an important factor during the early stages of CFS, although it has been hypothesized that it might play a role in exacerbating or perpetuating symptoms later on in the course of the illness .[109][110][111]

______________________________________________________

Cleare AJ (March 2004). "The HPA axis and the genesis of chronic fatigue syndrome.". Trends Endocrinol Metab 15 (2): 55–9. doi:10.1016/j.tem.2003.12.002. PMID 15036250.

• Reference not listed in IOM Report
• Reference not used in Main article: - superceded by more recent resources via IOM refs
• Sub Article text

It has been debated whether these disturbances would play a primary role in the pathogenesis of CFS, but prospective evidence suggests that the HPA axis is not an important factor during the early stages of CFS, although it has been hypothesized that it might play a role in exacerbating or perpetuating symptoms later on in the course of the illness .[109][110][111]

______________________________________________________

Tak LM, Cleare AJ, Ormel J, Manoharan A, Kok IC, Wessely S, Rosmalen JG (May 2011). "Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders.". Biol Psychol 87 (2): 183–94. doi:10.1016/j.biopsycho.2011.02.002. PMID 21315796.

• Reference not listed in IOM Report
• Reference used in Main article in Section: Pathophysiology
• Sub Article text

A 2011 meta-analysis reported a small but statistically significant hypocortisolism in CFS.[112] ______________________________________________________

Molecular Epidemiology Program". National Center for Infectious Diseases. 2005-07-25 .

• Reference not listed in IOM Report
• Reference not used in Main article: dead resource
• Sub Article text

CFS-related abnormalities in gene expression have been studied.[42]

______________________________________________________

Wyller VB (2007). "The chronic fatigue syndrome--an update". Acta Neurol. Scand., Suppl. 187: 7–14. doi:10.1111/j.1600-0404.2007.00840.x. PMID 17419822.

Reference not listed in IOM Report

Reference not used in Main article: speculative and unsupported

• Sub Article text

*A 2007 review stated that certain genetic polymorphisms might be regarded as predisposing factors.[126

Nosological Developments

The medical classification (nosology) of CFS is subject to ongoing research which is variously focussed upon epidemiology, upon clinical description and upon the establishment of biomarkers.

Epidemiology

Recent work o the epidemiology of CFS is limited to a single study on prevalence in a developing society.

Study	Reference	Authors	URL
Comparative epidemiology of chronic fatigue syndrome in Brazilian and British primary care: prevalence and recognition	The British Journal of Psychiatry (2009) 194: 117-122 doi:10.1192/bjp.bp.108.051813	Hyong Jin Cho et al	[3]

Clinical Descriptions

In addition to the operative descriptions employed by national health organisations such as the CDC and NICE, research has produced other clinical descriptions which as yet have not met with general medical consensus:

Study	Reference	Authors	URL
Immunological aspects of chronic fatigue syndrome	doi:10.1016/j.autrev.2008.08.003	Lorussoa et al	[4]
Conceptual Model for Physical Therapist Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis	doi:10.2522/?ptj.20090047 Physical Therapy April 2010 vol. 90 no. 4 602-614	Davenport et al	[5]
Neuropsychological functioning, illness perception, mood and quality of life in chronic fatigue syndrome, autoimmune thyroid disease and healthy participants	Psychological Medicine (2009), 39, 1567–1576. doi:10.1017/S0033291708004960	Dickson et al	[6]
Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes	J Clin Pathol2008;61:730-739 doi:10.1136/jcp.2007.053553	Kerr et al	[7]
Can sustained arousal explain the Chronic Fatigue Syndrome?	Behavioral and Brain Functions 2009, 5:10 doi:10.1186/1744-9081-5-10	Wyller et al	[8]
Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function	Clinical Science (2010) 118, (125–135)	Hurwitz et al	[9]
Chronic fatigue syndrome: aetiology, diagnosis and treatment	BMC Psychiatry 2009, 9(Suppl 1):S1 doi:10.1186/1471-244X-9-S1-S1	Fernández et al	[10]
Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome	doi:10.1111/j.1475-097X.2008.00822.x Clinical Physiology and Functional Imaging	Neary et al	[11]
Myalgic encephalomyelitis: International Consensus Criteria.	J Intern Med. 2011 Oct;270(4):327-38. doi:10.1111/j.1365-2796.2011.02428.x	Carruthers BM et al	[12]

Biomarkers

Successful identification of biomarkers would impact upon future directions in both the epidemiology and in the clinical description of CFS. There is no current general medical consensus on CFS biomarkers however the following have been proposed:

Biomarker	Study	Reference	Author	URL
ACCN3 (ASIC3	Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects	doi:10.1016/j.jpain.2009.06.003	Light et al	[13]
CD8	Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis	Journal of Translational Medicine 2011, 9:81	Brenu et al	[14]
CD26	Biomarkers in Chronic Fatigue Syndrome: Evaluation of Natural Killer Cell Function and Dipeptidyl Peptidase IV/CD26	PLoS ONE 5(5): e10817. doi:10.1371/journal.pone.0010817	Fletcher et al	[15]
Cortisol	Alterations in Diurnal Salivary Cortisol Rhythm in a Population-Based Sample of Cases With Chronic Fatigue Syndrome	Psychosomatic Medicine April 1, 2008 vol. 70 no. 3 298-305 doi:10.1097/?PSY.0b013e3181651025	James et al	[16]
FoxP3	Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis	Journal of Translational Medicine 2011, 9:81	Brenu et al	[17]
IFN-g	Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis	Journal of Translational Medicine 2011, 9:81	Brenu et al	[18]
IL1	Plasma cytokines in women with chronic fatigue syndrome	Journal of Translational Medicine 2009, 7:96 doi:10.1186/1479-5876-7-96,	Fletcher et al,	[19]
IL1	Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-a, PMN-elastase, lysozyme and neopterin	doi:10.1016/j.jad.2011.09.004 |	Maesa et al	[20]
IL4	Plasma cytokines in women with chronic fatigue syndrome	Journal of Translational Medicine 2009, 7:96 doi:10.1186/1479-5876-7-96	Fletcher et al	[21]
IL5	Plasma cytokines in women with chronic fatigue syndrome	Journal of Translational Medicine 2009, 7:96 doi:10.1186/1479-5876-7-96,	Fletcher et al,	[22]
IL6	Gene Expression Subtypes in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis	The Journal of Infectious Diseases 2008; 197:1171– 84 doi:10.1086/533453	Beverly et al	[23]
IL10	Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects	doi:10.1016/j.jpain.2009.06.003	Light et al	[24]
IL10	Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis	Journal of Translational Medicine 2011, 9:81	Brenu et al	[25]
Lipoteichoic acid	Plasma cytokines in women with chronic fatigue syndrome	Journal of Translational Medicine 2009, 7:96 doi:10.1186/1479-5876-7-96,	Fletcher et al,	[26]
Lysozyme	Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-a, PMN-elastase, lysozyme and neopterin	doi:10.1016/j.jad.2011.09.004 |	Maesa et al	[27]
Na-K-Cl cotransporter(NKCC)	Biomarkers in Chronic Fatigue Syndrome: Evaluation of Natural Killer Cell Function and Dipeptidyl Peptidase IV/CD26	PLoS ONE 5(5): e10817. doi:10.1371/journal.pone.0010817	Fletcher et al	[28]
Na-K-Cl cotransporter(NKCC)	Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis	Journal of Translational Medicine 2011, 9:81	Brenu et al	[29]
Neopterin	Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-a, PMN-elastase, lysozyme and neopterin	doi:10.1016/j.jad.2011.09.004 |	Maesa et al	[30]
P2RX4	Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects	doi:10.1016/j.jpain.2009.06.003	Light et al	[31]
P2RX5	Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects	doi:10.1016/j.jpain.2009.06.003	Light et al	[32]
Neuropeptide Y	Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome	Behavioral and Brain Functions 2010, 6:76	Fletcher et al	[33]
Plasma peroxides	Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).	Med Sci Monit. 2011 Apr;17(4):SC11-5.	Maes et al	[34]
Neutrophil elastase	Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-a, PMN-elastase, lysozyme and neopterin	doi:10.1016/j.jad.2011.09.004 |	Maesa et al	[35]
LDL	Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).	Med Sci Monit. 2011 Apr;17(4):SC11-5.	Maes et al	[36]
TNFa	Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis	Journal of Translational Medicine 2011, 9:81	Brenu et al	[37]
Toll-like receptor	Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects	doi:10.1016/j.jpain.2009.06.003	Light et al	[38]