Identification of actin network proteins, talin-1 & filamin-A, in circulating extracellular vesicles as blood biomarkers for human ME/CFS

Posted on 12/09/2019 by wames

Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/ chronic fatigue syndrome, by Akiko Eguchi, Sanae Fukuda, Hirohiko Kuratsune, Junzo Nojima, Yasuhito Nakatomi, Yasuyoshi Watanabe, Ariel E Feldstein, in Brain, Behavior, and Immunity November 2019 [ https://doi.org/10.1016/j.bbi.2019.11.015]

 

Highlights

  • Circulating EV number was increased in ME/CFS patients correlating to CRP and BAP.
  • AUROC for circulating EVs was 0.802 allowing correct diagnosis in 90–94% of ME/CFS.
  • Proteins in actin skeletal regulation and EB virus infection were identified in ME/CFS patients.
  • Talin-1, filamin-A and 14-3-3 proteins were the most abundant proteins representing highly specific ME/CFS.

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, debilitating disorder with a wide spectrum of symptoms, including pain, depression, and neurocognitive deterioration. Over 17 million people around the world have ME/CFS, predominantly women with peak onset at 30–50 years.

Given the wide spectrum of symptoms and unclear etiology, specific biomarkers for diagnosis and stratification of ME/CFS are lacking. Here we show that actin network proteins in circulating extracellular vesicles (EVs) offer specific non-invasive biomarkers for ME/CFS.

We found that circulating EVs were significantly increased in ME/CFS patients correlating to C-reactive protein, as well as biological antioxidant potential. Area under the receiver operating characteristic curve for circulating EVs was 0.80, allowing correct diagnosis in 90–94% of ME/CFS cases.

From two independent proteomic analyses using circulating EVs from ME/CFS, healthy controls, idiopathic chronic fatigue, and depression, proteins identified from ME/CFS patients are involved in focal adhesion, actin skeletal regulation, PI3K-Akt signaling pathway, and Epstein-Barr virus infection. In particular, talin-1, filamin-A, and 14-3-3 family proteins were the most abundant proteins, representing highly specific ME/CFS biomarkers.

Our results identified circulating EV number and EV-specific proteins as novel biomarkers for diagnosing ME/CFS, providing important information on the pathogenic mechanisms of ME/CFS.

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Is CFS related to a crash of the brain attention mechanism – hypervigilance correlates with fatigue & pain scales among individuals with CFS

Posted on 12/09/2019 by wames

Is Chronic fatigue syndrom (CFS) related to a crash of the brain attention mechanism – Hypervigilance correlates with fatigue and pain scales among individuals with CFS, by Camilla Marylene Minani. Master thesis, Norwegian University of Science and Technology, 2019.

 

Research abstract:

Chronic fatigue syndrome (CFS) is a disabling condition. About 70–85% of those affected attribute their daily dysfunction to reduced cognitive abilities and muscle pains in various parts of the body.

Neuroimaging studies point to structural and functional abnormalities of the central nervous system, with no relationship to the reported fatigue and pain scales. This complicates the development of the diagnosis. Evidence shows that mental fatigue and pain affect the efficiency of cognitive control.

Event-related potentials (ERPs) recorded from the human scalp provide essential information about how the human brain normally processes information and about how this processing becomes abnormal in neurological or psychiatric disorders.

Method: A visual continuous performance task (vCPT) requires sustained attention to respond to relevant visual cues and refrain from responding to irrelevant stimuli. In this study, after completing the Chalder and pain inventory tests, a vCPT test was administered to 42 individuals complying with the Fukuda criteria of CFS diagnosis.

Event-related potentials (ERPs), which show direct brain response to stimuli, were retrieved and compared to a database of health 102 health individuals. A correlation and regression analysis of the ERPs was then conducted and compared to self-rated fatigue and pain inventory tests.

Results and Discussion: Compared to the database, an enhanced P3cue component reflected hyper-vigilance amongst unexplained chronic fatigue patients along with delayed motor response and reduced error-detection resources, indicating abnormalities in executive function. This suggests that CFS could be related to central sensitisation due to long-term stress exposure.

Full paper not available

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The effect of curcumin in patients with CFS/ME

Posted on 12/06/2019 by wames

The effect of curcumin in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis disparate responses in different disease severities, by C (Linda) MC van Campen and Frans C Visser in Pharmacovigil and Pharmacoepi  Vol 2 Issue 1, pages 6, Nov 19, 2019

 

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is a chronic and often disabling disease. Although the exact pathophysiological mechanism of ME/CFS is unknown, immunological abnormalities may play an important role.

Curcumin is an herb with powerful anti-oxidative and anti-inflammatory properties. Therefore, we hypothesized that curcumin would have favorable effects on symptomatology in ME/CFS patients.

In an open trial among 65 ME/CFS participants, 6 stopped the use of curcumin because of side effects and 8 did not complete the end of study questionnaire. Before and 8 weeks after the use of curcumin complexed with phosphatidyl choline-, 500 mg bid, participants completed the CDC inventory for assessment of Chronic Fatigue Syndrome. The CDC questions (n=19) were scored and divided into 2 parts: the first being specific for CFS complaints (n=9), the second being scores of less specific symptoms (n=10); denoted as CDC other score.

Results showed that 8 weeks of curcumin significantly decreased the CDC CFS-related symptom scores and CDC other scores, especially in patients with mild disease.

Conclusion: in this open-labeled study 8 week curcumin use in a phosphatidyl choline complex reduced ME/CFS symptomatology, especially in patients with mild disease severity.

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Prevalence & treatment of CFS/ME & co-morbid severe health anxiety

Posted on 12/05/2019 by wames

Prevalence and treatment of Chronic Fatigue Syndrome/ME and co-morbid severe health Anxiety, by Jolene Daniels, Paul Salkovskis, Hannah Parker  in Journal of the International Neuropsychological Society, Nov 2019

 

Research abstract:

Background: Chronic Fatigue Syndrome/ME (CFS/ME) is a debilitating condition that affects 0.2–0.4% of the population.

Health focussed anxiety is common across medical conditions, and may be relevant in CFS/ME. This study sought to identify the prevalence and impact of health anxiety (HA) in CFS/ME and evaluate the effectiveness of Cognitive Behavioural Therapy for HA in CFS/ME.

Method: Cross sectional questionnaire methods and case-series design were used to achieve study aims.

Results: Analysis indicated that 41.9% of the CFS/ME clinic sample experienced threshold levels of health anxiety, which was associated with elevated symptom severity across several dimensions.  Stepwise multiple regression indicated physical functioning and depression accounted for 23.8% of variance in fatigue; depression, fatigue and HA, accounted for 32.9% of variance in physical functioning. Large effect sizes and clinically significant changes were generated in the treatment study.

Conclusion: HA is common in CFS/ME and likely to exacerbate fatigue and physical functioning. This study identifies HA as an important target for treatment, trial findings should be further replicated on a larger scale.

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Modification of immunological parameters, oxidative stress markers, mood symptoms, & well-being status in CFS patients after probiotic intake

Posted on 12/04/2019 by wames

Modification of immunological parameters, oxidative stress markers, mood symptoms, and well-being status in CFS patients after probiotic intake: observations from a pilot study, by Letizia Venturini, Sara Bacchi, Enrica Capelli, Lorenzo Lorusso, Giovanni Ricevuti, and Chiara Cusa in Oxidative Medicine and Cellular Longevity Vol 2019, 10 pages, 23 November 2019 [https://doi.org/10.1155/2019/1684198]

 

Research abstract:

The present study discusses about the effects of a combination of probiotics able to stimulate the immune system of patients affected by Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

To this purpose, patients diagnosed according to Fukuda’s criteria and treated with probiotics were analyzed by means of clinical and laboratory evaluations, before and after probiotic administrations. Probiotics were selected considering the possible pathogenic mechanisms of ME/CFS syndrome, which has been associated with an impaired immune response, dysregulation of Th1/Th2 ratio, and high oxidative stress with exhaustion of antioxidant reserve due to severe mitochondrial dysfunction.

Immune and oxidative dysfunction could be related with the gastrointestinal (GI) chronic low-grade inflammation in the lamina propria and intestinal mucosal surface associated with dysbiosis, leaky gut, bacterial translocation, and immune and oxidative dysfunction.

Literature data demonstrate that bacterial species are able to modulate the functions of the immune and oxidative systems and that the administration of some probiotics can improve mucosal barrier function, modulating the release of proinflammatory cytokines, in CFS/ME patients.

This study represents a preliminary investigation to verifying the safety and efficacy of a certain combination of probiotics in CFS/ME patients.

The results suggest that probiotics can modify the well-being status as well as inflammatory and oxidative indexes in CFS/ME patients. No adverse effects were observed except for one patient, which displayed a flare-up of symptoms, although all inflammatory parameters (i.e., cytokines, fecal calprotectin, ESR, and immunoglobulins) were reduced after probiotic intake. The reactivation of fatigue symptoms in this patient, whose clinical history reported the onset of CFS/ME following mononucleosis, could be related to an abnormal stimulation of the immune system as suggested by a recent study describing an exaggerated immune activation associated with chronic fatigue.

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Understanding neuromuscular disorders in CFS

Posted on 12/03/2019 by wames

Understanding neuromuscular disorders in chronic fatigue syndrome, by Yves Jammes, Frédérique Retornaz in F1000Research 2019, 8:2020 (https://doi.org/10.12688/f1000research.18660.1)

 

Review abstract:

Muscle failure has been demonstrated in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Neurophysiological tools demonstrate the existence of both central and peripheral fatigue in these patients. Central fatigue is deduced from the reduced amplitude of myopotentials evoked by transcranial magnetic stimulation of the motor cortex as well as by the muscle response to interpolated twitches during sustained fatiguing efforts.

An impaired muscle membrane conduction velocity assessed by the reduced amplitude and lengthened duration of myopotentials evoked by direct muscle stimulation is the defining feature of peripheral fatigue.

Some patients with ME/CFS show an increased oxidative stress response to exercise. The formation of lipid hydroperoxides in the sarcolemma, which alters ionic fluxes, could explain the reduction of muscle membrane excitability and potassium outflow often measured in these patients.

In patients with ME/CFS, the formation of heat shock proteins (HSPs) is also reduced. Because HSPs protect muscle cells against the deleterious effects of reactive oxygen species, the lack of their production could explain the augmented oxidative stress and the consecutive alterations of myopotentials which could open a way for future treatment of ME/CFS.

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‘The real me shining through M.E.’: visualizing masculinity & identity threat in men with ME/CFS

Posted on 12/02/2019 by wames

‘The real me shining through M.E.’: Visualizing masculinity and identity threat in men with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome using photovoice and IPA, by Lucina Wilde, Kerry Quincey, I.R Williamson in Psychology of Men & Masculinity, April 30, 2019

 

Research abstract:

Phenomenological research in the context of Myalgic Encephalomyelitis (M.E.) or Chronic Fatigue Syndrome (CFS) has predominantly explored women’s accounts. Due to the paucity of research highlighting men’s experiences of living with M.E./CFS, the aim of this research was to explore their visual and verbal accounts to gain a more in-depth understanding of how they make sense of their diagnosis and dual identity as a man with a stigmatized and often misunderstood chronic illness.

Working within a critical health psychology framework the study utilised a phenomenological approach and an adapted version of Photovoice to gather and interrogate self-authored photographs and interview accounts from ten men living with M.E./CFS.

An Interpretative Phenomenological Analysis of the integrated visual and verbal data led to the development of three themes:

  • ‘Loss of Masculine Identity as Man with M.E./CFS’,
  • ‘Marginalization attached to M.E./CFS and Masculinity’ and
  • ‘Coping with Dual Identity by Adjustments, Assimilation and Acceptance’.

The findings show how men with CFS cope with identity threat across personal, social, and cultural contexts, whilst making adaptations in their perceptions and performances of masculinity. We argue that participant-authored photographs could be used by researchers, activists and practitioners to facilitate increased understanding of and support for men with M.E./CFS.

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CFS/ME & FM: the foundation of a relationship

Posted on 11/28/2019 by wames

Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and Fibromyalgia (FM): the foundation of a relationship, by Pamela G Mckay, Colin R Martin, Helen Walker, Mick Fleming in British Journal of Pain Oct 2019 [doi.org/10.1177/2049463719875164]

Research abstract:

Introduction:
Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and fibromyalgia (FM) are both debilitating syndromes with complex polysymptomatology. Early research infers that a relationship may exist even though the diagnosis provided may influence the management trajectory. In the absence of a diagnostic test and treatment, this study aims to confirm the symptoms and their severity, which may infer a relationship and influence future research.

Method:
A quasi-experimental design was utilised, using Internet-based self-assessment questionnaires focusing on nine symptom areas: criteria, pain, sleep, fatigue, anxiety and depression, health-related quality of life, self-esteem and locus of control.

The questionnaires used for data collection are as follows: the American Centre for Disease Control and Prevention Symptom Inventory for CFS/ME (American CDC Symptom Inventory); the American College of Rheumatology (ACR) Criteria for FM; Fibromyalgia Impact Questionnaire (FIQ); McGill Pain Questionnaire (MPQ); Multidimensional Fatigue Inventory (MFI); Pittsburgh Sleep Quality Index (PSQI); Health-Related Quality of Life SF-36 V2 (HRQoL SF-36 V2); Hospital Anxiety and Depression Scale (HADS); Multidimensional Health Locus of Control (MHLOC) and the Rosenberg Self-Esteem Scale (RSES).

Setting and participants:
Participants were recruited from two distinct community groups, namely CFS/ME (n = 101) and FM (n = 107). Participants were male and female aged 17 (CFS/ME mean age 45.5 years; FM mean age 47.2 years).

Results:
All participants in the CFS/ME and FM groups satisfied the requirements of their individual criteria. Results confirmed that both groups experienced the debilitating symptoms measured, with the exception of anxiety and depression, impacting on their quality of life. Results suggest a relationship between CFS/ME and FM, indicating the requirement for future research.

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Low-dose naltrexone in the treatment of ME/CFS

Posted on 11/27/2019 by wames

Low-dose naltrexone in the treatment of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS), by Olli Polo, Pia Pesonen, Essi Tuominen in Fatigue: Biomedicine, Health & Behavior Nov 19, 2019 [doi/full/10.1080/21641846.2019.1692770]

 

Research abstract:

Background:
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a common medical condition that limits physical and cognitive functions, with no known effective medical treatment.

Methods:
We report on the safety and effectiveness data accumulated in clinical practice when treating ME/CFS with low-dose naltrexone (LDN, 3.0-4.5 mg/day). The medical records from 218 patients who received ar diagnosis of ME/CFS and LDN treatment during 2010-2014 were retrospectively analyzed.

Results:
Outcome data were available in 92.2% of patients with an average follow-up time of 1.7 years. A positive treatment response to LDN was reported by 73.9% of the patients. Most patients experienced improved vigilance/alertness and improved physical and cognitive performance. Some patients reported less pain and fever, while 18.3% of patients did not report any treatment response to LDN. Mild adverse effects (insomnia, nausea) were common at the beginning of the treatment. Neither severe adverse effects nor long-term adverse symptoms were reported.

Conclusions:
The high frequency of treatment response and good safety profile observed in this retrospective open label study could prompt prospective controlled studies to confirm the feasibility of LDN in alleviating ME/CFS symptoms.

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Relationship satisfaction, communication self-efficacy & CFS

Posted on 11/26/2019 by wames

Relationship satisfaction, communication self-efficacy, and chronic fatigue syndrome-related fatigue, by Sara F Milrad, Daniel L Hall, Devika R Jutagir, Emily G Lattie, Sara J Czaja, Dolores M Perdomo, Gail Ironson, Brian D Doss, Armando Mendez, Mary Ann Fletcher, Nancy Klimas, Michael H Antonia in Social Science & Medicine Vol 237, Sep 2019 [https://doi.org/10.1016/j.socscimed.2019.112392]

 

Research highlights:

  • Relationship satisfaction and depression can impact CFS-related fatigue.
  • Patient symptom disclosure satisfaction (PSDS) is a hypothesized intermediate.
  • Depression and PSDS were examined as intermediary variables of this relationship.
  • Relationship satisfaction was related to fatigue severity via depression and PSDS.
  • This underscores the importance of considering these factors in the context of CFS.

Research abstract:

Rationale
Relationship dissatisfaction has been linked with worse health outcomes in many patient populations, though the mechanism(s) underlying this effect are unclear. Among patients with chronic fatigue syndrome (CFS) and their partners, there is evidence for a bi-directional association between poorer relationship satisfaction and the severity of CFS-related fatigue.

Objective
Here, we hypothesized that relationship dissatisfaction negatively impacts fatigue severity through greater depression and less patient satisfaction about communication about symptoms to partners.

Method
Baseline data were drawn from diagnosed CFS patients (N = 150) participating in a trial testing the efficacy of a stress management intervention. Data derived from fatigue severity (Fatigue Symptom Index, FSI), depression (Center for Epidemiologic Survey-Depression, CES-D), relationship quality (Dyadic Adjustment Scale, DAS) and communication satisfaction (Patient Symptom Disclosure Satisfaction, PSDS) questionnaires were used for bootstrapped indirect effect analyses using parallel mediation structural equation modeling in Mplus (v8). Age and BMI were entered as covariates.

Results
Greater relationship satisfaction predicted greater communication satisfaction (p < 0.01) and lower CES-D scores (p < 0.01), which in turn were each significantly related to greater fatigue severity (p < 0.05). Tests of the indirect paths indicated that relationship satisfaction had a significant effect on fatigue severity through both constructs, but primarily via depression. There was no direct association between relationship satisfaction and fatigue severity after the intermediate variables (depression, communication satisfaction) were included in the model.

Conclusion
Results highlight the importance of considering depression and communication-related factors when examining the effects of relationship satisfaction on CFS symptoms such as fatigue. Further mechanism-based, longitudinal research might identify relationship-related mediating variables that can be targeted therapeutically.

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