Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Chronic Fatigue Syndrome: HELP
Articles by Donald R. Staines
Based on 48 articles published since 2010
(Why 48 articles?)
||||

Between 2010 and 2020, D. Staines wrote the following 48 articles about Fatigue Syndrome, Chronic.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis/chronic fatigue syndrome. 2019

Eaton-Fitch, Natalie / du Preez, Stanley / Cabanas, Hélène / Staines, Donald / Marshall-Gradisnik, Sonya. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · School of Medical Science, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia. · School of Medicine, Griffith University, Gold Coast, Australia. · School of Medical Science, Griffith University, Gold Coast, Australia. ·Syst Rev · Pubmed #31727160.

ABSTRACT: BACKGROUND: Compromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Other outcomes evaluated in NK cells of ME/CFS patients, however, remain equivocal. The aim of this study was to conduct a systematic review of the literature regarding NK cell phenotype, receptor expression, cytokine production and cytotoxicity in ME/CFS patients and determine the appropriateness as a model for ME/CFS. METHODS: Medline (EBSCOHost), Scopus, EMBASE and PubMed databases were systematically searched to source relevant papers published between 1994 and March 2018. This review included studies examining NK cells' features in ME/CFS patients compared with HC following administration of specific inclusion and exclusion criteria. Secondary outcomes included genetic analysis in isolated NK cells or quality of life assessment. Quality assessment was completed using the Downs and Black checklist in addition to The Joanna Briggs Institute checklist. RESULTS: Seventeen eligible publications were included in this review. All studies were observational case control studies. Of these, 11 investigated NK cell cytotoxicity, 14 investigated NK cell phenotype and receptor profiles, three examined NK cell cytokine production, six investigated NK cell lytic protein levels and four investigated NK cell degranulation. Impaired NK cell cytotoxicity remained the most consistent immunological report across all publications. Other outcomes investigated differed between studies. CONCLUSION: A consistent finding among all papers included in this review was impaired NK cell cytotoxicity, suggesting that it is a reliable and appropriate cellular model for continued research in ME/CFS patients. Aberrations in NK cell lytic protein levels were also reported. Although additional research is recommended, current research provides a foundation for subsequent investigations. It is possible that NK cell abnormalities can be used to characterise a subset of ME/CFS due to the heterogeneity of both the illness itself and findings between studies investigating specific features of NK function.

2 Review Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. 2017

Campagnolo, N / Johnston, S / Collatz, A / Staines, D / Marshall-Gradisnik, S. ·School of Medical Science, Griffith University, Gold Coast, QLD, Australia. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia. ·J Hum Nutr Diet · Pubmed #28111818.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such fatigue and quality of life. We reviewed and discussed the evidence for nutritional interventions that may assist in alleviating symptoms of CFS/ME. METHODS: Medline, Cinahl and Scopus were systematically searched from 1994 to May 2016. All studies on nutrition intervention were included where CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing). RESULTS: Seventeen studies were included that meet the inclusion criteria. Of these, 14 different interventions were investigated on study outcomes. Many studies did not show therapeutic benefit on CFS/ME. Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10. CONCLUSIONS: This review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms. Studies were limited by the number of studies investigating the interventions, small sample sizes, study duration, variety of instruments used, and studies not reporting dietary intake method. Further research is warranted in homogeneous CFS/ME populations.

3 Review A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. 2016

Collatz, Ansel / Johnston, Samantha C / Staines, Donald R / Marshall-Gradisnik, Sonya M. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia; School of Medical Sciences, Griffith University, Gold Coast, QLD, Australia. ·Clin Ther · Pubmed #27229907.

ABSTRACT: PURPOSE: The pathogenesis of chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is complex and remains poorly understood. Evidence regarding the use of drug therapies in CFS/ME is currently limited and conflicting. The aim of this systematic review was to examine the existing evidence on the efficacy of drug therapies and determine whether any can be recommended for patients with CFS/ME. METHODS: MEDLINE, EMBASE, and PubMed databases were searched from the start of their records to March 2016 to identify relevant studies. Randomized controlled trials focusing solely on drug therapy to alleviate and/or eliminate chronic fatigue symptoms were included in the review. Any trials that considered graded exercise therapy, cognitive behavior therapy, adaptive pacing, or any other nonpharmaceutical treatment plans were excluded. The inclusion criteria were examined to ensure that study participants met specific CFS/ME diagnostic criteria. Study size, intervention, and end point outcome domains were summarized. FINDINGS: A total of 1039 studies were identified with the search terms; 26 studies met all the criteria and were considered suitable for review. Three different diagnostic criteria were identified: the Holmes criteria, International Consensus Criteria, and the Fukuda criteria. Primary outcomes were identified as fatigue, pain, mood, neurocognitive dysfunction and sleep quality, symptom severity, functional status, and well-being or overall health status. Twenty pharmaceutical classes were trialed. Ten medications were shown to be slightly to moderately effective in their respective study groups (P < 0.05). IMPLICATIONS: These findings indicate that no universal pharmaceutical treatment can be recommended. The unknown etiology of CFS/ME, and complications arising from its heterogeneous nature, contributes to the lack of clear evidence for pharmaceutical interventions. However, patients report using a large number and variety of medications. This finding highlights the need for trials with clearly defined CFS/ME cohorts. Trials based on more specific criteria such as the International Consensus Criteria are recommended to identify specific subgroups of patients in whom treatments may be beneficial.

4 Review Severity Scales for Use in Primary Health Care to Assess Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. 2016

Hardcastle, Sharni Lee / Brenu, Ekua Weba / Johnston, Samantha / Staines, Donald / Marshall-Gradisnik, Sonya. ·a National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Centre , School of Medical Science, Griffith University , Gold Coast , Queensland , Australia. · b National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Centre, School of Medical Science , Griffith University; and Queensland Health, Gold Coast Public Health Unit , Gold Coast , Queensland , Australia. ·Health Care Women Int · Pubmed #25315708.

ABSTRACT: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a physical and cognitive disabling illness, characterized by severe fatigue and a range of physiological symptoms, that primarily affects women. The immense variation in clinical presentation suggests differences in severity based on symptomology and physical and cognitive functional capacities. In this article, we examine a number of severity scales used in assessing severity of patients with CFS/ME and the clinical aspects of CFS/ME severity subgroups. The use of severity scales may be important in CFS/ME because it permits the establishment of subgroups that may improve accuracy in both clinical and research settings.

5 Review The adoption of chronic fatigue syndrome/myalgic encephalomyelitis case definitions to assess prevalence: a systematic review. 2013

Johnston, Samantha / Brenu, Ekua W / Staines, Donald R / Marshall-Gradisnik, Sonya. ·Griffith Health Institute, School of Medical Sciences, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Parklands, QLD, Australia. samantha.johnston3@griffithuni.edu.au ·Ann Epidemiol · Pubmed #23683713.

ABSTRACT: PURPOSE: Prevalence estimates have been based on several case definitions of chronic fatigue syndrome (CFS). The purpose of this work is to provide a rigorous overview of their application in prevalence research. METHODS: A systematic review of primary studies reporting the prevalence of CFS since 1990 was conducted. Studies were summarized according to study design, prevalence estimates, and case definition used to ascertain cases. RESULTS: Thirty-one studies were retrieved, and eight different case definitions were found. Early estimates of CFS prevalence were based on the 1988 Centers for Disease Control and Prevention, Australian, and Oxford. The 1994 Centers for Disease Control and Prevention, however, has been adopted internationally, as a general standard. Only one study has reported prevalence according to the more recent, Canadian Consensus Criteria. Additional estimates were also found according to definitions by Ho-Yen, the 2005 Centers for Disease Control and Prevention empirical definition, and an epidemiological case definition. CONCLUSIONS: Advances in clinical case definitions during the past 10 years such as the Canadian Consensus Criteria have received little attention in prevalence research. Future assessments of prevalence should consider adopting more recent developments, such as the newly available International Consensus Criteria. This move could improve the surveillance of more specific cases found within CFS.

6 Review Myalgic encephalomyelitis: International Consensus Criteria. 2011

Carruthers, B M / van de Sande, M I / De Meirleir, K L / Klimas, N G / Broderick, G / Mitchell, T / Staines, D / Powles, A C P / Speight, N / Vallings, R / Bateman, L / Baumgarten-Austrheim, B / Bell, D S / Carlo-Stella, N / Chia, J / Darragh, A / Jo, D / Lewis, D / Light, A R / Marshall-Gradisnik, S / Mena, I / Mikovits, J A / Miwa, K / Murovska, M / Pall, M L / Stevens, S. ·Department of Physiology and Medicine, Vrije University of Brussels, Himmunitas Foundation, Brussels, Belgium. bcarruth@telus.net ·J Intern Med · Pubmed #21777306.

ABSTRACT: The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

7 Article Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study. 2020

Eaton-Fitch, N / Johnston, S C / Zalewski, P / Staines, D / Marshall-Gradisnik, S. ·School of Medical Science, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · Consortium Health International for Myalgic Encephalomyelitis, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · School of Medical Science, Griffith University, Gold Coast, Australia. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia. · Consortium Health International for Myalgic Encephalomyelitis, Griffith University, Gold Coast, Australia. · Department of Hygiene, Epidemiology and Ergonomy, Uniwersytet Mikolaja Kopernika Collegium Medicum, Bydgoszcz, Poland. ·Qual Life Res · Pubmed #31970624.

ABSTRACT: BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS. METHODS: Self-reported data collected from 480 individuals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL. RESULTS: Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties. CONCLUSION: This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.

8 Article Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients. 2019

Balinas, Cassandra / Cabanas, Helene / Staines, Donald / Marshall-Gradisnik, Sonya. ·The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, Gold Coast, QLD, 4222, Australia. cassandra.balinas@griffithuni.edu.au. · Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, Australia. cassandra.balinas@griffithuni.edu.au. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, Gold Coast, QLD, 4222, Australia. · Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, Australia. ·J Transl Med · Pubmed #31796045.

ABSTRACT: BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is hallmarked by a significant reduction in natural killer (NK) cell cytotoxicity, a mechanism tightly regulated by calcium (Ca METHODS: Ten ME/CFS patients (43.45 ± 12.36) and 10 HCs (43 ± 12.27) were age and sex-matched. Isolated NK cells were labelled with fluorescent antibodies to determine baseline and drug-treated TRPM2 and CD38 surface expression on NK cell subsets. Following IL-2 stimulation, NK cell cytotoxicity was measured following 8-Br-ADPR and N RESULTS: Baseline TRPM2 and CD38 surface expression was significantly higher on NK cell subsets in ME/CFS patients compared with HCs. Post IL-2 stimulation, TRPM2 and CD38 surface expression solely decreased on the CD56 CONCLUSION: Overexpression of TRPM2 on NK cells may function as a compensatory mechanism to alert a dysregulation in Ca

9 Article Naltrexone Restores Impaired Transient Receptor Potential Melastatin 3 Ion Channel Function in Natural Killer Cells From Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. 2019

Cabanas, Helene / Muraki, Katsuhiko / Staines, Donald / Marshall-Gradisnik, Sonya. ·School of Medical Science, Griffith University, Gold Coast, QLD, Australia. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia. · Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, Australia. · Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, Nagoya, Japan. ·Front Immunol · Pubmed #31736966.

ABSTRACT: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a seriously long-term and debilitating illness of unknown cause hallmarked by chronic pain and fatigue, memory and concentration impairment, and inflammation. ME/CFS hypothesis involves impaired Transient receptor potential melastatin 3 (TRPM3) ion channel function, affecting calcium signaling and Natural killer (NK) cell functions. Currently, substances called opioids, agonists of mu (μ)-opioid receptors (μOR), are the strongest painkillers clinically available for people suffering from strong or long-lasting pain characteristic of ME/CFS. μOR have been reported to specifically inhibit TRPM3 and to be expressed in immune cells where they play an immunomodulatory and immunosuppressive role. Naltrexone hydrochloride (NTX) acts as an antagonist to the μOR thus negating the inhibitory function of this opioid receptor on TRPM3. Therefore, understanding the mechanism of action for NTX in regulating and modulating TRPM3 channel function in NK cells will provide important information for the development of effective therapeutic interventions for ME/CFS. Whole-cell patch-clamp technique was used to measure TRPM3 activity in Interleukin-2 (IL-2) stimulated and NTX-treated NK cells for 24 h on eight ME/CFS patients and 8 age- and sex-matched healthy controls, after modulation with a TRPM3-agonist, pregnenolone sulfate (PregS), NTX and a TRPM3-antagonist, ononetin. We confirmed impaired TRPM3 function in ME/CFS patients through electrophysiological investigations in IL-2 stimulated NK cells after modulation with PregS and ononetin. Importantly, TRPM3 channel activity was restored in IL-2 stimulated NK cells isolated from ME/CFS patients after incubation for 24 h with NTX. Moreover, we demonstrated that NTX does not act as an agonist by directly coupling on the TRPM3 ion channel gating. The opioid antagonist NTX has the potential to negate the inhibitory function of opioid receptors on TRPM3 in NK cells from ME/CFS patients, resulting in calcium signals remodeling, which will in turn affect cell functions, supporting the hypothesis that NTX may have potential for use as a treatment for ME/CFS. Our results demonstrate, for the first time, and based on novel patch clamp electrophysiology, potential pharmaco-therapeutic interventions in ME/CFS.

10 Article Intra brainstem connectivity is impaired in chronic fatigue syndrome. 2019

Barnden, Leighton R / Shan, Zack Y / Staines, Donald R / Marshall-Gradisnik, Sonya / Finegan, Kevin / Ireland, Timothy / Bhuta, Sandeep. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. Electronic address: l.barnden@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia; Sunshine Coast Mind and Neuroscience Thompson Institute, University of the Sunshine Coast, Birtinya, QLD 4575, Australia. Electronic address: zhan@usc.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. Electronic address: d.staines@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. Electronic address: s.marshall-gradisnik@griffith.edu.au. · Medical Imaging Department, Gold Coast University Hospital, Parklands, QLD 4215, Australia. Electronic address: Finegan@health.qld.gov.au. · Medical Imaging Department, Gold Coast University Hospital, Parklands, QLD 4215, Australia. Electronic address: Ireland@health.qld.gov.au. · Medical Imaging Department, Gold Coast University Hospital, Parklands, QLD 4215, Australia. ·Neuroimage Clin · Pubmed #31671321.

ABSTRACT: In myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), abnormal MRI correlations with symptom severity and autonomic measures have suggested impaired nerve signal conduction within the brainstem. Here we analyse fMRI correlations to directly test connectivity within and from the brainstem. Resting and task functional MRI (fMRI) were acquired for 45 ME/CFS (Fukuda criteria) and 27 healthy controls (HC). We selected limited brainstem reticular activation system (RAS) regions-of-interest (ROIs) based on previous structural MRI findings in a different ME/CFS cohort (bilateral rostral medulla and midbrain cuneiform nucleus), the dorsal Raphe nucleus, and two subcortical ROIs (hippocampus subiculum and thalamus intralaminar nucleus) reported to have rich brainstem connections. When HC and ME/CFS were analysed separately, significant correlations were detected for both groups during both rest and task, with stronger correlations during task than rest. In ME/CFS, connections were absent between medulla and midbrain nuclei, although hippocampal connections with these nuclei were enhanced. When corresponding correlations from HC and ME/CFS were compared, ME/CFS connectivity deficits were detected within the brainstem between the medulla and cuneiform nucleus and between the brainstem and hippocampus and intralaminar thalamus, but only during task. In CFS/ME, weaker connectivity between some RAS nuclei was associated with increased symptom severity. RAS neuron oscillatory signals facilitate coherence in thalamo-cortical oscillations. Brainstem RAS connectivity deficits can explain autonomic changes and diminish cortical oscillatory coherence which can impair attention, memory, cognitive function, sleep quality and muscle tone, all symptoms of ME/CFS.

11 Article A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID). 2019

Corbitt, Matthew / Eaton-Fitch, Natalie / Staines, Donald / Cabanas, Hélène / Marshall-Gradisnik, Sonya. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia. · School of Medical Science, Griffith University, Gold Coast, Australia. · Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, Australia. ·BMC Neurol · Pubmed #31445522.

ABSTRACT: BACKGROUND: Cytokines in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) patients compared with healthy controls have been extensively studied. However, the evidence regarding whether a baseline difference between CFS/ME/SEID patients and the normal population remains unclear. The aim of this study was to conduct a systematic review of the literature regarding cytokines in CFS/ME/SEID and whether there is a significant difference in cytokine levels between this patient group and the normal population. METHODS: Pubmed, Scopus, Medline (EBSCOHost), and EMBASE databases were searched to source relevant studies for CFS/ME/SEID. The review included any studies examining cytokines in CFS/ME/SEID patients compared with healthy controls. Results of the literature search were summarised according to aspects of their study design and outcome measures, namely, cytokines. Quality assessment was also completed to summarise the level of evidence available. RESULTS: A total of 16,702 publications were returned using our search terms. After screening of papers according to our inclusion and exclusion criteria, 15 studies were included in the review. All the included studies were observational case control studies. Ten of the studies identified measured serum cytokines in CFS/ME/SEID patients, and four measured cytokines in other physiological fluids of CFS/ME/SEID patients. The overall quality assessment revealed most papers included in this systematic review to be consistent. CONCLUSIONS: Despite the availability of moderate quality studies, the findings of this review are inconclusive as to whether cytokines play any definitive role in CFS/ME/SEID, and consequently, they would not serve as reliable biomarkers. Therefore, in light of these results, it is recommended that further efforts toward a diagnostic test and treatment for CFS/ME/SEID continue to be developed in a range of research fields.

12 Article Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients. 2019

Cabanas, H / Muraki, K / Balinas, C / Eaton-Fitch, N / Staines, D / Marshall-Gradisnik, S. ·School of Medical Science, Griffith University, Gold Coast, QLD, Australia. h.cabanas@griffith.edu.au. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Southport, QLD, 4222, Australia. h.cabanas@griffith.edu.au. · Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, Australia. h.cabanas@griffith.edu.au. · Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, Chikusa, Nagoya, Japan. · Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, Australia. · School of Medical Science, Griffith University, Gold Coast, QLD, Australia. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Southport, QLD, 4222, Australia. ·Mol Med · Pubmed #31014226.

ABSTRACT: BACKGROUND: Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) is a complex multifactorial disorder of unknown cause having multi-system manifestations. Although the aetiology of CFS/ME remains elusive, immunological dysfunction and more particularly reduced cytotoxic activity in natural killer (NK) cells is the most consistent laboratory finding. The Transient Receptor Potential (TRP) superfamily of cation channels play a pivotal role in the pathophysiology of immune diseases and are therefore potential therapeutic targets. We have previously identified single nucleotide polymorphisms in TRP genes in peripheral NK cells from CFS/ME patients. We have also described biochemical pathway changes and calcium signaling perturbations in NK cells from CFS/ME patients. Notably, we have previously reported a decrease of TRP cation channel subfamily melastatin member 3 (TRPM3) function in NK cells isolated from CFS/ME patients compared with healthy controls after modulation with pregnenolone sulfate and ononetin using a patch-clamp technique. In the present study, we aim to confirm the previous results describing an impaired TRPM3 activity in a new cohort of CFS/ME patients using a whole cell patch-clamp technique after modulation with reversible TRPM3 agonists, pregnenolone sulfate and nifedipine, and an effective TRPM3 antagonist, ononetin. Indeed, no formal research has commented on using pregnenolone sulfate or nifedipine to treat CFS/ME patients while there is evidence that clinicians prescribe calcium channel blockers to improve different symptoms. METHODS: Whole-cell patch-clamp technique was used to measure TRPM3 activity in isolated NK cells from twelve age- and sex-matched healthy controls and CFS/ME patients, after activation with pregnenolone sulfate and nifedipine and inhibition with ononetin. RESULTS: We confirmed a significant reduction in amplitude of TRPM3 currents after pregnenolone sulfate stimulation in isolated NK cells from another cohort of CFS/ME patients compared with healthy controls. The pregnenolone sulfate-evoked ionic currents through TRPM3 channels were again significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients. In addition, we used nifedipine, another reversible TRPM3 agonist to support the previous findings and found similar results confirming a significant loss of the TRPM3 channel activity in CFS/ME patients. CONCLUSIONS: Impaired TRPM3 activity was validated in NK cells isolated from CFS/ME patients using different pharmacological tools and whole-cell patch-clamp technique as the gold standard for ion channel research. This investigation further helps to establish TRPM3 channels as a prognostic marker and/ or a potential therapeutic target for CFS/ME.

13 Article A systematic review of enteric dysbiosis in chronic fatigue syndrome/myalgic encephalomyelitis. 2018

Du Preez, S / Corbitt, M / Cabanas, H / Eaton, N / Staines, D / Marshall-Gradisnik, S. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · School of Medical Science, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia. · School of Medical Science, Griffith University, Gold Coast, Australia. ·Syst Rev · Pubmed #30572962.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is an illness characterised by profound and pervasive fatigue in addition to a heterogeneous constellation of symptoms. The aetiology of this condition remains unknown; however, it has been previously suggested that enteric dysbiosis is implicated in the pathogenesis of CFS/ME. This review examines the evidence currently available for the presence of abnormal microbial ecology in CFS/ME in comparison to healthy controls, with one exception being probiotic-supplemented CFS/ME patients, and whether the composition of the microbiome plays a role in symptom causation. METHODS: EMBASE, Medline (via EBSCOhost), Pubmed and Scopus were systematically searched from 1994 to March 2018. All studies that investigated the gut microbiome composition of CFS/ME patients were initially included prior to the application of specific exclusion criteria. The association between these findings and patient-centred outcomes (fatigue, quality of life, gastrointestinal symptoms, psychological wellbeing) are also reported. RESULTS: Seven studies that met the inclusion criteria were included in the review. The microbiome composition of CFS/ME patients was compared with healthy controls, with the exception of one study that compared to probiotic-supplemented CFS/ME patients. Differences were reported in each study; however, only three were considered statistically significant, and the findings across all studies were inconsistent. The quality of the studies included in this review scored between poor (< 54%), fair (54-72%) and good (94-100%) using the Downs and Black checklist. CONCLUSIONS: There is currently insufficient evidence for enteric dysbiosis playing a significant role in the pathomechanism of CFS/ME. Recommendations for future research in this field include the use of consistent criteria for the diagnosis of CFS/ME, reduction of confounding variables by controlling factors that influence microbiome composition prior to sample collection and including more severe cases of CFS/ME.

14 Article Hyperintense sensorimotor T1 spin echo MRI is associated with brainstem abnormality in chronic fatigue syndrome. 2018

Barnden, Leighton R / Shan, Zack Y / Staines, Donald R / Marshall-Gradisnik, Sonya / Finegan, Kevin / Ireland, Timothy / Bhuta, Sandeep. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. Electronic address: l.barnden@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. Electronic address: z.shan@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. Electronic address: d.staines@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. Electronic address: s.marshall-gradisnik@griffith.edu.au. · Medical Imaging Department, Gold Coast University Hospital, Parklands, QLD 4215, Australia. Electronic address: Kevin.Finegan@health.qld.gov.au. · Medical Imaging Department, Gold Coast University Hospital, Parklands, QLD 4215, Australia. Electronic address: Timothy.Ireland@health.qld.gov.au. · Medical Imaging Department, Gold Coast University Hospital, Parklands, QLD 4215, Australia. ·Neuroimage Clin · Pubmed #30497131.

ABSTRACT: We recruited 43 Chronic Fatigue Syndrome (CFS) subjects who met Fukuda criteria and 27 healthy controls and performed 3T MRI T1 and T2 weighted spin-echo (T1wSE and T2wSE) scans. T1wSE signal follows T1 relaxation rate (1/T1 relaxation time) and responds to myelin and iron (ferritin) concentrations. We performed MRI signal level group comparisons with SPM12. Spatial normalization after segmentation was performed using T2wSE scans and applied to the coregistered T1wSE scans. After global signal-level normalization of individual scans, the T1wSE group comparison detected decreased signal-levels in CFS in a brainstem region (cluster-based inference controlled for family wise error rate, P

15 Article Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. 2018

Cabanas, Hélène / Muraki, Katsuhiko / Eaton, Natalie / Balinas, Cassandra / Staines, Donald / Marshall-Gradisnik, Sonya. ·School of Medical Science, Griffith University, Gold Coast, QLD, Australia. h.cabanas@griffith.edu.au. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia. h.cabanas@griffith.edu.au. · Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, Chikusa, Nagoya, Japan. · School of Medical Science, Griffith University, Gold Coast, QLD, Australia. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia. ·Mol Med · Pubmed #30134818.

ABSTRACT: BACKGROUND: Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) is a debilitating disorder that is accompanied by reduced cytotoxic activity in natural killer (NK) cells. NK cells are an essential innate immune cell, responsible for recognising and inducing apoptosis of tumour and virus infected cells. Calcium is an essential component in mediating this cellular function. Transient Receptor Potential Melastatin 3 (TRPM3) cation channels have an important regulatory role in mediating calcium influx to help maintain cellular homeostasis. Several single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in patients with CFS/ME and have been proposed to correlate with illness presentation. Moreover, a significant reduction in both TRPM3 surface expression and intracellular calcium mobilisation in NK cells has been found in CFS/ME patients compared with healthy controls. Despite the functional importance of TRPM3, little is known about the ion channel function in NK cells and the epiphenomenon of CFS/ME. The objective of the present study was to characterise the TRPM3 ion channel function in NK cells from CFS/ME patients in comparison with healthy controls using whole cell patch-clamp techniques. METHODS: NK cells were isolated from 12 age- and sex-matched healthy controls and CFS patients. Whole cell electrophysiology recording has been used to assess TRPM3 ion channel activity after modulation with pregnenolone sulfate and ononetin. RESULTS: We report a significant reduction in amplitude of TRPM3 current after pregnenolone sulfate stimulation in isolated NK cells from CFS/ME patients compared with healthy controls. In addition, we found pregnenolone sulfate-evoked ionic currents through TRPM3 channels were significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients. CONCLUSIONS: TRPM3 activity is impaired in CFS/ME patients suggesting changes in intracellular Ca

16 Article Brain function characteristics of chronic fatigue syndrome: A task fMRI study. 2018

Shan, Zack Y / Finegan, Kevin / Bhuta, Sandeep / Ireland, Timothy / Staines, Donald R / Marshall-Gradisnik, Sonya M / Barnden, Leighton R. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. Electronic address: z.shan@griffith.edu.au. · Medical Imaging Department, Gold Coast University Hospital, Parklands, QLD 4215, Australia. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4222, Australia. ·Neuroimage Clin · Pubmed #30035022.

ABSTRACT: The mechanism underlying neurological dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is yet to be established. This study investigated the temporal complexity of blood oxygenation level dependent (BOLD) changes in response to the Stroop task in CFS patients. 43 CFS patients (47.4 ± 11.8 yrs) and 26 normal controls (NCs, 43.4 ± 13.9 yrs) were included in this study. Their mental component summary (MCS) and physical component summary (PCS) from the 36-item Short Form Health Survey (SF-36) questionnaire were recorded. Their Stroop colour-word task performance was measured by accuracy and response time (RT). The BOLD changes associated with the Stroop task were evaluated using a 2-level general linear model approach. The temporal complexity of the BOLD responses, a measure of information capacity and thus adaptability to a challenging environment, in each activated region was measured by sample entropy (SampEn). The CFS patients showed significantly longer RTs than the NCs (

17 Article Rituximab impedes natural killer cell function in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation. 2018

Eaton, Natalie / Cabanas, Hélène / Balinas, Cassandra / Klein, Anne / Staines, Donald / Marshall-Gradisnik, Sonya. ·School of Medical Science, Griffith University, QLD, Gold Coast, Australia. n.eaton@griffith.edu.au. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, QLD, Gold Coast, Australia. n.eaton@griffith.edu.au. · School of Medical Science, Griffith University, QLD, Gold Coast, Australia. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, QLD, Gold Coast, Australia. ·BMC Pharmacol Toxicol · Pubmed #29587879.

ABSTRACT: BACKGROUND: A recent in vitro pilot investigation reported Rituximab significantly reduced natural killer (NK) cell cytotoxicity in healthy donors. Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown etiology. A consistent finding is a significant reduction in NK cell cytotoxicity. Rituximab has been reported having questionable potential therapeutic benefits for the treatment of CFS/ME, however, the potential effects of Rituximab on NK cell cytotoxicity in CFS/ME patients are yet to be determined. METHODS: A total of eight CFS/ME patients (48.63 ± 15.69 years) and nine non-fatigued controls (NFC) (37.56 ± 11.06 years) were included using the Fukuda case definition. Apoptotic function, lytic proteins and degranulation markers were measured on isolated NK cells using flow cytometry following overnight incubation with Rituximab at 10 μg/ml and 100 μg/ml. RESULTS: There was a significant reduction in NK cell lysis between CFS/ME patients and NFC following incubation with Rituximab at 100 μg/ml at 12.5:1 and 6.25:1 effecter-target (E:T) ratios (p < 0.05). However, there was no significant difference for NFC following incubation with Rituximab at 10 μg/ml and 100 μg/ml. There was no significant difference between CFS/ME patients and NFC for granzyme A and granzyme B prior to incubation with Rituximab and following overnight incubation with Rituximab at 10 μg/ml. There was a significant decrease in granzyme B in CFS/ME patients compared to NFC with 100 μg/ml of Rituximab prior to K562 cells stimulation (p < 0.05). There was a significant increase in CD107a (p < 0.05) and CD107b expression (p < 0.01) in NFC after stimulation with K562 cells prior to incubation with Rituximab. There was a significant increase in CD107b expression between CFS/ME patients and NFC prior to incubation with Rituximab and without stimulation of K562 cells (p < 0.01). Importantly, there was a significant increase in CD107b following overnight incubation with 100 μg/ml of Rituximab in NFC prior to K562 cells stimulation (p < 0.01). CONCLUSION: This study reports significant decreases in NK cell lysis and a significant increase in NK cell degranulation following Rituximab incubation in vitro in CFS/ME patients, suggesting Rituximab may be toxic for NK cells. Caution should be observed in clinical trials until further investigations in a safe and controlled in vitro setting are completed.

18 Article A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). 2018

Corbitt, Matthew / Campagnolo, N / Staines, D / Marshall-Gradisnik, S. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia. ncned@griffith.edu.au. · National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia. · School of Medical Science, Griffith University, Gold Coast, Australia. ·Probiotics Antimicrob Proteins · Pubmed #29464501.

ABSTRACT: Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to conduct a systematic review of these symptoms in CFS/ME, along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline (EBSCOHost) and EMBASE databases were searched to source relevant studies for CFS/ME. The review included any studies examining GI symptoms, irritable bowel syndrome (IBS) and/or probiotic use. Studies were required to report criteria for CFS/ME and study design, intervention and outcome measures. Quality assessment was also completed to summarise the level of evidence available. A total of 3381 publications were returned using our search terms. Twenty-five studies were included in the review. Randomised control trials were the predominant study type (n = 24). Most of the studies identified examined the effect of probiotic supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms in CFS/ME patients, as well as some other significant secondary outcomes (e.g. quality of life, other gastrointestinal symptoms, psychological symptoms). The level of evidence identified for the use of probiotics in IBS was excellent in quality; however, the evidence available for the use of probiotic interventions in CFS/ME was poor and limited. There is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS. The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall. Standardisation of protocols and methodology in these studies is required.

19 Article Decreased Connectivity and Increased Blood Oxygenation Level Dependent Complexity in the Default Mode Network in Individuals with Chronic Fatigue Syndrome. 2018

Shan, Zack Y / Finegan, Kevin / Bhuta, Sandeep / Ireland, Timothy / Staines, Donald R / Marshall-Gradisnik, Sonya M / Barnden, Leighton R. ·1 National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University , Gold Coast, Australia . · 2 Medical Imaging Department, Gold Coast University Hospital , Southport, Australia . ·Brain Connect · Pubmed #29152994.

ABSTRACT: The chronic fatigue syndrome (CFS)/myalgic encephalomyelitis is a debilitating disease with unknown pathophysiology and no diagnostic test. This study investigated the default mode network (DMN) to understand the pathophysiology of CFS and to identify potential biomarkers. Using functional MRI (fMRI) collected from 72 subjects (45 CFS and 27 controls) with a temporal resolution of 0.798 sec, we evaluated the DMN using static functional connectivity (FC), dynamic functional connectivity (DFC) and DFC complexity, blood oxygenation level dependent (BOLD) activation maps, and complexity of activity. General linear model univariate analysis was used for intergroup comparison to account for age and gender differences. Hierarchical regression analysis was used to test whether fMRI measures could be used to explain variances of health scores. BOLD signals in the posterior cingulate cortex (PCC), the driving hub in the DMN, were more complex in CFS in both resting state and task (p < 0.05). The FCs between medial prefrontal cortex (mPFC) and both inferior parietal lobules (IPLs) were weaker (p < 0.05) during resting state, whereas during task mPFC-left IPL and mPFC-PCC were weaker (p < 0.05). The DFCs between the DMN hubs were more complex in CFS (p < 0.05) during task. Each of these differences accounted for 7-11% variability of health scores. This study showed that DMN activity is more complex and less coordinated in CFS, suggesting brain network analysis could be potentially used as a diagnostic biomarker for CFS.

20 Article Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome. 2017

Shan, Zack Y / Kwiatek, Richard / Burnet, Richard / Del Fante, Peter / Staines, Donald R / Marshall-Gradisnik, Sonya M / Barnden, Leighton R. ·National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. · Division of Medical Subspecialities, Lyell McEwin Hospital, Elizabeth Vale, South Austalia, Australia. · Endocrinology department, Royal Adelaide Hospital, Adelaide, South Austalia, Australia. · Healthfirst Network, Woodville, South Austalia, Australia. ·NMR Biomed · Pubmed #28661067.

ABSTRACT: Unrefreshing sleep is a hallmark of chronic fatigue syndrome/myalgic encephalomyelitis (CFS). This study examined brain structure variations associated with sleep quality in patients with CFS. 38 patients with CFS (34.8 ± 10.1 years old) and 14 normal controls (NCs) (34.7 ± 8.4 years old) were recruited. All subjects completed the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), and Chalder Fatigue Scale (CFQ) questionnaires. Brain MRI measures included global and regional grey and white matter volumes, magnetization transfer T

21 Article Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels. 2017

Nguyen, T / Johnston, S / Clarke, L / Smith, P / Staines, D / Marshall-Gradisnik, S. ·The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Gold Coast, QLD, Australia. · School of Medical Science, Griffith University, Gold Coast, QLD, Australia. ·Clin Exp Immunol · Pubmed #27727448.

ABSTRACT: Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca

22 Article Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients. 2017

Nguyen, Thao / Johnston, Samantha / Chacko, Anu / Gibson, Damien / Cepon, Julia / Smith, Peter / Staines, Donald / Marshall-Gradisnik, Sonya. ·School of Medical Science, Griffith University, Gold Coast, QLD, Australia. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia. ·Asian Pac J Allergy Immunol · Pubmed #27362406.

ABSTRACT: BACKGROUND: Mast cells (MCs) mediate inflammation through neuropeptides and cytokines, along with histamine and reactive oxygen species (ROS). Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an illness characterized by an unexplained disabling fatigue with multiple physiological impairments as well as dysregulated cytokine profiles. OBJECTIVE: To determine mast cell phenotypes in isolated human PBMCs, in healthy controls and in CFS/ME patients. Second, determine receptor expression of RAGE and its ligand high mobility group box 1 protein (HMGB1). METHOD: Moderately severe CFS/ME patients (n=12, mean age 39.25 ± SD3.52 years), severe CFS/ME patients (n=6, mean age 43.00 ± SD4.02 years) and healthy controls (n=13, mean age 42.69 ± SD3.87 years) were included in this study. CFS/ME patients were classified according to the 2011 International Consensus Criteria. LSRFortessa X-20 Flow cytometry was used for the identification of phenotypic peripheral mast cell population in PBMCs using an exclusion marker Lin2 cocktail (anti-CD3, anti-CD14, anti-CD19, anti-CD20 and anti-CD56) and inclusion markers (CD117, CD34, FCεRI, chymase, HLA-DR and CD154) following comparative investigation. HMGB1 and soluble RAGE expression in plasma was measured by sandwich ELISA assay. RESULTS: There was a significant increase in CD117⁺CD34⁺FCεRI-chymase- mast cell populations in moderate and severe CFS/ME patients compared with healthy controls. There was a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cell populations in the severe CFS/ME compared with healthy controls and moderate CFS/ME. There were no significant differences between groups for HMGB1 and sRAGE. CONCLUSIONS: This preliminary study investigates mast cell phenotypes from PBMCs in healthy controls. We report significant increase of naïve MCs in moderate and severe CFS/ME patients compared with healthy controls. Moreover, a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cells in severe CFS/ME patients. Peripheral MCs may be present in CFS/ME pathology however, further investigation to determine their role is required.

23 Article A targeted genome association study examining transient receptor potential ion channels, acetylcholine receptors, and adrenergic receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. 2016

Johnston, Samantha / Staines, Donald / Klein, Anne / Marshall-Gradisnik, Sonya. ·School of Medical Science, Griffith University, Gold Coast, Australia. samantha.johnston@griffith.edu.au. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, Gold Coast, QLD, 4222, Australia. samantha.johnston@griffith.edu.au. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, Gold Coast, QLD, 4222, Australia. · School of Medical Science, Griffith University, Gold Coast, Australia. ·BMC Med Genet · Pubmed #27835969.

ABSTRACT: BACKGROUND: Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (CFS/ME) is a debilitating condition of unknown aetiology. It is characterized by a range of physiological effects including neurological, sensory and motor disturbances. This study examined candidate genes for the above clinical manifestations to identify single nucleotide polymorphism (SNP) alleles associated with CFS/ME compared with healthy controls. METHODS: DNA was extracted and whole genome genotyping was performed using the HumanOmniExpress BeadChip array. Gene families for transient receptor potential ion channels, acetylcholine receptors, and adrenergic receptors, and acetylcholinesterase were targeted. The frequency of each SNP and their association between CFS/ME and healthy controls was examined using Fisher's exact test, and to adjust for multiple testing, False Detection Rate (FDR) and Bonferroni corrections were applied (p < 0.05). RESULTS: The study included 172 participants, consisting of 95 Fukuda defined CFS/ME patients (45.8 ± 8.9; 69 % female) and 77 healthy controls (42.3 ± 10.3; 63 % female). A total of 950 SNPs were included for analysis. 60 significant SNPs were associated with CFS/ME compared with healthy controls. After applying FDR and Bonferroni corrections, SNP rs2322333 in adrenergic receptor α1 (ADRA1A) was higher in CFS/ME compared with healthy controls (45.3 % vs. 23.4 %; p = 0.059). The genotype class that was homozygous minor (AA) was substantially lower in CFS/ME compared with healthy controls (4.2 % vs. 24.7 %). CONCLUSIONS: This study reports for the first time the identification of ADRA1A and a possible association between CFS/ME and genotype classes. Further examination of the functional role of this class of adrenergic receptors may elucidate the cause of particular clinical manifestations observed in CFS/ME.

24 Article Single nucleotide polymorphisms and genotypes of transient receptor potential ion channel and acetylcholine receptor genes from isolated B lymphocytes in myalgic encephalomyelitis/chronic fatigue syndrome patients. 2016

Marshall-Gradisnik, Sonya / Johnston, Samantha / Chacko, Anu / Nguyen, Thao / Smith, Peter / Staines, Donald. ·1 School of Medical Science, Griffith University, Gold Coast, QLD, Australia. · 2 The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia. ·J Int Med Res · Pubmed #27834303.

ABSTRACT: Objective The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca

25 Article Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients. 2016

Chacko, Anu / Staines, Donald R / Johnston, Samantha C / Marshall-Gradisnik, Sonya M. ·School of Medical Science, Griffith University, QLD, Australia.; The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, QLD, Australia. · The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, QLD, Australia. ·Gene Regul Syst Bio · Pubmed #27594784.

ABSTRACT: BACKGROUND: The etiology and pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are unknown. However, natural killer (NK) cell dysfunction, in particular reduced NK cytotoxic activity, is a consistent finding in CFS/ME patients. Previous research has reported significant changes in intracellular mitogen-activated protein kinase pathways from isolated NK cells. The purpose of this present investigation was to examine whether protein kinase genes have a role in abnormal NK cell intracellular signaling in CFS/ME. METHOD: Messenger RNA (mRNA) expression of 528 protein kinase genes in isolated NK cells was analyzed (nCounter GX Human Kinase Kit v2 (XT); NanoString Technologies) from moderate (n = 11; age, 54.9 ± 10.3 years) and severe (n = 12; age, 47.5 ± 8.0 years) CFS/ME patients (classified by the 2011 International Consensus Criteria) and nonfatigued controls (n = 11; age, 50.0 ± 12.3 years). RESULTS: The expression of 92 protein kinase genes was significantly different in the severe CFS/ME group compared with nonfatigued controls. Among these, 37 genes were significantly upregulated and 55 genes were significantly downregulated in severe CFS/ME patients compared with nonfatigued controls. CONCLUSIONS: In severe CFS/ME patients, dysfunction in protein kinase genes may contribute to impairments in NK cell intracellular signaling and effector function. Similar changes in protein kinase genes may be present in other cells, potentially contributing to the pathomechanism of this illness.

Next