Could you create a database for WAMES?

WAMES needs a relational database

We are urgently looking for a volunteer to create a database using Microsoft Access.

This database would enable us to monitor the work of WAMES and extract data to support funding applications.

The WAMES team has a clear plan for the database and will be able to input and manipulate the data once the database is set up. You would work from home with contact and information from the chair Jan Russell

For more information email jan@wames.org.uk

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Eukaryotes in the gut microbiota in ME/CFS

Research abstract:

Eukaryotes in the gut microbiota in myalgic encephalomyelitis/chronic fatigue syndrome, by Alexandra H. Mandarano, Ludovic Giloteaux, Betsy A. Keller, Susan M. Levine, Maureen R. Hanson in  PeerJ 6:e4282 [January 22, 2018]

Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often suffer from gastrointestinal symptoms and many are diagnosed with irritable bowel syndrome (IBS).

Previous studies, including from our laboratory, have demonstrated that the ME/CFS gut bacterial composition is altered and less diverse when compared to healthy individuals. Patients have increased biomarkers of inflammation and leaky gut syndrome.

To further investigate dysbiosis in the ME/CFS gut microbiome, we sought to characterize the eukaryotes present in the gut of 49 individuals with ME/CFS and 39 healthy controls.

Using 18S rRNA sequencing, we have identified eukaryotes in stool samples of 17 healthy individuals and 17 ME/CFS patients. Our analysis demonstrates a small, nonsignificant decrease in eukaryotic diversity in ME/CFS patients compared to healthy individuals.

In addition, ME/CFS patients show a nonsignificant increase in the ratio of fungal phyla Basidiomycota to Ascomycota, which is consistent with ongoing inflammation in ME/CFS. We did not identify specific eukaryotic taxa that are associated with ME/CFS disease status.

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Elevations of ventricular lactate levels occur in both CFS & FM

Research abstract:

Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia, by Benjamin H. Natelson, Diana Vu, Jeremy D. Coplan, Xiangling Mao, Michelle Blate, Guoxin Kang, Eli Soto, Tolga Kapusuz & Dikoma C. Shungu in Fatigue 2017; 5(1):15-20. [Epub 2017 Feb 20]

Background:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) frequently have overlapping symptoms, leading to the suggestion that the same disease processes may underpin the two disorders – the unitary hypothesis. However, studies investigating the two disorders have reported substantial clinical and/or biological differences between them, suggesting distinct pathophysiological underpinnings.

Purpose:

The purpose of this study was to further add to the body of evidence favoring different disease processes in CFS and FM by comparing ventricular cerebrospinal fluid lactate levels among patients with CFS alone, FM alone, overlapping CFS and FM symptoms, and healthy control subjects.

Methods:

Ventricular lactate was assessed in vivo with proton magnetic resonance spectroscopic imaging (1H MRSI) with the results normed across the 2 studies in which the data were collected.

Results:

Mean CSF lactate levels in CFS, FM and CFS+FM did not differ among the three groups, but were all significantly higher than the mean values for control subjects.

Conclusion:

While patients with CFS, FM and comorbid CFS and FM can be differentiated from healthy subjects based on measures of CFS lactate, this neuroimaging outcome measure is not a viable biomarker for differentiating CFS from FM or from patients in whom symptoms of the two disorders overlap.

Solve ME/CFS blog post, 23 January 2018:  Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia

CFS and FM were found to have statistically indistinguishable levels of lactate in the recent finding detailed in Fatigue, but we don’t have proof this reflects the same underlying cause. Nonetheless, ventricular lactate is indicated as a viable biomarker of underlying brain dysfunction for some patients with either or both diagnoses. The authors note that further research will be needed to further address if CFS and FM are different illnesses or variations of the same condition.

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Longitudinal associations of lymphocyte subsets with clinical outcomes in CFS

Research abstract:

Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome, by  Melissa L. Mehalick, Karen B. Schmaling , Daniel E. Sabath, & Dedra S. Buchwald in Fatigue: Biomedicine, Health & Behavior 2018 pp 1-12  [Published online: 12 Jan 2018]

Background:

Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms.

Purpose:

To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response.

Methods:

The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes – natural killer (NK) cells (CD3 − CD16+ and CD3 − CD56+) and naïve T cells (CD4 + CD45RA+) – to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes.

Results:

Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3 − CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms.

Conclusion:

These findings suggest that lymphocytes are modestly related to clinical outcomes over time.

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Genome-epigenome interactions associated with ME/CFS

Research abstract:

Genome-Epigenome Interactions Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, by Santiago Herrera, Wilfred C de Vega, David Ashbrook, Suzanne D Vernon, Patrick O McGowan in Biorxiv [preprint 22 Dec 2017]

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an example of a complex disease of unknown etiology.

Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as with specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, the association between DNA methylation and genetic background in relation to the ME/CFS is currently unknown.

In this study we explored this association by characterizing the genomic (~4.3 million SNPs) and epigenomic (~480 thousand CpG loci) variability between populations of ME/CFS patients and healthy controls.

We found significant associations of methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation phenotypes associated with ME/CFS.

The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS

Conclusions
We identified over one hundred differentially methylated CpG loci associated with ME/CFS in T lymphocytes. Approximately half of these were clustered in differentially methylated regions of 500bp in size or less. Our data and analyses suggest that there is an indirect role of genotype influencing DNA methylation patterns associated with ME/CFS. We found no substantial large-effect direct associations of specific genotypes with ME/CFS disease phenotype. Larger scale genome wide association studies are necessary to test for potential small-effect associations between genotype and ME/CFS phenotype.

All of the methylation values at differentially methylated loci in T lymphocytes had significant correlations with specific genotypes at neighboring SNPs (within a window of 1 Mbp), indicating that particular genetic backgrounds may influence methylation levels differently in ME/CFS patients than in controls. The genomic elements associated with genetic and epigenetic variants characteristic of ME/CFS patients in this study constitute targets for future research. Understanding the molecular mechanisms of genetic-epigenetic interactions of these targets will be key to develop new treatments for ME/CFS, and can serve as a model to understand the molecular basis of related complex diseases.

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Vision in ME – restricted spatial windows of visibility

Research abstract:

Restricted spatial windows of visibility in Myalgic Encephalomyelitis (ME), by Nadia S Ahmed, Irene Gottlob, Frank A Proudlock and Claire V Hutchinson in Vision 2018, 2(1), 2; doi:10.3390/vision2010002 [Published: 17 January 2018]

Myalgic encephalomyelitis (ME) is a devastating disorder marked by debilitating fatigue. It not well understood and its diagnosis is controversial. It is very important therefore that significant clinical features are investigated.

Visual symptoms in ME represent a group of distinct, quantifiable, clinical features that could significantly improve diagnosis and provide insights into underlying pathology. The purpose of the present study was therefore to explore the effect of ME on spatial windows of visibility using the spatial contrast sensitivity function.

Contrast sensitivity was determined for stationary luminance-defined sinusoidal gratings spanning a five-octave range of spatial frequencies (0.5 to 16 c/deg) in a group of 19 individuals with ME and a group of 19 matched (age, gender) controls. Compared to controls, the ME group exhibited a restricted spatial window of visibility for encoding stimulus contrast. This was characterised principally by a contrast sensitivity deficit at lower spatial frequencies and a narrower bandwidth.

Our findings suggest that contrast sensitivity deficits may represent a visual marker of ME, and be indicative of abnormal visual processing at the level of the retina and in the cortical and subcortical visual pathways.

More about spatial vision

 

 

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UK ME CFS Biobank Q&A

Science for ME blogpost, 14 Dec 2017: UK ME/CFS Biobank Ask Me Anything thread

UK ME/CFS Biobank team:

  • Project Lead & Clinical Lecturer, Dr Eliana Lacerda,
  • Co-Principal Investigator Dr Luis Nacul,
  • Research Nurse & Biobank Coordinator Caroline Kingdon
  • Project Manager (Administrative & Financial) Jack Butterworth

 

To read about the vital work they do, visit CureME: leading research into ME/CFS

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Cortical connectivity in CFS and neurocognitive impairment

Research abstract:

Small-world network analysis of cortical connectivity in Chronic Fatigue Syndrome using quantitative EEG, by Mark A Zinn, Marcie L Zinn, Leonard A Jason in NeuroRegulation, 4(3–4), 125–137, Dec 2017

The aim of this study was to explore the relationship between complex brain networks in people with Chronic Fatigue Syndrome (CFS) and neurocognitive impairment.

Quantitative EEG (qEEG) recordings were taken from 14 people with CFS and 15 healthy controls (HCs) during an eye-closed resting condition. Exact low resolution electromagnetic tomography (eLORETA) was used to estimate cortical sources and perform a functional connectivity analysis.

The graph theory approach was used to characterize network representations for each participant and derive the “small-worldness” index, a measure of the overall homeostatic balance between local and long-distance connectedness.

Results showed that small-worldness for the delta band was significantly lower for patients with CFS compared to HCs. In addition, delta small-worldness was negatively associated with neurocognitive impairment scores on the DePaul Symptom Questionnaire (DSQ). Finally, delta small-worldness indicated a greater risk of complex brain network inefficiency for the CFS group.

These results suggest that CFS pathology may be functionally disruptive to small-world networks. In turn, small-world characteristics might serve as a neurophysiological indicator for confirming a biological basis of cognitive symptoms, treatment outcome, and neurophysiological status of people with CFS.

 

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Elevated brain natriuretic peptide levels in CFS associate with cardiac dysfunction

Research abstract:

Elevated brain natriuretic peptide levels in chronic fatigue syndrome associate with cardiac dysfunction: a case control study Cara Tomas, Andreas Finkelmeyer, Tim Hodgson, Laura MacLachlan, Guy A MacGowan, Andrew M Blamire, Julia L Newton in BMJ Openheart 4:2 2017

Key questions
What is already known about this subject?

  • Structural and functional cardiac abnormalities have been reported in chronic fatigue syndrome (CFS).
  • Magnetic resonance spectroscopy studies have suggested a subclinical cardiomyopathy in some of those with CFS.

What does this study add?

  • Brain natriuretic peptide (BNP) levels were significantly higher in CFS compared with matched controls.
  • There were significantly lower cardiac volumes in those with higher BNP levels in both end-systolic and end-diastolic volumes.
  • There were no relationships between fatigue severity, length of illness and BNP levels confirming that our findings are unlikely to be related to deconditioning.

How might this impact on clinical practice?

  • This study confirms an association between reduced cardiac volumes and BNP in CFS.
  • Lack of relationship between length of disease suggests that findings are not secondary to deconditioning.
  • Further studies are needed to explore the utility of BNP to act as a stratification paradigm in CFS that directs targeted treatments.

Objectives:

To explore levels of the brain natriuretic peptide (BNP) and how these associate with the cardiac abnormalities recently identified in chronic fatigue syndrome (CFS).

Methods:

Cardiac magnetic resonance examinations were performed using 3T Philips Intera Achieva scanner (Best, Netherlands) in CFS (Fukuda) participants and sedentary controls matched group wise for age and sex. BNP was also measured by using an enzyme immunoassay in plasma from 42 patients with CFS and 10 controls.

Results:

BNP levels were significantly higher in the CFS cohort compared with the matched controls (P=0.013). When we compared cardiac volumes (end-diastolic and end-systolic) between those with high BNP levels (BNP>400 pg/mL) and low BNP (<400 pg/mL), there were significantly lower cardiac volumes in those with the higher BNP levels in both end-systolic and end-diastolic volumes (P=0.05). There were no relationships between fatigue severity, length of disease and BNP levels (P=0.2) suggesting that our findings are unlikely to be related to deconditioning.

Conclusion:

This study confirms an association between reduced cardiac volumes and BNP in CFS. Lack of relationship between length of disease suggests that findings are not secondary to deconditioning. Further studies are needed to explore the utility of BNP to act as a stratification paradigm in CFS that directs targeted treatments.

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Autonomic Nervous System functioning related to nocturnal sleep in patients with CFS

Research abstract:

Autonomic nervous system functioning related to nocturnal sleep in patients with Chronic Fatigue Syndrome compared to tired controls, by Source: M Orjatsalo, A Alakuijala, M Partinen in J Clin Sleep Med. 2017 Dec 13. pii: jc-17-00330. [Epub ahead of print]

STUDY OBJECTIVES: Autonomic nervous system (ANS) dysfunction is common in chronic fatigue syndrome (CFS). One of the main complaints in CFS is unrefreshing sleep. We aimed to study the nocturnal cardiac ANS in different sleep stages in patients filling the 2015 Institute of Medicine CFS diagnostic criteria.

METHODS: In this case series study, the nocturnal heart rate variability and blood pressure (BP) variables in polysomnography were studied in groups of patients with CFS (n = 8) and tired controls (n = 8) aged 16-49 years. Five of the patients with CFS and controls were female. The heart rate variability and BP parameters and heart rate were studied in all sleep stages and wake.

RESULTS: The amount of low-frequency oscillations of the electrocardiography R-R-intervals spectra (LF; predominantly reflects sympathetic activity) was higher for patients with CFS in all sleep stages compared to controls (P< .001). During wake, the amount of LF was lower for the patients with CFS (P< .05). The amount of high-frequency oscillations (HF; reflects parasympathetic activity) was lower in stage N3 sleep in the patients with CFS than for the controls (P< .0001), but, in total, HF was higher in patients with CFS (P< .001). Patients with CFS had higher overall nocturnal systolic and mean BP (P< .0001) and lower heart rate (P< .0001) than controls. No significant differences were found in sleep stage distributions.

CONCLUSIONS: The results suggest a nocturnal dysfunction of the cardiac ANS in CFS, presenting as lower parasympathetic tone in deep sleep and higher sympathetic tone asleep.

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