Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by medically unexplained debilitating fatigue with suggested altered immunological state. Our study aimed to explore peripheral blood mononuclear cells (PBMCs) for microRNAs (miRNAs) expression in ME/CFS subjects under an exercise challenge. The findings highlight the immune response and inflammation links to differential miRNA expression in ME/CFS. The present study is particularly important in being the first to uncover the differences that exist in miRNA expression patterns in males and females with ME/CFS in response to exercise. This provides new evidence for the understanding of differential miRNA expression patterns and post-exertional malaise in ME/CFS. We also report miRNA expression pattern differences associating with the nutritional status in individuals with ME/CFS, highlighting the effect of subjects' metabolic state on molecular changes to be considered in clinical research within the NINDS/CDC ME/CFS Common Data Elements. The identification of gender-based miRNAs importantly provides new insights into gender-specific ME/CFS susceptibility and demands exploration of sex-suited ME/CFS therapeutics.     

Ethical classification of ME/CFS in the United Kingdom

Few conditions have sparked as much controversy as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Professional consensus has long suggested that the condition should be classified as psychiatric, while patients and advocacy groups have insisted it is a serious biological disease that requires medical care and research to develop it. This longstanding debate shifted in 2015, when U.S. governmental health authorities fully embraced medical classification and management. Given that some globally respected health authorities now insist that ME/CFS is a serious biological disease, this paper asks whether it can be ethical for the U.K. practice guideline now in development to characterize the condition as a mental health disorder. Following a brief history of ME/CFS controversy, I offer three arguments to show that it would be unethical for the U.K. to now characterize ME/CFS as a mental health condition, considering the relevance of that conclusion for ME/CFS guidelines elsewhere and for other contested conditions.     

Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.     

Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS

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Metagenomic Investigation of Plasma in Individuals with ME/CFS Highlights the Importance of Technical Controls to Elucidate Contamination and Batch Effects

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease causing indefinite fatigue. ME/CFS has long been hypothesised to have an infectious cause; however, no specific infectious agent has been identified. We used metagenomics to analyse the RNA from plasma samples from 25 individuals with ME/CFS and compare their microbial content to technical controls as well as three control groups: individuals with alternatively diagnosed chronic Lyme syndrome (N = 13), systemic lupus erythematosus (N = 11), and healthy controls (N = 25). We found that the majority of sequencing reads were removed during host subtraction, thus there was very low microbial RNA content in the plasma. The effects of sample batching and contamination during sample processing proved to outweigh the effects of study group on microbial RNA content, as the few differences in bacterial or viral RNA abundance we did observe between study groups were most likely caused by contamination and batch effects. Our results highlight the importance of including negative controls in all metagenomic analyses, since there was considerable overlap between bacterial content identified in study samples and control samples. For example, Proteobacteria, Firmicutes, Actinobacteria, and Bacteriodes were found in both study samples and plasma-free negative controls. Many of the taxonomic groups we saw in our plasma-free negative control samples have previously been associated with diseases, including ME/CFS, demonstrating how incorrect conclusions may arise if controls are not used and batch effects not accounted for.     

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

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.     

The impact of uncertainty on phytoremediation project costs

Pollution of the environment by metals and organic contaminants is an intractable global problem, with cleanup costs running into billions of dollars using current engineering technologies. The availability of alternative, cheap and effective technologies would significantly improve the prospects of cleaning-up metal contaminated sites. Phytoremediation has been proposed as an economical and 'green' method of exploiting plants to extract or degrade the contaminants in the soil. To date, the majority of phytoremediation efforts have been directed at leaping the biological biochemical and agronomic hurdles to deliver a working technology, with scant attention to the economic outlook other than simple estimates of the cost advantages ofphytoremediation over other techniques. In this paper we use a deterministic actauarial model to show that uncertainty in project success (the possibility that full clean up may not be realized) may significantly increase the perceived costs of remediation works for decision-makers.     

The future impact of societal and cultural factors on parasitic disease -- some emerging issues

A variety of societal and cultural factors will increase host exposure or susceptibility to infectious agents, particularly parasites. Such factors have already had a major impact on the emergence of infectious diseases and the situation is likely to worsen further as we enter the new millennium. The changes that are enhancing the spread and transmission of parasitic diseases, as well as those which are adversely affecting host responsiveness, are examined with reference to specific parasites.     

Individual variation in reproductive costs of reproduction: high-quality females always do better

1. Although life-history theory predicts substantial costs of reproduction, individuals often show positive correlations among life-history traits, rather than trade-offs. The apparent absence of reproductive costs may result from heterogeneity in individual quality. 2. Using detailed longitudinal data from three contrasted ungulate populations (mountain goats, Oreamnos americanus; bighorn sheep, Ovis canadensis; and roe deer, Capreolus capreolus), we assessed how individual quality affects the probability of detecting a cost of current reproduction on future reproduction for females. We used a composite measure of individual quality based on variations in longevity (all species), success in the last breeding opportunity before death (goats and sheep), adult mass (all species), and social rank (goats only). 3. In all species, high-quality females consistently had a higher probability of reproduction, irrespective of previous reproductive status. In mountain goats, we detected a cost of reproduction only after accounting for differences in individual quality. Only low-quality female goats were less likely to reproduce following years of breeding than of nonbreeding. Offspring survival was lower in bighorn ewes following years of successful breeding than after years when no lamb was produced, but only for low-quality females, suggesting that a cost of reproduction only occurred for low-quality females. 4. Because costs of reproduction differ among females, studies of life-history evolution must account for heterogeneity in individual quality.     

Economic costs of invasive alien ants worldwide

Biological Invasions - Invasive ants are amongst the most destructive and widespread invaders across the globe; they can strongly alter invaded ecosystems and are responsible for the loss of native...     

Long-term impact of war on healthcare costs: an eight-country study

Objective

Exposure to war can negatively affect health and may impact on healthcare costs. Estimating these costs and identifying their predictors is important for appropriate service planning. We aimed to measure use of health services in an adult population who had experienced war in the former-Yugoslavia on average 8 years previously, and to identify characteristics associated with the use and costs of healthcare.

Method

War-affected community samples in Bosnia-Herzegovina, Croatia, Kosovo, FYR Macedonia, and Serbia were recruited through a random walk technique. Refugees in Germany, Italy and the UK were contacted through registers, organisations and networking. Current service use was measured for the previous three months and combined with unit costs for each country for the year 2006/7. A two-part approach was used, to identify predictors of service use with a multiple logistic regression model and predictors of cost with a generalised linear regression model.

Results

3,313 participants were interviewed in Balkan countries and 854 refugees in Western European countries. In the Balkan countries, traumatic events and mental health status were related to greater service use while in Western countries these associations were not found. Participants in Balkan countries with post traumatic stress disorder (PTSD) had costs that were 63% higher (p = 0.005) than those without PTSD. Distress experienced during the most traumatic war event was associated with higher costs (p = 0.013). In Western European countries costs were 76% higher if non-PTSD anxiety disorders were present (0.027) and 63% higher for mood disorders (p = 0.006).

Conclusions

War experiences and their effects on mental health are associated with increased health care costs even many years later, especially for those who stayed in the area of conflict. Focussing on the mental health impact of war is important for many reasons including those of an economic nature.     

Internalized societal attitudes moderate the impact of weight stigma on avoidance of exercise

Experiences with weight stigma negatively impact both psychological outcomes (e.g., body dissatisfaction, depression) and behavioral outcomes (e.g., dieting, exercise). However, not everyone is equally affected by experiences with weight stigma. This study examined whether internalized societal attitudes about weight moderated the impact of weight stigma. Adult participants (n = 111) completed measures of experiences with weight stigma, as well as two indexes of internalized societal attitudes (the moderators): Internalized anti-fat attitudes and internalization of societal standards of attractiveness. Psychological outcomes included self-esteem, body dissatisfaction, drive for thinness, and bulimic symptoms; behavioral outcomes included avoidance of exercise and self-reported exercise behavior. Weight stigma was positively correlated with body dissatisfaction, drive for thinness, and bulimic symptoms, and was negatively correlated with state and trait self-esteem. Both indexes of internalized attitudes moderated the association between weight stigma and avoidance of exercise: Individuals high in anti-fat attitudes and high in internalization of societal standards of attractiveness were more motivated to avoid exercise if they also experienced a high degree of weight stigma; individuals low in anti-fat attitudes and low in internalization were relatively unaffected. Avoidance of exercise was negatively correlated with self-reported strenuous exercise. These findings suggest that weight stigma can negatively influence motivation to exercise, particularly among individuals who have internalized societal attitudes about weight. Reducing internalization might be a means of minimizing the negative impact of weight stigma and of facilitating healthy weight management efforts.     

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways

There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels. This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis hypoactivity in ME/CFS, considering two possibilities: (a) Activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms, or (b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPA axis hypoactivity. Electronic databases, i.e., PUBMED, Scopus, and Google Scholar, were used as sources for this narrative review by using keywords CFS, ME, cortisol, ACTH, CRH, HPA axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, and O&NS. Findings show that activation of immune-inflammatory and O&NS pathways in ME/CFS are probably not secondary to HPA axis hypoactivity and that activation of these pathways may underpin HPA axis hypofunction in ME/CFS. Mechanistic explanations comprise increased levels of tumor necrosis factor-α, T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-β, elevated levels of nitric oxide, and viral/bacterial-mediated mechanisms. HPA axis hypoactivity in ME/CFS is most likely a consequence and not a cause of a wide variety of activated immune-inflammatory and O&NS pathways in that illness.     

The Effect of Perceived Regional Accents on Individual Economic Behavior: A Lab Experiment on Linguistic Performance,Cognitive Ratings and Economic Decisions

Does it matter if you speak with a regional accent? Speaking immediately reveals something of one’s own social and cultural identity, be it consciously or unconsciously. Perceiving accents involves not only reconstructing such imprints but also augmenting them with particular attitudes and stereotypes. Even though we know much about attitudes and stereotypes that are transmitted by, e.g. skin color, names or physical attractiveness, we do not yet have satisfactory answers how accent perception affects human behavior. How do people act in economically relevant contexts when they are confronted with regional accents? This paper reports a laboratory experiment where we address this question. Participants in our experiment conduct cognitive tests where they can choose to either cooperate or compete with a randomly matched male opponent identified only via his rendering of a standardized text in either a regional accent or standard accent. We find a strong connection between the linguistic performance and the cognitive rating of the opponent. When matched with an opponent who speaks the accent of the participant’s home region—the in-group opponent –, individuals tend to cooperate significantly more often. By contrast, they are more likely to compete when matched with an accent speaker from outside their home region, the out-group opponent. Our findings demonstrate, firstly, that the perception of an out-group accent leads not only to social discrimination but also influences economic decisions. Secondly, they suggest that this economic behavior is not necessarily attributable to the perception of a regional accent per se, but rather to the social rating of linguistic distance and the in-group/out-group perception it evokes.