Research Research Digest Research Digest 11/12/20 Welcome to the 61st Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles. You can also join our community and choose to have the Digest delivered straight to your inbox every fortnight on a Friday afternoon by signing up to our mailing list here. We appreciate the support of everyone who reads the Digest – we encourage regular subscribers to support us with a monthly suggested donation of $2. You can sign up for monthly giving here. Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology Authors: Nepotchatykh E, Elremaly W, Caraus I, Godbout C, Leveau C, Chalder L, ... Moreau A (Université de Montréal, Canada)Publication: Scientific ReportsLink: https://www.nature.com/articles/s41598-020-76438-y This study performed extensive profiling of circulating micro RNAs (miRNAs) on plasma samples of housebound patients with severe ME/CFS, both at baseline and in response to the application of a post-exertional stress challenge.Two cohorts were examined: a discovery cohort of 11 ME/CFS patients and eight matched controls, and a replication cohort of 32 ME/CFS patients and 17 matched controls. The ME/CFS patients were diagnosed using the Canadian Consensus Criteria. A 90-minute post-exertional stress challenge, which involved an inflatable cuff applied to the arm of each participant, was used to stimulate post-exertional malaise (PEM). Blood samples were taken both before and after the stress challenge to determine changes in miRNA expression.The analysis identified 11 miRNAs associated with ME/CFS in response to the post-exertional stress challenge. Of these 11, six were found to be significantly higher at baseline in ME/CFS patients than controls, and three were found to be significantly higher after the stress test in ME/CFS patients. Modelling using the 11 miRNAs could predict ME/CFS with 90% accuracy, and also identified four clusters associated with different symptom severity. The authors conclude that this protocol could be developed into a new non-invasive diagnostic test for ME/CFS. Accurate and objective determination of myalgic encephalomyelitis/chronic fatigue syndrome disease severity with a wearable sensor Author: Palombo T, Campos A, Vernon SD, Roundy S (University of Utah, USA)Publisher: Journal of Translational MedicineLink: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02583-7 This pilot study aimed to test the use of a sensor-based method of measuring upright activity, defined as time with feet on the floor and referred to as UpTime, as an indicator of ME/CFS severity. A total of 15 participants were included (five healthy controls, five participants with moderate-level ME/CFS and five participants with severe-level ME/CFS). UpTime was measured with an inertial measurement unit (IMU) called Shimmer and was defined as critical leg angles of less than 39 degrees from vertical, which indicated foot on floor time (see Figure 1 below). Measurements were taken over six days, three days before and after an orthostatic challenge.Results showed that UpTime was a significant measure of ME/CFS severity. Severely ill ME/CFS patients spent less than 20% of each day with feet on the floor. Moderately ill ME/CFS patients spent between 20–30% of each day with feet on the floor. Healthy controls had greater than 30% UpTime per day. Participants tended to overestimate their hours upright activity (HUA) and there was no relationship between subjective HUA ratings and UpTime measurements in either patient groups. The authors conclude that IMU UpTime is an accurate and objective measure of upright activity and could be used to measure ME/CFS patient severity, although it requires further study in a larger cohort. It could also be useful as an outcome measure for clinical trials to evaluate the efficacy of treatments. Figure 1. The critical angle (θc) of a participants lower leg allowed the authors to determine whether a participant was standing upright (feet on the floor) or not upright. In this study, the critical angle was equal to 39 degrees from vertical. Leg angles of less than 39 degrees indicated that a participants foot was on the floor (highlighted in blue) and angles greater than 39 degrees indicated that the lower leg was reclined/horizontal (highlighted in red). Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome in Japanese population Authors: Kitami T, Fukuda S, Kato T, Yamaguti K, Nakatomi Y, Yamano E, ... Watanabe Y (Osaka City University, Japan)Publication: Scientific Reports Link: https://www.nature.com/articles/s41598-020-77105-y Despite several omics studies in ME/CFS, differences in patient cohorts between studies make it difficult to relate results found between one type of omics study and the results found in another. The purpose of this study was to undertake deep phenotyping of ME/CFS across five different molecular platforms, using the same patient cohort, to identify potential markers of ME/CFS and uncover relationships between these markers for insights into the condition.This Japanese cohort consisted of 48 ME/CFS patients (diagnosed according to the Fukuda criteria and International Consensus Criteria) and 52 matched controls. Multi-omics profiling of blood and faecal samples was undertaken. Participants also completed questionnaires and simple cognitive tests, and actigraphy was used to measure sleep and activity.The analysis identified 26 potential molecular markers of ME/CFS. Monocyte number, microbiome profiles and lipoprotein profiles were the most useful for distinguishing patients from controls, though the authors noted that approximately half of the patients could not be distinguished from controls using the identified markers. Lipoprotein and microbiome profiles most closely correlated with sleep disruption while other markers (such as increased faecal Coprobacillus bacteria) correlated with a cognitive parameter.The authors note that a limitation of their study is that some of the markers identified may reflect comorbidities of ME/CFS (such as irritable bowel syndrome or depression) rather than ME/CFS itself.Given that unrefreshing sleep is a key feature of ME/CFS, the authors suggest that molecular markers of sleep disturbance in ME/CFS should be explored as potential diagnostic markers. Finding hope for those living with Chronic Fatigue Syndrome Author: Harper H (ABC)Publication: Life Matters, ABC Radio NationalLink: https://www.abc.net.au/radionational/programs/lifematters/finding-hope-for-those-living-with-chronic-fatigue-syndrome/12761110In a recent episode of ABC Radio National's Life Matters, host Hilary Harper spoke with ME/CFS patient Sue Collins, Emerge Australia CEO Dr Heidi Nicholl and Deakin University researcher Professor Ken Walder about ME/CFS.The segment covered the impact of ME/CFS on those living with the disease, the importance of support services and networks, and new research being conducted in Melbourne at Deakin University..The segment runs for approximately 16 minutes.