A newsletter was sent out today to study participants.I wish there was more data but I clipped study update section.“The Post-Infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (PI-ME/CFS) study has been active since fall of 2016. Our team has decided to put together this newsletter in order to keep all study participants updated in regards to our research. Thus far, we have had 51 study participants - 27 ME/CFS patients and 24 healthy volunteers.Of the 27 ME/CFS patients, 19 have been adjudicated in so far for the second phase of the study after review using an expert physician committee and published guidelines. Basic demographic participant data is shown on the following page.Currently, sixty-two individuals from fourteen different institutes have collaborated in this study, making it truly interdisciplinary. Wide-ranging data analyses are currently underway. They include, but are not limited to:• RNA sequencing by Michael N. Sack, MD., PhD and lab (NHLBI)• Microbiome analysis by Giorgio Trinchieri, MD and lab (NCI/CCR)• Magnetic Resonance Imaging (MRI) and Transcranial Magnetic Stimulationanalysis by Mark Hallett, MD and lab (NINDS)• Autonomic function analysis by David S. Goldstein, MD., PhD and lab (NINDS)• Immunologic function analysis by Dr. Avindra Nath, MD., PhD and Dr. StevenJacobson, PhD (NINDS)The end goal of this study is to explore the clinical and biological phenotypes of PI-ME/CFS, which can then help us generate new hypotheses to understand the mechanistic under- -pinnings of this condition.Figure 1. A map of the United States depicting the residencies of our study participants. ME/CFS Patients (light blue), Healthy Volunteers (mid-blue), and both groups (dark blue). Not pictured is the Canadian territory of Ontario.Figure 2. Table depicting study participants organized by gender and ME/CFS status.Age Range of Participants76543210Figure 3. Graphical depiction of the range, average, maximum, and minimum values of age of study participants during initial, phenotyping visit.GenderMale FemaleME/CFS Healthy Volunteers14 12 13 1218 to 24 25 to 34 35 to 44 45 to 54 55 to 60 Age GroupME/CFS Healthy VolunteersNumber of ParticipantsThe Bioenergetics of ME/CFSwith Dr. Rebekah FengExtreme fatigue and post-exertional malaise (PEM) are two cardinal characteristicsof ME/CFS. Both are prominent features of the International Consensus Criteria (ICC),the Fukuda Criteria, and the Canadian Criteria of ME/CFS. One method by which we can explore these complex symptoms is to understand the processes that lead to the production and utilization of energy.The fundamental energy currency of our body at the molecular level isadenosine triphosphate (ATP) [figure 4]. It is required for nearly all cellular processes, including the immune response and muscle contraction. The majority of ATP (nearly 90 per- -cent) is produced by the mitochondria, the “powerhouse” of the cell. Dysfunction of the mitochondria leads to inefficiency of energy production, affecting all systems of the body. For example, the symptoms of many mitochondrial myopathies include exercise intolerance, elevated markers of muscle injury, fatigue, and muscle pain.H2NHigh energy bond NOOO N OPOPOPO ONOOOFigure 4. Adenosine Triphosphate. The energy from this molecule comes from the phosphate bonds.OH OHOne way we are measuring mitochondrial function at the NIH is by using the extracellular flux assay. This work is being overseen by Dr. Rebekah Feng and her lab. “This assay,”Dr. Feng states, “allows us to examine how efficiently our peripheral blood mononuclear cells are producing energy. Specifically, it measures two variables. The first is oxygen con- -sumption and the second is proton concentration.” Oxygen consumption plays a vital rolein aerobic respiration, the efficient process by which mitochondria produce between 30 and 36 ATP molecules. Proton concentration, on the other hand, allows us to measure glycolysis, the inefficient and anaerobic process by which our cells convert glucose into pyruvate, which produces only 2 ATP molecules. Analyzing the relationship and ratio of rates of these two processes can help us better understand mitochondrial efficiency in ME/CFS.“In regards to the current project, we have had some pretty interesting findings. Even with the current sample size, the data is still statistically significant. We saw changes in mito- chondrial function from before exercise to after exercise in ME/CFS patients, compared to their matched controls. That tells us that there may be something going on at the cellular level.” says Dr. Feng.As far as future directions, Dr. Feng and her group are looking to explore bioenergetics in muscle tissue extracted via the muscle biopsies that many of you have undergone, in addition to PBMCs.Dr. Rebekah Feng is a research fellow at the NIH. She received her Ph.D in Neuroscience from GeorgetownUniversity, and since then has published over thirty peer- reviewed articles in esteemed journals such as Science and Oncology. Her current research focuses on mechanisms of fatigue in chronic conditions such as cancer and ME/CFS.”