as a result of decreased NK cell regulation or viral mimicry. In 2015, a large German study found 29% of ME/CFS patients had elevated autoantibodies to M3 and M4 muscarinic acetylcholine receptors as well as to ß2 adrenergic receptors. A 2016 Australian study found that ME/CFS patients had significantly greater numbers of single nucleotide polymorphisms associated with the gene encoding for M3 muscarinic acetylcholine receptors. Energy metabolism Studies have observed mitochondrial abnormalities in cellular energy production, but recent focus has concentrated on secondary effects that may result in aberrant mitochondrial function because inherent problems with the mitochondria structure or genetics have not been replicated. Diagnosis No characteristic laboratory abnormalities are approved to diagnose CFS; while physical abnormalities can be found, no single finding is considered sufficient for diagnosis. Blood, urine, and other tests are used to rule out other conditions that could be responsible for the symptoms. The CDC states that a medical history should be taken and a mental and physical examination should be done to aid diagnosis. Diagnostic tools The CDC recommends considering the questionnaires and tools described in the 2015 Institute of Medicine report, which include: The Chalder Fatigue Scale Multidimensional Fatigue Inventory Fisk Fatigue Impact Scale The Krupp Fatigue Severity Scale DePaul Symptom Questionnaire CDC Symptom Inventory for CFS Work and Social Adjustment Scale (WSAS) SF-36 / RAND-36 A two-day cardiopulmonary exercise test (CPET) is not necessary for diagnosis, although lower readings on the second day may be helpful in supporting a claim for social security disability. A two-day CPET cannot be used to rule out chronic fatigue syndrome. Definitions Notable definitions include: Centers for Disease Control and Prevention (CDC) definition (1994), the most widely used clinical and research description of CFS, is also called the Fukuda definition and is a revision of the Holmes or CDC 1988 scoring system. The 1994 criteria require the presence of four or more symptoms beyond fatigue, while the 1988 criteria require six to eight. The ME/CFS 2003 Canadian Clinical working definition states: "A patient with ME/CFS will meet the criteria for fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; have two or more neurological/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendocrine, and immune manifestations; and the illness persists for at least 6 months". The Myalgic Encephalomyelitis International Consensus Criteria (ICC) published in 2011 is based on the Canadian working definition and