Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping

Myalgic encephalomyelitis; Blood analytics; DiagnosisEncefalomielitis miálgica; Análisis de sangre; DiagnósticoEncefalomielitis miàlgica; Anàlisi de sang; DiagnòsticBackground: Routine blood analytics are systematically used in the clinic to diagnose disease or confirm individuals’ healthy status. For myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease relying exclusively on clinical symptoms for its diagnosis, blood analytics only serve to rule out underlying conditions leading to exerting fatigue. However, studies evaluating complete and large blood datasets by combinatorial approaches to evidence ME/CFS condition or detect/identify case subgroups are still scarce. Methods: This study used unbiased hierarchical cluster analysis of a large cohort of 250 carefully phenotyped female ME/CFS cases toward exploring this possibility. Results: The results show three symptom-based clusters, classified as severe, moderate, and mild, presenting significant differences (p < 0.05) in five blood parameters. Unexpectedly the study also revealed high levels of circulating complement factor C1q in 107/250 (43%) of the participants, placing C1q as a key molecule to identify an ME/CFS subtype/subgroup with more apparent pain symptoms. Conclusions: The results obtained have important implications for the research of ME/CFS etiology and, most likely, for the implementation of future diagnosis methods and treatments of ME/CFS in the clinic.This research was partially funded by the Association of Patients with ME/CFS and Fibromyalgia in Catalonia, Spain (ACAF; www.fibromyalgia.cat (accessed on 23 March 2019) to J.C.-M. and J.A.-M., and by a UCV 2020-270-001 grant to E.O

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

Identificación de biomarcadores del Síndrome de Fatiga Crónica / Encefalomielitis Miálgica en sangre periférica

El Síndrome de Fatiga Crónica / Encefalomielitis Miálgica (SFC/EM) es una enfermedad multisistémica debilitante de etiología desconocida, con prevalencia al alza. Su diagnóstico se basa exclusivamente en parámetros clínicos debido a la ausencia total de biomarcadores específicos. La falta de éxito de los esfuerzos dirigidos a la identificación de biomarcadores de SFC/EM podría deberse a la heterogeneidad de los participantes, las diferencias en el tipo de muestra analizada o las inconsistencias metodológicas entre estudios. Para minimizar estos posibles sesgos, el presente estudio se centró en el análisis de muestras de casos graves procedentes del biobanco monográfico de casos de ME en Reino Unido. El diagnóstico y fenotipado lo realizaron médicos especialistas y las muestras se obtuvieron mediante procedimientos operativos estándar. Nuestros resultados muestran diferencias significativas en la expresión de ciertos microARNs de células mononucleares de sangre periférica (CMSP) y en vesículas extracelulares (VEs). Además, también se observaron diferencias en el número de VEs, tamaño promedio, potencial de membrana, composición y función. Todas estas variables mostraron una capacidad discriminatoria aceptable a nivel individual, indicando su potencial como biomarcadores de la enfermedad.Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a debilitating multisystemic disease of unknown ethiology, with a reported increasing prevalence. Its diagnosis is exclusively based on clinical parameters due to a total absence of specific biomarkers. The lack of success of the efforts towards CFS/ME biomarker identification could be due to participant heterogeneity, differences in the type of sample analyzed or methodological inconsistencies across studies. To minimize these potential biases this study focused on the analysis of samples from severe cases proceeding from the monographic UK ME Biobank. Participants were carefully diagnosed and phenotyped by highly qualified medical specialists and the samples obtained by standard operating procedures (SOPs). Our results show significant differences in the expression of certain microRNAs in PBMCs (peripheral blood mononuclear cells) and in EVs (extracellular vesicles). Additionally differences in EV yields, average size, membrane potential, composition and function were also found. All these variables have shown an acceptable discrimination capacity at the individual level, indicative of their potential as biomarkers of this disease.BiotecnologíaCiencias de la Vida y del Medio Natura

Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking Back on Treatments

Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are diseases of unknown etiology presenting complex and often overlapping symptomatology. Despite promising advances on the study of miRNomes of these diseases, no validated molecular diagnostic biomarker yet exists. Since FM and ME/CFS patient treatments commonly include polypharmacy, it is of concern that biomarker miRNAs are masked by drug interactions. Aiming at discriminating between drug-effects and true disease-associated differential miRNA expression, we evaluated the potential impact of commonly prescribed drugs on disease miRNomes, as reported by the literature. By using the web search tools SM2miR, Pharmaco-miR, and repoDB, we found a list of commonly prescribed drugs that impact FM and ME/CFS miRNomes and therefore could be interfering in the process of biomarker discovery. On another end, disease-associated miRNomes may incline a patient&rsquo;s response to treatment and toxicity. Here, we explored treatments for diseases in general that could be affected by FM and ME/CFS miRNomes, finding a long list of them, including treatments for lymphoma, a type of cancer affecting ME/CFS patients at a higher rate than healthy population. We conclude that FM and ME/CFS miRNomes could help refine pharmacogenomic/pharmacoepigenomic analysis to elevate future personalized medicine and precision medicine programs in the clinic

Contenidos virtuales para neurorrehabilitación funcional de la extremidad superior

La utilización de entornos virtuales de rehabilitación que hacen uso de dispositivos comerciales para el entretenimiento ha adquirido un gran interés en el área de neurorrehabilitación. El objetivo del presente trabajo es diseñar y desarrollar contenidos virtuales (CVs) para rehabilitación funcional en pacientes con Traumatismo Craneoencefálico (TCE). Para ello se han diseñado dos actividades de rehabilitación que hacen uso del sensor de profundidad de bajo coste Microsoft Kinect junto con dispositivos de control, especialmente diseñados para los CVs de rehabilitación, que sirvan como herramienta de monitorización e interacción. Los CVs desarrollados se han basado en actividad

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