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

Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology

Síndrome de fatiga crònica; Diferències de gènere; Variabilitat de la freqüència cardíacaSíndrome de fatiga crónica; Diferencias de género; Variabilidad del ritmo cardíacoChronic fatigue syndrome; Gender differences; Heart rate variabilityIn a previous study using mobile-health technology (mHealth), we reported a robust association between chronic fatigue symptoms and heart rate variability (HRV) in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study explores HRV analysis as an objective, non-invasive and easy-to-apply marker of ME/CFS using mHealth technology, and evaluates differential gender effects on HRV and ME/CFS core symptoms. In our methodology, participants included 77 ME/CFS patients (32 men and 45 women) and 44 age-matched healthy controls (19 men and 25 women), all self-reporting subjective scores for fatigue, sleep quality, anxiety, and depression, and neurovegetative symptoms of autonomic dysfunction. The inter-beat cardiac intervals are continuously monitored/recorded over three 5-min periods, and HRV is analyzed using a custom-made application (iOS) on a mobile device connected via Bluetooth to a wearable cardiac chest band. Male ME/CFS patients show increased scores compared with control men in all symptoms and scores of fatigue, and autonomic dysfunction, as with women in the first study. No differences in any HRV parameter appear between male ME/CFS patients and controls, in contrast to our findings in women. However, we have found negative correlations of ME/CFS symptomatology with cardiac variability (SDNN, RMSSD, pNN50, LF) in men. We have also found a significant relationship between fatigue symptomatology and HRV parameters in ME/CFS patients, but not in healthy control men. Gender effects appear in HF, LF/HF, and HFnu HRV parameters. A MANOVA analysis shows differential gender effects depending on the experimental condition in autonomic dysfunction symptoms and HF and HFnu HRV parameters. A decreased HRV pattern in ME/CFS women compared to ME/CFS men may reflect a sex-related cardiac autonomic dysfunction in ME/CFS illness that could be used as a predictive marker of disease progression. In conclusion, we show that HRV analysis using mHealth technology is an objective, non-invasive tool that can be useful for clinical prediction of fatigue severity, especially in women with ME/CFS.This research was funded by “Ministerio de Ciencia e Innovación” of the Spanish Government, grant number PID2019-107473RB-C2

Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Coenzima Q10; Mitocondrias; Encefalomielitis miálgicaCoenzyme Q10; Mitochondria; Myalgic encephalomyelitisCoenzim Q10; Mitocondris; Encefalomielitis miàlgicaMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating neuroimmune disease, probably of post-viral multifactorial etiology. Unfortunately, no accurate diagnostic or laboratory tests have been established, nor are any universally effective approved drugs currently available for its treatment. This study aimed to examine whether oral coenzyme Q10 and NADH (reduced form of nicotinamide adenine dinucleotide) co-supplementation could improve perceived fatigue, unrefreshing sleep, and health-related quality of life in ME/CFS patients. A 12-week prospective, randomized, double-blind, placebo-controlled trial was conducted in 207 patients with ME/CFS, who were randomly allocated to one of two groups to receive either 200 mg of CoQ10 and 20 mg of NADH (n = 104) or matching placebo (n = 103) once daily. Endpoints were simultaneously evaluated at baseline, and then reassessed at 4- and 8-week treatment visits and four weeks after treatment cessation, using validated patient-reported outcome measures. A significant reduction in cognitive fatigue perception and overall FIS-40 score (p < 0.001 and p = 0.022, respectively) and an improvement in HRQoL (health-related quality of life (SF-36)) (p < 0.05) from baseline were observed within the experimental group over time. Statistically significant differences were also shown for sleep duration at 4 weeks and habitual sleep efficiency at 8 weeks in follow-up visits from baseline within the experimental group (p = 0.018 and p = 0.038, respectively). Overall, these findings support the use of CoQ10 plus NADH supplementation as a potentially safe therapeutic option for reducing perceived cognitive fatigue and improving the health-related quality of life in ME/CFS patients. Future interventions are needed to corroborate these clinical benefits and also explore the underlying pathomechanisms of CoQ10 and NADH administration in ME/CFS.J.C.-M. received financial support and honoraria from Vitae Health Innovation Co., S.L. (Montmeló, Barcelona, Spain). This study was partially supported by the Vall d’Hebron Hospital Research Institute (Barcelona, Spain). Vitae Health Innovation Co. supplied both treatments (Coenzyme Q10 and NADH supplement tablets and placebo)

European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe

Encefalomielitis miàlgica/síndrome de fatiga crònica; Cura; DiagnòsticMyalgic encephalomyelitis/chronic fatigue syndrome; Care; DiagnosisEncefalomielitis miálgica/síndrome de fatiga crónica; Cuidado; DiagnósticoDesigned by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)—COST action 15111—from 2016 to 2020. The main goal of the Cost Action was to assess the existing knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report our findings and make recommendations for clinical diagnosis, health services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS.This research received no external funding. EUROMENE receives funding for networking activities from the COST programme (COST Action 15111), via the COST Association

Diagnóstico operativo empresarial de la empresa Acería del Ecuador C.A.

El presente diagnóstico operativo se realizó en la empresa Acerías del Ecuador, mejor conocida como ADELCA C.A., su actividad principal es la transformación de chatarra en productos de acero y la distribución de su mercancía a lo largo del territorio Ecuatoriano y en los países vecinos; a través de su sistema de producción y distribución, ADELCA satisface las necesidades del sector construcción, metalmecánico e industrial, por ello, el desarrollo del presente trabajo se enfoca en evaluar el estado de las prácticas organizacionales y operativas bajo las cuales se rige empresa. Para desarrollar la evaluación propuesta, se recopiló información en cuanto a la ubicación y dimensionamiento de planta, planeamiento y diseño de productos, planeamiento y diseño del trabajo, planeamiento agregado, programación de las operaciones productivas, gestión logística, gestión de costos, gestión y control de la calidad, gestión del mantenimiento y gestión de la cadena de suministro. Del tratamiento de la información recopilada y el contraste con las mejores prácticas, se sugieren propuesta de mejora que abordan el incremento de la productividad y eficiencia de los procesos, todo ello con el fin de generar un impacto positivo en el estado de resultados. La implementación de las propuestas permitirá que la empresa elimine sobre costos y genere ahorros aproximados de USD 23’033,331.63 con una inversión de USD 13’494,040.00 aportando un beneficio económico de USD 9’539,291.63, los cuales no sólo brindarán mayor competitividad a la empresa, también aportarán valor al ciclo operacional incrementando la posibilidad de perdurabilidad en el mercado nacional e internacional.The current operative diagnosis was performed in the company Acerías del Ecuador, better known as ADELCA C.A., the main activity is to transform the scrap into steel products and the distribution of its merchandise throughout the Ecuadorian territory and in neighboring countries; through its production and distribution system, ADELCA meets the needs of the construction, metalworking and industrial sectors, Therefore, the development of this work is focused on evaluating the state of the organizational and operational practices under which the company is governed. To develop the proposed evaluation, the information was collected regarding the location and sizing of the plant, planning and design of products, planning and design of work, aggregate planning, programming of productive operations, logistics management, cost management, management and quality control, maintenance management, and supply chain management. Based on the information collected and the contrast with the best practices, improvement proposals are suggested that address the increase the productivity and efficiency of the processes, with the purpose of generating a positive impact on the income statement. The implementation of the proposals will allow the company to eliminate costs and generate savings of approximately USD 23’033,331.63. The entity would invest USD 13’494,040.00 to obtain a benefit of USD 9’539,291.63 which will not only provide greater competitiveness to the company, they will also add value to the operational cycle, increasing its presence in the local and international markets.Tesi

The Conners Continuous Performance Test CPT3™: Is it a reliable marker to predict neurocognitive dysfunction in Myalgic encephalomyelitis/chronic fatigue syndrome?

Chronic fatigue syndrome; Continuous performance test; Neurocognitive dysfunctionSíndrome de fatiga crónica; Prueba de rendimiento continuo; Disfunción neurocognitivaSíndrome de fatiga crònica; Prova de rendiment contínua; Disfunció neurocognitivaIntroduction: The main objective is to delimit the cognitive dysfunction associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in adult patients by applying the Continuous Performance Test (CPT3™). Additionally, provide empirical evidence on the usefulness of this computerized neuropsychological test to assess ME/CFS. Method: The final sample (n = 225; 158 Patients/67 Healthy controls) were recruited in a Central Sensitization Syndromes (CSS) specialized unit in a tertiary hospital. All participants were administered this neuropsychological test. Results: There were significant differences between ME/CFS and healthy controls in all the main measures of CPT3™. Mainly, patients had a worse indicator of inattentiveness, sustained attention, vigilance, impulsivity, slow reaction time, and more atypical T-scores, which is associated with a likelihood of having a disorder characterized by attention deficits, such as Attention Deficit Hyperactivity Disorder (ADHD). In addition, relevant correlations were obtained between the CPT3™ variables in the patient's group. The most discriminative indicators of ME/CFS patients were Variability and Hit Reaction Time, both measures of response speed. Conclusion: The CPT3™ is a helpful tool to discriminate neurocognitive impairments from attention and response speed in ME/CFS patients, and it could be used as a marker of ME/CFS severity for diagnosing or monitoring this disease

Personalized Management of Fatigue in Individuals With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Using a Smart Digital mHealth Solution: Protocol for a Participatory Design Approach

Fatigue; Myalgic encephalomyelitis/chronic fatigue syndrome; Personalized self-managementFatiga; Encefalomielitis miálgica/síndrome de fatiga crónica; Autogestión personalizadaFatiga; Encefalomielitis miàlgica/síndrome de fatiga crònica; Autogestió personalitzadaBackground: Fatigue is the most common symptom in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, impacting patients’ quality of life; however, there is currently a lack of evidence-based context-aware tools for fatigue self-management in these populations. Objective: This study aimed to (1) address fatigue in ME/CFS and long COVID through the development of digital mobile health solutions for self-management, (2) predict perceived fatigue severity using real-time data, and (3) assess the feasibility and potential benefits of personalized digital mobile health solutions. Methods: The MyFatigue project adopts a patient-centered approach within the participatory health informatics domain. Patient representatives will be actively involved in decision-making processes. This study combines inductive and deductive research approaches, using qualitative studies to generate new knowledge and quantitative methods to test hypotheses regarding the relationship between factors like physical activity, sleep behaviors, and perceived fatigue in ME/CFS and long COVID. Co-design methods will be used to develop a personalized digital solution for fatigue self-management based on the generated knowledge. Finally, a pilot study will evaluate the feasibility, acceptance, and potential benefits of the digital health solution. Results: The MyFatigue project opened to enrollment in November 2023. Initial results are expected to be published by the end of 2024. Conclusions: This study protocol holds the potential to expand understanding, create personalized self-management approaches, engage stakeholders, and ultimately improve the well-being of individuals with ME/CFS and long COVID.This study received funding from the Spanish Ministry of Science and Innovation (Knowledge Generation Project Grant PID-2021-125528OB-I00), and it was cofunded by the 2020 European Union’s Research and Innovation Funding Program

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.&lt;p&gt;&lt;/p&gt; Methods: Sixty-six non-HLA SNPs showing a P value &#60;10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.&lt;p&gt;&lt;/p&gt; Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials

[EN] Purpose—To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods—Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results—Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of “operational cure” was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion—Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM

A regulated deficit irrigation strategy for hedgerow olive orchards with high plant density

Background & Aims There is not a consensus on the best irrigation approach for super-high density (SHD) olive orchards. Our aim was to design and test a regulated deficit irrigation (RDI) strategy for a sustainable balance between water saving, tree vigour and oil production. Methods We tested our RDI strategy for 3 years in an ‘Arbequina’ orchard with 1,667 trees ha−1. Two levels of irrigation reduction were applied, 60RDI and 30RDI, scaled to replacing 60 % and 30 %, respectively, of the of irrigation needs (IN). We also had a full irrigation (FI) treatment as control, with IN totalling 4,701 m3 ha−1 Results The 30RDI treatment showed the best balance between water saving, tree vigour and oil production. With a yearly irrigation amount (IA) of 1,366 m3 ha−1, which meant 72 % water saving as compared to FI, the reduction in oil yield was 26 % only. Conclusions Our results, together with recent knowledge on the effect of water stress on fruit development, allowed us to suggest a potentially improved RDI strategy for which a total IA of ca. 2,100 m3 ha−1 was calculated. Both some management details and the benefits of this suggested RDI strategy are still to be tested