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1.
BMC Musculoskelet Disord ; 22(1): 419, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952227

RESUMO

BACKGROUND: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) sometimes present with stiffness of the cervical muscles. To investigate the pathophysiology of ME/CFS, this observational study compared patients with versus without recovery from ME/CFS through local modulation of the cervical muscles. METHODS: Over a period of 11 years, a total of 1226 inpatients with ME/CFS who did not respond to outpatient care were enrolled in this study. All patients received daily cervical muscle physical therapy during hospitalization. Self-rated records documenting the presence or absence of ME/CFS, as well as the representative eight symptoms that frequently accompany it at admission and discharge, were compared. Pupil diameter was also measured to examine autonomic nervous system function involvement. RESULTS: The recovery rate of ME/CFS after local therapy was 55.5%, and did not differ significantly by sex, age strata, and hospitalization period. The recovery rates of the eight symptoms were variable (36.6-86.9%); however, those of ME/CFS in the symptom subpopulations were similar (52.3-55.8%). The recovery rates of all symptoms showed strong associations with that of ME/CFS (p < 0.001). The pupil diameter was more constricted in the ME/CFS-recovered patients than in the ME/CFS-unrecovered patients in the total population and the subpopulations stratified by sex, age, and hospitalization period. CONCLUSIONS: There was a strong association between the recovery of ME/CFS and other related whole-body symptoms. The recovery of ME/CFS may be partly linked to amelioration of the autonomic nervous system in the cervical muscles. TRIAL REGISTRATION: UMIN000036634 . Registered 1 May 2019 - Retrospectively registered.


Assuntos
Síndrome de Fadiga Crônica , Sistema Nervoso Autônomo , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/epidemiologia , Humanos , Músculos
2.
J Orthop Sports Phys Ther ; 51(5): 197-200, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33930983

RESUMO

SYNOPSIS: The term long COVID was coined by patients to describe the long-term consequences of COVID-19. One year into the pandemic, it was clear that all patients-those hospitalized with COVID-19 and those who lived with the disease in the community-were at risk of developing debilitating sequelae that would impact their quality of life. Patients with long COVID asked for rehabilitation. Many of them, including previously healthy and fit clinicians, tried to fight postviral fatigue with exercise-based rehabilitation. We observed a growing number of patients with long COVID who experienced adverse effects from exercise therapy and symptoms strikingly similar to those of myalgic encephalomyelitis (ME). Community-based physical therapists, including those in private practice, unaware of safety issues, are preparing to help an influx of patients with long COVID. In this editorial, we expose growing concerns about long COVID and ME. We issue safety recommendations for rehabilitation and share resources to improve care for those with postviral illnesses. J Orthop Sports Phys Ther 2021;51(5):197-200. doi:10.2519/jospt.2021.0106.


Assuntos
/complicações , Síndrome de Fadiga Crônica/etiologia , Síndrome de Fadiga Crônica/terapia , Fadiga/etiologia , Fadiga/terapia , Terapia por Exercício/efeitos adversos , Humanos , Qualidade de Vida , Descanso
3.
Medicine (Baltimore) ; 100(18): e25742, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950958

RESUMO

BACKGROUND: The pathogenesis of chronic fatigue syndrome (CFS) is not clear. The main purpose of treatment is to improve autoimmune function and relieve fatigue symptoms. Moxibustion is often used to treat diseases caused by low autoimmunity, especially in relieving fatigue symptoms. It is a superior therapy for CFS in traditional Chinese medicine. At present, there is a lack of the high level clinical evidence to support the moxibustion in the treatment of CFS, so this study will systematically review and analyze the currently available randomized controlled trials to evaluate the efficacy and safety of moxibustion in the treatment of CFS. METHODS: We will systematically search PubMed, EMBASE, Cochrane library, Sinomed, CNKI, VIP, and Wanfang Database, ClinicalTrials.gov and Chinese Clinical Trial Registry will also be searched. The time range for the search will be from database activation to March 31, 2021. The randomized controlled trials (RCTs) associated with moxibustion for CFS will be included, regardless of language.We will use the standard proposed in Cochrane Handbook 5.1.0 to assess the bias risk of a single RCT. The main outcome index of the study is Fatigue Assessment Instrument (FAI), secondary outcome indexes will include Fatigue Scale -14 (FS-14), Fatigue Severity Scale (FSS), Pittsburgh sleep quality index (PSQI), natural killer (NK) cells, interleukin- 2 (IL-2), T lymphocyte subsets (CD4+, CD8+), cure rate, total efficiency and adverse reactions. The random effect model meta was used to analyze the effect data of a single RCT. Heterogeneity will be measured by Cochran Q test and I-squared statistics. We will use 2 subgroup analyses to explore the source of heterogeneity. RCTs with high bias risk was excluded and adjustment effect model was used for sensitivity analysis to test the robustness of the meta-analysis results. The publication bias included in RCTs will be assessed by funnel plot and Egger test. RESULTS: This study will objectively and comprehensively evaluate the efficacy and safety of randomized controlled trials of moxibustion in the treatment of chronic fatigue syndrome, and the results will be submitted to peer-reviewed journals for publication. CONCLUSION: This systematic review will provide clinicians with the latest high-quality evidence for the use of moxibustion in the treatment of chronic fatigue syndrome. INPLASY REGISTRATION NUMBER: INPLASY202140063.


Assuntos
Síndrome de Fadiga Crônica/terapia , Moxibustão/efeitos adversos , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
4.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806649

RESUMO

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is one of the most refractory diseases in humans and is characterized by severe central fatigue accompanied with various symptoms that affect daily life, such as impaired memory, depression, and somatic pain. However, the etiology and pathophysiological mechanisms of CFS remain unknown. To investigate the pathophysiological role of transforming growth factor (TGF)-ß1, we injected a cytokine into the lateral ventricle of a C57BL/6 mouse. The intracranial injection of TGF-ß1 increased the immobility duration in a forced swimming test (FST) and time spent at the closed arm in elevated plus maze (EPM) analysis. The mice injected with TGF-ß1 into their brain showed increased sensitivity to pain in a von Frey test, and had a decreased retention time on rotarod and latency time in a bright box in a passive avoidance test. In addition, the serum levels of muscle fatigue biomarkers, lactate dehydrogenase (LDH) and creatine kinase (CK), were significantly increased after administration of TGF-ß1. Intracranial injection of TGF-ß1 significantly reduced the production of tyrosine hydroxylase (TH) in the ventral tegmental area, accompanied by a decreased level of dopamine in the striatum. The suppression of TH expression by TGF-ß1 was confirmed in the human neuroblastoma cell line, SH-SY5Y. These results, which show that TGF-ß1 induced fatigue-like behaviors by suppressing dopamine production, suggest that TGF-ß1 plays a critical role in the development of central fatigue and is, therefore, a potential therapeutic target of the disease.


Assuntos
Dopamina/metabolismo , Fadiga/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Área Tegmentar Ventral/metabolismo , Animais , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Síndrome de Fadiga Crônica/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Natação/fisiologia
5.
Medicine (Baltimore) ; 100(14): e24572, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832063

RESUMO

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating chronic disease of unknown etiology that is recognized by the World Health Organization (WHO) and the United States Center for Disease Control and Prevention (US CDC) as a disorder of the brain. CFS affects 1% (17-24 million people) of the world's population and is a major and costly public health problem. In traditional Chinese medicine (TCM), acupuncture can achieve a certain effect in the treatment of chronic fatigue syndrome, but evidence-based medicine is controversial. This protocol aims to multi-evaluate the literature quality and evidence quality of the current systematic reviews (SRs)/meta-analyses (MAs) of acupuncture treatment for chronic fatigue syndrome, and provide intuitive and reliable evidence synthesis and decision-making basis for clinical treatment. METHODS: Eight databases will be searched from their inception to 1 June, 2020: the Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed, and Cochrane Library. Published systematic reviews that were reported in Chinese or English, and the included studies were randomized controlled clinical trials (RCTs) for acupuncture in people with CFS will be included. Reviews selection, data extraction and management, and assessment of the study quality will be completed independently by 2 or more reviewers. The quality of evidence, methodological quality, and reporting quality will be evaluated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), A Measurement Tool to Assessment of Multiple Systematic Reviews-2 (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Adobe Illustrator Creative Cloud (Adobe Illustrator CC) will be used to draw and optimize the radar plot. RESULTS: The article in this overview will be submitted for publication in a peer-reviewed journal. CONCLUSION: We hope to collect evidence from accessible and useful systematic reviews of acupuncture treatment for chronic fatigue syndrome, to provide visual and scientific decision-making methods for more clinical practice and medical research. SYSTEMATIC REVIEW REGISTRATION: INPLASY 202060052.


Assuntos
Terapia por Acupuntura/métodos , Síndrome de Fadiga Crônica/terapia , Humanos , Revisões Sistemáticas como Assunto
6.
J Transl Med ; 19(1): 159, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33874961

RESUMO

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease accompanied by muscular fatigue and pain. A functional measure to assess muscle fatigability of ME/CFS patients is, however, not established in clinical routine. The aim of this study is to evaluate by assessing repeat maximum handgrip strength (HGS), muscle fatigability as a diagnostic tool and its correlation with clinical parameters. METHODS: We assessed the HGS of 105 patients with ME/CFS, 18 patients with Cancer related fatigue (CRF) and 66 healthy controls (HC) using an electric dynamometer assessing maximal (Fmax) and mean force (Fmean) of ten repetitive measurements. Results were correlated with clinical parameters, creatinine kinase (CK) and lactate dehydrogenase (LDH). Further, maximum isometric quadriceps strength measurement was conducted in eight ME/CFS patients and eight HC. RESULTS: ME/CFS patients have a significantly lower Fmax and Fmean HGS compared to HC (p < 0.0001). Further, Fatigue Ratio assessing decline in strength during repeat maximal HGS measurement (Fmax/Fmean) was higher (p ≤ 0.0012). The Recovery Ratio after an identical second testing 60 min later was significantly lower in ME/CFS compared to HC (Fmean2/Fmean1; p ≤ 0.0020). Lower HGS parameters correlated with severity of disease, post-exertional malaise and muscle pain and with higher CK and LDH levels after exertion. CONCLUSION: Repeat HGS assessment is a sensitive diagnostic test to assess muscular fatigue and fatigability and an objective measure to assess disease severity in ME/CFS.


Assuntos
Síndrome de Fadiga Crônica , Síndrome de Fadiga Crônica/diagnóstico , Força da Mão , Humanos , Dor
7.
J Transl Med ; 19(1): 162, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882940

RESUMO

Chronic Fatigue Syndrome or Myalgic Encephaloymelitis (ME/CFS) is a frequent debilitating disease with an enigmatic etiology. The finding of autoantibodies against ß2-adrenergic receptors (ß2AdR) prompted us to hypothesize that ß2AdR dysfunction is of critical importance in the pathophysiology of ME/CFS. Our hypothesis published previously considers ME/CFS as a disease caused by a dysfunctional autonomic nervous system (ANS) system: sympathetic overactivity in the presence of vascular dysregulation by ß2AdR dysfunction causes predominance of vasoconstrictor influences in brain and skeletal muscles, which in the latter is opposed by the metabolically stimulated release of endogenous vasodilators (functional sympatholysis). An enigmatic bioenergetic disturbance in skeletal muscle strongly contributes to this release. Excessive generation of these vasodilators with algesic properties and spillover into the systemic circulation could explain hypovolemia, suppression of renin (paradoxon) and the enigmatic symptoms. In this hypothesis paper the mechanisms underlying the energetic disturbance in muscles will be explained and merged with the first hypothesis. The key information is that ß2AdR also stimulates the Na+/K+-ATPase in skeletal muscles. Appropriate muscular perfusion as well as function of the Na+/K+-ATPase determine muscle fatigability. We presume that dysfunction of the ß2AdR also leads to an insufficient stimulation of the Na+/K+-ATPase causing sodium overload which reverses the transport direction of the sodium-calcium exchanger (NCX) to import calcium instead of exporting it as is also known from the ischemia-reperfusion paradigm. The ensuing calcium overload affects the mitochondria, cytoplasmatic metabolism and the endothelium which further worsens the energetic situation (vicious circle) to explain postexertional malaise, exercise intolerance and chronification. Reduced Na+/K+-ATPase activity is not the only cause for cellular sodium loading. In poor energetic situations increased proton production raises intracellular sodium via sodium-proton-exchanger subtype-1 (NHE1), the most important proton-extruder in skeletal muscle. Finally, sodium overload is due to diminished sodium outward transport and enhanced cellular sodium loading. As soon as this disturbance would have occurred in a severe manner the threshold for re-induction would be strongly lowered, mainly due to an upregulated NHE1, so that it could repeat at low levels of exercise, even by activities of everyday life, re-inducing mitochondrial, metabolic and vascular dysfunction to perpetuate the disease.


Assuntos
Síndrome de Fadiga Crônica , Sistema Nervoso Autônomo , Metabolismo Energético , Humanos , Mitocôndrias , Músculo Esquelético
8.
Medicina (Kaunas) ; 57(3)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806902

RESUMO

Background and Objectives: A comparative survey of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients was carried out in three countries, with the aim of identifying appropriate policy measures designed to alleviate the burden of disease both on patients and their families, and also on public institutions. The survey addressed demographic features, the economic impact of the disease on household incomes, patterns of medical and social care, specific therapies, social relationships, and the impact of the illness on quality of life. Materials and Methods: Parallel surveys were undertaken in Italy, Latvia, and the UK. There were 88 completed responses from Italy, 75 from Latvia, and 448 from the UK. To facilitate comparisons, 95% confidence intervals were calculated in respect of responses to questions from all three countries. To explore to what extent general practitioners (GPs) manage ME/CFS disease, a separate questionnaire for GPs, with questions about the criteria for granting a diagnosis, laboratory examinations, the involvement of specialists, and methods of treatment, was undertaken in Latvia, and there were 91 completed responses from GPs. Results: The results are presented in respect of sociodemographic information, household income, disease progression and management, perceived effectiveness of treatment, responsibility for medical care, personal care, difficulty explaining the illness, and quality of life. Demographic details were similar in all three countries, and the impact of illness on net household incomes and quality of life. There were significant differences between the three countries in illness progression and management, which may reflect differences in patterns of health care and in societal attitudes. Graded exercise therapy, practiced in the UK, was found to be universally ineffective. Conclusions: There were similarities between respondents in all three countries in terms of demographic features, the impact of the illness on household incomes and on quality of life, and on difficulties experienced by respondents in discussing their illness with doctors, but also differences in patterns of medical care, availability of social care, and societal attitudes to ME/CFS.


Assuntos
Síndrome de Fadiga Crônica , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/terapia , Humanos , Itália , Letônia , Qualidade de Vida , Fatores Socioeconômicos , Inquéritos e Questionários , Reino Unido
9.
Medicina (Kaunas) ; 57(5)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33925784

RESUMO

Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness-myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions. Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology. Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study. Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.


Assuntos
Síndrome de Fadiga Crônica , Síndrome de Fadiga Crônica/diagnóstico , Humanos , Projetos de Pesquisa
10.
Zhongguo Zhen Jiu ; 41(3): 269-74, 2021 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-33798308

RESUMO

OBJECTIVE: To observe the effect of ginger-separated moxibustion on fatigue state and intestinal flora in patients with chronic fatigue syndrome (CFS). METHODS: A total of 62 patients with CFS were randomly divided into an observation group (31 cases, 3 cases dropped off) and a control group (31 cases, 2 cases dropped off). The patients in the control group were treated with normal diet and moderate exercise; on the basis of the control group, the patients in the observation group were treated with ginger-separated moxibustion at Zhongwan (CV 12), Shenque (CV 8) and Guanyuan (CV 4), 30 min each time, once every other day, three times a week. Both groups were intervened for 4 weeks. Before and after treatment, the fatigue scale-14 (FS-14) was used to observe the improvement of fatigue state, and 16S rRNA detection technology was used to detect the distribution of intestinal flora. RESULTS: Compared before treatment, the FS-14 score was reduced after treatment in the observation group (P<0.01), and the reduction in the observation group was larger than that in the control group (P<0.01). The relative abundance of intestinal flora was similar between the observation group and control group at the phylum and genus level before treatment. After treatment, there was no significant change of intestinal flora in the control group. However, the enterobacteriaceae, corynebacterium, erysipelothrix, actinomycetes were increased in the observation group (P<0.05), and actinomycetes, ruminococcus, lactarius had obvious flora advantages compared with the control group (P<0.05). CONCLUSION: The ginger-separated moxibustion could significantly improve the fatigue state in CFS patients, which may be related to the regulation of intestinal flora structure and the repair of intestinal barrier.


Assuntos
Síndrome de Fadiga Crônica , Microbioma Gastrointestinal , Gengibre , Moxibustão , Pontos de Acupuntura , Síndrome de Fadiga Crônica/terapia , Humanos , RNA Ribossômico 16S
11.
Medicina (Kaunas) ; 57(4)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923830

RESUMO

This report addresses the extent to which there may be scope for preventive programmes for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and, if so, what economic benefits may accrue from the implementation of such programmes. We consider the economic case for prevention programmes, whether there is scope for preventive programmes for ME/CFS, and what are the health and economic benefits to be derived from the implementation of such programmes. We conclude that there is little scope for primary prevention programmes, given that ME/CFS is attributable to a combination of host and environmental risk factors, with host factors appearing to be most prominent, and that there are few identified modifiable risk factors that could be the focus of such programmes. The exception is in the use of agricultural chemicals, particularly organophosphates, where there is scope for intervention, and where Europe-wide programmes of health education to encourage safe use would be beneficial. There is a need for more research on risk factors for ME/CFS to establish a basis for the development of primary prevention programmes, particularly in respect of occupational risk factors. Secondary prevention offers the greatest scope for intervention, to minimise diagnostic delays associated with prolonged illness, increased severity, and increased costs.


Assuntos
Síndrome de Fadiga Crônica , Europa (Continente) , Humanos , Fatores Socioeconômicos
12.
Artigo em Inglês | MEDLINE | ID: mdl-33671082

RESUMO

Background: Evidence is emerging that individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may suffer from chronic vascular dysfunction as a result of illness-related oxidative stress and vascular inflammation. The study aimed to examine the impact of maximal-intensity aerobic exercise on vascular function 48 and 72 h into recovery. Methods: ME/CFS (n = 11) with gender and age-matched controls (n = 11) were randomly assigned to either a 48 h or 72 h protocol. Each participant had measures of brachial blood pressure, augmentation index (AIx75, standardized to 75 bpm) and carotid-radial pulse wave velocity (crPWV) taken. This was followed by a maximal incremental cycle exercise test. Resting measures were repeated 48 or 72 h later (depending on group allocation). Results: No significant differences were found when ME/CFS were directly compared to controls at baseline. During recovery, the 48 h control group experienced a significant 7.2% reduction in AIx75 from baseline measures (p < 0.05), while the matched ME/CFS experienced no change in AIx75. The 72 h ME/CFS group experienced a non-significant increase of 1.4% from baseline measures. The 48 h and 72 h ME/CFS groups both experienced non-significant improvements in crPWV (0.56 ms-1 and 1.55 ms-1, respectively). Conclusions: The findings suggest that those with ME/CFS may not experience exercise-induced vasodilation due to chronic vascular damage, which may be a contributor to the onset of post-exertional malaise (PEM).


Assuntos
Síndrome de Fadiga Crônica , Rigidez Vascular , Exercício Físico , Teste de Esforço , Humanos , Análise de Onda de Pulso
13.
Medicina (Kaunas) ; 57(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652622

RESUMO

The potential benefits of the scientific insights gleaned from years of treating ME/CFS for the emerging symptoms of COVID-19, and in particular Longhaul- or Longhauler-COVID-19 are discussed in this opinion article. Longhaul COVID-19 is the current name being given to the long-term sequelae (symptoms lasting beyond 6 weeks) of SARS-CoV-2 infection. Multiple case definitions for ME/CFS exist, but post-exertional malaise (PEM) is currently emerging as the 'hallmark' symptom. The inability to identify a unique trigger of ME/CFS, as well as the inability to identify a specific, diagnostic laboratory test, led many physicians to conclude that the illness was psychosomatic or non-existent. However, recent research in the US and the UK, championed by patient organizations and their use of the internet and social media, suggest underlying pathophysiologies, e.g., oxidative stress and mitochondrial dysfunction. The similarity and overlap of ME/CFS and Longhaul COVID-19 symptoms suggest to us similar pathological processes. We put forward a unifying hypothesis that explains the precipitating events such as viral triggers and other documented exposures: For their overlap in symptoms, ME/CFS and Longhaul COVID-19 should be described as Post Active Phase of Infection Syndromes (PAPIS). We further propose that the underlying biochemical pathways and pathophysiological processes of similar symptoms are similar regardless of the initiating trigger. Exploration of the biochemical pathways and pathophysiological processes should yield effective therapies for these conditions and others that may exhibit these symptoms. ME/CFS patients have suffered far too long. Longhaul COVD-19 patients should not be subject to a similar fate. We caution that failure to meet the now combined challenges of ME/CFS and Longhaul COVID-19 will impose serious socioeconomic as well as clinical consequences for patients, the families of patients, and society as a whole.


Assuntos
/complicações , Síndrome de Fadiga Crônica/virologia , Humanos , Tempo
14.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669532

RESUMO

Although understanding of the biomedical basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is growing, the underlying pathological mechanisms remain uncertain. We recently reported a reduction in the proportion of basal oxygen consumption due to ATP synthesis by Complex V in ME/CFS patient-derived lymphoblast cell lines, suggesting mitochondrial respiratory inefficiency. This was accompanied by elevated respiratory capacity, elevated mammalian target of rapamycin complex 1 (mTORC1) signaling activity and elevated expression of enzymes involved in the TCA cycle, fatty acid ß-oxidation and mitochondrial transport. These and other observations led us to hypothesise the dysregulation of pathways providing the mitochondria with oxidisable substrates. In our current study, we aimed to revisit this hypothesis by applying a combination of whole-cell transcriptomics, proteomics and energy stress signaling activity measures using subsets of up to 34 ME/CFS and 31 healthy control lymphoblast cell lines from our growing library. While levels of glycolytic enzymes were unchanged in accordance with our previous observations of unaltered glycolytic rates, the whole-cell proteomes of ME/CFS lymphoblasts contained elevated levels of enzymes involved in the TCA cycle (p = 1.03 × 10-4), the pentose phosphate pathway (p = 0.034, G6PD p = 5.5 × 10-4), mitochondrial fatty acid ß-oxidation (p = 9.2 × 10-3), and degradation of amino acids including glutamine/glutamate (GLS p = 0.034, GLUD1 p = 0.048, GOT2 p = 0.026), branched-chain amino acids (BCKDHA p = 0.028, BCKDHB p = 0.031) and essential amino acids (FAH p = 0.036, GCDH p = 0.006). The activity of the major cellular energy stress sensor, AMPK, was elevated but the increase did not reach statistical significance. The results suggest that ME/CFS metabolism is dysregulated such that alternatives to glycolysis are more heavily utilised than in controls to provide the mitochondria with oxidisable substrates.


Assuntos
Síndrome de Fadiga Crônica/metabolismo , Linfócitos/metabolismo , Mitocôndrias/metabolismo , Adulto , Idoso , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Oxirredução , Fosforilação Oxidativa , Complexo de Endopeptidases do Proteassoma/metabolismo , Subunidades Proteicas/metabolismo , Proteoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Especificidade por Substrato , Transcriptoma/genética
15.
Medicina (Kaunas) ; 57(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652747

RESUMO

Background and Objectives: We have conducted a survey of academic and clinical experts who are participants in the European ME/CFS Research Network (EUROMENE) to elicit perceptions of general practitioner (GP) knowledge and understanding of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and suggestions as to how this could be improved. Materials and Methods: A questionnaire was sent to all national representatives and members of the EUROMENE Core Group and Management Committee. Survey responses were collated and then summarized based on the numbers and percentages of respondents selecting each response option, while weighted average responses were calculated for questions with numerical value response options. Free text responses were analysed using thematic analysis. Results: Overall there were 23 responses to the survey from participants across 19 different European countries, with a 95% country-level response rate. Serious concerns were expressed about GPs' knowledge and understanding of ME/CFS, and, it was felt, about 60% of patients with ME/CFS went undiagnosed as a result. The vast majority of GPs were perceived to lack confidence in either diagnosing or managing the condition. Disbelief, and misleading illness attributions, were perceived to be widespread, and the unavailability of specialist centres to which GPs could refer patients and seek advice and support was frequently commented upon. There was widespread support for more training on ME/CFS at both undergraduate and postgraduate levels. Conclusion: The results of this survey are consistent with the existing scientific literature. ME/CFS experts report that lack of knowledge and understanding of ME/CFS among GPs is a major cause of missed and delayed diagnoses, which renders problematic attempts to determine the incidence and prevalence of the disease, and to measure its economic impact. It also contributes to the burden of disease through mismanagement in its early stages.


Assuntos
Síndrome de Fadiga Crônica , Médicos de Atenção Primária , Europa (Continente) , Síndrome de Fadiga Crônica/epidemiologia , Humanos , Percepção , Inquéritos e Questionários
16.
BMJ Case Rep ; 14(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753384

RESUMO

Many patients with chronic fatigue syndrome (CFS) fail to derive benefit from evidence-based treatments such as cognitive-behavioural therapy (CBT) and graded exercise therapy leading to permanent disability. To discover whether a repeat prescription of modafinil might potentiate the benefits of CBT leading to social recovery as defined by 2 or more point improvement in energy and muscular pain/concentration and return to work or full-time training. Three patients with treatment-resistant CFS (mean duration 17.66 years) treated with modafinil and CBT in a Liaison Psychiatry clinic were retrospectively reviewed. Progress was reviewed at baseline, 4-6 months and 10-24 months. Patients rated their fatigue, pain and concentration using 10-point Likert scales. 2/3 achieved clinically meaningful improvements in energy and pain/concentration and 3/3 achieved social recovery. Modafinil, when prescribed over the medium term, would appear to be a potentially useful potentiating agent when added to CBT.


Assuntos
Terapia Cognitivo-Comportamental , Síndrome de Fadiga Crônica , Síndrome de Fadiga Crônica/tratamento farmacológico , Humanos , Modafinila , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
19.
Pharmacol Res ; 165: 105465, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33529750

RESUMO

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease characterized by severe and disabling fatigue that fails to improve with rest; it is commonly accompanied by multifocal pain, as well as sleep disruption, and cognitive dysfunction. Even mild exertion can exacerbate symptoms. The prevalence of ME/CFS in the U.S. is estimated to be 0.5-1.5 % and is higher among females. Viral infection is an established trigger for the onset of ME/CFS symptoms, raising the possibility of an increase in ME/CFS prevalence resulting from the ongoing COVID-19 pandemic. Current treatments are largely palliative and limited to alleviating symptoms and addressing the psychological sequelae associated with long-term disability. While ME/CFS is characterized by broad heterogeneity, common features include immune dysregulation and mitochondrial dysfunction. However, the underlying mechanistic basis of the disease remains poorly understood. Herein, we review the current understanding, diagnosis and treatment of ME/CFS and summarize past clinical studies aimed at identifying effective therapies. We describe the current status of mechanistic studies, including the identification of multiple targets for potential pharmacological intervention, and ongoing efforts towards the discovery of new medicines for ME/CFS treatment.


Assuntos
Descoberta de Drogas , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Descoberta de Drogas/métodos , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/virologia , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico
20.
Nutrients ; 13(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33557013

RESUMO

Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure. Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue levels of creatine in the brain, the rates of phosphocreatine resynthesis in the skeletal muscle, or the concentrations of the enzyme creatine kinase in the blood. Furthermore, supplemental creatine and related guanidino compounds appear to impact both patient- and clinician-reported outcomes in syndromes and maladies with chronic fatigue. This paper critically overviews the most common disturbances in creatine metabolism in various PVFS populations, summarizes human trials on dietary creatine and creatine analogs in the syndrome, and discusses new frontiers and open questions for using creatine in a post-COVID-19 world.


Assuntos
Creatina/administração & dosagem , Creatina/metabolismo , Síndrome de Fadiga Crônica/dietoterapia , Síndrome de Fadiga Crônica/metabolismo , Biomarcadores/metabolismo , Encéfalo/metabolismo , Creatina/análogos & derivados , Suplementos Nutricionais , Síndrome de Fadiga Crônica/diagnóstico , Humanos , Músculo Esquelético/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto
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