- MeSH
- fibromyalgie * diagnóza psychologie terapie MeSH
- lidé MeSH
- psychosomatické a relaxační terapie MeSH
- somatoformní poruchy psychologie terapie MeSH
- syndrom chronické únavy * diagnóza psychologie terapie MeSH
- syndrom dráždivého tračníku * diagnóza psychologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Causative genetic variants cannot yet be found for many disorders with a clear heritable component, including chronic fatigue disorders like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These conditions may involve genes in difficult-to-align genomic regions that are refractory to short read approaches. Structural variants in these regions can be particularly hard to detect or define with short reads, yet may account for a significant number of cases. Long read sequencing can overcome these difficulties but so far little data is available regarding the specific analytical challenges inherent in such regions, which need to be taken into account to ensure that variants are correctly identified. Research into chronic fatigue disorders faces the additional challenge that the heterogeneous patient populations likely encompass multiple aetiologies with overlapping symptoms, rather than a single disease entity, such that each individual abnormality may lack statistical significance within a larger sample. Better delineation of patient subgroups is needed to target research and treatment. METHODS: We use nanopore sequencing in a case of unexplained severe fatigue to identify and fully characterise a large inversion in a highly homologous region spanning the AKR1C gene locus, which was indicated but could not be resolved by short-read sequencing. We then use GC-MS/MS serum steroid analysis to investigate the functional consequences. RESULTS: Several commonly used bioinformatics tools are confounded by the homology but a combined approach including visual inspection allows the variant to be accurately resolved. The DNA inversion appears to increase the expression of AKR1C2 while limiting AKR1C1 activity, resulting in a relative increase of inhibitory GABAergic neurosteroids and impaired progesterone metabolism which could suppress neuronal activity and interfere with cellular function in a wide range of tissues. CONCLUSIONS: This study provides an example of how long read sequencing can improve diagnostic yield in research and clinical care, and highlights some of the analytical challenges presented by regions containing tandem arrays of genes. It also proposes a novel gene associated with a novel disease aetiology that may be an underlying cause of complex chronic fatigue. It reveals biomarkers that could now be assessed in a larger cohort, potentially identifying a subset of patients who might respond to treatments suggested by the aetiology.
- MeSH
- biologické markery MeSH
- hydroxysteroidní dehydrogenasy MeSH
- lidé MeSH
- syndrom chronické únavy * MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.
- MeSH
- kognitivně behaviorální terapie * MeSH
- lidé MeSH
- průzkumy a dotazníky MeSH
- syndrom chronické únavy * diagnóza terapie MeSH
- terapie cvičením MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- autoimunitní nemoci * diagnóza imunologie terapie MeSH
- časná přecitlivělost diagnóza etiologie terapie MeSH
- fibromyalgie diagnóza etiologie terapie MeSH
- komorbidita MeSH
- léková alergie diagnóza etiologie imunologie MeSH
- lidé MeSH
- multimorbidita MeSH
- syndrom chronické únavy diagnóza etiologie terapie MeSH
- syndromy imunologické nedostatečnosti diagnóza etiologie komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
INTRODUCTION: The circumflex scapular artery (CSA) has been described in detail in the literature, but the groove, i.e., the circumflex sulcus (CFS), formed by the artery on the lateral pillar of the scapula has been completely neglected. The aim of the present study was to describe the variability and anatomy of the CFS. MATERIALS AND METHODS: The study was based on the examination of 103 pairs of dry bone specimens of adult scapulae, i.e., 206 specimens, including 92 (46 pairs) male and 114 (57 pairs) female specimens. In the first step, quantitative criteria were defined for assessment of the CFS presence and type. Subsequently, statistical analysis of the obtained data was performed. RESULTS: The study revealed considerable variability of the arterial groove, which was well developed in 33% (type A), shallow in 40% (type B), and absent in 27% (type C) of cases. The mean distance between CFS and the infraglenoid tubercle was 3.3 cm CI0.95 (3.1-3.3), which corresponds to the proximal third of the lateral border of the scapula. CONCLUSION: The study has confirmed variability of the arterial groove (CFS) and its localization in relation to the inferior glenoid rim. The findings are clinically important, particularly in relation to the Judet approach to scapular fractures (localization of the CSA course).
- MeSH
- arterie anatomie a histologie MeSH
- dospělí MeSH
- lidé MeSH
- lopatka anatomie a histologie MeSH
- syndrom chronické únavy * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.
SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine. The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis. In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses.
- MeSH
- COVID-19 * komplikace MeSH
- lidé MeSH
- progrese nemoci MeSH
- SARS-CoV-2 MeSH
- syndrom chronické únavy * diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
