Background
Cerebral microbleeds (CMBs) may have a differential impact on clinical outcome in stroke patients with atrial fibrillation (AF) treated with different types of oral anticoagulation (OAC).
...Methods
Observational single-center study on AF-stroke-patients treated with OAC. Magnetic-resonance-imaging was performed to assess CMBs. Outcome measures consisted of recurrent ischemic stroke (IS), intracranial hemorrhage (ICH), death, and their combined analysis. Functional disability was assessed by mRS. Using adjusted logistic regression and Cox proportional-hazards models, we assessed the association of the presence of CMBs and OAC type (vitamin K antagonists VKAs vs. direct oral anticoagulants DOACs) with clinical outcome.
Results
Of 310 AF-stroke patients treated with OAC DOACs:
n
= 234 (75%); VKAs:
n
= 76 (25%), CMBs were present in 86 (28%) patients; of these, 66 (77%) received DOACs. In both groups, CMBs were associated with an increased risk for the composite outcome: VKAs: HR 3.654 1.614; 8.277;
p
= 0.002; DOACs: HR 2.230 1.233; 4.034;
p
= 0.008. Patients with CMBs had ~50% higher absolute rates of the composite outcome compared to the overall cohort, with a comparable ratio between treatment groups VKAs 13/20(65%) vs. DOACs 19/66(29%);
p
< 0.01. The VKA-group had a 2-fold higher IS VKAs:4 (20%) vs. DOACs:6 (9%);
p
= 0.35 and a 10-fold higher ICH rate VKAs: 3 (15%) vs. DOACs: 1 (1.5%);
p
= 0.038. No significant interaction was observed between type of OAC and presence of CMBs. DOAC-patients showed a significantly better functional outcome (OR 0.40 0.17; 0.94;
p
= 0.04).
Conclusions
In AF-stroke patients treated with OAC, the presence of CMBs was associated with an unfavorable composite outcome for both VKAs and DOACs, with a higher risk for recurrent IS than for ICH. Strokes were numerically higher under VKAs and increased in the presence of CMBs.
Clinical trial registration
http://www.clinicaltrials.gov
, Unique identifier: NCT03826927.
Background:
Compared to 1.5 T, 3 T magnetic resonance imaging (MRI) increases signal-to-noise ratio leading to improved image quality. However, its clinical relevance in clinically isolated syndrome ...suggestive of multiple sclerosis remains uncertain.
Objectives:
The purpose of this study was to investigate how 3 T MRI affects the agreement between raters on lesion detection and diagnosis.
Methods:
We selected 30 patients and 10 healthy controls from our ongoing prospective multicentre cohort. All subjects received baseline 1.5 and 3 T brain and spinal cord MRI. Patients also received follow-up brain MRI at 3–6 months. Four experienced neuroradiologists and four less-experienced raters scored the number of lesions per anatomical region and determined dissemination in space and time (McDonald 2010).
Results:
In controls, the mean number of lesions per rater was 0.16 at 1.5 T and 0.38 at 3 T (p = 0.005). For patients, this was 4.18 and 4.40, respectively (p = 0.657). Inter-rater agreement on involvement per anatomical region and dissemination in space and time was moderate to good for both field strengths. 3 T slightly improved agreement between experienced raters, but slightly decreased agreement between less-experienced raters.
Conclusion:
Overall, the interobserver agreement was moderate to good. 3 T appears to improve the reading for experienced readers, underlining the benefit of additional training.
ABSTRACT
BACKGROUND AND PURPOSE
This study assesses whether magnetization transfer (MT) imaging provides additive information to conventional MRI in brain tumors.
METHODS
MT data of 26 patients with ...neoplastic and metastatic brain tumors were analyzed at 1.5 T. For the 3 largest tumor groups investigated in this study—glioblastoma multiforme (GBM), meningiomas, and metastases—statistical comparisons were performed. Analyzed MT parameters included the magnetization transfer ratio (MTR) and 4 quantitative MT parameters (qMT): Relaxation times (T1, T2), exchange rate (kf), and macromolecular content (F). Total imaging time of high‐resolution whole brain MTR and qMT imaging with balanced steady‐state free precession required 9 minutes. Five ROIs were chosen: Contrast‐enhancing (T1W‐CE), noncontrast‐enhancing (T1W‐non‐CE), proximal hyperintensity (T2W‐pSI), distal hyperintensity (T2W‐dSI), and a reference (ref).
RESULTS
Pathologies showed significant (P < .05) MT changes (MTR and qMT) compared to the reference. The T1W‐CE, T1W‐non‐CE, and T2W‐pSI ROIs of GBMs, meningiomas, and metastases showed significant differences in MTR and qMT estimates. Similar MTR with significant different qMT values were observed in several ROIs among different lesions. MT maps (MTR and qMT) indicated changes in tissue appearing unaffected on MRI in most glial tumors.
CONCLUSIONS
MTR and qMT imaging enables a better differentiation between brain tumors and provides additive information to MRI.
Background:
It is commonly assumed that there are clear lines of demarcation between anxiety and depressive disorders on the one hand and psychosis on the other. Recent evidence, however, suggests ...that this principle may be in need of updating.
Methods:
Depressive and/or anxiety disorders, with no previous history of psychotic disorder, were examined for the presence of psychotic symptoms in a representative community sample of adolescents and young adults (Early Developmental Stages of Psychopathology study; n = 3021). Associations and consequences of psychotic symptomatology in the course of these disorders were examined in terms of demographic distribution, illness severity, onset of service use, and risk factors.
Results:
Around 27% of those with disorders of anxiety and depression displayed one or more psychotic symptoms, vs 14% in those without these disorders (OR 2.23, 95% CI 1.89-2.66, P < .001). Presence as compared with nonpresence of psychotic symptomatology was associated with younger age (P < .0001), male sex (P < .0058), and poorer illness course (P < .0002). In addition, there was greater persistence of schizotypal (P < .0001) and negative symptoms (P < .0170), more observable illness behavior (P < .0001), greater likelihood of service use (P < .0069), as well as more evidence of familial liability for mental illness (P < .0100), exposure to trauma (P < .0150), recent and more distant life events (P < .0006-.0244), cannabis use (P < .0009), and any drug use (P < .0008).
Conclusion:
Copresence of psychotic symptomatology in disorders of anxiety and depression is common and a functionally and etiologically highly relevant feature, reinforcing the view that psychopathology is represented by a network or overlapping and reciprocally impacting dimensional liabilities.
Phylogenomic studies have improved understanding of deep metazoan phylogeny and show promise for resolving incongruences among analyses based on limited numbers of loci. One region of the animal tree ...that has been especially difficult to resolve, even with phylogenomic approaches, is relationships within Lophotrochozoa (the animal clade that includes molluscs, annelids, and flatworms among others). Lack of resolution in phylogenomic analyses could be due to insufficient phylogenetic signal, limitations in taxon and/or gene sampling, or systematic error. Here, we investigated why lophotrochozoan phylogeny has been such a difficult question to answer by identifying and reducing sources of systematic error. We supplemented existing data with 32 new transcriptomes spanning the diversity of Lophotrochozoa and constructed a new set of Lophotrochozoa-specific core orthologs. Of these, 638 orthologous groups (OGs) passed strict screening for paralogy using a tree-based approach. In order to reduce possible sources of systematic error, we calculated branch-length heterogeneity, evolutionary rate, percent missing data, compositional bias, and saturation for each OG and analyzed increasingly stricter subsets of only the most stringent (best) OGs for these five variables. Principal component analysis of the values for each factor examined for each OG revealed that compositional heterogeneity and average patristic distance contributed most to the variance observed along the first principal component while branch-length heterogeneity and, to a lesser extent, saturation contributed most to the variance observed along the second. Missing data did not strongly contribute to either. Additional sensitivity analyses examined effects of removing taxa with heterogeneous branch lengths, large amounts of missing data, and compositional heterogeneity. Although our analyses do not unambiguously resolve lophotrochozoan phylogeny, we advance the field by reducing the list of viable hypotheses. Moreover, our systematic approach for dissection of phylogenomic data can be applied to explore sources of incongruence and poor support in any phylogenomic data set.
Evolutionary relationships among the eight major lineages of Mollusca have remained unresolved despite their diversity and importance. Previous investigations of molluscan phylogeny, based primarily ...on nuclear ribosomal gene sequences or morphological data, have been unsuccessful at elucidating these relationships. Recently, phylogenomic studies using dozens to hundreds of genes have greatly improved our understanding of deep animal relationships. However, limited genomic resources spanning molluscan diversity has prevented use of a phylogenomic approach. Here we use transcriptome and genome data from all major lineages (except Monoplacophora) and recover a well-supported topology for Mollusca. Our results strongly support the Aculifera hypothesis placing Polyplacophora (chitons) in a clade with a monophyletic Aplacophora (worm-like molluscs). Additionally, within Conchifera, a sister-taxon relationship between Gastropoda and Bivalvia is supported. This grouping has received little consideration and contains most (>95%) molluscan species. Thus we propose the node-based name Pleistomollusca. In light of these results, we examined the evolution of morphological characters and found support for advanced cephalization and shells as possibly having multiple origins within Mollusca.
Abstract
Background: FCGR2A binds antibody–antigen complexes to regulate the abundance of circulating and deposited complexes along with downstream immune and autoimmune responses. Although the ...abundance of FCRG2A may be critical in immune-mediated diseases, little is known about whether its surface expression is regulated through cis genomic elements and non-coding variants. In the current study, we aimed to characterize the regulation of FCGR2A expression, the impact of genetic variation and its association with autoimmune disease. Methods: We applied CRISPR-based interference and editing to scrutinize 1.7 Mb of open chromatin surrounding the FCGR2A gene to identify regulatory elements. Relevant transcription factors (TFs) binding to these regions were defined through public databases. Genetic variants affecting regulation were identified using luciferase reporter assays and were verified in a cohort of 1996 genotyped healthy individuals using flow cytometry. Results: We identified a complex proximal region and five distal enhancers regulating FCGR2A. The proximal region split into subregions upstream and downstream of the transcription start site, was enriched in binding of inflammation-regulated TFs, and harbored a variant associated with FCGR2A expression in primary myeloid cells. One distal enhancer region was occupied by CCCTC-binding factor (CTCF) whose binding site was disrupted by a rare genetic variant, altering gene expression. Conclusions: The FCGR2A gene is regulated by multiple proximal and distal genomic regions, with links to autoimmune disease. These findings may open up novel therapeutic avenues where fine-tuning of FCGR2A levels may constitute a part of treatment strategies for immune-mediated diseases.
Distressing intrusive memories of a traumatic event are one of the hallmark symptoms of posttraumatic stress disorder. Thus, it is crucial to identify early interventions that prevent the occurrence ...of intrusive memories. Both, sleep and sleep deprivation have been discussed as such interventions, yet previous studies yielded contradicting effects. Our systematic review aims at evaluating existing evidence by means of traditional and individual participant data (IPD) meta-analyses to overcome power issues of sleep research. Until May 16th, 2022, six databases were searched for experimental analog studies examining the effect of post-trauma sleep versus wakefulness on intrusive memories. Nine studies were included in our traditional meta-analysis (8 in the IPD meta-analysis). Our analysis provided evidence for a small effect favoring sleep over wakefulness, log-ROM = 0.25, p < .001, suggesting that sleep is associated with a lower number of intrusions but unrelated to the occurrence of any versus no intrusions. We found no evidence for an effect of sleep on intrusion distress. Heterogeneity was low and certainty of evidence for our primary analysis was moderate. Our findings suggest that post-trauma sleep has the potential to be protective by reducing intrusion frequency. More research is needed to determine the impact following real-world trauma and the potential clinical significance.
•Two-level meta-analysis based on aggregated and individual participant data.•Comparison of the effects of sleep vs. wakefulness on intrusions of analog trauma.•For those who experience intrusions after trauma, sleep predicts fewer intrusions.•No effect on the occurrence of any vs. no intrusions and intrusion distress.•Future studies need to critically examine the clinical significance of this effect.
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