Sex-specific microRNAs in neurovascular units in ischemic stroke

Accumulating evidence pinpoints sex differences in stroke incidence, etiology and outcome. Therefore, more understanding of the sex-specific mechanisms that lead to ischemic stroke and aggravation of secondary damage after stroke is needed. Our current mechanistic understanding of cerebral ischemia states that endothelial quiescence in neurovascular units (NVUs) is a major physiological parameter affecting the cellular response to neuron, astrocyte and vascular smooth muscle cell (VSMC) injury. Although a hallmark of the response to injury in these cells is transcriptional activation, noncoding RNAs such as microRNAs exhibit cell-type and context dependent regulation of gene expression at the post-transcriptional level. This review assesses whether sex-specific microRNA expression (either derived from X-chromosome loci following incomplete X-chromosome inactivation or regulated by estrogen in their biogenesis) in these cells controls NVU quiescence, and as such, could differentiate stroke pathophysiology in women compared to men. Their adverse expression was found to decrease tight junction affinity in endothelial cells and activate VSMC proliferation, while their regulation of paracrine astrocyte signaling was shown to neutralize sex-specific apoptotic pathways in neurons. As such, these microRNAs have cell type-specific functions in astrocytes and vascular cells which act on one another, thereby affecting the cell viability of neurons. Furthermore, these microRNAs display actual and potential clinical implications as diagnostic and prognostic biomarkers in ischemic stroke and in predicting therapeutic response to antiplatelet therapy. In conclusion, this review improves the current mechanistic understanding of the molecular mechanisms leading to ischemic stroke in women and highlights the clinical promise of sex-specific microRNAs as novel diagnostic biomarkers for (silent) ischemic stroke.Paroxysmal Cerebral Disorder

Optimal patient protocols in regional acute stroke care

In acute stroke care two proven reperfusion treatments exist: (1) a blood thinner and (2) an interventional procedure. The interventional procedure can only be given in a stroke centre with specialized facilities. Rapid initiation of either is key to improving the functional outcome (often emphasized by the common phrase in acute stroke care "time=brain"). Delays between the moment the ambulance is called and the initiation of one or both reperfusion treatment(s) should therefore be as short as possible. The speed of the process strongly depends on five factors: patient location, regional patient allocation by emergency medical services (EMS), travel times of EMS, treatment locations, and in-hospital delays. Regional patient allocation by EMS and treatment locations are sub-optimally configured in daily practice. Our aim is to construct a mathematical model for the joint decision of treatment locations and allocation of acute stroke patients in a region, such that the time until treatment is minimized. We describe acute stroke care as a multi-flow two-level hierarchical facility location problem and the model is formulated as a mixed integer linear program. The objective of the model is the minimization of the total time until treatment in a region and it incorporates volume-dependent in-hospital delays. The resulting model is used to gain insight in the performance of practically oriented patient allocation protocols, used by EMS. We observe that the protocol of directly driving to the nearest stroke centre with special facilities (i.e., the mothership protocol) performs closest to optimal, with an average total time delay that is 3.9% above optimal. Driving to the nearest regional stroke centre (i.e., the drip-and-ship protocol) is on average 8.6% worse than optimal. However, drip-and-ship performs better than the mothership protocol in rural areas and when a small fraction of the population (at most 30%) requires the second procedure, assuming sufficient patient volumes per stroke centre. In the experiments, the time until treatment using the optimal model is reduced by at most 18.9 minutes per treated patient. In economical terms, assuming 150 interventional procedures per year, the value of medical intervention in acute stroke can be improved upon up to euro 1,800,000 per year.Paroxysmal Cerebral Disorder

The immunologic etiology of psychiatric manifestations in systemic lupus erythematosus: a narrative review on the role of the blood brain barrier, antibodies, cytokines and chemokines

Introduction: The aim of this narrative review is to provide an overview of the literature on the possible immunologic pathophysiology of psychiatric manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE).Methods: A systematic search on PubMed was conducted. English studies with full text availability that investigated the correlation between blood-brain barrier (BBB) dysfunction, intrathecal synthesis of antibodies, antibodies, cytokines, chemokines, metalloproteinases, complement and psychiatric NPSLE manifestations in adults were included.Results: Both transient BBB-dysfunction with consequent access of antibodies to the cerebrospinal fluid (CSF) and intrathecal synthesis of antibodies could occur in psychiatric NPSLE. Anti-phospholipid antibodies, anti-NMDA antibodies and anti-ribosomal protein p antibodies seem to mediate concentration dependent neuronal dysfunction. Interferon-a may induce microglial engulfment of neurons, direct neuronal damage and production of cytokines and chemokines in psychiatric NPSLE. Several cytokines, chemokines and matrix metalloproteinase-9 may contribute to the pathophysiology of psychiatric NPSLE by attracting and activating Th1-cells and B-cells.Discussion: This potential pathophysiology may help understand NPSLE and may have implications for the diagnostic management and therapy of psychiatric NPSLE. However, the presented pathophysiological model is based on correlations between potential immunologic etiologies and psychiatric NPSLE that remain questionable. More research on this topic is necessary to further elucidate the pathophysiology of NPSLE.Paroxysmal Cerebral Disorder

Optimal patient protocols in regional acute stroke care

In acute stroke care two proven reperfusion treatments exist: (1) a blood thinner and (2) an interventional procedure. The interventional procedure can only be given in a stroke centre with specialized facilities. Rapid initiation of either is key to improving the functional outcome (often emphasized by the common phrase in acute stroke care “time=brain”). Delays between the moment the ambulance is called and the initiation of one or both reperfusion treatment(s) should therefore be as short as possible. The speed of the process strongly depends on five factors: patient location, regional patient allocation by emergency medical services (EMS), travel times of EMS, treatment locations, and in-hospital delays. Regional patient allocation by EMS and treatment locations are sub-optimally configured in daily practice. Our aim is to construct

Получение эффективных катодолюминесцентных структур на базе пленочной технологии

Получены и исследованы катодолюминесцентные структуры с яркостью свечения до 1000 кд/м² на пленках толщиной 7-9 мкм, на базе которых могут быть созданы средства отображения информации с высокой разрешающей способностью

Current Imaging Modalities for Diagnosing Cerebral Vein Thrombosis - A Critical Review

Cerebral vein thrombosis (CVT) is a rare presentation of venous thromboembolism. Prompt and accurate diagnosis is essential as delayed recognition and treatment may lead to permanent disability or even death. Since no validated diagnostic algorithms exist, the diagnosis of CVT mainly relies on neuroimaging. Digital subtraction angiography (DSA) is the historical diagnostic standard for CVT, but is rarely used nowadays and replaced by computed tomography (CT) and magnetic resonance imaging (MRI). High quality studies to evaluate the diagnostic test characteristics of state of the art imaging modalities are however unavailable to date. This review provides an overview of the best available evidence regarding the diagnostic performance of CT and MRI for the diagnosis of CVT. Notably, available studies are observational, mostly small, outdated, and with a high risk of bias. Therefore, direct comparison between studies is difficult due to large diversity in study design, imaging method, reference standard, patient selection and sample size. In general, contrast-enhanced techniques are more accurate for the diagnosis of CVT then non-contrast-enhanced techniques. CT venography and MRI have been both reported to be adequate for establishing a final diagnosis of CVT, but choice of modality as used in clinical practice depends on availability, local preference and experience, as well as patient characteristics. Our review underlines the need for high-quality diagnostic studies comparing CT venography and MRI in specific settings, to improve clinical care and standardize clinical trials.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Sex Differences in Presentation of Stroke: A Systematic Review and Meta-Analysis

Background and Purpose: Women have worse outcomes than men after stroke. Differences in presentation may lead to misdiagnosis and, in part, explain these disparities. We investigated whether there are sex differences in clinical presentation of acute stroke or transient ischemic attack. Methods: We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were (1) cohort, cross-sectional, case-control, or randomized controlled trial design; (2) admission for (suspicion of) ischemic or hemorrhagic stroke or transient ischemic attack; and (3) comparisons possible between sexes in >= 1 nonfocal or focal acute stroke symptom(s). A random-effects model was used for our analyses. We performed sensitivity and subanalyses to help explain heterogeneity and used the Newcastle-Ottawa Scale to assess bias. Results: We included 60 studies (n=582 844; 50% women). In women, headache (pooled odds ratio [OR], 1.24 [95% CI, 1.11-1.39]; I-2=75.2%; 30 studies) occurred more frequently than in men with any type of stroke, as well as changes in consciousness/mental status (OR, 1.38 [95% CI, 1.19-1.61]; I-2=95.0%; 17 studies) and coma/stupor (OR, 1.39 [95% CI, 1.25-1.55]; I-2=27.0%; 13 studies). Aspecific or other neurological symptoms (nonrotatory dizziness and non-neurological symptoms) occurred less frequently in women (OR, 0.96 [95% CI, 0.94-0.97]; I-2=0.1%; 5 studies). Overall, the presence of focal symptoms was not associated with sex (pooled OR, 1.03) although dysarthria (OR, 1.14 [95% CI, 1.04-1.24]; I-2=48.6%; 11 studies) and vertigo (OR, 1.23 [95% CI, 1.13-1.34]; I-2=44.0%; 8 studies) occurred more frequently, whereas symptoms of paresis/hemiparesis (OR, 0.73 [95% CI, 0.54-0.97]; I-2=72.6%; 7 studies) and focal visual disturbances (OR, 0.83 [95% CI, 0.70-0.99]; I-2=62.8%; 16 studies) occurred less frequently in women compared with men with any type of stroke. Most studies contained possible sources of bias. Conclusions: There may be substantive differences in nonfocal and focal stroke symptoms between men and women presenting with acute stroke or transient ischemic attack, but sufficiently high-quality studies are lacking. More studies are needed to address this because sex differences in presentation may lead to misdiagnosis and undertreatment.Public Health and primary carePrevention, Population and Disease management (PrePoD