Acute symptomatic seizures in cerebral venous thrombosis.

Objective: To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium.

Methods: We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS.

Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway.

We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines.

Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw.

Pediatric brain tumor care in a Sub-Saharan setting: current poise of a precariously loaded dice.

Objective: To evaluate the current status of pediatric brain tumor (PBT) care and identify determinants and profiles of survival and school attendance.

Methods: An 8-year institution-based prospective longitudinal study. All cases investigated with neuroimaging and treated were enrolled.

School and pre-school children with type 1 diabetes during Covid-19 quarantine: The synergic effect of parental care and technology.

Introduction: Management of Type 1 Diabetes (T1D) poses numerous challenges, especially for young children and their families. Parental care positively influencesthe outcomesofchildren with T1D, while there are often criticisms in school environment. The COVID-19 pandemic has forced children and parents to spend many hours at home and diabetes care has returned mainly in the hands of parents.

Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium.

Objective: To determine changes in the incidence of dementia between 1988 and 2015.

Methods: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence.

Reactive Oxygen-Forming Nox5 Links Vascular Smooth Muscle Cell Phenotypic Switching and Extracellular Vesicle-Mediated Vascular Calcification.

Rationale: Vascular calcification, the formation of calcium phosphate crystals in the vessel wall, is mediated by vascular smooth muscle cells (VSMCs). However, the underlying molecular mechanisms remain elusive, precluding mechanism-based therapies.

Objective: Phenotypic switching denotes a loss of contractile proteins and an increase in migration and proliferation, whereby VSMCs are termed synthetic.

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk.

Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used.

Frequency and Predictors of Major Bleeding in Patients With Embolic Strokes of Undetermined Source: NAVIGATE-ESUS Trial.

Background And Purpose: Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source.

Methods: Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily.

Results: During a median follow-up of 11 months, 85 major bleeds occurred.

Effect of selective I inhibition by XAF-1407 in an equine model of tachypacing-induced persistent atrial fibrillation.

Background And Purpose: Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, I may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific I inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF.

Experimental Approach: The pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels.

Diagnostic accuracy of acute diverticulitis with unenhanced low-dose CT.

Background: The aim of this study was to evaluate the diagnostic accuracy of unenhanced low-dose CT (LDCT) in acute colonic diverticulitis in comparison with contrast-enhanced standard-dose CT (SDCT).

Methods: All patients with clinically suspected diverticulitis who underwent LDCT followed by SDCT between January and October 2017 were evaluated prospectively. CT examinations were assessed for signs of diverticulitis, complications and other differential diagnoses by three independent radiologists (two consultants and one fourth-year resident) using SDCT as the reference method.

Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders.

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer's disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.

Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial.

Aim: To investigate the long-term efficacy and safety of dapagliflozin as an adjunct to adjustable insulin in adults with type 1 diabetes (T1D) and inadequate glycaemic control.

Materials And Methods: Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-2) was a placebo-controlled, double-blind, multicentre, phase III study of adults with T1D (HbA1c 7.5%-10.

Long-term effect of mobile phone use on sleep quality: Results from the cohort study of mobile phone use and health (COSMOS).

Background: Effects of radiofrequency electromagnetic field exposure (RF-EMF) from mobile phone use on sleep quality has mainly been investigated in cross-sectional studies. The few previous prospective cohort studies found no or inconsistent associations, but had limited statistical power and short follow-up. In this large prospective cohort study, our aim was to estimate the effect of RF-EMF from mobile phone use on different sleep outcomes.

Exploring the Limits of Transition-Metal Fluorination at High Pressures.

Fluorination is a proven method for challenging the limits of chemistry, both structurally and electronically. Here we explore computationally how pressures below 300 GPa affect the fluorination of several transition metals. A plethora of new structural phases are predicted along with the possibility for synthesizing four unobserved compounds: TcF , CdF , OsF , and IrF .

Phenotypic high-throughput screening platform identifies novel chemotypes for necroptosis inhibition.

Regulated necrosis or necroptosis, mediated by receptor-interacting kinase 1 (RIPK1), RIPK3 and pseudokinase mixed lineage kinase domain-like protein (MLKL), contributes to the pathogenesis of inflammatory, infectious and degenerative diseases. Recently identified necroptosis inhibitors display moderate specificity, suboptimal pharmacokinetics, off-target effects and toxicity, preventing these molecules from reaching the clinic. Here, we developed a cell-based high-throughput screening (HTS) cascade for the identification of small-molecule inhibitors of necroptosis.

High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease.

Background And Purpose: Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling-derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease.

Materials And Methods: Eight patients with Moyamoya disease were included before or after revascularization surgery.

Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction.

Background: Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction, especially with contemporary assays. Both peptides were measured at screening in the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure).

Deep sequencing of mitochondrial DNA and characterization of a novel mutation in a patient with arPEO.

Objective: To determine the pathogenicity of a novel mutation in a man with late-onset autosomal recessive progressive external ophthalmoplegia using clinical, molecular, and biochemical analyses.

Methods: A multipronged approach with detailed neurologic examinations, muscle biopsy analyses, molecular genetic studies, and in vitro biochemical characterization.

Results: The patient had slowly progressive bilateral ptosis and severely reduced horizontal and vertical gaze.

Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial.

Background: Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). SGLT2 (sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL.

Absence of Long-Term Benefit of Revascularization in Patients With Intermittent Claudication: Five-Year Results From the IRONIC Randomized Controlled Trial.

Background: The long-term benefit of revascularization for intermittent claudication is poorly understood. The aim of this study was to investigate the long-term effectiveness and cost-effectiveness compared with a noninvasive approach.

Methods: The IRONIC trial (Invasive Revascularization or Not in Intermittent Claudication) randomized patients with mild-to-severe intermittent claudication to either revascularization + best medical therapy + structured exercise therapy (the revascularization group) or best medical therapy + structured exercise therapy (the nonrevascularization group).

Antibody Responses against Enterovirus Proteases are Potential Markers for an Acute Infection.

Background: Enteroviruses are a group of common non-enveloped RNA viruses that cause symptoms ranging from mild respiratory infections to paralysis. Due to the abundance of enterovirus infections it is hard to distinguish between on-going and previous infections using immunological assays unless the IgM fraction is studied.

Methods: In this study we show using Indirect ELISA and capture IgM ELISA that an IgG antibody response against the nonstructural enteroviral proteins 2A and 3C can be used to distinguish between IgM positive ( = 22) and IgM negative ( = 20) human patients with 83% accuracy and a diagnostic odds ratio of 30.