Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults.

Objectives: Mutations in the X-linked endosomal Na+/H+ exchanger 6 (NHE6) cause Christianson syndrome (CS). Here, in the largest study to date, we examine genetic diversity and clinical progression in CS into adulthood.

Method: Data were collected as part of the International Christianson Syndrome and () Gene Network Study.

Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels.

The two-pore domain potassium (K) channels TREK-1 and TREK-2 link neuronal excitability to a variety of stimuli including mechanical force, lipids, temperature and phosphorylation. This regulation involves the C-terminus as a polymodal stimulus sensor and the selectivity filter (SF) as channel gate. Using crystallographic up- and down-state structures of TREK-2 as a template for full atomistic molecular dynamics (MD) simulations, we reveal that the SF in down-state undergoes inactivation via conformational changes, while the up-state structure maintains a stable and conductive SF.

[After the pandemic is before the pandemic: And how interdisciplinary research can help here].

Aviation is among the social sectors most impacted by the COVID-19 pandemic, and at the same time has contributed to the rapid global spread of the SARS-CoV-2 virus. SARS-CoV-2 is one of the coronaviruses that have led to outbreaks such as MERS-CoV in the past. This group of pathogens, as well as others that may be unknown at this time, will continue to challenge our society in the future.

Christianson Syndrome across the Lifespan: An International Longitudinal Study in Children, Adolescents, and Adults.

Mutations in the X-linked endosomal Na+/H+ Exchanger 6 (NHE6) causes Christianson Syndrome (CS). In the largest study to date, we examine genetic diversity and clinical progression, including cerebellar degeneration, in CS into adulthood. Data were collected as part of the International Christianson Syndrome and NHE6 (SLC9A6) Gene Network Study.

Influence of rosuvastatin on apolipoproteins and coagulation factor levels: Results from the STAtin Reduce Thrombophilia trial.

Background: The STAtins Reduce Thrombophilia trial showed that, in patients with prior venous thrombosis, rosuvastatin decreased various coagulation factor levels.

Objectives: Here, we investigated the hypothesis that statins decrease coagulation factor levels through shared mechanisms of synthesis or regulatory pathways with apolipoproteins.

Methods: We measured the levels of apolipoprotein (Apo)A-I, A-II, A-IV, (a), B-100, B-total, C-I, C-II, C-III, and E in patients (n = 126) randomized to 28 days of rosuvastatin use.

Mechanism of Calcium Permeation in a Glutamate Receptor Ion Channel.

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are neurotransmitter-activated cation channels ubiquitously expressed in vertebrate brains. The regulation of calcium flux through the channel pore by RNA-editing is linked to synaptic plasticity while excessive calcium influx poses a risk for neurodegeneration. Unfortunately, the molecular mechanisms underlying this key process are mostly unknown.

Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model.

The IDH1 mutation in glioma results in the neoenzymatic function of IDH1, leading to the production of the oncometabolite 2-hydroxyglutarate (2-HG), alterations in energy metabolism and changes in the cellular redox household. Although shifts in the redox ratio NADPH/NADP were described, the consequences for the NAD synthesis pathways and potential therapeutic interventions were largely unexplored. Here, we describe the effects of heterozygous IDH1 on the redox system in a CRISPR/Cas edited glioblastoma model and compare them with IDH1 wild-type (IDH1) cells.

The Immediate Effect of COVID-19 Vaccination on Anticoagulation Control in Patients Using Vitamin K Antagonists.

Background:  In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.

The predictive role of early CRP values for one-year mortality in the first 2 d after acute myocardial infarction.

Background: An excessive inflammatory reaction after acute myocardial infarction (AMI) is known to be harmful. New anti-inflammatory therapies are required.

Purpose: This study assessed the predictive role of early CRP in patients with STEMI.

Rosuvastatin treatment decreases plasma procoagulant phospholipid activity after a VTE: A randomized controlled trial.

Background: Venous thromboembolism (VTE) is a frequent cardiovascular disease with severe complications, including recurrence and death. There is a great need for alternative prophylactic treatment options as anticoagulation is accompanied by increased bleeding risk. Statins are reported to reduce the risk of incident and recurrent VTE, but the mechanisms are elusive.

Nonselective cation permeation in an AMPA-type glutamate receptor.

Fast excitatory synaptic transmission in the central nervous system relies on the AMPA-type glutamate receptor (AMPAR). This receptor incorporates a nonselective cation channel, which is opened by the binding of glutamate. Although the open pore structure has recently became available from cryo-electron microscopy (Cryo-EM), the molecular mechanisms governing cation permeability in AMPA receptors are not understood.

Rosuvastatin use increases plasma fibrinolytic potential: a randomised clinical trial.

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy.

Effectiveness and safety of vedolizumab in inflammatory bowel disease patients aged 60 and over: an observational multicenter UK experience.

Background: The GEMINI trials established the efficacy of vedolizumab in moderate-to-severe inflammatory bowel disease (IBD) and demonstrated a favorable safety profile, suggesting it may be advantageous in older patients at greater risk of treatment-related complications. However, there is a paucity of data exploring the outcomes of vedolizumab in this group. Our objective was to determine the clinical effectiveness and safety of vedolizumab in older IBD patients within a real-world multicenter UK cohort.

EUS-guided stent removal in buried lumen-apposing metal stent syndrome: a case series.

Background And Aims: Lumen-apposing metal stents (LAMSs) play an increasing role in transgastric and transduodenal drainage of pancreatic fluid collections and allow novel EUS-guided interventions. Alongside the main adverse events of bleeding and occlusion, LAMSs can be overgrown by mucosa, which leads to the inability to visualize the stent in endoscopy.

Methods: We describe a series of 4 cases of buried LAMSs that were removed under EUS guidance for identification of the stent followed by removal with rat-tooth forceps.

Mutant IDH1 Differently Affects Redox State and Metabolism in Glial Cells of Normal and Tumor Origin.

IDH1 (isocitrate dehydrogenase 1) mutations play a key role in the development of low-grade gliomas. IDH1 converts isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP), whereas IDH1 uses α-ketoglutarate and NADPH to generate the oncometabolite 2-hydroxyglutarate (2-HG). While the effects of 2-HG have been the subject of intense research, the 2-HG independent effects of IDH1 are still ambiguous.

A Latent Profile Analysis of Violent Offenders Based on PCL-R Factor Scores: Criminogenic Needs and Recidivism Risk.

Clinicians and theorists have often proposed the two psychopathic subtypes of "primary" and "secondary" psychopathy, with recent research indicating some empirical support for both psychopathy subtypes, though the findings across studies are far from uniform. For the current study, latent profile analysis was used to investigate if homogeneous latent classes exist within a sample of 215 adult male violent offenders from Berlin, Germany. The age of the offenders at the time of the index offense ranged from 19 to 59 years.

Relative importance of four functional measures as predictors of 15-year mortality in the older Dutch population.

Background: Decreased physical function is known to raise mortality risk. Little is known about how different physical function measures compare in predicting mortality risk in older men and women. The objective of this study was to compare four, objective and self-reported, physical function measures in predicting 15-year mortality risk in older men and women.

Rosuvastatin use reduces thrombin generation potential in patients with venous thromboembolism: a randomized controlled trial.

Essentials The role of statins in hemostasis and venous thromboembolism (VTE) prophylaxis is not clear. This trial assessed whether rosuvastatin use affects thrombin generation in patients with VTE. Endogenous thrombin potential and peak were decreased by 10% and 5% with rosuvastatin therapy.

Clinical outcome of patients with a vitamin K antagonist-associated bleeding treated with prothrombin complex concentrate.

Background: Vitamin K antagonists (VKA) are used for the treatment of thromboembolism. Patients with severe VKA-associated bleeding require immediate restoration of haemostasis. Clinical studies on the effect of prothrombin complex concentrate (PCC) are heterogeneous with respect to outcome of bleeding.

Clinical effects of antiplatelet drugs and statins on D-dimer levels.

Background: Acute pulmonary embolism may be ruled out by combining nonhigh clinical probability and a normal D-dimer level. Both antiplatelet drugs and HMG-CoA reductase inhibitors (statins) have been associated with effects on thrombus formation, potentially influencing D-dimer levels in this setting, leading to a higher rate of false-negative tests. Therefore, we determined whether D-dimer levels in patients with suspected pulmonary embolism are affected by concomitant use of antiplatelet drugs and/or statins and evaluated whether the effect of antiplatelet drugs or statins might affect diagnostic accuracy.

Development of a clinical prediction model for an international normalised ratio ≥ 4·5 in hospitalised patients using vitamin K antagonists.

Vitamin K antagonists (VKAs) used for the prevention and treatment of thromboembolic disease, increase the risk of bleeding complications. We developed and validated a model to predict the risk of an international normalised ratio (INR) ≥ 4·5 during a hospital stay. Adult patients admitted to a tertiary hospital and treated with VKAs between 2006 and 2010 were analysed.

Rosuvastatin use improves measures of coagulation in patients with venous thrombosis.

Aims: Observational studies indicate that statins reduce the risk of recurrent venous thrombosis (VT). However, trials have not been performed and the mechanism is unknown. We aimed to determine whether statin therapy improves the coagulation profile in patients with prior VT.

Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis.

Unlabelled: Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic.

Predictors of oral cavity bleeding and clinical outcome after dental procedures in patients on vitamin K antagonists. A cohort study.

Patients on vitamin K antagonists (VKA) often undergo invasive dental procedures. International guidelines consider all dental procedures as low-risk procedures, while bleeding risk may differ between standard low-risk (e. g.