Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse.

T cell receptor (TCR) engagement opens Ca(2+) release-activated Ca(2+) (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and duration of TCR signaling. We find that Ca(2+) influx is required to drive actin organization and dynamics at the synapse.

Impact of Doximity Residency Rankings on Emergency Medicine Applicant Rank Lists.

Introduction: This study investigates the impact of the Doximity rankings on the rank list choices made by residency applicants in emergency medicine (EM).

Methods: We sent an 11-item survey by email to all students who applied to EM residency programs at four different institutions representing diverse geographical regions. Students were asked questions about their perception of Doximity rankings and how it may have impacted their rank list decisions.

Clinical Implications of Leaks Following Left Atrial Appendage Ligation With the LARIAT Device.

Objectives: The aim of this study was to evaluate the incidence and clinical implications of leaks (acute incomplete occlusion, early and late reopenings) following LAA ligation with the LARIAT device.

Background: Percutaneous LAA ligation with the LARIAT device may represent an alternative for stroke prevention in high-risk patients with atrial fibrillation with contraindications to oral anticoagulation.

Methods: This was a retrospective, multicenter study of 98 consecutive patients undergoing successful LAA ligation with the LARIAT device.

Impact of Rotor Ablation in Nonparoxysmal Atrial Fibrillation Patients: Results From the Randomized OASIS Trial.

Background: Nonrandomized studies have reported focal impulse and rotor modulation (FIRM)-guided ablation to be superior to pulmonary vein antrum isolation (PVAI) for persistent atrial fibrillation and long-standing persistent atrial fibrillation.

Objectives: This study sought to compare efficacy of FIRM ablation with or without PVAI versus PVAI plus non-PV trigger ablation in randomized persistent atrial fibrillation and long-standing persistent atrial fibrillation patients.

Methods: Nonparoxysmal atrial fibrillation (AF) patients undergoing first ablation were randomized to FIRM only (group 1), FIRM + PVAI (group 2) or PVAI + posterior wall + non-PV trigger ablation (group 3).

Pulmonary Vein Antrum Isolation in Patients With Paroxysmal Atrial Fibrillation: More Than a Decade of Follow-Up.

Background: We report the outcome of pulmonary vein (PV) antrum isolation in paroxysmal atrial fibrillation (AF) patients over more than a decade of follow-up.

Methods And Results: A total of 513 paroxysmal AF patients (age 54±11 years, 73% males) undergoing catheter ablation at our institutions were included in this analysis. PV antrum isolation extended to the posterior wall between PVs plus empirical isolation of the superior vena cava was performed in all.

The AVICH Score: A Novel Grading System to Predict Clinical Outcome in Arteriovenous Malformation-Related Intracerebral Hemorrhage.

Objective: To establish an arteriovenous malformation (AVM) grading score for patients with ruptured AVM and associated intracerebral hemorrhage (ICH) to predict clinical outcome.

Methods: Patient data from January 2006 to December 2013 with newly diagnosed ICH caused by ruptured AVM and a modified Rankin Scale (mRS) score <2 before ICH were included for this analysis. Clinical outcome was dichotomized in favorable (mRS score, 0-2) and unfavorable (mRS score, 3-6) to find predictors for outcome and to establish a new score based on the areas under the receiver-operating characteristic curves (AUROC) at 3 months, 1 year, and at last follow-up (mean, 31 months).

Atrial Fibrillation Ablation and Stroke.

Catheter ablation has become a widely available and accepted treatment to restore sinus rhythm in atrial fibrillation patients who fail antiarrhythmic drug therapy. Although generally safe, the procedure carries a non-negligible risk of complications, including periprocedural cerebral insults. Uninterrupted anticoagulation, maintenance of an adequate ACT during the procedure, and measures to avoid and detect thrombus build-up on sheaths and atheters during the procedure, appears useful to reduce the risk of embolic events.

Characterizing "Adversity" of Pathology Findings in Nonclinical Toxicity Studies: Results from the 4th ESTP International Expert Workshop.

The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports, to serve as a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP.

Competency-based education: programme design and challenges to implementation.

Context: Competency-based education (CBE) has been widely cited as an educational framework for medical students and residents, and provides a framework for designing educational programmes that reflect four critical features: a focus on outcomes, an emphasis on abilities, a reduction of emphasis on time-based training, and promotion of learner centredness. Each of these features has implications and potential challenges for implementing CBE.

Methods: As an experiment in CBE programme design and implementation, the University of Michigan Master of Health Professions Education (UM-MHPE) degree programme was examined for lessons to be learned when putting CBE into practice.

A novel tyrosine-modified low molecular weight polyethylenimine (P10Y) for efficient siRNA delivery in vitro and in vivo.

The delivery of nucleic acids, particularly of small RNA molecules like siRNAs for the induction of RNA interference (RNAi), still represents a major hurdle with regard to their application in vivo. Possible therapeutic applications thus rely on the development of efficient non-viral gene delivery vectors. While low molecular weight polyethylenimines (PEIs) have been successfully explored, the introduction of chemical modifications offers an avenue towards the development of more efficient vectors.

Twin-like appearance of an unruptured intracerebral anterior communicating artery (ACom) aneurysm in a male sibling of a patient with a ruptured ACom aneurysm.

Background: Increased risk of intracranial aneurysm rupture with subsequent subarachnoid haemorrhage (SAH) is related to several possible factors, including first-grade familial aneurysms.

Methods And Results: Here we present a case of one ruptured and one unruptured identical twin-like anterior communicating artery (ACom) aneurysm present in two male siblings, without any proven genetic predisposition. According to evidence-based scores, aneurysm rupture risk for the younger (51 years old) sibling (with an unruptured ACom aneurysm) would be low, leaving the decision for either treatment or clinical follow-up to the discretion of the treating physician.

Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial.

Background: Whether catheter ablation (CA) is superior to amiodarone (AMIO) for the treatment of persistent atrial fibrillation (AF) in patients with heart failure is unknown.

Methods And Results: This was an open-label, randomized, parallel-group, multicenter study. Patients with persistent AF, dual-chamber implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator, New York Heart Association II to III, and left ventricular ejection fraction <40% within the past 6 months were randomly assigned (1:1 ratio) to undergo CA for AF (group 1, n=102) or receive AMIO (group 2, n=101).

Action and Traction: Cytoskeletal Control of Receptor Triggering at the Immunological Synapse.

It is well known that F-actin dynamics drive the micron-scale cell shape changes required for migration and immunological synapse (IS) formation. In addition, recent evidence points to a more intimate role for the actin cytoskeleton in promoting T cell activation. Mechanotransduction, the conversion of mechanical input into intracellular biochemical changes, is thought to play a critical role in several aspects of immunoreceptor triggering and downstream signal transduction.

Embracing the Enemy: Cell-to-Cell Force Transmission Enhances Cytotoxicity.

Cells respond to the mechanical properties of their environment, but how biomechanics contributes to intercellular signaling remains unclear. Reporting in Cell, Basu et al. (2016) showed that forces exerted by cytotoxic T lymphocytes enhance the function of the pore-forming protein perforin, thereby leading to more effective target cell killing.

Is transesophageal echocardiogram mandatory in patients undergoing ablation of atrial fibrillation with uninterrupted novel oral anticoagulants? Results from a prospective multicenter registry.

Background: Transesophageal echocardiography (TEE) is recommended in patients undergoing atrial fibrillation (AF) ablation, but use of this strategy is variable.

Objective: To evaluate whether TEE is necessary before AF ablation in patients treated with novel oral anticoagulants (NOACs).

Methods: We performed a prospective multicenter registry of AF patients undergoing radiofrequency catheter ablation on uninterrupted NOACs (apixaban and rivaroxaban).

Remote Magnetic Navigation: A Focus on Catheter Ablation of Ventricular Arrhythmias.

VT ablation is based on percutaneous catheter insertion under fluoroscopic guidance to selectively destroy (i.e., ablate) myocardial tissue regions responsible for the initiation or propagation of ventricular arrhythmias.

Vdrive Evaluation of Remote Steering and Testing in Lasso Electrophysiology Procedures Study: The VERSATILE Study in Atrial Fibrillation Ablation.

Introduction: Circular mapping catheters (CMC) are an essential tool in most atrial fibrillation ablation procedures. The Vdrive™ with V-Loop™ system enables a physician to remotely manipulate a CMC during electrophysiology studies. Our aim was to compare the clinical performance of the system to conventional CMC navigation according to efficiency and safety endpoints.

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence.

Introduction: Current MRI sequences are limited in identifying brain areas at risk for high grade glioma recurrence. We employed intraoperative 3-Tesla functional MRI to assess cerebrovascular reactivity (CVR) after high-grade glioma resection and analyzed regional CVR responses in areas of tumor recurrence on clinical follow-up imaging.

Methods: Five subjects with high-grade glioma that underwent an intraoperative Blood Oxygen-Level Dependent (BOLD) MRI CVR examination and had a clinical follow-up of at least 18months were selected from a prospective database.

Pituitary surgery and volumetric assessment of extent of resection: a paradigm shift in the use of intraoperative magnetic resonance imaging.

Objective: The aim of this study was to quantitatively assess the role of intraoperative high-field 3-T MRI (3T-iMRI) in improving the gross-total resection (GTR) rate and the extent of resection (EOR) in endoscopic transsphenoidal surgery (TSS) for pituitary adenomas.

Methods: Radiological and clinical data from a prospective database were retrospectively analyzed. Volumetric measurements of adenoma volumes pre-, intraoperatively, and 3 months postoperatively were performed in a consecutive series of patients who had undergone endoscopic TSS.

Blood oxygen-level dependent functional assessment of cerebrovascular reactivity: Feasibility for intraoperative 3 Tesla MRI.

Purpose: To assess the feasibility of functional blood oxygen-level dependent (BOLD) MRI to evaluate intraoperative cerebrovascular reactivity (CVR) at 3 Tesla field strength.

Methods: Ten consecutive neurosurgical subjects scheduled for a clinical intraoperative MRI examination were enrolled in this study. In addition to the clinical protocol a BOLD sequence was implemented with three cycles of 44 s apnea to calculate CVR values on a voxel-by-voxel basis throughout the brain.

Preoperative angiotensin converting enzyme inhibitor usage in patients with chronic subdural hematoma: Associations with initial presentation and clinical outcome.

The aim of this study is to analyze the association of preoperative usage of angiotensin converting enzyme (ACE) inhibitors with the initial presentation and clinical outcome of patients with chronic subdural hematoma (cSDH). Patients treated for cSDH between 2009 and 2013 at our institution were included in this retrospective case-control study. Medical charts were reviewed retrospectively and data were analyzed using descriptive and inferential statistics.

Residents values in a rational decision-making model: an interest in academics in emergency medicine.

Academic physicians train the next generation of doctors. It is important to understand the factors that lead residents to choose an academic career to continue to effectively recruit residents who will join the national medical faculty. A decision-making theory-driven, large scale assessment of this process has not been previously undertaken.

68Gallium-DOTATATE PET in meningioma: A reliable predictor of tumor growth rate?

Background: DOTATATE-based radionuclides have added new options in the diagnosis and treatment of meningiomas; however, a reliable predictor of tumor growth has still not been established.

Methods: We analyzed 64 meningiomas imaged with (68)Ga-DOTATATE PET. Tumor growth rates were calculated by volumetric analysis of sequential MRI scans.

The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma.

The purpose of the present study is to analyze the impact of intraoperative resection control modalities on overall survival (OS) and progression-free survival (PFS) following gross total resection (GTR) of glioblastoma. We analyzed data of 76 glioblastoma patients (30f, mean age 57.4 ± 11.

Is Science the Only Driver in Species Selection? An Internal Study to Evaluate Compound Requirements in the Minipig Compared to the Dog in Preclinical Studies.

Dogs have been often chosen as a nonrodent species for preclinical development of small molecule drugs mainly due to availability and relative ease of handling. Recently, focus has increased on the minipig as a potential alternative to the dog, based on either scientific rationale or public opinion concerns. There are, however, other factors influencing nonrodent choices, in particular drug amount and synthesis time, which differ between species and therefore may impact the milestones of a drug development program.