Supporting Survival of Transplanted Stem-Cell-Derived Insulin-Producing Cells in an Encapsulation Device Augmented with Controlled Release of Amino Acids.

Pancreatic islet transplantation is a promising treatment for type I diabetes, which is a chronic autoimmune disease in which the host immune cells attack insulin-producing beta cells. The impact of this therapy is limited due to tissue availability and dependence on immunosuppressive drugs that prevent immune rejection of the transplanted cells. These issues can be solved by encapsulating stem cell-derived insulin-producing cells in an immunoprotective device.

Variable Presentations and Ablation Sites for Manifest Nodoventricular/Nodofascicular Fibers.

Background: Nodofascicular and nodoventricular (NFV) accessory pathways connect the atrioventricular node and the Purkinje system or ventricular myocardium, respectively. Concealed NFV pathways participate as the retrograde limb of supraventricular tachycardia (SVT). Manifest NFV pathways can comprise the anterograde limb of wide-complex SVT but are quite rare.

Diuretic Activity of a Novel Peripherally-Restricted Orally-Active Kappa Opioid Receptor Agonist.

-opioid agonists (KOAs) enhance cardiac performance, as well as reduce infarct size and prevent deleterious cardiac remodeling following myocardial infarction. Additionally, KOAs promote diuresis; however, there has been limited development of KOAs as a class due to the promotion of untoward central nervous system (CNS)-mediated side effects. Our laboratory has developed a peripherally-restricted, orally-active, KOA () for the treatment of pain and cardiovascular disease.

Screening and treating hospitalized trauma survivors for posttraumatic stress disorder and depression.

Traumatic injury affects over 2.6 million U.S.

Myocardial Fibrosis in Classical Low-Flow, Low-Gradient Aortic Stenosis.

Background Few data exist on the degree of interstitial myocardial fibrosis in patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS) and its association with left ventricular flow reserve (FR) on dobutamine stress echocardiography. This study sought to evaluate the diffuse interstitial fibrosis measured by T1 mapping cardiac magnetic resonance technique in LFLG-AS patients with and without FR. Methods Prospective study including 65 consecutive patients (41 LFLG-AS [mean age, 67.

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

Purpose: We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo.

Methods: Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of ∼40 and 20 μm for timolol and brimonidine compartments, respectively.

Electromagnetic Interference with Protocolized Electrosurgery Dispersive Electrode Positioning in Patients with Implantable Cardioverter Defibrillators.

What We Already Know About This Topic: Electromagnetic interference from monopolar electrosurgery may disrupt implantable cardioverter defibrillators.Current management recommendations by the American Society of Anesthesiologists and Heart Rhythm Society are based on expert clinical opinion since there is a paucity of data regarding the risk of electromagnetic interference to implantable cardioverter defibrillators during surgery.

What This Article Tells Us That Is New: With protocolized electrosurgery dispersive electrode positioning in patients with implantable cardioverter defibrillators, the risk of clinically meaningful electromagnetic interference was 7% in above-the-umbilicus noncardiac surgery and 0% in below-the-umbilicus surgery.

Effects of homozygosity on sex determination in zebrafish Danio rerio.

Gynogenetic zebrafish Danio rerio were obtained by activating D. rerio oocytes with UV irradiated common carp Cyprinus carpio sperm and then applying one of four different shocks [two (early) meiotic and two (late) mitotic shocks]. Gynogens produced by three of the shocks survived to maturity.

DBS of the PSA and the VIM in essential tremor: A randomized, double-blind, crossover trial.

Objective: To evaluate deep brain stimulation (DBS) of the posterior subthalamic area (PSA) in essential tremor (ET) and compare it to the ventral intermediate nucleus of the thalamus (VIM) in terms of stimulation efficacy, efficiency, and side effects.

Methods: DBS leads were implanted such that contacts were placed in the VIM, on the intercommissural line, and in the PSA. Thirteen patients with ET entered a randomized, double-blind crossover phase and completed a 1-year follow-up.

Six-month follow-up of the injured trauma survivor screen: Clinical implications and future directions.

Background: The injured trauma survivor screen (ITSS) has been shown to predict posttraumatic stress disorder (PTSD) and depression risk at 1 month after traumatic injury. This study explored the ability of the ITSS to predict chronic distress after injury, as well as the impact of combining the ITSS with an additional screening measure.

Methods: Patients were enrolled following admission to a Level I trauma center.

Survival after radiation for stage I and II non-small cell lung cancer with positive margins.

Background: There is limited data guiding treatment for positive margins following lobectomy for early-stage non-small cell lung cancer (NSCLC). Using data from the National Cancer Data Base, we sought to determine whether radiation therapy following lobectomy for stage I or II NSCLC was associated with improved overall survival in patients with positive margins.

Methods: Patients who underwent lobectomy without induction therapy for stage I or II NSCLC (1998-2006) with positive resection margins were selected.

Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

Background: Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance.

Methods And Results: We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor.

Long-term intraocular pressure reduction with intracameral polycaprolactone glaucoma devices that deliver a novel anti-glaucoma agent.

Long-term treatment of glaucoma, a major leading cause of blindness, is challenging due to poor patient compliance. Therefore, a drug delivery device that can achieve drug release over several months can be highly beneficial for glaucoma management. Here, we evaluate the long-term pharmacokinetics and therapeutic efficacy of polycaprolactone intracameral drug delivery devices in rabbit eyes.

Functional Characterization of the Coronary Artery Disease Risk Locus.

Background: A chromosomal locus at 4q32.1 has been genome-wide significantly associated with coronary artery disease risk. The locus encompasses , which encodes the α subunit of the soluble guanylyl cyclase (sGC), a key enzyme in the nitric oxide/cGMP signaling pathway.

Profiling protein expression in circulating tumour cells using microfluidic western blotting.

Circulating tumour cells (CTCs) are rare tumour cells found in the circulatory system of certain cancer patients. The clinical and functional significance of CTCs is still under investigation. Protein profiling of CTCs would complement the recent advances in enumeration, transcriptomic and genomic characterization of these rare cells and help define their characteristics.

Traumatic muscle fibrosis: From pathway to prevention.

Muscle fibrosis, the disruption, of functional parenchyma by stromal elements, is an often overlooked sequela of traumatic muscle injury, ageing, and congenital disease. The remarkable regenerative capacity of skeletal muscle is dependent on the interaction of myogenic progenitors and the same stromal connective tissue elements responsible for fibrosis generation and propagation. The coordination of effective therapeutic strategies to mitigate muscle fibrosis following injury requires a clear understanding of the prominent cellular progenitors, extracellular constituents, and signaling mechanisms involved in muscle healing.

Utility of the injured trauma survivor screen to predict PTSD and depression during hospital admission.

Background: The brief, easily administered screen, the Injured Trauma Survivor Screen (ITSS), was created to identify trauma survivors at risk for development of posttraumatic stress disorder (PTSD) and depression.

Methods: An item pool of PTSD risk factors was created and given, along with a previously created screen, to patients admitted to two Level 1 trauma centers. The Clinician Administered PTSD Scale for DSM-5, the PTSD Checklist for DSM-5, and the Center for Epidemiological Studies Depression Scale Revised were given during a 1-month follow-up.

Multicenter Study of a Novel Topical Interleukin-1 Receptor Inhibitor, Isunakinra, in Subjects With Moderate to Severe Dry Eye Disease.

Objectives: Isunakinra, formerly known as EBI-005, is a novel interleukin (IL)-1 receptor inhibitor developed for topical treatment of patients with dry eye disease (DED). This phase 1b/2a multicenter, double-masked, randomized, vehicle controlled environmental trial assessed the safety and biological activity of isunakinra in patients with moderate to severe DED.

Methods: Subjects (N=74) were randomized to vehicle (placebo) or isunakinra (5 or 20 mg/mL) 3×/daily for 6 weeks.

Improved Therapeutic Benefits by Combining Physical Cooling With Pharmacological Hypothermia After Severe Stroke in Rats.

Background And Purpose: Therapeutic hypothermia is a promising strategy for treatment of acute stroke. Clinical translation of therapeutic hypothermia, however, has been hindered because of the lack of efficiency and adverse effects. We sought to enhance the clinical potential of therapeutic hypothermia by combining physical cooling (PC) with pharmacologically induced hypothermia after ischemic stroke.

Consumption of Caffeinated Products and Cardiac Ectopy.

Background: Premature cardiac contractions are associated with increased morbidity and mortality. Though experts associate premature atrial contractions (PACs) and premature ventricular contractions (PVCs) with caffeine, there are no data to support this relationship in the general population. As certain caffeinated products may have cardiovascular benefits, recommendations against them may be detrimental.

Rac1 Signaling Is Required for Anterior Second Heart Field Cellular Organization and Cardiac Outflow Tract Development.

Background: The small GTPase Rac1 regulates diverse cellular functions, including both apicobasal and planar cell polarity pathways; however, its role in cardiac outflow tract (OFT) development remains unknown. In the present study, we aimed to examine the role of Rac1 in the anterior second heart field (SHF) splanchnic mesoderm and subsequent OFT development during heart morphogenesis.

Methods And Results: Using the Cre/loxP system, mice with an anterior SHF-specific deletion of Rac1 (Rac1(SHF)) were generated.

Sublobar Resection for Clinical Stage IA Non-small-cell Lung Cancer in the United States.

Background: This study evaluated the use of lobectomy and sublobar resection for clinical stage IA non-small-cell lung cancer (NSCLC) in the National Cancer Data Base (NCDB).

Methods: The NCDB from 2003 to 2011 was analyzed to determine factors associated with the use of a sublobar resection versus a lobectomy for the treatment of clinical stage IA NSCLC. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazard modeling.

A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study.

Background: The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin. In previous phase II trials (ACTIVATE/ACT II), rindopepimut was well tolerated with robust EGFRvIII-specific immune responses and promising progression-free and overall survival.