Analytical study of gyrophase, pitch angle, and normal speed of particles leaving an ideal magnetohydrodynamic discontinuity surface.

Particle populations that have velocity distributions with only a small spread of gyrophase angles are commonly observed in the vicinity of magnetohydrodynamic (MHD) discontinuity surfaces such as collisionless shocks. Previous theoretical particle trajectory studies have concentrated on ion behavior at an ideal planar Earth's bow shock and have either assumed that a gyrotropic incident initial velocity distribution is reflected at the surface or instead focused on unique fixed initial gyrophase and pitch angle values specified by the generation mechanism assumed for the particle. In this analytical study of trajectories of particles departing an ideal planar MHD surface we demonstrate that a particle's initial gyrophase and pitch angle determine completely whether it will escape the surface or return to it, regardless of its initial energy.

Carbon monoxide-releasing molecules inhibit the cystic fibrosis transmembrane conductance regulator Cl channel.

The gasotransmitter carbon monoxide (CO) regulates fluid and electrolyte movements across epithelial tissues. However, its action on anion channels is incompletely understood. Here, we investigate the direct action of CO on the cystic fibrosis transmembrane conductance regulator (CFTR) by applying CO-releasing molecules (CO-RMs) to the intracellular side of excised inside-out membrane patches from cells heterologously expressing wild-type human CFTR.

The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR.

Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal.

Error recovery by dialysis technicians.

Experts are believed to make fewer errors than novices. Researchers in other domains have shown that experts not only make less errors, they also detect and recover from these errors better than non-experts. To investigate this phenomenon among dialysis technicians working in hemodialysis, we evaluated the ability of dialysis technicians to detect and recover from healthcare errors.

Error detection and recovery in dialysis nursing.

Objectives: Our aim for this study was to evaluate dialysis nurses' ability to detect and recover from nursing errors.

Methods: Two clinical cases with a total of 12 embedded errors were constructed. The errors were based on real events but were modified for the experimental design by an expert dialysis nurse.

Alveolar epithelial CNGA1 channels mediate cGMP-stimulated, amiloride-insensitive, lung liquid absorption.

Impairment of lung liquid absorption can lead to severe respiratory symptoms, such as those observed in pulmonary oedema. In the adult lung, liquid absorption is driven by cation transport through two pathways: a well-established amiloride-sensitive Na(+) channel (ENaC) and, more controversially, an amiloride-insensitive channel that may belong to the cyclic nucleotide-gated (CNG) channel family. Here, we show robust CNGA1 (but not CNGA2 or CNGA3) channel expression principally in rat alveolar type I cells; CNGA3 was expressed in ciliated airway epithelial cells.

Carbon monoxide: an emerging regulator of ion channels.

Carbon monoxide is rapidly emerging as an important cellular messenger, regulating a wide range of physiological processes. Crucial to its role in both physiology and disease is its ability differentially to regulate several classes of ion channels, including examples from calcium-activated K(+) (BK(Ca)), voltage-activated K(+) (K(v)) and Ca(2+) channel (L-type) families, ligand-gated P2X receptors (P2X2 and P2X4), tandem P domain K(+) channels (TREK1) and the epithelial Na(+) channel (ENaC). The mechanisms by which CO regulates these ion channels are still unclear and remain somewhat controversial.

The carbon monoxide donor, CORM-2, is an antagonist of ATP-gated, human P2X4 receptors.

Carbon monoxide (CO) is produced endogenously by heme oxygenase (HO) enzymes. HO-1 is highly expressed in many inflammatory disease states, where it is broadly protective. The protective effects of HO-1 expression can be largely mimicked by the exogenous application of CO and CO-releasing molecules (CORMs).

An exon 5-less splice variant of the extracellular calcium-sensing receptor rescues absence of the full-length receptor in the developing mouse lung.

The authors have recently demonstrated that, in the developing mouse lung, fetal plasma Ca(2+) suppresses branching morphogenesis and cell proliferation while promoting fluid secretion via activation of the extracellular Ca(2+)-sensing receptor (CaSR). The aim of the current study was to further elucidate the role of Ca(2+) in lung development by studying the effects of extracellular Ca(2+) on fetal lung development in mice lacking the CaSR. These mice were produced by exon 5 deletion in the CaSR gene.

Computerized self-monitoring and technology-assisted feedback for weight loss with and without an enhanced behavioral component.

Objective: The purpose of this study was to develop and evaluate a 12-week weight management intervention involving computerized self-monitoring and technology-assisted feedback with and without an enhanced behavioral component.

Methods: 120 overweight (30.5±2.

P2X receptor channels show threefold symmetry in ionic charge selectivity and unitary conductance.

In the closed structure of the P2X cation channel, three α-helical transmembrane domains cross the membrane obliquely. In rat P2X2 receptors, these intersect at Thr(339). Replacing Thr(339) by lysine in one, two or three subunits progressively increased chloride permeability and reduced unitary conductance.

Mechanism of inhibition by hydrogen sulfide of native and recombinant BKCa channels.

Recent evidence suggests that H(2)S contributes to activation of the carotid body by hypoxia by inhibiting K(+) channels. Here, we determine both the molecular identity of the K(+) channel target within the carotid body and the biophysical characteristics of the H(2)S-evoked inhibition by analyzing native rat and human recombinant BK(Ca) channel activity in voltage-clamped, inside-out membrane patches. Rat glomus cells express the enzymes necessary for the endogenous generation of H(2)S, cystathionine-beta-synthase and cystathionine-gamma-lyase.

Enzyme-linked oxygen sensing by potassium channels.

The ability of ion channels to respond to an acute perturbation in oxygen tension is a widespread phenomenon, which encompasses many of the major ion channel families. Integral to the ability of several ion channels to respond to acute hypoxic challenge is modulation by upstream enzymatic reactions, suggesting that many ion channels sense oxygen via enzyme-linked processes. Several enzyme-linked oxygen sensing systems have been proposed, including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent production of hydrogen peroxide, hemoxygenase-dependent generation of carbon monoxide, adenosine monophosphate (AMP) kinase-dependent channel phosphorylation, and src-Lck protein tyrosine kinase, via a currently undetermined mechanism.

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR.

The capacity to sense and adapt to changes in environmental cues is of paramount importance for every living organism. From yeast to man, cells must be able to match cellular activities to growth environment and nutrient availability. Key to this process is the development of membrane-bound systems that can detect modifications in the extracellular environment and to translate these into biological responses.

Purinergic signaling in the pulmonary neuroepithelial body microenvironment unraveled by live cell imaging.

Pulmonary neuroepithelial bodies (NEBs) are densely innervated groups of complex sensory airway receptors involved in the regulation of breathing. Together with their surrounding Clara-like cells, they exhibit stem cell potential through their capacity to regenerate depopulated areas of the epithelium following lung injury. We have employed confocal live cell imaging microscopy and novel electrophysiological techniques in a new ex vivo lung slice model to unravel potential purinergic signaling pathways within the NEB microenvironment.

Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR.

Postnatal lung function is critically dependent upon optimal embryonic lung development. As the free ionized plasma calcium concentration ([Ca(2+)](o)) of the fetus is higher than that of the adult, the process of lung development occurs in a hypercalcaemic environment. In the adult, [Ca(2+)](o) is monitored by the G-protein coupled, extracellular calcium-sensing receptor (CaR), but neither its ontogeny nor its potential role in lung development are known.

Azimilide for the treatment of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia: results of a randomized trial and insights on the concordance of symptoms and recurrent arrhythmias.

Introduction: Azimilide hydrochloride is an investigational antiarrhythmic medication that had shown evidence of efficacy in prolonging the time to recurrence of atrial fibrillation (AF) or atrial flutter (AFL) and paroxysmal supraventricular tachycardia (PSVT). This study was designed to confirm efficacy of 125 mg daily azimilide.

Methods And Results: The primary endpoint was ECG-documented recurrence of AF, AFL, or PSVT, followed for a maximum of 180 days.

Indicators of activity-friendly communities: an evidence-based consensus process.

Background: Regular physical activity, even at modest intensities, is associated with many health benefits. Most Americans, however, do not engage in the recommended levels. As practitioners seek ways to increase population rates of physical activity, interventions and advocacy efforts are being targeted to the community level.

Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures.

Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease activity.

Role of ectodomain lysines in the subunits of the heteromeric P2X2/3 receptor.

Lysine residues near each end of the receptor ectodomain (in rat P2X2 Lys69 and Lys308) have been implicated in ATP binding to P2X receptors. We recorded membrane currents from human embryonic kidney cells expressing P2X subunits and found that lysine-to-alanine substitutions at equivalent positions in the P2X3 receptor (Lys63 and Lys299) also prevented channel function. Heteromeric P2X2/3 receptors are formed when P2X2 and P2X3 subunits are expressed together; they can be distinguished by their relatively sustained response to alphabeta-methylene-ATP.

Efficacy of azimilide for the maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation in the presence and absence of structural heart disease.

Azimilide hydrochloride (azimilide), an investigational antiarrhythmic drug, has shown variable efficacy in preventing atrial fibrillation (AF). This study was designed to assess its efficacy in maintaining sinus rhythm in patients with paroxysmal AF and heart disease. Patients with symptomatic paroxysmal AF were screened for 1 month by transtelephonic monitoring.

Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm.

Background: Azimilide dihydrochloride (azimilide) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias. In patients with atrial fibrillation, it has shown excellent efficacy in some previous trials and minimal efficacy in others.

Methods: Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter, randomized, placebo-controlled clinical trial.

Symptoms at the time of arrhythmia recurrence in patients receiving azimilide for control of atrial fibrillation or flutter: results from randomized trials.

Background: Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide on time to first recurrence of symptomatic AF. This paper examines the data collected during those studies regarding the symptoms reported by patients at the time of AF recurrence

Methods: At the time that patients reported their first documented symptomatic recurrence of arrhythmia, they were systematically asked whether or not they were experiencing any of the following 6 symptoms: palpitation, fatigue, chest pain, shortness of breath, dizziness, or sweating.

Asymptomatic or "silent" atrial fibrillation: frequency in untreated patients and patients receiving azimilide.

Background: Asymptomatic, or "silent" atrial fibrillation could increase the risk of stroke. Little is known about the frequency of asymptomatic atrial fibrillation in patients who also have symptomatic atrial fibrillation; similarly, little is known about the effect of antiarrhythmic drug therapy on asymptomatic atrial fibrillation.

Methods And Results: Patients in sinus rhythm with a history of symptomatic atrial fibrillation or atrial flutter received placebo or azimilide (35 to 125 mg) once daily for 6 or 9 months in 4 similar double-blind trials.

An examination of factors predicting prioritization for liver transplantation.

With the recent transition of the liver transplant allocation system to the Model for End-Stage Liver Disease, a major change is its reliance entirely on objective criteria. In previous reports, potential donor families and members of the transplant community have questioned the fairness of the subjective nature of previous systems. Therefore, we examined the United Network for Organ Sharing database to determine if the previous allocation system benefited a particular group in prioritization for transplant.