Challenges with retention and recovery of impurities containing acidic moieties during analytical UHPLC method development and validation for gefapixant freebase.

Gefapixant citrate is a P2X3 purinergic receptor antagonist developed for the treatment of chronic cough. Gefapixant freebase is the penultimate intermediate in the commercial manufacturing route for gefapixant citrate and contains a complex impurity profile consisting of acidic and basic analytes. A UHPLC method was developed for assay and purity determination of gefapixant freebase utilizing a Waters Acquity Charged Surface Hybrid (CSH) C18 column (2.

Environmental health perceptions of urban youth from low-income communities: A qualitative photovoice study and framework.

Background: Children are amongst the most susceptible groups to environmental exposures, for both immediate and life-course health outcomes. Despite their increased susceptibility, children's knowledge, experiences and voices are understudied. A deeper understanding of children's environmental health perceptions has the potential to better inform policy, develop targeted interventions and improve public health outcomes.

Planar carbon electrodes for real-time quantification of hydrogen sulfide release from cells.

A planar electrode system was developed to permit the real-time, selective detection of hydrogen sulfide (HS) from stimulated cells. Planar carbon electrodes were produced stencil printing carbon ink through a laser cut vinyl mask. Electrodes were preconditioned using a constant potential amperometry methodology to prevent sensor drift resulting from elemental sulfur adsorption.

Endophyte-Promoted Phosphorus Solubilization in .

Phosphorus is one of the essential nutrients for plant growth, but it may be relatively unavailable to plants because of its chemistry. In soil, the majority of phosphorus is present in the form of a phosphate, usually as metal complexes making it bound to minerals or organic matter. Therefore, inorganic phosphate solubilization is an important process of plant growth promotion by plant associated bacteria and fungi.

Mode of nitric oxide delivery affects antibacterial action.

Nitric oxide (NO) is a broad-spectrum antibacterial agent, making it an attractive alternative to traditional antibiotics for treating infections. To date, a direct comparison of the antibacterial activity of gaseous NO (gNO) versus water-soluble NO-releasing biopolymers has not been reported. In this study, the bactericidal action of NO-releasing chitosan oligosaccharides was compared to gNO treatment against cystic fibrosis-relevant Gram-positive and Gram-negative bacteria.

Nitric oxide diffusion through cystic fibrosis-relevant media and lung tissue.

A simplified diffusion cell methodology was employed to measure the diffusion coefficient of nitric oxide (NO) through phosphate buffered saline (PBS) and artificial sputum medium (ASM)-an in vitro analog for airway mucus. Diffusion through the proteinaceous ASM yielded a significantly lower diffusion coefficient compared to PBS, which is attributed to both the physical obstruction by the mucin mesh and reactive nature of NO radicals towards the biological compounds in ASM. To further confirm that ASM was restricting NO from diffusing freely, a macromolecular propylamine-modified cyclodextrin donor (CD-PA) was employed to release the NO more slowly.

A direct and selective electrochemical hydrogen sulfide sensor.

Continuous, in situ detection of hydrogen sulfide (HS) in biological milieu is made possible with electrochemical methods, but direct amperometry is constrained by the generation of elemental sulfur as an oxidative byproduct. Deposition of a sulfur layer passivates the working electrode, reducing sensitivity and causing performance variability. Herein, we report on the use of a surface preconditioning procedure to deposit elemental sulfur on a glassy carbon electrode prior to measurement and evaluate performance with common analytical metrics.

Direct Electrochemical Sensing of Hydrogen Sulfide without Sulfur Poisoning.

An electrochemical method capable of direct, real-time detection of hydrogen sulfide was developed using triple pulse amperometry (TPA) to mitigate sulfur poisoning and its related passivation of the working electrode surface. Through repeated cycles of discrete potential pulses, the electrooxidation of surface-adsorbed elemental sulfur to water-soluble sulfate ions was exploited to regenerate the glassy carbon electrode surface and maintain consistent sensor performance. Amperometric measurements and X-ray photoelectron spectroscopy surface analysis demonstrated that the TPA sensors provided enhanced analytical performance via decreased sulfur accumulation relative to low-potential (≤+0.

Structure-function relationships affecting the sensing mechanism of monolayer-protected cluster doped xerogel amperometric glucose biosensors.

A systematic study of the structure-function relationships critical to understanding the sensing mechanism of 1st generation amperometric glucose biosensors with an embedded nanoparticle (NP) network is presented. Xerogel-based films featuring embedded glucose oxidase enzyme and doped with alkanethiolate-protected gold NPs, known as monolayer protected clusters (MPCs), exhibit significantly enhanced performance compared to analogous systems without NPs including higher sensitivity, faster response time, and extended linear/dynamic ranges. The proposed mechanism involves diffusion of the glucose to glucose oxidase within the xerogel, enzymatic reaction production of H2O2 with subsequent diffusion to the embedded network of MPCs where it is oxidized, an event immediately reported via fast electron transfer (ET) through the MPC system to the working electrode.

Functional layer-by-layer design of xerogel-based first-generation amperometric glucose biosensors.

Xerogel-based first-generation amperometric glucose biosensors, constructed through specific layer-by-layer assembly of films featuring glucose oxidase doped xerogel, a diffusion-limiting xerogel layer, and capped with both electropolymerized polyphenol and blended polyurethane semipermeable membranes, are presented. The specific combination of xerogels formed from specific silane precursors, including propyl-trimethoxysilane, isobutyl-trimethoxysilane, octyl-trimethoxysilane, and hydroxymethyl-triethoxysilane, exhibit impressive dynamic and linear ranges of detection (e.g.

Brain natriuretic peptide and cardiac resynchronization therapy in patients with mildly symptomatic heart failure.

Background: There are limited data on the prognostic implications of brain natriuretic peptide (BNP) assessment in patients with mildly symptomatic heart failure (HF) who receive cardiac resynchronization therapy with a defibrillator (CRT-D).

Methods And Results: The effect of elevated baseline and 1-year BNP levels (dichotomized at the upper tertile BNP of 120 pg/mL) on the risk of HF or death was assessed among the cohort of 1197 patients with baseline BNP data enrolled in MADIT (Multicenter Automated Defibrillator Implantation Trial)-CRT. Elevated baseline BNP was associated with a significant 68% (P=0.

Right ventricular function, pulmonary pressure estimation, and clinical outcomes in cardiac resynchronization therapy.

Background: Right ventricular function (RVF) is an important determinant of outcome in patients with heart failure, and those with severe RV dysfunction have worse outcome after cardiac resynchronization therapy (CRT). We used data from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) Trial to determine whether therapy with CRT is influenced by or affects RV function and to define the relationship between RV function and outcomes.

Methods And Results: A total of 1820 patients were randomly assigned to CRT plus implantable cardioverter defibrillator or implantable cardioverter defibrillator-only in a 3:2 ratio.

Monolayer-protected nanoparticle doped xerogels as functional components of amperometric glucose biosensors.

First-generation amperometric glucose biosensors incorporating alkanethiolate-protected gold nanoparticles, monolayer protected clusters (MPCs), within a xerogel matrix are investigated as model systems for nanomaterial-assisted electrochemical sensing strategies. The xerogel biosensors are comprised of platinum electrodes modified with composite films of (3-mercaptopropyl)trimethoxy silane xerogel embedded with glucose oxidase enzyme, doped with Au225(C6)75 MPCs, and coated with an outer polyurethane layer. Electrochemistry and scanning/transmission electron microscopy, including cross-sectional TEM, show sensor construction, humidity effects on xerogel structure, and successful incorporation of MPCs.

Survival of patients receiving a primary prevention implantable cardioverter-defibrillator in clinical practice vs clinical trials.

Importance: Randomized clinical trials have shown that implantable cardioverter-defibrillator (ICD) therapy saves lives. Whether the survival of patients who received an ICD in primary prevention clinical trials differs from that of trial-eligible patients receiving a primary prevention ICD in clinical practice is unknown.

Objective: To determine whether trial-eligible patients who received a primary prevention ICD as documented in a large national registry have a survival rate that differs from the survival rate of similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n = 742) and SCD-HeFT (n = 829).

Reduction in inappropriate therapy and mortality through ICD programming.

Background: The implantable cardioverter-defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential adverse effects.

Methods: We randomly assigned 1500 patients with a primary-prevention indication to receive an ICD with one of three programming configurations. The primary objective was to determine whether programmed high-rate therapy (with a 2.

Cardiac resynchronization and quality of life in patients with minimally symptomatic heart failure.

Objectives: This study compared the quality of life (QOL) of patients with cardiac resynchronization therapy (CRT) and an implantable cardioverter-defibrillator (ICD) to patients with an ICD only.

Background: CRT with ICD is associated with a reduction in heart failure risk among minimally symptomatic patients. It is unknown whether this improves QOL.

Effect of cardiac resynchronization therapy on the risk of first and recurrent ventricular tachyarrhythmic events in MADIT-CRT.

Objectives: This study aimed to evaluate the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risks of first and recurrent ventricular tachyarrhythmic events (VTEs) in the MADIT-CRT.

Background: Reverse remodeling associated with CRT-D therapy was suggested to reduce arrhythmic risk. However, the effect of the device on the risk of recurrent VTEs among patients who experience a first arrhythmic event has not been investigated.

Multicenter automatic defibrillator implantation trial: reduce inappropriate therapy (MADIT-RIT): background, rationale, and clinical protocol.

The implantable cardioverter defibrillator (ICD) is highly effective in reducing mortality due to cardiac arrhythmias in high-risk cardiac patients. However, inappropriate therapies caused predominantly by supraventricular tachyarrhythmias (SVTs) remain a significant side effect of ICD therapy despite medical treatment, affecting 8-40% of patients. The MADIT-RIT is a global, prospective, randomized, nonblinded, three-arm, multicenter clinical investigation to be performed in the Unites States, Europe, Canada, Israel and Japan, and will utilize approximately 90 centers with plan to enroll 1500 patients programmed to three treatment arms.

Reduction in life-threatening ventricular tachyarrhythmias in statin-treated patients with nonischemic cardiomyopathy enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).

Objectives: This study hypothesized that time-dependent statin therapy will reduce the risk of life-threatening ventricular tachyarrhythmias among patients with nonischemic cardiomyopathy (NICM) enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).

Background: Prior studies suggested that statin therapy exerts antiarrhythmic properties among patients with coronary artery disease. However, data regarding the effect of statins on arrhythmic risk among patients with NICM are limited.

Predictors of response to cardiac resynchronization therapy in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT).

Background: We hypothesized that combined assessment of factors that are associated with favorable reverse remodeling after cardiac resynchronization-defibrillator therapy (CRT-D) can be used to predict clinical response to the device.

Methods And Results: The study population comprised 1761 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). Best-subset regression analysis was performed to identify factors associated with echocardiographic response (defined as percent reduction in left ventricular end-diastolic volume 1 year after CRT-D implantation) and to create a response score.

Reduction of the risk of recurring heart failure events with cardiac resynchronization therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).

Objectives: The evaluation of the risk of recurring heart failure events (HFEs) was a pre-specified substudy of MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).

Background: There are limited data regarding the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the occurrence of recurring heart failure episodes after a first post-implantation HFE.

Methods: Data with regard to recurring HFEs were prospectively collected for all 1,820 MADIT-CRT participants.

Risk of recurrent cardiac events after onset of menopause in women with congenital long-QT syndrome types 1 and 2.

Background: Women with congenital long-QT syndrome experience an increased risk for cardiac events after the onset of adolescence that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population.

Methods And Results: We used a repeated-events analysis to evaluate the risk for recurrent syncope during the menopause transition and postmenopausal periods (5 years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the Long-QT Syndrome Registry.

Relationship between improvement in left ventricular dyssynchrony and contractile function and clinical outcome with cardiac resynchronization therapy: the MADIT-CRT trial.

Aims: To assess long-term effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) dyssynchrony and contractile function, by two-dimensional speckle-tracking echocardiography, compared with implantable cardioverter defibrillator (ICD) only in MADIT-CRT.

Methods And Results: We studied 761 patients in New York Heart Association I/II, ejection fraction ≤30%, and QRS ≥130 ms [n = 434, CRT-defibrillator (CRT-D), n = 327, ICD] with echocardiographic studies available at baseline and 12 months. Dyssynchrony was determined as the standard deviation of time to peak transverse strain between 12 segments of apical four- and two-chamber views, and contractile function as global longitudinal strain (GLS) by averaging longitudinal strain over these 12 segments.

Dyssynchrony, contractile function, and response to cardiac resynchronization therapy.

Background: Despite benefits of cardiac resynchronization therapy (CRT) in patients with severe but less symptomatic heart failure, approximately 30% of patients do not fully respond to treatment. We hypothesized that a combined assessment of left ventricular (LV) dyssynchrony and contractile function by strain-based imaging would identify patients who would most benefit from CRT.

Methods And Results: We studied 1077 patients with New York Heart Association class I/II, LV ejection fraction ≤30% and QRS width ≥130 ms enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial with sufficient echocardiographic image quality for cardiac deformation analysis (implantable cardioverter-defibrillator [ICD], n=416; CRT, n=661).