Results of a study examining the use of onabotulinumtoxinA in pediatric patients with overactive bladder.

Background: There is a lack of approved treatments for pediatric patients with overactive bladder (OAB) with inadequate response to anticholinergic therapy. OnabotulinumtoxinA 100U is approved to treat OAB in adults based on data from randomized, pivotal trials.

Objective: To investigate the efficacy and safety of onabotulinumtoxinA treatment of OAB in children aged 12-17 years who were not adequately managed with anticholinergics.

Implementation of a pediatric bed prioritization process in a rural Minnesota community-based hospital.

Inpatient capacity constraints have been a pervasive challenge for hospitals throughout the COVID-19 pandemic. The Mayo Clinic Health System - Southwest Minnesota region primarily serves patients in rural southwestern Minnesota and part of Iowa and consists of 1 postacute care hospital, 1 tertiary care medical center, and 3 critical access hospitals. The main hub, Mayo Clinic Health System in Mankato, Minnesota, has a pediatric unit with dedicated pediatric hospitalists.

A Regional Analysis of Potentially Preventable Injuries Sustained From Burning Garbage and Yard Waste.

Due to high prevalence in the south, understanding the injury pattern, healthcare burden, and cost of burn injuries associated with burning yard and trash debris are important for effective prevention. This 5-year retrospective, single-center study included patients sustaining an open flame burn injury due to burning brush or trash. Based on primary residence of the 136 patients, 56% had access to free municipal waste disposal, 25% could have had access with additional payment, and 18% did not have access.

Long-term Safety and Tolerability of Repeated Treatments With OnabotulinumtoxinA in Children With Neurogenic Detrusor Overactivity.

Purpose: OnabotulinumtoxinA is an approved treatment for neurogenic detrusor overactivity in adults inadequately managed with anticholinergics, and more recently was approved in children on the basis of a phase 3, 48-week, single-treatment study (NCT01852045). Given the paucity of long-term pediatric data, we report on the continued safety in these patients after repeated onabotulinumtoxinA treatment.

Materials And Methods: This was a multicenter, double-blind, repeat-treatment extension study (NCT01852058) in patients who entered from the preceding single-treatment study.

Intravesical Instillation of OnabotulinumtoxinA in the Treatment of Refractory Overactive Bladder in Participants with Urinary Incontinence.

Purpose: Intradetrusor injections of onabotulinumtoxinA are efficacious for the treatment of overactive bladder with urgency urinary incontinence in adults refractory to or intolerant of anticholinergics. Delivery of onabotulinumtoxinA via instillation would reduce the need for intradetrusor injections. The objective of this trial was to assess the efficacy and safety of intravesical instillation of an onabotulinumtoxinA + hydrogel admixture.

Quantum Walks: Schur Functions Meet Symmetry Protected Topological Phases.

This paper uncovers and exploits a link between a central object in harmonic analysis, the so-called Schur functions, and the very hot topic of symmetry protected topological phases of quantum matter. This connection is found in the setting of quantum walks, i.e.

Protein Targets of Acetaminophen Covalent Binding in Rat and Mouse Liver Studied by LC-MS/MS.

Acetaminophen (APAP) is a mild analgesic and antipyretic used commonly worldwide. Although considered a safe and effective over-the-counter medication, it is also the leading cause of drug-induced acute liver failure. Its hepatotoxicity has been linked to the covalent binding of its reactive metabolite, -acetyl -benzoquinone imine (NAPQI), to proteins.

Safety, tolerability, and efficacy of LiRIS 400 mg in women with interstitial cystitis/bladder pain syndrome with or without Hunner lesions.

Aims: Two phase 2 studies were conducted to assess the efficacy and safety of lidocaine-releasing intravesical system (LiRIS) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with (Study 001; NCT02395042) or without, (Study 002; NCT02411110) Hunner lesions (HL).

Methods: Both were multicenter, randomized, double-blind, placebo-controlled, and enrolled women aged ≥18 years. In Study 001, patients were randomized 2:1:1 to LiRIS 400 mg/LiRIS 400 mg, placebo/LiRIS 400 mg, or placebo/placebo for a continuous 28 (2 × 14)-day period.

Value-Added Use of Invasive Plant-Derived Fibers as PHBV Fillers for Biocomposite Development.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a promising biobased, biodegradable thermoplastic with limited industrial applications due to its brittleness and high cost. To improve these properties, lignocellulosic fibers from two invasive plants ( and ) were used as PHBV reinforcing agents. Alkali treatment of the fibers improved the PHBV-fiber interfacial bond by up to 300%.

Determining site occupancy of acetaminophen covalent binding to target proteins in vitro.

Acetaminophen (APAP)-related toxicity is caused by the formation of -acetyl -benzoquinone imine (NAPQI), a reactive metabolite able to covalently bind to protein thiols. A targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, using multiple reaction monitoring (MRM), was developed to measure APAP binding on selected target proteins, including glutathione -transferases (GSTs). In vitro incubations with CYP3A4 were performed to form APAP in the presence of different proteins, including four purified GST isozymes.

OnabotulinumtoxinA for the treatment of neurogenic detrusor overactivity in children.

Aims: This study evaluated whether one (or more) of three doses of onabotulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children.

Methods: This was a 48-week prospective, multicenter, randomized, double-blind study in children (aged 5-17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes.

Identification of 4-hydroxynonenal-modified proteins in human osteoarthritic chondrocytes.

The α,β-unsaturated aldehyde 4-hydroxynonenal (HNE) is formed through lipid peroxidation during oxidative stress. As a highly reactive electrophile, it is able to form adducts with various biomolecules, including proteins. These protein modifications could modulate many signaling pathways, as well as cell differentiation and proliferation, and thus could be highly important in the context of the extracellular matrix and degradation of articular cartilage.

Investigation of Clozapine and Olanzapine Reactive Metabolite Formation and Protein Binding by Liquid Chromatography-Tandem Mass Spectrometry.

Drug-induced toxicity has, in many cases, been linked to oxidative metabolism resulting in the formation of reactive metabolites and subsequent covalent binding to biomolecules. Two structurally related antipsychotic drugs, clozapine (CLZ) and olanzapine (OLZ), are known to form similar nitrenium ion reactive metabolites. CLZ-derived reactive metabolites have been linked to agranulocytosis and hepatotoxicity.

Liquid Chromatography-Tandem Mass Spectrometry Analysis of Acetaminophen Covalent Binding to Glutathione -Transferases.

Acetaminophen (APAP)-induced hepatotoxicity is the most common cause of acute liver failure in the Western world. APAP is bioactivated to -acetyl -benzoquinone imine (NAPQI), a reactive metabolite, which can subsequently covalently bind to glutathione and protein thiols. In this study, we have used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to characterize NAPQI binding to human glutathione -transferases (GSTs) .

Seamless phase IIa/IIb adaptive design with the same primary endpoint for proof of concept and dose finding.

This paper considers combining a proof of concept (POC) study and a dose finding (DF) study where the POC and the DF share the same primary endpoint. An example based on real study conditions shows that compared to a conventional design the proposed adaptive design tests more active doses, with a smaller sample size and a shorter overall duration leading to a budget saving of 30% in study operations.

Absolute quantitation of acetaminophen-modified human serum albumin in acute liver failure patients by liquid chromatography/tandem mass spectrometry.

Rationale: Acetaminophen (APAP) is a well-known analgesic, deemed a very safe over-the-counter medication. However, it is also the main cause of acute liver failure (ALF) in the Western world, via the formation of its reactive metabolite, N-acetyl p-benzoquinone imine (NAPQI), and its covalent attachment to liver proteins. The aim of this study was to develop a sensitive and robust quantitative assay to monitor APAP-protein binding to human serum albumin (HSA) in patient samples.

Efficacy and safety of single-dose onabotulinumtoxinA in the treatment of symptoms of osteoarthritis of the knee: results of a placebo-controlled, double-blind study.

Objective: To evaluate intraarticular onabotulinumtoxinA 400 U and 200 U in reducing symptoms of knee osteoarthritis (OA) in patients with nociceptive pain.

Design: A multicenter, double-blind, randomized, placebo-controlled study was conducted in adults with knee OA and a painDETECT questionnaire score of ≤12 (indicating nociceptive pain). Patients were randomized to receive intraarticular onabotulinumtoxinA 400 U or 200 U or placebo (saline) in the study knee on a 1:1:2 ratio and were followed-up for 24 weeks posttreatment.

Identification of 4-hydroxynonenal protein targets in rat, mouse and human liver microsomes by two-dimensional liquid chromatography/tandem mass spectrometry.

Rationale: 4-Hydroxynonenal (HNE), endogenously generated through peroxidation and breakdown of polyunsaturated fatty acids, has been linked to a number of adverse biological effects through carbonylation of essential biomolecules. Covalent binding of HNE to proteins can alter their structure and functions, causing cell damage as well as adverse immune responses. The liver plays a predominant role in metabolic transformations and hepatic proteins are often targeted by reactive metabolites.

Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum.

We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments.

Fragmentation patterns of boron-dipyrromethene (BODIPY) dyes by electrospray ionization high-resolution tandem mass spectrometry.

Rationale: 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene derivatives (BODIPYs) are fluorescent organic dyes that are widely used as non-radioactive labels in biological analyses. The fragmentation behaviour of ten structurally related BODIPYs was studied using tandem mass spectrometry (MS/MS), to support the structural elucidation process during synthesis.

Methods: The BODIPYs were investigated by electrospray ionization (ESI)-MS/MS, utilizing collision-induced dissociation (CID) data from triple quadrupole MS and high-resolution, accurate mass CID data from Fourier transform ion cyclotron resonance (FTICR) experiments.

Determining the Binding Sites of β-Cyclodextrin and Peptides by Electron-Capture Dissociation High Resolution Tandem Mass Spectrometry.

Cyclodextrins (CDs) are a group of cyclic oligosaccharides, which readily form inclusion complexes with hydrophobic compounds to increase bioavailability, thus making CDs ideal drug excipients. Recent studies have also shown that CDs exhibit a wide range of protective effects, preventing proteins from aggregation, degradation, and folding. These effects strongly depend on the binding sites on the protein surface.

A simple micro-extraction plate assay for automated LC-MS/MS analysis of human serum 25-hydroxyvitamin D levels.

This short application note describes a simple and automated assay for determination of 25-hydroxyvitamin D (25(OH)D) levels in very small volumes of human serum. It utilizes commercial 96-well micro-extraction plates with commercial 25(OH)D isotope calibration and quality control kits. Separation was achieved using a pentafluorophenyl liquid chromatography column followed by multiple reaction monitoring-based quantification on an electrospray triple quadrupole mass spectrometer.

On the isobaric space of 25-hydroxyvitamin D in human serum: potential for interferences in liquid chromatography/tandem mass spectrometry, systematic errors and accuracy issues.

Rationale: Isobaric interferences in human serum can potentially influence the measured concentration levels of 25-hydroxyvitamin D [25(OH)D], when low resolving power liquid chromatography/tandem mass spectrometry (LC/MS/MS) instruments and non-specific MS/MS product ions are employed for analysis. In this study, we provide a detailed characterization of these interferences and a technical solution to reduce the associated systematic errors.

Methods: Detailed electrospray ionization Fourier transform ion cyclotron resonance (FTICR) high-resolution mass spectrometry (HRMS) experiments were used to characterize co-extracted isobaric components of 25(OH)D from human serum.