Trauma Center Hospitals Charged Higher Prices For Some Nontrauma Care Than Non-Trauma Center Hospitals, 2012-18.

Rising prices are a major cause of increased health care spending and health insurance premiums in the US. Hospital prices, specifically-for both inpatient and outpatient care-are the largest driver of rising health care spending in the commercial insurance market. As a result, policy makers and employers are increasingly interested in understanding the determinants of hospital prices.

Use of V agents and V-analogue compounds to probe the active site of atypical butyrylcholinesterase from Oryzias latipes.

The atypical butyrylcholinesterase (aBuChE) from Oryzias latipes shares approximately 65% sequence similarity to both acetylcholinesterase and butyrylcholinesterase and was studied for its capacity to spontaneously reactivate following inhibition by organophosphorus nerve agents. Like other cholinesterases, aBuChE was inhibited by all G- and V-type nerve agents. Interestingly, aBuChE was able to undergo spontaneous reactivation after inhibition with VR (t = 5.

Interactions of a potent cyclic peptide inhibitor with the light chain of botulinum neurotoxin A: Insights from X-ray crystallography.

The seven antigenically distinct serotypes (A-G) of botulinum neurotoxin (BoNT) are responsible for the deadly disease botulism. BoNT serotype A (BoNT/A) exerts its lethal action by cleaving the SNARE protein SNAP-25, leading to inhibition of neurotransmitter release, flaccid paralysis and autonomic dysfunction. BoNTs are dichain proteins consisting of a ∼ 100 kDa heavy chain and a ∼ 50 kDa light chain; the former is responsible for neurospecific binding, internalization and translocation, and the latter for cleavage of neuronal SNARE proteins.

A rationally designed mutant of plasma platelet-activating factor acetylhydrolase hydrolyzes the organophosphorus nerve agent soman.

Organophosphorus compounds (OPs) such as sarin and soman are some of the most toxic chemicals synthesized by man. They exert toxic effects by inactivating acetylcholinesterase (AChE) and bind secondary target protein. Organophosphorus compounds are hemi-substrates for enzymes of the serine hydrolase superfamily.

Design, synthesis, and characterization of novel, nonquaternary reactivators of GF-inhibited human acetylcholinesterase.

The goal of this research was to identify structurally novel, non-quaternarypyridinium reactivators of GF (cyclosarin)-inhibited hAChE that possess the capacity to mediate in vitro reactivation of GF-inhibited human acetylcholinesterase (hAChE). New compounds were designed, synthesized and assessed in GF-inhibited hAChE assays. Structure activity relationships for AChE binding and reactivation of GF-inhibited hAChE were developed.

EMS provider compliance with infection control recommendations is suboptimal.

Introduction: Standard precautions are disease transmission prevention strategies recommended by both the World Health Organization (WHO) and by the Centers for Disease Control and Prevention (CDC). Emergency medical services (EMS) personnel are expected to utilize standard precautions.

Methods: This was a prospective observational study of the use of standard precautions by EMS providers arriving at a large urban emergency department (ED).

A common mechanism for resistance to oxime reactivation of acetylcholinesterase inhibited by organophosphorus compounds.

Administration of oxime therapy is currently the standard approach used to reverse the acute toxicity of organophosphorus (OP) compounds, which is usually attributed to OP inhibition of acetylcholinesterase (AChE). Rate constants for reactivation of OP-inhibited AChE by even the best oximes, such as HI-6 and obidoxime, can vary >100-fold between OP-AChE conjugates that are easily reactivated and those that are difficult to reactivate. To gain a better understanding of this oxime specificity problem for future design of improved reactivators, we conducted a QSAR analysis for oxime reactivation of AChE inhibited by OP agents and their analogues.

Role of acetylcholinesterase on the structure and function of cholinergic synapses: insights gained from studies on knockout mice.

Electrophysiological and ultrastructural studies were performed on phrenic nerve-hemidiaphragm preparations isolated from wild-type and acetylcholinesterase (AChE) knockout (KO) mice to determine the compensatory mechanisms manifested by the neuromuscular junction to excess acetylcholine (ACh). The diaphragm was selected since it is the primary muscle of respiration, and it must adapt to allow for survival of the organism in the absence of AChE. Nerve-elicited muscle contractions, miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) were recorded by conventional electrophysiological techniques from phrenic nerve-hemidiaphragm preparations isolated from 1.

Characterization of vancomycin pharmacokinetics in the adult acute myeloid leukemia population.

Current vancomycin dosing guidelines in our acute myeloid leukemia population too often achieve suboptimal initial drug concentrations. Our aim was to assess vancomycin pharmacokinetic parameters in acute myeloid leukemia patients and develop an improved dosing equation to attain more accurate initial therapeutic trough levels. Acute myeloid leukemia patients receiving vancomycin for a presumed or documented gram positive infection were eligible.

Nilotinib: a new tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder arising from a single genetic mutation that leads to an increase in immature myeloid cells in the bone marrow and the accumulation of these cells in the blood. Typically, CML represents 15-20% of all adult leukemias, with 4830 new cases expected in 2008. The cytogenetic hallmark of CML is the Philadelphia chromosome, which is the result of the reciprocal translocation and conjugation of the breakpoint cluster region (BCR) gene, BCR, on chromosome 22 and the Abelson (ABL) kinase gene, ABL, on chromosome 9.

A structure-activity analysis of the variation in oxime efficacy against nerve agents.

A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent.

A gas chromatographic-mass spectrometric approach to examining stereoselective interaction of human plasma proteins with soman.

The organophosphorus (OP) nerve agent soman (GD) contains two chiral centers (a carbon and a phosphorus atom), resulting in four stereoisomers (C+P+, C-P+, C+P-, and C-P-); the P- isomers exhibit a mammalian toxicity that is approximately 1000-fold greater than that of the P+ isomers. The capacity to assess the binding or hydrolysis of each of the four stereoisomers is an important tool in the development of enzymes with the potential to protect against GD intoxication. Using a gas chromatography-mass spectrometry-based approach, we have examined the capacity of plasma-derived human serum albumin, plasma-purified human butyrylcholinesterase, goat milk-derived recombinant human butyrylcholinesterase, and recombinant human paraoxonase 1 to interact with each of the four stereoisomers of GD in vitro at pH 7.

Direct detection of stereospecific soman hydrolysis by wild-type human serum paraoxonase.

Human serum paraoxonase 1 (HuPON1; EC 3.1.8.

Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review.

Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE; PharmAthene Inc.

Acetylcholinesterase inhibition: does it explain the toxicity of organophosphorus compounds?

The hypothesis that acetylcholinesterase (AChE) inhibition is the mechanism of toxicity of organophosphorus (OP) compounds was examined by mathematically modeling the in vivo lethal effects of OP compounds and determining the amount of variation in OP toxicity that is explained by AChE inhibition. Mortality dose-response curves for several OP compounds (i.e.

A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes of soman in multiple species.

A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(+/-)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 x LD(50)), medium (2-3 x LD(50)) and high (6 x LD(50)) levels of soman challenge in three species (rat, guinea pig, marmoset).

The constitution of mineral trioxide aggregate.

Objectives: The aim of this study was to determine the constitution of a commercially available root-end filling material, mineral trioxide aggregate, (MTA) (ProRoot MTA, Tulsa Dental, Tulsa, OK, USA). The surface morphology of the material with various treatment conditions was also evaluated.

Methods: The constitution of two commercial versions of MTA was determined before and after mixing with water.

Neutralization effects of interleukin-6 (IL-6) antibodies on sulfur mustard (HD)-induced IL-6 secretion on human epidermal keratinocytes.

The proinflammatory cytokine human interleukin-6 (hIL-6) plays an important role in the early and late courses of inflammation, trauma, and wound healing caused by sulfur mustard (HD). Previously, we demonstrated that hIL-6 might be involved in the early event of structural changes of the signal transducer glycoprotein, which indirectly initiates the cascade of events, such as skin irritation and blister formation observed in the pathophysiology of HD injury. In this present work, we focus on the neutralization effect of IL-6 antibodies with regard to the modulation of hIL-6 secretion.

Behavioral data management using Visual Basics for Applications to automate data capture and analysis.

Many researchers are familiar with the spreadsheet capabilities of Microsoft Excel, but have never explored using customized VISUAL BASIC FOR APPLICATIONS (VBA) macros embedded in the program. At the United States Army Medical Research Institute of Chemical Defense (USAMRICD), the implementation of VBA program code to carry out repetitive operations has resulted in a tremendous savings in both the time and manpower required to reliably capture, analyze, and plot data from research protocols. A set of "template" workbooks was developed and is used to organize data from different types of studies.

A theoretical expression for the protection associated with stoichiometric and catalytic scavengers in a single compartment model of organophosphorus poisoning.

The ability of certain organophosphorus (OP) compounds to inhibit acetylcholinesterase (AChE) has made them useful for industrial (insecticides) and military (nerve agents) purposes. We have previously published a single compartment mathematical model of the interactions between OP nerve agents and the enzymes affected by these agents. That model, which could be used to predict the LD50 of seven nerve agents in rats, has been extended to include the protective actions of stoichiometric and catalytic OP-scavenger enzymes (delivered as pretreatments) so that protective ratios attributable to the scavengers may be predicted.