Acute kidney failure from ingestion of "wood bleach" beekeeping miticide.

Wood bleach is >95 % oxalic acid formulation used off-label as a miticide for Varroa mites by hobbyist beekeepers. Wood bleach (oxalic acid) ingestions are poorly documented in the medical literature. A 46-year-old man presented to the emergency department nauseated and vomiting after accidentally ingesting "bleach and grain ethanol intended for use in beekeeping.

The salience of social context, opioid antagonist use, and prior opioid exposure as determinants of fatal and non-fatal opioid overdoses.

This study examines the salience of social context for opioid overdoses in Boston from 2014 to 2019. Longitudinal negative binomial models with random effects indicated that higher levels of concentrated disadvantage, residential instability, and illicit drug activity increased annual block group counts of opioid overdoses. Logistic hierarchical and cross-classified random effects models indicated that the use of Narcan and greater exposure to drugs through previous opioid overdose and contextual lillicit drug crime activity reduced the odds of fatal opioid overdose relative to non-fatal opioid overdose.

Multimodal thromboprophylaxis in low-risk patients undergoing lower limb arthroplasty: A retrospective observational cohort analysis of 1400 patients with ultrasound screening.

Purpose: This study reports the results of a multimodal thromboprophylaxis protocol for lower limb arthroplasty involving risk stratification, intraoperative calf compression, aspirin prophylaxis and early (within 4 h) post-operative mobilisation facilitated by the use of local infiltration analgesia. The study also aimed to identify risk factors for venous thromboembolism (VTE) within a 3-month period following surgery for patients deemed not at elevated risk.

Methods: Patients undergoing knee/hip arthroplasty or hip resurfacing were preoperatively screened for VTE risk factors, and those at standard risk were placed on a thromboprophylaxis protocol consisting of intraoperative intermittent calf compression during surgery, 300 mg/day aspirin for 6 weeks from surgery and early mobilisation.

Robotic and navigation systems in orthopaedic surgery: how much do our patients understand?

Background: Technology in orthopaedic surgery has become more widespread in the past 20 years, with emerging evidence of its benefits in arthroplasty. Although patients are aware of benefits of conventional joint replacement, little is known on patients' knowledge of the prevalence, benefits or drawbacks of surgery involving navigation or robotic systems.

Methods: In an outpatient arthroplasty clinic, 100 consecutive patients were approached and given questionnaires to assess their knowledge of navigation and robotics in orthopaedic surgery.

Double Ring Array Catheter for In Vivo Real-Time 3D Ultrasound.

We developed new forward-viewing matrix transducers consisting of double ring arrays of 118 total PZT elements integrated into catheters used to deploy medical interventional devices. Our goal is 3D ultrasound guidance of medical device implantation to reduce x-ray fluoroscopy exposure. The double ring arrays were fabricated on inner and outer custom polyimide flexible circuits with inter-element spacing of 0.

Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase.

1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure.

The work of adult and pediatric intensive care unit nurses.

Background: Researchers have used various methods to describe and quantify the work of nurses. Many of these studies were focused on nursing in general care settings; therefore, less is known about the unique work nurses perform in intensive care units (ICUs).

Objectives: The aim of this study was to observe adult and pediatric ICU nurses in order to quantify and compare the duration and frequency of nursing tasks across four ICUs as well as within two discrete workflows: nurse handoffs at shift change and patient interdisciplinary rounds.

Conducting an efficient proactive risk assessment prior to CPOE implementation in an intensive care unit.

Purpose: To develop, conduct, and evaluate a proactive risk assessment (PRA) of the design and implementation of CPOE in an ICU.

Methods: We developed a PRA method based on issues identified from documented experience with conventional PRA methods and the constraints of an organization about to implement CPOE in an intensive care unit. The PRA method consists of three phases: planning (three months), team (one five-hour meeting), and evaluation (short- and long-term).

NADPH oxidase-dependent and -independent mechanisms of reported inhibitors of reactive oxygen generation.

NADPH oxidase isoform-2 (NOX2) generates reactive oxygen species (ROS) that contribute to neurodegenerative and cardiovascular pathologies. However, validation of NOX2 as a pharmacotherapeutic target has been hampered by a lack of mechanistically-defined inhibitors. Using cellular and biochemical assays, we explored previously reported inhibitors of ROS production (perhexiline, suramin, VAS2870 and two Shionogi patent compounds) as direct NOX2 inhibitors.

Chronic urotensin II receptor antagonist treatment does not alter hypertrophy or fibrosis in a rat model of pressure-overload hypertrophy.

Urotensin II (UII) is a potential mediator in the pathogenesis of cardiovascular disease, and inhibition of its actions at the urotensin receptor (UT) has been shown to improve cardiac function and structural changes of the myocardium in a model of myocardial infarction. In this study we utilized a model of pressure-overload hypertrophy induced by abdominal aortic constriction (AAC) which resulted in hypertrophy, increased fibrosis and impaired diastolic and systolic function. These changes were associated with a 4-fold increase in UII protein expression in the myocardium.

Teaching quality improvement.

Practicing nurses are required to engage in quality improvement work as a part of their clinical practice, but few undergraduate nursing education programs offer course work and applied experience in this area. This article presents a description of class content and teaching strategies, assignments, and evaluation strategies designed to achieve the Quality and Safety Education in Nursing competencies related to quality improvement and interdisciplinary teams. Students demonstrate their application of the quality improvement process by designing and implementing a small-scale quality improvement project that they report in storyboard format on a virtual conference Web site.

Use of failure mode and effects analysis for proactive identification of communication and handoff failures from organ procurement to transplantation.

A multidisciplinary team from the University of Wisconsin Hospital and Clinics transplant program used failure mode and effects analysis to proactively examine opportunities for communication and handoff failures across the continuum of care from organ procurement to transplantation. The team performed a modified failure mode and effects analysis that isolated the multiple linked, serial, and complex information exchanges occurring during the transplantation of one solid organ. Failure mode and effects analysis proved effective for engaging a diverse group of persons who had an investment in the outcome in analysis and discussion of opportunities to improve the system's resilience for avoiding errors during a time-pressured and complex process.

Direct inotropic effects of exogenous and endogenous urotensin-II: divergent actions in failing and nonfailing human myocardium.

Background: Urotensin-II (U-II) is an endogenous peptide upregulated in failing hearts. To date, insights into the myocardial actions of U-II have been obscured by its potent vasoconstrictor effects and interspecies differences in physiological responses to U-II.

Methods And Results: We examined the direct effects of exogenous U-II on in vitro contractility in nonfailing and failing human myocardial trabeculae (n=47).

Urotensin II receptor knockout mice on an ApoE knockout background fed a high-fat diet exhibit an enhanced hyperlipidemic and atherosclerotic phenotype.

Rationale: Expression of the vasoactive peptide Urotensin II (UII) is elevated in a number of cardiovascular diseases.

Objective: Here, we sought to determine the effect of UII receptor (UT) gene deletion in a mouse model of atherosclerosis.

Methods And Results: UT knockout (KO) mice were crossed with ApoE KO mice to generate UT/ApoE double knockout (DKO) mice.

The effects of benzodiazepines on urotensin II-stimulated norepinephrine release from rat cerebrocortical slices.

Background: Urotensin II (UII) and its receptor (UT) are implicated in mood disorders, such as stress and anxiety, and this may result, at least in part, from increased norepinephrine release from the cerebral cortex. Benzodiazepines have been widely used as hypnotics and anxiolytics, producing a decrease in cerebrocortical norepinephrine release. We hypothesized that there was some interaction between benzodiazepines and the UII system in the cerebral cortex.

Heme-oxygenase induction inhibits arteriolar thrombosis in vivo: effect of the non-substrate inducer cobalt protoporphyrin.

Heme oxygenase-1 (HO) metabolizes heme to form the vasodilator carbon monoxide and antioxidant biliverdin. Upregulation of HO-1 by hemin, which is also a substrate attenuates thrombosis in rodent models, however, whether protection is due to HO-1 upregulation or to increased substrate availability is unknown. This study tested the hypothesis that treatment of mice with cobalt protoporphyrin (CoPP), a non-substrate HO-1 inducer, would protect the endothelium from laser injury.

Targeted overexpression of the human urotensin receptor transgene in smooth muscle cells: effect of UT antagonism in ApoE knockout mice fed with Western diet.

Urotensin II (UII) and its receptor UT are upregulated in the pathological setting of various cardiovascular diseases including atherosclerosis. However, their exact role in atherosclerosis remains to be determined. In the present study we used four strains of mice; wild-type (WT), UT(+) (a transgenic strain expressing human UT driven by the alpha-smooth muscle-specific, SM22, promoter), ApoE knockout (ko), and UT(+)/ApoE ko.

Epoxyeicosatrienoic acids function as selective, endogenous antagonists of native thromboxane receptors: identification of a novel mechanism of vasodilation.

Epoxy- and dihydroxy-eicosatrienoic acids (EETs and DHETs) are vasoactive cytochrome P450 metabolites of arachidonic acid. Interestingly, however, the mechanism(s) by which EETs/DHETs mediate smooth muscle relaxation remains unclear. In contrast to previous reports, where dilation was purportedly large-conductance Ca(2+)-activated K(+) (BK(Ca)) and/or transient receptor potential cation channel, subfamily V, member 4 (TRPV4) channel-mediated, 14,15-EET-induced vasodilation [reversal of contractile tone established with the thromboxane receptor (TP) agonist 15-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic acid (U-46619)] was unaltered in BK(Ca) and TRPV4 knockout mouse isolated aortae compared with wild-type controls, indicating a significant BK(Ca)/TRPV4-resistant mechanism.

N-alkyl-5H-pyrido[4,3-b]indol-1-amines and derivatives as novel urotensin-II receptor antagonists.

High throughput screening of our compound collection led to the discovery of a novel series of N-alkyl-5H-pyrido[4,3-b]indol-1-amines as urotensin-II receptor antagonists. Synthesis, initial structure and activity relationships, functional and animal ortholog activities of the series are described.

Aminomethylpiperazines as selective urotensin antagonists.

Aminomethylpiperazines, reported previously as being kappa-opioid receptor agonists, were identified as lead compounds in the development of selective urotensin receptor antagonists. Optimized substitution of the piperazine moiety has provided high affinity urotensin receptor antagonists with greater than 100-fold selectivity over the kappa-opioid receptor. Select compounds were found to inhibit urotensin-induced vasoconstriction in isolated rat aortic rings consistent with the hypothesis that an urotensin antagonist may be useful for the treatment of hypertension.

Urotensin-II receptor antagonists: synthesis and SAR of N-cyclic azaalkyl benzamides.

SAR exploration of the central diamine, benzyl, and terminal aminoalkoxy regions of the N-cyclic azaalkyl benzamide series led to the identification of very potent human urotensin-II receptor antagonists such as 1a with a K(i) of 4 nM. The synthesis and structure-activity relationships (SAR) of N-cyclic azaalkyl benzamides are described.

Urotensin II evokes neurotransmitter release from rat cerebrocortical slices.

Urotensin II (UII) has been reported to modulate rapid eye movement (REM) sleep via activation of brainstem cholinergic neurons and REM sleep is regulated by locus coerleus (LC)-cerebrocortical noradrenergic neurons. We hypothesized that UII may activate LC-cerebrocortical noradrenergic neurons. To test this hypothesis, we have examined the effects of UII on norepinephrine release from rat cerebrocortical slices.

Potent and selective small-molecule human urotensin-II antagonists with improved pharmacokinetic profiles.

Lead compound 1 was successfully redesigned to provide compounds with improved pharmacokinetic profiles for this series of human urotensin-II antagonists. Replacement of the 2-pyrrolidinylmethyl-3-phenyl-piperidine core of 1 with a substituted N-methyl-2-(1-pyrrolidinyl)ethanamine core as in compound 7 resulted in compounds with improved oral bioavailability in rats. The relationship between stereochemistry and selectivity for hUT over the kappa-opioid receptor was also explored.

Development of potent and selective small-molecule human Urotensin-II antagonists.

This work describes the development of potent and selective human Urotensin-II receptor antagonists starting from lead compound 1, (3,4-dichlorophenyl)methyl{2-oxo-2-[3-phenyl-2-(1-pyrrolidinylmethyl)-1-piperidinyl]ethyl}amine. Several problems relating to oral bioavailability, cytochrome P450 inhibition, and off-target activity at the kappa opioid receptor and cardiac sodium channel were addressed during lead development. hUT binding affinity relative to compound 1 was improved by more than 40-fold in some analogs, and a structural modification was identified which significantly attenuated both off-target activities.

2-Aminomethyl piperidines as novel urotensin-II receptor antagonists.

A series of 2-aminomethyl piperidines has been discovered as novel urotensin-II receptor antagonists. The synthesis, initial structure-activity relationships, and optimization of the initial hit that resulted in the identification of potent, cross-species active, and functional urotensin-II receptor antagonists such as 1a and 11a are described.