Pulmonary Embolism Response Teams-Evidence of Benefits? A Systematic Review and Meta-Analysis.

Venous thromboembolisms constitute a major cause of morbidity and mortality with 60,000 to 100,000 deaths attributed to pulmonary embolism in the US annually. Both clinical presentations and treatment strategies can vary greatly, and the selection of an appropriate therapeutic strategy is often provider specific. A pulmonary embolism response team (PERT) offers a multidisciplinary approach to clinical decision making and the management of high-risk pulmonary emboli.

IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling.

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation.

Creating a Chest Wall Injury and Reconstructive program: A single center experience with rib fractures.

Background: New Chest Wall Injury and Reconstructive Centers (CWIRC) are emerging; this study aims to investigate the potential benefits of implementing a CWIRC at a single institution. We hypothesized that patients treated at CWIRC will have improved outcomes.

Methods: We instituted a CWIRC in 2019 at our American College of Surgeons (ACS) Level One Trauma Center.

Victims of Violence and Post-Discharge Adverse Events: A Prospective Modified Trauma Quality Improvement Program (TQIP) Study.

Introduction Trauma patients frequently return to an emergency department (ED) soon after discharge; often for non-urgent reasons. Social factors contribute to higher ED usage. At present, there is no standardized system for reporting of ED visits and readmissions among trauma care.

Scholl Cyclizations of Aryl Naphthalenes: Rearrangement Precedes Cyclization.

In 1910, Scholl, Seer, and Weitzenbock reported the AlCl3-catalyzed cyclization of 1,1'-binaphthyl to perylene. We provide evidence that this classic organic name reaction proceeds through sequential and reversible formation of 1,2'- and 2,2'-binaphthyl isomers. Acid-catalyzed isomerization of 1,1'-binaphthyl to 2,2'-binaphthyl has been noted previously.

Slowed Diffusion and Excluded Volume Both Contribute to the Effects of Macromolecular Crowding on Alcohol Dehydrogenase Steady-State Kinetics.

To understand the consequences of macromolecular crowding, studies have largely employed in vitro experiments with synthetic polymers assumed to be both pure and "inert". These polymers alter enzyme kinetics by excluding volume that would otherwise be available to the enzymes, substrates, and products. Presented here is evidence that other factors, in addition to excluded volume, must be considered in the interpretation of crowding studies with synthetic polymers.

A nationwide 2010-2012 analysis of U.S. health care utilization in inflammatory bowel diseases.

Background: Implementation of the 2010 Affordable Care Act (ACA) calls for a collaborative effort to transform the U.S. health care system toward patient-centered and value-based care.

Incidental findings in trauma patients: dedicated communication with the primary care physician ensures adequate follow-up.

Background: Frequent use of computed tomography (CT) in trauma patients results in frequent detection of non-trauma-related incidental findings (IFs). Inpatient documentation and disclosure at discharge are infrequent, even when they are potentially serious. We aimed to not only identify the incidence of IFs but also to evaluate the effectiveness of an intervention to trigger follow-up.

Phenyl shifts in substituted arenes via ipso arenium ions.

The isomerization of substituted arenes through ipso arenium ions is an important and general molecular rearrangement that leads to interconversions of constitutional isomers. We show here that the superacid trifluoromethanesulfonic acid (TfOH), ca. 1 M in dichloroethane (DCE), provides reliable catalytic reaction conditions for these rearrangements, easily applied at ambient temperature, reflux (84 °C), or in a microwave reactor for higher temperatures.

CC chemokine receptor-3 (CCR3) antagonists: improving the selectivity of DPC168 by reducing central ring lipophilicity.

DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2D6 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520.

Structural insights into the design of nonpeptidic isothiazolidinone-containing inhibitors of protein-tyrosine phosphatase 1B.

Structural analyses of the protein-tyrosine phosphatase 1B (PTP1B) active site and inhibitor complexes have aided in optimization of a peptide inhibitor containing the novel (S)-isothiazolidinone (IZD) phosphonate mimetic. Potency and permeability were simultaneously improved by replacing the polar peptidic backbone of the inhibitor with nonpeptidic moieties. The C-terminal primary amide was replaced with a benzimidazole ring, which hydrogen bonds to the carboxylate of Asp(48), and the N terminus of the peptide was replaced with an aryl sulfonamide, which hydrogen bonds to Asp(48) and the backbone NH of Arg(47) via a water molecule.

Potent benzimidazole sulfonamide protein tyrosine phosphatase 1B inhibitors containing the heterocyclic (S)-isothiazolidinone phosphotyrosine mimetic.

Potent nonpeptidic benzimidazole sulfonamide inhibitors of protein tyrosine phosphatase 1B (PTP1B) were derived from the optimization of a tripeptide containing the novel (S)-isothiazolidinone ((S)-IZD) phosphotyrosine (pTyr) mimetic. An X-ray cocrystal structure of inhibitor 46/PTP1B at 1.8 A resolution demonstrated that the benzimidazole sulfonamides form a bidentate H bond to Asp48 as designed, although the aryl group of the sulfonamide unexpectedly interacts intramolecularly in a pi-stacking manner with the benzimidazole.

Concise approach to novel isothiazolidinone phosphotyrosine mimetics: microwave-assisted addition of bisulfite to activated olefins.

[reaction: see text] A novel and efficient synthesis of isothiazolidinone protein tyrosine phosphatase mimetics is presented. A practical, regiospecific microwave-assisted addition of bisulfite to activated olefins, including unprecedented reactions with styrene derivatives, is highlighted.

Structure-based design and discovery of protein tyrosine phosphatase inhibitors incorporating novel isothiazolidinone heterocyclic phosphotyrosine mimetics.

Structure-based design led to the discovery of novel (S)-isothiazolidinone ((S)-IZD) heterocyclic phosphotyrosine (pTyr) mimetics that when incorporated into dipeptides are exceptionally potent, competitive, and reversible inhibitors of protein tyrosine phosphatase 1B (PTP1B). The crystal structure of PTP1B in complex with our most potent inhibitor 12 revealed that the (S)-IZD heterocycle interacts extensively with the phosphate binding loop precisely as designed in silico. Our data provide strong evidence that the (S)-IZD is the most potent pTyr mimetic reported to date.