Oxidant-free,three-component synthesis of 7-amino-6H-benzo[c]chromen-6-ones under green conditions

An oxidant-free three-component synthesis of biologically significant 7-amino-6H-benzo[c]chromen-6-ones was established involving a Sc(OTf)₃ catalyzed three-component reaction between primary amines, β-ketoesters and 2-hydroxychalcones under green conditions. In this strategy, both the B and C rings of 6H-benzo[c]chromen-6-ones were constructed simultaneously starting from acyclic precursors by generating four new bonds including two C–C, one C–N and one C–O in a single synthetic operation. The mechanism of this sequential cascade process involves the initial formation of a β-enaminone intermediate followed by Michael addition with 2-hydroxychalcone, intramolecular cyclization, dehydration, lactonization and aromatization steps. Unlike the related literature approaches, this reaction delivered the products without the addition of any external oxidants to achieve the key aromatization step.

Three-component synthesis of 7-amino-6H-benzo[c]chromen-6-ones was achieved under oxidant-free green conditions.     

Factors associated with external ventricular drain placement accuracy: data from an electronic health record repository

Background

We evaluated external ventricular drain placement for factors associated with placement accuracy. Data were acquired using an electronic health record data requisition tool.

Method

Medical records of all patients who underwent ventriculostomy from 2003 to 2010 were identified and evaluated. Patient demographics, diagnosis, type of guidance and number of catheter passes were searched for and recorded. Post-procedural hemorrhage and/or infection were identified. A grading scale was used to classify accuracy of catheter placements. A multiple logistic regression model was developed to assess features associated with accurate catheter placement.

Results

One hundred nine patients who underwent 111 ventriculostomies from 2003 to 2010 were identified. Patient diagnoses were classified into vascular (63 %), tumor (21 %), trauma (14 %), and cyst (2 %). Procedures were performed freehand in 90 (81 %), with the Ghajar guide in 17 (15 %), and with image guidance in 4 (4 %) patients. Eighty-eight (79 %) catheters were placed in the correct location. Trauma patients were more likely to have catheters misplaced (p?=?0.007) whereas patients in other diagnostic categories were not significantly associated with misplaced catheters. Post-procedural hemorrhage was noted in 2 (1.8 %) patients on post-procedural imaging studies. Five (4.5 %) definite and 6 (5.4 %) suspected infections were identified.

Conclusions

External ventricular drain placement can be performed accurately in most patients. Patients with trauma are more likely to have catheters misplaced. Further development is required to identify and evaluate procedure outcomes using an electronic health record repository.     

Understanding the interaction of Lipoarabinomannan with membrane mimetic architectures

Lipoarabinomannan (LAM) is a critical virulence factor in the pathogenesis of Mycobacterium tuberculosis, the causative agent of tuberculosis. LAM is secreted in urine and serum from infected patients and is being studied as a potential diagnostic indicator for the disease. Herein, we present a novel ultra-sensitive and specific detection strategy for monomeric LAM based on its amphiphilic nature and consequent interaction with supported lipid bilayers. Our strategy involves the capture of LAM on waveguides functionalized with membrane mimetic architectures, followed by detection with a fluorescently labeled polyclonal antibody. This approach offers ultra-sensitive detection of lipoarabinomannan (10?fM, within 15?min) and may be extended to other amphiphilic markers. We also show that chemical deacylation of LAM completely abrogates its association with the supported lipid bilayers. The loss of signal using the waveguide assay for deacylated LAM, as well as atomic force microscopy (AFM) images that show no change in height upon addition of deacylated LAM support this hypothesis. Mass spectrometry of chemically deacylated LAM indicates the presence of LAM-specific carbohydrate chains, which maintain antigenicity in immunoassays. Further, we have developed the first three-dimensional structural model of mannose-capped LAM that provides insights into the orientation of LAM on supported lipid bilayers.