Efficacy and Safety of the Ultrasonic Bone Scalpel in Lumbar Laminectomies.

Introduction: Despite recent advances in applied instruments and surgical techniques, the incidence of iatrogenic durotomies caused by traditional techniques remains significant. The ultrasonic bone scalpel (UBS) has been shown to improve speed and reduce complications in laminectomies in the cervical and thoracic spine when compared to traditional methods utilizing high-speed burr, punch forceps, or rongeurs. Thus, in this study, we aim to evaluate whether the use of the UBS in the lumbar spine would result in equivalent safety, efficacy, and patient-reported outcomes (PROs) improvement when compared to traditional methods of laminectomy.

Confirmation of COL4A6 variants in X-linked nonsyndromic hearing loss and its clinical implications.

Hearing loss (HL) is one of the most common sensory defects, of which X-linked nonsyndromic hearing loss (NSHL) accounts for only 1-2%. While a COL4A6 variant has been reported in a single Hungarian family with NSHL associated with inner ear malformation, causative role of COL4A6 variants and their phenotypic consequences in NSHL remain elusive. Here we report two families in which we identified a male member with X-linked HL.

Analyses of del(GJB6-D13S1830) and del(GJB6-D13S1834) deletions in a large cohort with hearing loss: Caveats to interpretation of molecular test results in multiplex families.

Background: Mutations involving the closely linked GJB2 and GJB6 at the DFNB1 locus are a common genetic cause of profound congenital hearing loss in many populations. In some deaf GJB2 heterozygotes, a 309 kb deletion involving the GJB6 has been found to be the cause for hearing loss when inherited in trans to a GJB2 mutation.

Methods: We screened 2,376 probands from a National DNA Repository of deaf individuals.

Investigation of a Weak Temperature-Rate Relationship in the Carbamoylation of a Barbituric Acid Pharmaceutical Intermediate.

The rate of reaction between N, N'-dicyclohexylbarbituric acid 1 and ethyl 2-isocyanatoacetate 2 is invariant with temperature. Positive orders in each reactant and dissociation of triethylammonium salts of 1 and product 3 at elevated temperature indicate that reaction occurs via a catalytic mechanism where changes to the positions of equilibria negate changes in the rate of the turnover-limiting step. A model for the consumption of 1 in a flow reactor accurately predicted the outcome of a laboratory-scale multivariate study.

Using Prosopagnosia to Test and Modify Visual Recognition Theory.

Biederman's contemporary theory of basic visual object recognition (Recognition-by-Components) is based on structural descriptions of objects and presumes 36 visual primitives (geons) people can discriminate, but there has been no empirical test of the actual use of these 36 geons to visually distinguish objects. In this study, we tested for the actual use of these geons in basic visual discrimination by comparing object discrimination performance patterns (when distinguishing varied stimuli) of an acquired prosopagnosia patient (LB) and healthy control participants. LB's prosopagnosia left her heavily reliant on structural descriptions or categorical object differences in visual discrimination tasks versus the control participants' additional ability to use face recognition or coordinate systems (Coordinate Relations Hypothesis).

In Situ FTIR Spectroscopic Monitoring of Electrochemically Controlled Organic Reactions in a Recycle Reactor.

An electrochemical cell coupled with a recycle loop through a transmission FTIR cell is employed in studies of two free radical organic reactions, the oxidation of allylic alcohols and the trifluoromethylation of heteroarenes. Rapid mixing through the recycle loop allows continuous monitoring of reaction progress. Electrochemical generation of free radicals allows their controlled mediation into the reaction mixture for more efficient reaction.

Radical C-H functionalization of heteroarenes under electrochemical control.

Electrochemical reactions are shown to be effective for the C-H functionalization of a number of heterocyclic substrates that are recalcitrant to conventional peroxide radical initiation conditions. Monitoring reaction progress under electrochemical conditions provides mechanistic insight into the C-H functionalization of a series of heterocycles of interest in medicinal chemistry.

Total synthesis of dixiamycin B by electrochemical oxidation.

N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. This method is also general for N-N dimerization of substituted carbazoles and β-carbolines, providing entry into seldom explored chemical space.

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks.

We present the solid phase synthesis of carbohydrate-functionalized oligo(amidoamines) with different functionalization patterns utilizing a novel alphabet of six differently glycosylated building blocks. Highly efficient in flow conjugation of thioglycosides to a double-bond presenting diethylentriamine precursor is the key step to prepare these building blocks suitable for fully automated solid-phase synthesis. Introduction of the sugar ligands via functionalized building blocks rather than postfunctionalization of the oligomeric backbone allows for the straightforward synthesis of multivalent glycoligands with full control over monomer sequence and functionalization pattern.

Preparation and purification of zinc sulfinate reagents for drug discovery.

The present protocol details the synthesis of zinc bis(alkanesulfinate)s that can be used as general reagents for the formation of radical species. The zinc sulfinates described herein are generated from the corresponding sulfonyl chlorides by treatment with zinc dust. The products may be used crude, or a simple purification procedure may be performed to minimize incorporation of water and zinc chloride.

Synthesis of carbohydrate-functionalised sequence-defined oligo(amidoamine)s by photochemical thiol-ene coupling in a continuous flow reactor.

Poly/oligo(amidoamine)s (PAAs) have recently been recognised for their potential as well-defined scaffolds for multiple carbohydrate presentation and as multivalent ligands. Herein, we report two complimentary strategies for the preparation of such sequence-defined carbohydrate-functionalised PAAs that use photochemical thiol-ene coupling (TEC) as an alternative to the established azide-alkyne cycloaddition ("click") reaction. In the first approach, PAAs that contained multiple olefins were synthesised on a solid support from a new building block and subsequent conjugation with unprotected thio-carbohydrates.

Continuous synthesis and purification by direct coupling of a flow reactor with simulated moving-bed chromatography.

Continuous synthesis meets continuous purification to produce pure products from crude reaction mixtures. In the nucleophilic aromatic substitution of 2,4-difluoronitrobenzene with morpholine the desired monosubstituted product can be continuously separated from the byproducts in a purity of over 99 % by coupling a flow reactor to a simulated moving bed (SMB) chromatography module.

Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones.

Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP) tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.

Claisen rearrangements of equilibrating allylic azides.

Equilibrating mixtures of allylic azide-containing allylic alcohols or allylic 2-tolylsulfonylacetic esters undergo Johnson-Claisen or Ireland-Claisen rearrangement reactions to give unsaturated γ-azidoesters and -acids, respectively. Decarboxylation of the acids under basic conditions gives azidosulfones, with moderate to high diastereoselectivity.

Continuous flow thermolysis of azidoacrylates for the synthesis of heterocycles and pharmaceutical intermediates.

An efficient, safe and scalable procedure for the continuous flow thermolysis of azidoacrylates to yield indoles has been developed and was applied to the synthesis of related heterocycles. The scalability of the process was demonstrated in the continuous flow synthesis of a precursor to the DAAO inhibitor 4H-furo[3,2-b]pyrrole-5-carboxylic acid.

Exopericyclic stereocontrol in Johnson-Claisen rearrangements of allylic sulfides.

A study of the effects of exopericyclic stereocentres on the stereoselectivity of Johnson-Claisen rearrangements of thioether-containing allylic alcohols shows that selectivity is highly dependent upon allylic substitution patterns.