Synthesis of 13C-labeled parabens from isotopically enriched phenols using the Houben–Hoesch reaction

Parabens are antimicrobial additives found in a wide array of consumer products. However, the halogenated compounds formed from parabens during wastewater disinfection are a potential environmental concern. In order to identify these transformation products and investigate their mechanism of formation, a synthetic route to ethyl parabens labeled with the stable isotope carbon-13 at specific positions within the benzene ring was developed. This efficient two-step procedure starts from commercially available ¹³C-labeled phenols and involves (1) initial acylation of the phenol via a Houben–Hoesch reaction with trichloroacetonitrile followed by (2) a modified haloform reaction of the resulting trichloromethyl ketone to afford the corresponding ¹³C-labeled ethyl parabens in 65%–80% overall yield. The scope of the modified haloform reaction was also investigated, allowing for the synthesis of other parabens derived from primary or secondary alcohols, including ¹³C- and deuterium-labeled esters. In addition, 4-hydroxybenzoic acid can be formed directly from the common trichloromethyl ketone intermediate upon treatment with lithium hydroxide. This protocol complements existing methods for preparing ¹³C-labeled paraben derivatives and offers the specific advantages of exhibiting complete regioselectivity in the Houben–Hoesch reaction (to form the para-disubstituted product) and avoiding the need for protecting groups in the modified haloform reaction that forms the paraben esters.     

Paresthesia‐Free Spinal Nerve Root Stimulation for the Treatment of Chronic Neuropathic Pain

ObjectiveStimulation of the dorsal spinal roots, or spinal nerve root stimulation (SNRS), is a neuromodulation modality that can target pain within specific dermatomal distributions. The use of paresthesia-free stimulation has been described with conventional dorsal column spinal cord stimulation, although has yet to be described for SNRS. This objective of this study was to investigate the efficacy of paresthesia-free high-frequency (1000–1200 Hz) SNRS in the treatment of intractable, dermatomal neuropathic pain.Materials and MethodsA retrospective chart review was performed on 14 patients implanted with SNRS in varying distributions: Ten patients initially received tonic stimulation and crossed over to a paresthesia-free paradigm and four patients received only paresthesia-free stimulation. The primary outcome was reduction in pain severity (visual analog scale [VAS]), measured at baseline and follow-up to 24 months with paresthesia-free stimulation.ResultsAll 14 patients who received paresthesia-free stimulation had significant improvement in pain severity at a mean follow-up of 1.39 ± 0.15 years (VAS 7.46 at baseline vs. 3.25 at most recent follow-up, p < 0.001). Ten patients were initially treated with tonic stimulation and crossed over to paresthesia-free stimulation after a mean of 61.7 months. Baseline pain in these crossover patients was significantly improved at last follow-up with tonic stimulation (VAS 7.65 at baseline vs. 2.83 at 48 months, p < 0.001), although all patients developed uncomfortable paresthesias. There was no significant difference in pain severity between patients receiving tonic and paresthesia-free stimulation.ConclusionsWe present real-world outcomes of patients with intractable dermatomal neuropathic pain treated with paresthesia-free, high-frequency SNRS. We demonstrate its effectiveness in providing pain reduction at a level comparable to tonic SNRS up to 24 months follow-up, without producing uncomfortable paresthesias.     

Ceftaroline fosamil for the treatment of Gram-positive endocarditis: CAPTURE study experience

Background

The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the USA.

Self-regulation and social and behavioral functioning following childhood traumatic brain injury.

This study examined the impact of childhood traumatic brain injury (TBI) on self-regulation and social and behavioral functioning, and the role of self-regulation as a predictor of children's social and behavioral functioning. Participants included 65 children with moderate to severe TBI and 65 children without TBI, all between 6 and 11 years of age. Self-regulation and social and behavioral functioning were assessed 2 to 5 years following injury. Children with TBI displayed deficits in self-regulation and social and behavioral functioning, after controlling for socioeconomic status (SES), although the magnitude of the deficits was not related to injury severity. Self-regulation accounted for significant variance in children's social and behavioral functioning, after controlling for SES and group membership. Self-regulation may be an important determinant of children's social and behavioral functioning following TBI.