Direct determination of absolute stereochemistry of α-methylselenocysteine using the Mosher method

Mosher amides of α-methylselenocysteine were synthesized to determine the absolute stereochemistry of the sterically hindered α-carbon utilizing 1H, 13C, 19F, and 77Se NMR spectroscopies. After analysis of these spectra using the established Mosher method, the stereochemistry of the α-carbon was determined to be (R), which was subsequently confirmed using x-ray crystallography

Efficient Esterification of Oxidized l-Glutathione and Other Small Peptides

xidized l-glutathione was esterified to the tetra methyl ester using thionyl chloride in methanol solvent. Other alcohols were tested and the reaction progress was monitored via ESI-MS. This procedure proved to be compatible with other small peptides not containing serine and cysteine residues. In contrast to previously reported methods this procedure provided convenient access to esterified peptides requiring no purification, extended reaction times, or complicated reaction setups

An Enantiodivergent Synthesis of C\u3csup\u3eα\u3c/sup\u3e-Methyl Nipecotic Acid Analogues From δ-Lactam Derivatives Obtained Through a Highly Stereoselective Cyclization Strategy

A stereoselective and enantiodivergent strategy for the construction of δ-lactams is described. The strategy utilizes chiral malonic esters prepared from enantiomerically enriched mono esters of disubstituted malonic acid. A cyclization occurs with the selective displacement of a substituted benzyl alcohol as the leaving group. The resulting δ-lactams are then converted into nipecotic acid analogues using straightforward transformations. The resulting nipecotic acid analogues proved capable organocatalysts in Mannich reactions

UV/Optical disk reverberation lags despite a faint X-ray corona in the AGN Mrk 335

We present the first results from a 100-day Swift, NICER and ground-based X-ray/UV/optical reverberation mapping campaign of the Narrow-Line Seyfert 1 Mrk 335, when it was in an unprecedented low X-ray flux state. Despite dramatic suppression of the X-ray variability, we still observe UV/optical lags as expected from disk reverberation. Moreover, the UV/optical lags are consistent with archival observations when the X-ray luminosity was >10 times higher. Interestingly, both low- and high-flux states reveal UV/optical lags that are 6-11 times longer than expected from a thin disk. These long lags are often interpreted as due to contamination from the broad line region, however the u band excess lag (containing the Balmer jump from the diffuse continuum) is less prevalent than in other AGN. The Swift campaign showed a low X-ray-to-optical correlation (similar to previous campaigns), but NICER and ground-based monitoring continued for another two weeks, during which the optical rose to the highest level of the campaign, followed ~10 days later by a sharp rise in X-rays. While the low X-ray countrate and relatively large systematic uncertainties in the NICER background make this measurement challenging, if the optical does lead X-rays in this flare, this indicates a departure from the zeroth-order reprocessing picture. If the optical flare is due to an increase in mass accretion rate, this occurs on much shorter than the viscous timescale. Alternatively, the optical could be responding to an intrinsic rise in X-rays that is initially hidden from our line-of-sight.Comment: Accepted for publication in the Astrophysical Journal. 15 pages, 8 figures, 3 table

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

Using the Mini-Session Course Format To Train Students in the Practical Aspects of Modern Mass Spectrometry

Mass spectrometry (MS) has been gaining in popularity in recent years owing in large part to the development of soft-ionization techniques such as matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI). These soft-ionization techniques have opened up the field of MS analysis to biomolecules, polymers, and other high molecular weight materials. The growing publication rate and a quick survey of available job postings requiring MS skill sets illustrate the importance of properly training students in the use of modern MS techniques. Many colleges and universities are unable to hire full-time technical staff devoted to student training on the use of MS equipment. The lack of technical staff results in less than adequate student training on the use of MS equipment, which ultimately leads to student apprehension about using the instruments regularly in their research projects. Herein, we report on our efforts utilizing a mini-session course format (one week with 40 contact hours) to properly train graduate students in the use of modern MS equipment and techniques. The course consists of three components: (i) a lecture component of approximately 2 h each day to introduce the basic theory of the days topics, (ii) a hands-on laboratory component illustrating the use of both MALDI and ESI instruments to gather a variety of data, and (iii) a student project utilizing the MS equipment in their own graduate research during the regular semester following the mini-session course. The students receive three hours of graduate credit and receive permission, upon successful completion of the course, to use the MS facilities unsupervised. The faculty member teaching the course receives teaching credit for the training efforts

Free-Radical Azidation with Gamma-N-15-Labeled Phenylsulfonyl Azide

The γ-nitrogen of phenylsulfonyl azide can be readily ­labeled with 15N by treating benzenesulfonyl hydrazide with Na15NO2. The resulting γ-15N-labeled sulfonyl azide reacts with carbon-centered free radicals to produce alkyl azides exclusively containing a C-15N bond. This chemistry provides valuable insight into the free-radical azidation mechanism as well as providing a mild method for the production of 15N-amines

An Improved Method for the Preparation of Protected (R)-2-Methylcysteine: Solution-Phase Synthesis of a Glutathione Analogue

A synthetic method for the preparation of (R)-2-methylcysteine that dramatically improves the overall yield of this important unnatural amino acid has been refined. The key steps in the preparation of (R)-2-methylcysteine were improved such that necessary intermediates were prepared in high yields and of sufficient purity to avoid the need for distillation or column chromatography. The ( R)-2-methylcysteine was prepared (\u3e 90% ee) in appropriately protected form and used in a novel solution phase synthesis of a glutathione analogue