Feasibility of a tailored operative strategy from organ preservation to pelvic exenteration for cT4 rectal cancer depending on neoadjuvant response.

Purpose: Improvements in neoadjuvant therapy for locally advanced cT4 rectal cancer have led to improved tumour response and thus a variety of suitable management strategies. The aim of this study was to report management and outcomes of patients with cT4 rectal cancer undergoing a spectrum of treatment strategies from organ preservation (OP) to pelvic exenteration (PE).

Methods: Patients who underwent elective treatment for cT4 rectal cancer between 2016 and 2021 were included.

Hearing impairment in children living with HIV in Haiti.

Objective: To identify the prevalence of hearing impairment and associated risk factors in children living with human immunodeficiency virus (HIV) in Haiti.

Methods: A validated smartphone-based platform with pure-tone audiometry was used to screen 341 HIV-infected children for hearing impairment in Port-au-Prince, Haiti from March 2019 to September 2020. If screening was failed, a more comprehensive pure-tone audiometric evaluation was administered.

LSA-50 paper: An alternative to P81 phosphocellulose paper for radiometric protein kinase assays.

Radiometric assays have widely been used for measuring protein kinase activity for decades. In addition, several non-radiometric kinase assay formats have been developed over the years, including luciferase-based and fluorescence-based assays. However, radiometric assays are still considered as the "gold standard" for protein kinase assays, because of their direct readout, high sensitivity, reproducibility, reliability, and very low background signals.

Solvent-free N-Boc deprotection by ex situ generation of hydrogen chloride gas.

An efficient, scalable and sustainable method for the quantitative deprotection of the tert-butyl carbamate (N-Boc) protecting group is described, using down to near-stoichiometric amounts of hydrogen chloride gas in solvent-free conditions. We demonstrate the ex situ generation of hydrogen chloride gas from sodium chloride and sulfuric acid in a two-chamber reactor, introducing a straightforward method for controlled and stoichiometric release of HCl gas. The solvent-free conditions allow deprotection of a wide variety of N-Boc derivatives to obtain the hydrochloride salts in quantitative yields.

Developments in the Discovery and Design of Protein Kinase D Inhibitors.

Protein kinase D (PKD) is a serine/threonine kinase family belonging to the Ca2+/calmodulin-dependent protein kinase group. Since its discovery two decades ago, many efforts have been put in elucidating PKD's structure, cellular role and functioning. The PKD family consists of three highly homologous isoforms: PKD1, PKD2 and PKD3.

Concomitant positive patch test reactions in FreeStyle-allergic patients sensitized to isobornyl acrylate.

Background: Concomitant positive patch test reactions in patients sensitized to isobornyl acrylate (IBOA) have rarely been documented.

Objectives: To report concomitant sensitizations in patients with allergic contact dermatitis (ACD) from the glucose sensor FreeStyle Libre and sensitized to IBOA.

Methods: In 2019, 26 patients with suspected ACD from FreeStyle Libre were patch tested to a baseline series and to a (meth) acrylate series containing IBOA and 2-phenoxyethyl acrylate (PEA) 0.

Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyrimidine-based protein kinase D inhibitors.

The multiple roles of protein kinase D (PKD) in various cancer hallmarks have been repeatedly reported. Therefore, the search for novel PKD inhibitors and their evaluation as antitumor agents has gained considerable attention. In this work, novel pyrazolo[3,4-d]pyrimidine based pan-PKD inhibitors with structural variety at position 1 were synthesized and evaluated for biological activity.

Concomitant Use of Cotrimoxazole and Atazanavir in HIV-infected Patients: A Therapeutic Drug Monitoring and Pharmacovigilance Based Dual Approach.

Background: Cotrimoxazole is the main antibiotic used in primary prophylaxis for opportunistic infections in advanced HIV infection. This drug can inhibit one of the metabolic pathways of atazanavir (ATV), such as the cytochromes P450 (CYP) 2C8/2C9 and could interfere with its safety and efficacy.

Objective: We studied the drug-drug interaction (DDI) between cotrimoxazole and ATV by using therapeutic drug monitoring (TDM) and pharmacovigilance (PV) approaches.

Synthesis of N-Acyl Sulfamates from Fluorosulfates and Amides.

A novel synthetic strategy toward  N-acyl sulfamates was developed. Interestingly, fluorosulfates, a new emerging class of electrophiles, were used to construct the sulfamate core. This precludes handling of chlorosulfonyl isocyanate and sulfamoyl chloride.

Taking Free Flap Surgery Abroad: A Collaborative Approach to a Complex Surgical Problem.

Accessibility to health care, especially complex surgical care, represents one of the major health care disparities in developing countries. While surgical teams may be willing to travel to these areas to help address these needs, there are many logistical and ethical dilemmas inherent in this pursuit. We reviewed our approach to the establishment of the team-based surgical outreach program, wherein we perform head and neck free tissue transfer surgery in Haiti.

Measurements of Atmospheric Proteinaceous Aerosol in the Arctic Using a Selective UHPLC/ESI-MS/MS Strategy.

In this article, an analytical methodology to investigate the proteinaceous content in atmospheric size-resolved aerosols collected at the Zeppelin observatory (79 °N, 12 °E) at Ny Ålesund, Svalbard, from September to December 2015, is proposed. Quantitative determination was performed after acidic hydrolysis using ultrahigh-performance liquid chromatography in reversed-phase mode coupled to electrospray ionization tandem mass spectrometry. Chromatographic separation, as well as specificity in the identification, was achieved by derivatization of the amino acids with N-butyl nicotinic acid N-hydroxysuccinimide ester prior to the analysis.

Ex Situ Generation of Sulfuryl Fluoride for the Synthesis of Aryl Fluorosulfates.

A convenient transformation of phenols into the corresponding aryl fluorosulfates is presented: the first protocol to completely circumvent direct handling of gaseous sulfuryl fluoride (SOF). The proposed method employs 1,1'-sulfonyldiimidazole as a precursor to generate near-stoichiometric amounts of SOF gas using a two-chamber reactor. With NMR studies, it was shown that this ex situ gas evolution is extremely rapid, and a variety of phenols and hydroxylated heteroarenes were fluorosulfated in good to excellent yields.

High-Affinity Copolymers Inhibit Digestive Enzymes by Surface Recognition.

This account presents a general method for the construction of polymeric surface binders for digestion enzymes. Two prominent parts, namely, the modification of the copolymer composition and the screening assay for the most powerful inhibitors are both amenable to parallelization. The concept hinges on the appropriate selection of amino-acid-selective comonomers, their free radical copolymerization, and subsequent screening of the resulting copolymer library for efficient enzyme inhibition.

Carbonylation as a novel method for the assembly of pyrazine based oligoamide alpha-helix mimetics.

The design and synthesis of oligoamide α-helix peptidomimetics is reported. The oligoamide type systems are prepared in a modular fashion by coupling the monomers using palladium-catalyzed carbonylation chemistry. This enabled us to use substrates with a low nucleophilicity, leading to previously unreported pyrazine based oligoamide α-helix mimetics.

Affinity polymers tailored for the protein A binding site of immunoglobulin G proteins.

Rational design in combination with a screening process was used to develop affinity polymers for a specific binding site on the surface of immunoglobulin G (IgG) proteins. The concept starts with the identification of critical amino acid residues on the protein interface and their topological arrangement. Appropriate binding monomers were subsequently synthesized.

SmI2-mediated cross-coupling of nitrones with β-silyl acrylates: synthesis of (+)-australine.

The SmI(2)-mediated cross-coupling of nitrones with β-silyl-α,β-unsaturated esters, followed by zinc reduction, allows an efficient and highly diastereoselective preparation of β-silyl lactams, which are precursors of β-hydroxy lactams through Tamao-Fleming oxidation. By applying the method to a cyclic, carbohydrate-derived nitrone, a new synthesis of (+)-australine has been realized in only 11 steps and in 21% overall yield from L-xylose.

Asymmetric synthesis of β2-tryptophan analogues via Friedel-Crafts alkylation of indoles with a chiral nitroacrylate.

The asymmetric Friedel-Crafts alkylation of various indoles with a chiral nitroacrylate provides optically active β-tryptophan analogues after reduction of the nitro group and removal of the chiral auxiliary. This reaction generally occurs in good yield and high diastereoselectivity (up to 90:10).

Job acquisition for people with severe mental illness enrolled in supported employment programs: a theoretically grounded empirical study.

Introduction: The main purpose of this study was to test a conceptual model based on the theory of planned behaviour (TPB) to explain competitive job acquisition of people with severe mental disorders enrolled in supported employment programs.

Methods: Using a sample of 281 people with severe mental disorders participating in a prospective study design, the authors examined the contribution of the TPB in a model including clinical (e.g.

The External RNA Controls Consortium: a progress report.

Standard controls and best practice guidelines advance acceptance of data from research, preclinical and clinical laboratories by providing a means for evaluating data quality. The External RNA Controls Consortium (ERCC) is developing commonly agreed-upon and tested controls for use in expression assays, a true industry-wide standard control.

Development of a DNA-labeling system for array-based comparative genomic hybridization.

Chromosomal amplifications and deletions are critical components of tumorigenesis and DNA copy-number variations also correlate with changes in mRNA expression levels. Genome-wide microarray comparative genomic hybridization (CGH) has become an important method for detecting and mapping chromosomal changes in tumors. Thus, the ability to detect twofold differences in fluorescent intensity between samples on microarrays depends on the generation of high-quality labeled probes.

Identification of regional varieties by intonational cues. An experimental study on Hamburg and Berlin German.

Two experiments examined the commonly held belief that regional varieties of German can be identified by intonational features alone. In both experiments, listeners were presented with regional intonational contours of German. In the first experiment, listeners judged contours of Hamburg urban vernacular compared with contours of Northern Standard German.

ICD malfunction caused by excessive defibrillation charge time.

A 71-year-old man with a history of myocardial infarction and syncopal ventricular tachycardia received an ICD. Progressively, increased defibrillation charge times of the ICD were observed. During a fast ventricular tachycardia, the patient collapsed.

Inhibition of CCR5-dependent HIV-1 infection by hairpin ribozyme gene therapy against CC-chemokine receptor 5.

CCR-5 is a major cellular coreceptor for R5 strains of HIV-1. Individuals carrying a homozygous 32-base-pair deletion in this gene are apparently healthy and are relatively resistant to HIV-1 infection. Since CCR5 appears to be dispensable for the host, but important for initial HIV-1 infection, CCR5 mRNA is an excellent therapeutic target for inhibiting HIV-1 replication via ribozyme knockout.

Single nucleotide polymorphic discrimination by an electronic dot blot assay on semiconductor microchips.

We have developed a rapid assay for single nucleotide polymorphism (SNP) detection that utilizes electronic circuitry on silicon microchips. The method was validated by the accurate discrimination of blinded DNA samples for the complex quadra-allelic SNP of mannose binding protein. The microchip directed the transport, concentration, and attachment of amplified patient DNA to selected electrodes (test sites) creating an array of DNA samples.