Gender differences in individuals with obesity and binge eating disorder: A retrospective comparison of phenotypical features and treatment outcomes.

OBJECTIVE: Phenotypical comparisons between individuals with obesity without binge eating disorder (OB) and individuals with obesity and comorbid binge eating disorder (OB + BED) are subject to ongoing investigations. At the same time, gender-related differences have rarely been explored, raising the question whether men and women with OB and OB + BED may require differently tailored treatments. METHOD: We retrospectively compared pre- versus post-treatment data in a matched sample of n = 180 men and n = 180 women with OB or OB + BED who received inpatient treatment. RESULTS: We found that men displayed higher weight loss than women independent of diagnostic group. In addition, men with OB + BED showed higher weight loss than men with OB after 7 weeks of treatment. CONCLUSIONS: The present findings add to an emerging yet overall still sparse body of studies comparing phenotypical features and treatment outcomes in men and women with OB and OB + BED; implications for further research are discussed. CLINICAL TRIAL REGISTRATION: The study was prospectively registered with the German Clinical Trial Register as part of application DRKS00028441.

Probing Ligand Binding Sites on Large Proteins by Nuclear Magnetic Resonance Spectroscopy of Genetically Encoded Non-Canonical Amino Acids.

N6-(((trimethylsilyl)-methoxy)carbonyl)-l-lysine (TMSK) and N6-trifluoroacetyl-l-lysine (TFAK) are non-canonical amino acids, which can be installed in proteins by genetic encoding. In addition, we describe a new aminoacyl-tRNA synthetase specific for N6-(((trimethylsilyl)methyl)-carbamoyl)-l-lysine (TMSNK), which is chemically more stable than TMSK. Using the dimeric SARS-CoV-2 main protease (Mpro) as a model system with three different ligands, we show that the 1H and 19F nuclei of the solvent-exposed trimethylsilyl and CF3 groups produce intense signals in the nuclear magnetic resonance (NMR) spectrum. Their response to active-site ligands differed significantly when positioned near rather than far from the active site. Conversely, the NMR probes failed to confirm the previously reported binding site of the ligand pelitinib, which was found to enhance the activity of Mpro by promoting the formation of the enzymatically active dimer. In summary, the amino acids TMSK, TMSNK, and TFAK open an attractive path for site-specific NMR analysis of ligand binding to large proteins of limited stability and at low concentrations.

Site-selective generation of lanthanoid binding sites on proteins using 4-fluoro-2,6-dicyanopyridine

The paramagnetism of a lanthanoid tag site-specifically installed on a protein provides a rich source of structural information accessible by nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy. Here we report a lanthanoid tag for selective reaction with cysteine or selenocysteine with formation of a (seleno)thioether bond and a short tether between the lanthanoid ion and the protein backbone. The tag is assembled on the protein in three steps, comprising (i) reaction with 4-fluoro-2,6-dicyanopyridine (FDCP);(ii) reaction of the cyano groups withα-cysteine, penicillamine or β-cysteine to complete the lanthanoid chelating moiety;and (iii) titration with a lanthanoid ion. FDCP reacts much faster with selenocysteine than cysteine, opening a route for selective tagging in the presence of solvent-exposed cysteine residues. Loaded with Tb3+ and Tm3+ ions, pseudocontact shifts were observed in protein NMR spectra, confirming that the tag delivers good immobilisation of the lanthanoid ion relative to the protein, which was also manifested in residual dipolar couplings. Completion of the tag with different 1,2-aminothiol compounds resulted in different magnetic susceptibility tensors. In addition, the tag proved suitable for measuring distance distributions in double electron–electron resonance experiments after titration with Gd3+ ions.

Implementation of the Vascular Surgery Board virtual certifying examination.

OBJECTIVE: The onset of the COVID-19 (coronavirus disease 2019) pandemic mandated postponement of the in-person Vascular Surgery Board 2020 certifying examination (CE). Vascular surgery virtual CEs (VVCEs) were developed for the scheduled 2020 CEs (rescheduled to January 2021) and 2021 CEs (rescheduled to July 2021) to avoid postponing the certification testing. In the present study, we have reported the development, implementation, and outcomes of the first two VVCEs. METHODS: The VVCE was similar to the in-person format (three 30-minutes sessions, two examiners, four questions) but required a proctor and a host. In contrast to the general surgery VCEs, the VVCE also incorporated images. The candidates and examiners were instructed on the format, and technology checks were performed before the VVCE. The candidates were given the opportunity to invalidate their examination for technology-related reasons immediately after the examination. Postexamination surveys were administered to all the participants. RESULTS: The VVCEs were completed by 356 of 357 candidates (99.7%). The pass rates for the January 2021 and July 2021 examinations were 97.6% (first time, 99.4%; retake, 70%) and 94.7% (first time, 94.6%; retake, 100%), respectively. The pass rates were not significantly different from the 2019 in-person CE (χ2 = 2.30; P = .13; and χ2 = 0.01; P = .91, for the January 2021 and July 2021 examinations, respectively). None of the candidates had invalidated their examination. The candidates (162 of 356; 46%), examiners (64 of 118; 54%), proctors (25 of 27; 93%), and hosts (8 of 9; 89%) completing the survey were very satisfied with the examination (Likert score 4 or 5: candidates, 92.6%; noncandidates, 96.9%) and found the technology domains (Zoom, audio, video, viewing images) to be very good (Likert score 4 or 5), with candidate and other responder scores of 73% to 84% and >94%, respectively. Significantly more of the candidates had favored a future VVCE compared with the examiners (87% vs 32%; χ2 = 67.1; P < .001). The free text responses from all responders had commented favorably on the organization and implementation of the examination. However, some candidates had expressed concerns about image sizes, and some examiners had expressed concern about the time constraints for the question format. The candidates appreciated the convenience of an at-home examination, especially the avoidance of travel costs. CONCLUSIONS: The two Vascular Surgery Board VCEs were shown to be psychometrically sound and were overwhelmingly successful, demonstrating that image-based virtual examinations are feasible and could become the standard for the future.

Principles and practice for SARS-CoV-2 decontamination of N95 masks with UV-C.

A mainstay of personal protective equipment during the coronavirus disease 2019 pandemic is the N95 filtering facepiece respirator. N95 respirators are commonly used to protect healthcare workers from respiratory pathogens, including the novel coronavirus severe acute respiratory syndrome coronavirus 2, and are increasingly employed by other frontline workers and the general public. Under routine circumstances, these masks are disposable, single-use items, but extended use and reuse practices have been broadly enacted to alleviate critical supply shortages during the coronavirus disease 2019 pandemic. Although extended-time single use presents a low risk of pathogen transfer, repeated donning and doffing of potentially contaminated masks presents increased risk of pathogen transfer. Therefore, efficient and safe decontamination methods for N95 masks are needed to reduce the risk of reuse and mitigate local supply shortages. Here, we review the available literature concerning use of germicidal ultraviolet-C (UV-C) light to decontaminate N95 masks. We propose a practical method for repeated point-of-use decontamination using commercially available UV-C cross-linker boxes from molecular biology laboratories to expose each side of the mask to 800-1200 mJ/cm2 of UV-C. We measure the dose that penetrated to the interior of the respirators and model the potential germicidal action on coronaviruses. Our experimental results, in combination with modeled data, suggest that such a UV-C treatment cycle should induce a >3-log-order reduction in viral bioburden on the surface of the respirators and a 2-log-order reduction throughout the interior. We find that a dose 50-fold greater does not impair filtration or fit of 3M 8210 N95 masks, indicating that decontamination can be performed repeatedly. As such, UV-C germicidal irradiation is a practical strategy for small-scale point-of-use decontamination of N95s.