Rapid Postgrafting Reaction to Prepare Quaternized Polycarbazoles.

We report a rapid postgrafting reaction to prepare alkyl ammonium functionalized polycarbazoles from a commercially available monomer. This novel synthetic approach provides benefit to preparing the high molecular weight quaternized polycarbazoles within 1 h of Friedel-Crafts polycondensation, avoiding the synthesis and purification step to prepare a functionalized monomer. The postgrafting reaction produces hexyl alkyl ammonium functionalized polycarbazole with 100% grafting degree. However, the postgrafting reaction produced only 60% grafting with propyl alkyl ammonium due to the competitive elimination reaction because of the higher acidity of ß-hydrogen in the propyl alkyl group resulting from the proximity of the bromide and ammonium groups. The hexyl alkyl ammonium functionalized polycarbazole has a high hydroxide conductivity of 103 mS cm-1 at 80 °C and showed excellent alkaline stability with less than 3% loss of ion group after 1 M NaOH treatment at 80 °C for 500 h. This study highlights that the postgrafting reaction provides a pathway for the scale-up synthesis of quaternized aryl ether-free polyaromatics.

Colloidal Nafion Particles: Are Cylinders Ubiquitous?

Colloidal Nafion morphology plays a critical role in determining the performance of fuel cells and electrolyzers. While small-angle neutron scattering (SANS) studies previously described Nafion in liquid media as dispersed cylinders, the analysis remains nonunique with multiple possible morphological descriptions of the data. Here, using SANS and all-atomistic molecular dynamics, we confirm that Nafion morphology in liquid media differs substantially depending on dispersing agent and dispersion method. H+ Nafion dispersed in N-methyl pyrrolidone forms swollen cluster particles with physically cross-linked ionic groups. Scattering profiles from dispersed Nafion membrane have a large structure factor feature not observed for redispersed Nafion D-521. H+ Nafion dispersed in water has a highly elongated cylindrical morphology (radius = 10 ± 1.5 Å, height = 358 ± 4.7 Å) with fully dissociated and solvated sulfonic acid groups on the particle wall. These results highlight an important discrepancy between the methods of preparing Nafion dispersions and the use of simplified analysis techniques to describe Nafion morphology.

Cardiothoracic Radiologist Workload, Work Capacity, and Burnout Post-COVID: Results of a Survey From the Society of Thoracic Radiology.

In this report and analysis of the results of a late 2021 post-COVID pandemic survey of members of the Society of Thoracic Radiology, we compared cardiothoracic radiologist workloads and burnout rates with those obtained from a prepandemic survey of society members. The more recent survey also asked respondents to provide a subjective assessment of their individual workload capacity should they be required to read cases at a section average daily case work volume, and this assessment was correlated with burnout rates. To measure nonrelative value unit workload, we requested data on non-case-related work responsibilities including teaching and multidisciplinary conferences that were not assessed in the first survey. In addition, we asked respondents to provide information on the availability of support services, personnel, and hardware and software tools that could improve work efficiency and reduce radiologist stress levels thereby mitigating burnout. We found that postpandemic case workload and cardiothoracic radiologists' burnout rates were similarly high compared with prepandemic levels with an overall burnout rate of 88% including a 100% burnout rate among women which had significantly increased. The range of radiologists' workload capacity is broad, although 80% of respondents reported that reading at an average sectional case volume was at or above their capacity, and the perceived capacity correlated with burnout measures. The presence of fellows and computer-aided diagnosis/artificial intelligence tools were each associated with significant decreases in burnout, providing 2 potential strategies that could be employed to address high cardiothoracic radiologist burnout rates.

Pulmonary Embolism after Liposuction Totally by Tumescent Local Anesthesia in a Patient with Large Uterine Fibroids.

A fatal pulmonary embolism occurred in a 43-year-old black woman after tumescent liposuction totally by local anesthesia. An autopsy revealed large uterine fibroids, peri-uterine vascular thrombi, and a large saddle pulmonary embolism. Large uterine fibroids are a risk factor for postsurgical venous thromboembolism. Fatal outcomes after tumescent liposuction totally by local anesthesia are exceedingly rare.

Solvation Structure, Dynamics, and Charge Transfer Kinetics of Cu2+ and Cu+ in Choline Chloride Ethylene Glycol Electrolytes.

Experimental measurements and classical molecular dynamics (MD) simulations were carried out to study electrolytes containing CuCl2 and CuCl salts in mixtures of choline chloride (ChCl) and ethylene glycol (EG). The study focused on the concentration of 100 mM of both CuCl2 and CuCl with the ratio of ChCl/EG varied from 1:2, 1:3, 1:4, to 1:5. It was found that the Cu2+ and Cu+ have different solvation environments in their first solvation shell. Cu2+ is coordinated by both Cl- anions and EG molecules, whereas Cu+ is only solvated by EG. However, both Cu2+ and Cu+ show strong interactions with their second solvation shells, which include both Cl- anions and EG molecules. Considering both the first and second solvation shells, the concentrations of Cu2+ and Cu+ that have various coordination numbers in each solution were calculated and were found to correlate qualitatively with the exchange current density trends reported in previous experiments of Cu2+ reduction to Cu+. This finding makes a connection between atomic solvation structure observed in MD simulations and redox reaction kinetics measured in electrochemical experiments, thus revealing the significance of the solvation environment of reduced and oxidized species for electrokinetics in deep eutectic solvents.

Penetration Enhancement Strategies for Intradermal Delivery of Cromolyn Sodium.

This study aimed to explore the use of chemical and physical enhancement strategies for the intradermal delivery of cromolyn sodium (CS) for treatment of atopic dermatitis. CS gels were formulated to individually contain 2.5 and 9% salcaprozate sodium (SNAC) as a potential chemical enhancer. The effect of microneedles, alone and in combination with SNAC, was investigated via in vitro permeation studies. Skin impedance and FTIR evaluation of SNAC-treated stratum corneum (SC) was done and compared to the control. The amount of drug delivered in the dermis after 24 h by the 2.5% and 9% SNAC gels was 23.29 ± 1.89 µg/cm2 and 35.87 ± 2.23 µg/cm2, respectively, which were significantly higher than the control (p < 0.05) but were not remarkably different from each other (p > 0.05). Microneedles enhanced permeation in both the control and 2.5% SNAC groups (p < 0.05); however, no synergistic enhancement was observed when microneedle and SNAC treatments were combined (p > 0.05). Over 24 h of treating the SC with 2.5% SNAC, FTIR evaluation showed stretches on the CH2 asymmetric and symmetric stretching vibrations observed at 2920.23 cm-1 and 2850.79 cm-1 respectively in untreated SC, which shifted to higher wavenumbers and indicated some lipid fluidizing effect. However, no significant drop in skin impedance was seen with SNAC as compared to the control (p > 0.05). SNAC was concluded to have skin permeation enhancement effect on CS, while microneedles effectively enhanced CS permeation even in the absence of SNAC.

Association of Accuracy, Conclusions, and Reporting Completeness With Acceptance by Radiology Conferences and Journals.

BACKGROUND: Preferential publication of studies with positive findings can lead to overestimation of diagnostic test accuracy (i.e. publication bias). Understanding the contribution of the editorial process to publication bias could inform interventions to optimize the evidence guiding clinical decisions. PURPOSE/HYPOTHESIS: To evaluate whether accuracy estimates, abstract conclusion positivity, and completeness of abstract reporting are associated with acceptance to radiology conferences and journals. STUDY TYPE: Meta-research. POPULATION: Abstracts submitted to radiology conferences (European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and International Society for Magnetic Resonance in Medicine (ISMRM)) from 2008 to 2018 and manuscripts submitted to radiology journals (Radiology, Journal of Magnetic Resonance Imaging [JMRI]) from 2017 to 2018. Primary clinical studies evaluating sensitivity and specificity of a diagnostic imaging test in humans with available editorial decisions were included. ASSESSMENT: Primary variables (Youden's index [YI > 0.8 vs. <0.8], abstract conclusion positivity [positive vs. neutral/negative], number of reported items on the Standards for Reporting of Diagnostic Accuracy Studies [STARD] for Abstract guideline) and confounding variables (prospective vs. retrospective/unreported, sample size, study duration, interobserver agreement assessment, subspecialty, modality) were extracted. STATISTICAL TESTS: Multivariable logistic regression to obtain adjusted odds ratio (OR) as a measure of the association between the primary variables and acceptance by radiology conferences and journals; 95% confidence intervals (CIs) and P-values were obtained; the threshold for statistical significance was P < 0.05. RESULTS: A total of 1000 conference abstracts (500 ESGAR and 500 ISMRM) and 1000 journal manuscripts (505 Radiology and 495 JMRI) were included. Conference abstract acceptance was not significantly associated with YI (adjusted OR = 0.97 for YI > 0.8; CI = 0.70-1.35), conclusion positivity (OR = 1.21 for positive conclusions; CI = 0.75-1.90) or STARD for Abstracts adherence (OR = 0.96 per unit increase in reported items; CI = 0.82-1.18). Manuscripts with positive abstract conclusions were less likely to be accepted by radiology journals (OR = 0.45; CI = 0.24-0.86), while YI (OR = 0.85; CI = 0.56-1.29) and STARD for Abstracts adherence (OR = 1.06; CI = 0.87-1.30) showed no significant association. Positive conclusions were present in 86.7% of submitted conference abstracts and 90.2% of journal manuscripts. DATA CONCLUSION: Diagnostic test accuracy studies with positive findings were not preferentially accepted by the evaluated radiology conferences or journals. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Development of an IgG-Fc fusion COVID-19 subunit vaccine, AKS-452.

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.