Human keratinocytes grown at a gas-permeable interface in vitro stratify correctly to generate engineered human epidermis.

Background: One of the key functions of human skin is to provide a barrier, protecting the body from the surrounding environment and maintaining homeostasis of the internal environment. A mature, stratified epidermis is critical to achieve skin barrier function and is particularly important when producing skin grafts in vitro for wound treatment. For decades epidermal stratification has been achieved in vitro by culturing keratinocytes at an air-liquid interface, triggering proliferating basal keratinocytes to differentiate and form all epidermal layers.

Enhanced glucose processing in gestational diabetes diagnosis: Effects on health equity and clinical outcomes.

Objectives: Gestational diabetes is diagnosed using an oral glucose tolerance test (OGTT), which has limited accuracy, reproducibility and practicality. We assessed the effect of enhanced pre-analytical glucose processing upon glucose concentrations, gestational diabetes diagnosis, health equity and pregnancy outcomes, and if HbA1c was a suitable alternative.

Methods: We recruited pregnant women with ≥1 risk factor to a prospective observational cohort study of pregnancy hyperglycaemia, endocrine causes, lipids, insulin and autoimmunity (OPHELIA), from nine UK centres.

Cross-cutting studies of per- and polyfluorinated alkyl substances (PFAS) in Arctic wildlife and humans.

This cross-cutting review focuses on the presence and impacts of per- and polyfluoroalkyl substances (PFAS) in the Arctic. Several PFAS undergo long-range transport via atmospheric (volatile polyfluorinated compounds) and oceanic pathways (perfluorinated alkyl acids, PFAAs), causing widespread contamination of the Arctic. Beyond targeting a few well-known PFAS, applying sum parameters, suspect and non-targeted screening are promising approaches to elucidate predominant sources, transport, and pathways of PFAS in the Arctic environment, wildlife, and humans, and establish their time-trends.

Highly efficient CRISPR/Cas9-mediated exon skipping for recessive dystrophic epidermolysis bullosa.

Gene therapy based on the CRISPR/Cas9 system has emerged as a promising strategy for treating the monogenic fragile skin disorder recessive dystrophic epidermolysis bullosa (RDEB). With this approach problematic wounds could be grafted with gene edited, patient-specific skin equivalents. Precise gene editing using homology-directed repair (HDR) is the ultimate goal, however low efficiencies have hindered progress.

[Extracorporeal cardiopulmonary resuscitation-An orientation].

Both in-hospital and out-of-hospital cardiac arrests are associated with a high mortality. In the past survival advantages for patients could be achieved by optimizing the chain of rescue and postresuscitation treatment; however, for patients with refractory cardiac arrest, there have so far been few promising treatment options. For selected patients with refractory cardiac arrest who do not achieve return of spontaneous circulation with conventional cardiopulmonary resuscitation (CPR), extracorporeal (e)CPR using venoarterial extracorporeal membrane oxygenation is an option to improve the probability of survival.

[Extracorporeal cardiopulmonary resuscitation-An orientation].

Both in-hospital and out-of-hospital cardiac arrests are associated with a high mortality. In the past survival advantages for patients could be achieved by optimizing the chain of rescue and postresuscitation treatment; however, for patients with refractory cardiac arrest, there have so far been few promising treatment options. For selected patients with refractory cardiac arrest who do not achieve return of spontaneous circulation with conventional cardiopulmonary resuscitation (CPR), extracorporeal (e)CPR using venoarterial extracorporeal membrane oxygenation is an option to improve the probability of survival.

Distinct profiles of oxylipid mediators in liver, lung, and placenta after maternal nano-TiO nanoparticle inhalation exposure.

Nano-titanium dioxide (nano-TiO) is a widely used nanomaterial found in several industrial and consumer products, including surface coatings, paints, sunscreens and cosmetics, among others. Studies have linked gestational exposure to nano-TiO with negative maternal and fetal health outcomes. For example, maternal pulmonary exposure to nano-TiO during gestation has been associated not only with maternal, but also fetal microvascular dysfunction in a rat model.

Unintended CRISPR-Cas9 editing outcomes: a review of the detection and prevalence of structural variants generated by gene-editing in human cells.

Genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) gene-editing system (CRISPR-Cas) is a valuable tool for fundamental and applied research applications. Significant improvements in editing efficacy have advanced genome editing strategies into phase 3 human clinical trials. However, recent studies suggest that our understanding of editing outcomes has lagged behind the developments made in generating the edits themselves.

Total Synthesis of Strempeliopidine and Non-Natural Stereoisomers through a Convergent Petasis Borono-Mannich Reaction.

Strempeliopidine is a member of the monoterpenoid bisindole alkaloid family, a class of natural products that have been shown to elicit an array of biological responses including modulating protein-protein interactions in human cancer cells. Our synthesis of strempeliopidine leverages palladium-catalyzed decarboxylative asymmetric allylic alkylations to install the requisite all-carbon quaternary centers found in each of the two monomeric natural products, aspidospermidine and eburnamine. Initial studies employing Suzuki-Miyaura cross-coupling followed by diastereoselective hydrogenation provided evidence for a structural reassignment of the natural product.

Treatment of Acquired von Willebrand Disease due to Extracorporeal Membrane Oxygenation in a Pediatric COVID-19 Patient with Vonicog Alfa: A Case Report and Literature Review.

Acquired von Willebrand disease (aVWD) is frequently observed in patients with the need for extracorporeal membrane oxygenation (ECMO). aVWD can be treated by plasma-derived concentrates containing factor VIII (FVIII) and/or von Willebrand factor (VWF) and recombinant VWF concentrate as well as adjuvant therapies such as tranexamic acid and desmopressin. However, all of these therapeutic options possibly cause thromboembolism.

Development of a Non-Directed Petasis-Type Reaction by an Aromaticity-Disrupting Strategy.

The Petasis-type reaction, which couples an imine and boronic acid, is an important tool for C-C bond formation in organic synthesis. However, the generality of this transformation has been limited by the requirement for a directing heteroatom to enable reactivity. Herein, we report the development of a non-directed Petasis-type reaction that allows for the coupling of trifluoroborate salts with α-hydroxyindoles.

[Intensive care management of acute diseases of the aorta].

Acute aortic diseases represent a group of complex severe and often fatal medical conditions. Although they are significantly rarer than cardiac or thromboembolic events, they are an important differential diagnosis to be ruled out, e.g.

What is a Cross-Coupling? An Argument for a Universal Definition.

Despite amazing advances in cross-coupling technologies over the past several decades, there is not a consistent definition of what a cross-coupling reaction is. Often, definitions rely on comparison to "traditional" palladium-catalyzed cross-couplings pioneered in the 1970s by chemists such as Suzuki, Negishi, and Heck. While these reactions provide a basis for a cross-coupling definition, they do not define this type of transformation, originally described by Linstead almost 20 years prior.

Extreme obesity is a strong predictor for in-hospital mortality and the prevalence of long-COVID in severe COVID-19 patients with acute respiratory distress syndrome.

Acute Respiratory Distress Syndrome (ARDS) is common in COVID-19 patients and is associated with high mortality. The aim of this observational study was to describe patients' characteristics and outcome, identifying potential risk factors for in-hospital mortality and for developing Long-COVID symptoms. This retrospective study included all patients with COVID-19 associated ARDS (cARDS) in the period from March 2020 to March 2021 who were invasively ventilated at the intensive care unit (ICU) of the University Hospital Dresden, Germany.

Investigations into mechanism and origin of regioselectivity in the metallaphotoredox-catalyzed α-arylation of -alkylbenzamides.

A mechanistic study on the α-arylation of -alkylbenzamides catalyzed by a dual nickel/photoredox system using aryl bromides is reported herein. This study elucidates the origins of site-selectivity of the transformation, which is controlled by the generation of a hydrogen atom transfer (HAT) agent by a photocatalyst and bromide ions in solution. Tetrabutylammonium bromide was identified as a crucial additive and source of a potent HAT agent, which led to increases in yields and a lowering of the stoichiometries of the aryl bromide coupling partner.

Epidermolysis Bullosa: A Review of the Tissue-Engineered Skin Substitutes Used to Treat Wounds.

Skin wound healing is a crucial process for regenerating healthy skin and avoiding the undesired consequences associated with open skin wounds. For epidermolysis bullosa (EB), a debilitating group of fragile skin disorders currently without a cure, skin blistering can often be severe and heal poorly, increasing susceptibility to life-threatening complications. To prevent these, investigational therapies have been exploring the use of tissue-engineered skin substitutes (TESSs) aimed at replacing damaged skin and promoting long-term wound closure.

Targeted and Suspect Screening of Per- and Polyfluoroalkyl Substances in Cosmetics and Personal Care Products.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic chemicals reported in cosmetics and personal care products as ingredients, possible impurities in the raw material manufacturing process, or degradation products. The purpose of this study was to further delineate contributions of these varying PFAS sources to these products. Thirty-eight cosmetics and personal care products were selected and analyzed for polyfluoroalkyl phosphates (PAPs), perfluoroalkyl carboxylic acids (PFCAs), fluorotelomer sulfonic acids (FTSAs), and perfluoroalkyl sulfonic acids (PFSAs) using targeted liquid chromatography tandem mass spectrometry (LC-MS/MS).

The human fecal microbiome contributes to the biotransformation of the PFAS surfactant 8:2 monosubstituted polyfluoroalkyl phosphate ester.

Polyfluoroalkyl phosphate esters (PAPs) can be found throughout society due to their numerous commercial applications. However, they also pose an environmental and health concern given their ability to undergo hydrolysis and oxidation to several bioactive and persistent products, including the perfluorocarboxylic acids (PFCAs). The metabolism of PAPs has been shown to occur in mammalian liver and intestine, however metabolism by the gut microbiome has not yet been investigated.

Discriminating protein tags on a dsDNA construct using a Dual Nanopore Device.

We report Brownian dynamics simulation results with the specific goal to identify key parameters controlling the experimentally measurable characteristics of protein tags on a dsDNA construct translocating through a double nanopore setup. First, we validate the simulation scheme in silico by reproducing and explaining the physical origin of the asymmetric experimental dwell time distributions of the oligonucleotide flap markers on a 48 kbp long dsDNA at the left and the right pore. We study the effect of the electric field inside and beyond the pores, critical to discriminate the protein tags based on their effective charges and masses revealed through a generic power-law dependence of the average dwell time at each pore.

Electronic Mapping of a Bacterial Genome with Dual Solid-State Nanopores and Active Single-Molecule Control.

We present an electronic mapping of a bacterial genome using solid-state nanopore technology. A dual-nanopore architecture and active control logic are used to produce single-molecule data that enables estimation of distances between physical tags installed at sequence motifs within double-stranded DNA. Previously developed "DNA flossing" control logic generates multiple scans of each captured DNA.

[Organ donation-Not only a responsibility of intensive care medicine].

In 2019 a total of 756 people died in Germany while registered on the waiting list for an organ transplantation. With 10.8 organ donors/million inhabitants in 2019, Germany belongs to the bottom group in the Eurotransplant foundation as well as worldwide.

Emerging investigator series: human CYP2A6 catalyzes the oxidation of 6:2 fluorotelomer alcohol.

The biotransformation of 6:2 fluorotelomer alcohol (6:2 FTOH) results in the production of bioactive and persistent metabolites, including perfluorinated carboxylic acids (PFCAs). While the products of 6:2 FTOH metabolism have been elucidated in several animal models, the responsible cytochrome P450 (CYP) isoform(s) have not been reported. Here, we characterized the oxidation of 6:2 FTOH using human liver microsomes and recombinant human CYPs.

Sulfur isotopes as a proxy for human diet and mobility from the preclassic through colonial periods in the Eastern Maya lowlands.

Maya archaeologists have long been interested in understanding ancient diets because they provide information about broad-scale economic and societal transformations. Though paleodietary studies have primarily relied on stable carbon (δ13C) and nitrogen (δ15N) isotopic analyses of human bone collagen to document the types of food people consumed, stable sulfur (δ34S) isotope analysis can potentially provide valuable data to identify terrestrial, freshwater, or marine/coastal food sources, as well as determine human mobility and migration patterns. Here we assess applications of δ34S for investigating Maya diet and migration through stable isotope analyses of human bone collagen (δ13C, δ15N, and δ34S) from 114 individuals from 12 sites in the Eastern Maya lowlands, temporally spanning from the Late Preclassic (300 BCE-300 CE) through Colonial periods (1520-1800 CE).