Background: Cardiopulmonary bypass (CPB) triggers marked cytokine release often followed by a systemic inflammatory response syndrome, associated with adverse postoperative outcomes. This trial investigates the intraoperative use of haemoadsorption (HA) during cardiac surgery with CPB to assess its impact on postoperative systemic inflammatory response.
Methods: In this prospective randomised controlled trial (ethics approval no.
Lexical dynamics, just as epidemiological dynamics, represent spreading phenomena. In both domains, constituents (words, pathogens) are transmitted within populations of individuals. In linguistics, such dynamics have been modeled by drawing on mathematical models originating from epidemiology.
View Article and Find Full Text PDFThe optical properties of lead halide perovskite semiconductors in vicinity of the bandgap are controlled by excitons, so that investigation of their fundamental properties is of critical importance. The exciton Landé or g-factor g is the key parameter, determining the exciton Zeeman spin splitting in magnetic fields. The exciton, electron, and hole carrier g-factors provide information on the band structure, including its anisotropy, and the parameters contributing to the electron and hole effective masses.
View Article and Find Full Text PDFBackground: The presence of Nucleated Red Blood Cells (NRBCs) in critically ill patients is associated with higher mortality and poor prognosis. Although patients on extracorporeal support such as veno-venous or veno-arterial extracorporeal membrane oxygenation (VV/VA-ECMO) are severely ill, NRBCs have rarely been investigated regarding their predictive value so far.
Methods: As part of a retrospective study, we examined all cardiothoracic surgery patients from July 2019 to September 2020 who received ECMO treatment during their inpatient stay.
Poorly immunogenic small molecules pose challenges for the production of clinically efficacious vaccines and antibodies. To address this, we generate an immunization platform derived from the immunogenic surface coat of the African trypanosome. Through sortase-based conjugation of the target molecules to the variant surface glycoprotein (VSG) of the trypanosome surface coat, we develop VSG-immunogen array by sortase tagging (VAST).
View Article and Find Full Text PDFMonoclonal antibodies (mAbs) deliver great benefits to patients with chronic and/or severe diseases thanks to their strong specificity to the therapeutic target. As a result of this specificity, non-human primates (NHP) are often the only preclinical species in which therapeutic antibodies cross-react with the target. Here, we highlight the value and limitations that NHP studies bring to the design of safe and efficient early clinical trials.
View Article and Find Full Text PDFScalable asymmetric syntheses of two kallikrein-related protease 6 (KLK6) inhibitors are reported. The inhibitors are assembled by linking enantiomerically enriched fragments amide bond formation, followed by conversion of a cyano group to an amidine. One fragment, an amine, was prepared using the Ellman auxiliary, and a lack of clarity in the literature regarding the stereochemical outcome of this reaction was solved X-ray crystallographic analysis of two derivatives.
View Article and Find Full Text PDFThe aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score.
View Article and Find Full Text PDFObjectives: Inhalative anesthesia is of common use, but is generally known to potentiate postoperative nausea and vomiting (PONV). With an internal change of anesthesia regimen from total intravenous anesthesia (TIVA) to isoflurane (in terms of myocardial protection) in cardiac anesthesia a higher incidence of PONV was to be expected. Therefore, we evaluated the incidence of PONV after the simultaneous implementation of PONV prophylaxis.
View Article and Find Full Text PDFNew challenges and other topics in non-clinical safety testing of biotherapeutics were presented and discussed at the nineth European BioSafe Annual General Membership meeting in November 2019. The session topics were selected by European BioSafe organization committee members based on recent company achievements, agency interactions and new data obtained in the non-clinical safety testing of biotherapeutics, for which data sharing would be of interest and considered as valuable information. The presented session topics ranged from strategies of testing, immunogenicity prediction, bioimaging, and developmental and reproductive toxicology (DART) assessments to first-in-human (FIH) dose prediction and bioanalytical challenges, reflecting the entire space of different areas of expertise and different molecular modalities.
View Article and Find Full Text PDFSafety assessment of biological drugs has its challenges due to the multiple new different modalities, for example, antibody-drug conjugates, bispecifics, nanobodies, fusion proteins and advanced therapy medicinal products (ATMPs), their different pharmacokinetic and pharmacodynamic properties, and their ability to trigger immunogenicity and toxicity. In the public and in the pharmaceutical industry, there is a strong and general desire to reduce the number of animals used in research and development of drugs and in particular reducing the use of nonhuman primates. Important discussions and activities are ongoing investigating the smarter designs of early research and dose range finding studies, reuse of animals, and replacing animal experiments with in vitro studies.
View Article and Find Full Text PDFStable ankle fractures can be successfully managed nonoperatively. Unstable fractures on the other hand should be treated surgically as operative management consistently leads to better outcomes. How to define stability in ankle fractures continues to be a controversial issue.
View Article and Find Full Text PDFReadily accessible tetraorganoborate salts undergo selective coupling reactions under blue light irradiation in the presence of catalytic amounts of transition-metal-free acridinium photocatalysts to furnish unsymmetrical biaryls, heterobiaryls and arylated olefins. This represents an interesting conceptual approach to forge C-C bonds between aryl, heteroaryl and alkenyl groups under smooth photochemical conditions. Computational studies were conducted to investigate the mechanism of the transformation.
View Article and Find Full Text PDFThis paper investigates whether typical stress patterns in English nouns and verbs are available as a prosodic cue for categorisation and accelerated word learning during first language acquisition. The stress typicality hypothesis states that left-stressed nouns and right-stressed verbs should be acquired earlier than the reverse configurations if stress effectively signals lexical class membership. In this view, class-typical stress patterns are expected to facilitate learning of novel items.
View Article and Find Full Text PDFTwo prominent statistical laws in language and other complex systems are Zipf's law and Heaps' law. We investigate the extent to which these two laws apply to the linguistic domain of phonotactics-that is, to sequences of sounds. We analyze phonotactic sequences with different lengths within words and across word boundaries taken from a corpus of spoken English (Buckeye).
View Article and Find Full Text PDFBackground: The vascular endothelial glycocalyx is susceptible to ischemia and hypoxia. Released soluble components of the endothelial glycocalyx (EG) have been identified as potential damage associated molecular patterns (DAMPs) able to enhance an ongoing inflammatory response. Shedding of the EG has been associated with released atrial-natriuretic peptide (ANP) during cardiac surgery procedures.
View Article and Find Full Text PDFConventional methods carrying out C(sp )-C(sp ) bond formations are typically mediated by transition-metal-based catalysts. Herein, we conceptualize a complementary avenue to access such bonds by exploiting the potential of electrochemistry in combination with organoboron chemistry. We demonstrate a transition metal catalyst-free electrocoupling between (hetero)aryls and alkenes through readily available alkenyl-tri(hetero)aryl borate salts (ATBs) in a stereoconvergent fashion.
View Article and Find Full Text PDFThiete dioxide units have been employed as a template for further functionalization through C-H activation strategies. Using simple thiete dioxide building blocks, a new library of axially chiral molecules has been synthesized that owe their stability to electrostatic interactions in the solid state. Similar starting materials were further engaged in the formation of cyclic trimeric structures, opening the pathway to unprecedented macrocyclic ring systems.
View Article and Find Full Text PDFWe report herein versatile, transition metal-free and additive-free (hetero)aryl-aryl coupling reactions promoted by the oxidative electrocoupling of unsymmetrical tetra(hetero)arylborates (TABs) prepared from ligand-exchange reactions on potassium trifluoroarylborates. Exploiting the power of electrochemical oxidations, this method complements the existing organoboron toolbox. We demonstrate the broad scope, scalability, and robustness of this unconventional catalyst-free transformation, leading to functionalized biaryls and ultimately furnishing drug-like small molecules, as well as late stage derivatization of natural compounds.
View Article and Find Full Text PDFABO blood group has a profound influence on hemostasis as it is a major determinant of plasma levels of von Willebrand Factor. In vitro studies suggest that blood group O is a risk factor for increased severe bleeding while blood group non-O is a risk factor for thromboembolic events. Yet, the impact of ABO blood group outcome after multiple trauma is unknown.
View Article and Find Full Text PDFα-Galactosylceramides are glycosphingolipids that show promise in cancer immunotherapy. After presentation by CD1d, they activate natural killer T cells (NKT), which results in the production of a variety of pro-inflammatory and immunomodulatory cytokines. Herein, we report the synthesis and biological evaluation of photochromic derivatives of KRN-7000, the activity of which can be modulated with light.
View Article and Find Full Text PDFRecently, several studies have investigated dielectric properties as a possible origin of the exceptional optoelectronic properties of metal halide perovskites (MHPs). In this study we investigated the temperature-dependent dielectric behavior of different MHP films at different frequencies. In the gigahertz regime, dielectric losses in methylammonium-based samples are dominated by the rotational dynamics of the organic cation.
View Article and Find Full Text PDFObjectives: Veno-arterial extracorporeal membrane oxygenation represents the last therapy option in refractory cardiogenic shock. Successful weaning becomes difficult if the myocardial function recovers but pulmonary impairment persists. We present our experience with a new weaning strategy, using a stepwise mode-switch from veno-arterial to veno-veno-arterial and veno-venous extracorporeal membrane oxygenation setting for patients with primary cardiogenic shock and subsequent respiratory failure.
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