Oxidative stress, systemic inflammation, and metabolic derangements are hallmarks of burn pathophysiology. Severely burned patients are highly susceptible to infectious complications. Selenium-binding protein 1 (SELENBP1) modulates intracellular redox homeostasis, and elevated serum concentrations have been associated with adverse clinical outcomes in trauma patients. We hypothesized that serum SELENBP1 at hospital admission and during hospitalization may constitute a meaningful biomarker of disease severity and the clinical course in burn injury, with pulmonary infection as primary endpoint. To this end, we conducted a prospective cohort study that included 90 adult patients admitted to the Burn Center of the University Hospital Zurich, Switzerland. Patients were treated according to the local standard of care, with high-dose selenium supplementation during the first week. Serum SELENBP1 was determined at nine time-points up to six months postburn and the data were correlated to clinical parameters. SELENBP1 was initially elevated and rapidly declined within the first day. Baseline SELENBP1 levels correlated positively with the Abbreviated Burn Severity Index (ABSI) (R = 0.408; p < 0.0001). In multiple logistic regression, a higher ABSI was significantly associated with increased pulmonary infection risk (OR, 14.4; 95% CI, 3.2-88.8; p = 0.001). Similarly, baseline SELENBP1 levels constituted a novel but less accurate predictor of pulmonary infection risk (OR, 2.5; 95% CI, 0.7-8.9; p = 0.164). Further studies are needed to explore the additional value of serum SELENBP1 when stratifying patients with respect to the clinical course following major burns and, potentially, for monitoring therapeutic measures aimed at reducing tissue damage and oxidative stress.
View lessBackground: Operational tolerance as the ability to accept the liver transplant without pharmacological immunosuppression is a common phenomenon in the long-term course. However, it is currently underutilized due to a lack of simple diagnostic support and fear of rejection despite its recognized benefits. In the present work, we present a simple score based on clinical parameters to estimate the probability of tolerance. Patients and methods: In order to estimate the probability of tolerance, clinical parameters from 82 patients after LT who underwent weaning from the IS for various reasons at our transplant center were extracted from a prospectively organized database and analyzed retrospectively. Univariate testing as well as multivariable logistic regression analysis were performed to assess the association of clinical variables with tolerance in the real-world setting. Results: The most important factors associated with tolerance after multivariable logistic regression were IS monotherapy, male sex, history of hepatocellular carcinoma pretransplant, time since LT, and lack of rejection. These five predictors were retained in an approximate model that could be presented as a simple scoring system to estimate the clinical probability of tolerance or IS dispensability with good predictive performance (AUC = 0.89). Conclusion: In parallel with the existence of a tremendous need for further research on tolerance mechanisms, the presented score, after validation in a larger collective preferably in a multicenter setting, could be easily and safely applied in the real world and already now address all three levels of prevention in LT patients over the long-term course.
View lessCongenital heart disease (CHD) is one of the most common organ-specific birth defects and a major cause of infant morbidity and mortality. Despite ultrasound screening guidelines, the detection rate of CHD is limited. Fetal intelligent navigation echocardiography (FINE) has been introduced to extract reference planes and cardiac axis from cardiac spatiotemporal image correlation (STIC) volume datasets. This study analyses the cardiac axis in fetuses affected by CHD/thoracic masses (n = 545) compared to healthy fetuses (n = 1543) generated by FINE. After marking seven anatomical structures, the FINE software generated semi-automatically nine echocardiography standard planes and calculated the cardiac axis. Our study reveals that depending on the type of CHD, the cardiac axis varies. In approximately 86% (471 of 542 volumes) of our pathological cases, an abnormal cardiac axis (normal median = 40-45(degrees)) was detectable. Significant differences between the fetal axis of the normal heart versus CHD were detected in HLHS, pulmonary atresia, TOF (p-value < 0.0001), RAA, situs ambiguus (p-value = 0.0001-0.001) and absent pulmonary valve syndrome, DORV, thoracic masses (p-value = 0.001-0.01). This analysis confirms that in fetuses with CHD, the cardiac axis can significantly deviate from the normal range. FINE appears to be a valuable tool to identify cardiac defects.
View lessCYP2A7 is one of the most understudied human cytochrome P450 enzymes and its contributions to either drug metabolism or endogenous biosynthesis pathways are not understood, as its only known enzymatic activities are the conversions of two proluciferin probe substrates. In addition, the CYP2A7 gene contains four single-nucleotide polymorphisms (SNPs) that cause missense mutations and have minor allele frequencies (MAFs) above 0.5. This means that the resulting amino acid changes occur in the majority of humans. In a previous study, we employed the reference standard sequence (called CYP2A7*1 in P450 nomenclature). For the present study, we created another CYP2A7 sequence that contains all four amino acid changes (Cys311, Glu169, Gly479, and Arg274) and labeled it CYP2A7-WT. Thus, it was the aim of this study to identify new substrates and inhibitors of CYP2A7 and to compare the properties of CYP2A7-WT with CYP2A7*1. We found several new proluciferin probe substrates for both enzyme variants (we also performed in silico studies to understand the activity difference between CYP2A7-WT and CYP2A7*1 on specific substrates), and we show that while they do not act on the standard CYP2A6 substrates nicotine, coumarin, or 7-ethoxycoumarin, both can hydroxylate diclofenac (as can CYP2A6). Moreover, we found ketoconazole, 1-benzylimidazole, and letrozole to be CYP2A7 inhibitors.
View lessThis literature review analyzes the historical development of polo, its organizational structure, the course of the game, as well as the breeding, rearing, and training practices of polo horses. Frequently occurring ailments, such as musculoskeletal injuries, respiratory diseases, and internal illnesses, are highlighted. Lameness is a major problem, with injuries to the superficial digital flexor tendon being the most common cause. Other notable diseases include exercise-induced pulmonary hemorrhage (EIPH), myositis, rhabdomyolysis, and equine infectious anemia (EIA). To ensure the welfare of polo horses, effective prevention and management strategies are crucial. These include proper training, the adaptation of the ground surface, appropriate shoeing, and compliance with animal welfare guidelines and association rules. Collaboration between associations, players, organizers, and veterinarians is crucial. Promoting responsible management practices and raising awareness among stakeholders can help ensure that polo continues to thrive while maintaining high animal welfare standards.
View lessThe long- and short-range structural chemistry of the C-type bixbyite compounds Th0.40Nd0.48Ce0.12O1.76, Th0.47Nd0.43Ce0.10O1.785, and Th0.45Nd0.37Ce0.18O1.815 is systematically examined using synchrotron X-ray powder diffraction (S-PXRD), high-energy resolution fluorescence detection X-ray absorption near edge (HERFD-XANES), and extended X-ray absorption fine structure spectroscopy (EXAFS) measurements supported by electronic structure calculations. S-PXRD measurements revealed that the title compounds all form classical C-type bixbyite structures in space group Ia3̅ that have disordered cationic crystallographic sites with further observation of characteristic superlattice reflections corresponding to oxygen vacancies. Despite the occurrence of oxygen vacancies, HERFD-XANES measurements on the Ce L3-edge revealed that Ce incorporates as Ce4+ into the structures but involves local distortion that resembles cluster behavior and loss of nearest-neighbors. In comparison, HERFD-XANES measurements on the Nd L3-edge supported by electronic structure calculations reveal that Nd3+ adopts a local coordination environment similar to the long-range C-type structure while providing charge balancing for the formation of oxygen defects. Th L3-edge EXAFS analysis reveals shorter average Th–O distances in the title compounds in comparison to pristine ThO2 in addition to shorter Th–O and Th–Ce distances compared to Th–Th or Ce–Ce in the corresponding F-type binary oxides (ThO2 and CeO2). These distances are further found to decrease with the increased Nd content of the structures despite simultaneous observation of the overall lattice structure progressively expanding. Linear combination calculations of the M-O bond lengths are used to help explain these observations, where the role of oxygen defects, via Nd3+ incorporation, induces local bond contraction and enhanced Th cation valence, leading to the observed increased lattice expansion with progressive Nd3+ incorporation. Overall, the investigation points to the significance of dissimilar cations exhibiting variable short-range chemical behavior and how it can affect the long-range structural chemistry of complex oxides.
View lessThe vanadium redox flow battery (VRFB) is considered a promising candidate for large-scale energy storage in the transition from fossil fuels to renewable energy sources. VRFBs store energy by electrochemical reactions of different electroactive species dissolved in electrolyte solutions. The redox couples of VRFBs are VO2+/VO2+ and V2+/V3+, the ratio of which to the total vanadium content determines the state of charge (SOC). V(iv) and V(ii) are paramagnetic half-integer spin species detectable and quantifiable with electron paramagnetic resonance spectroscopy (EPR). Common commercial EPR spectrometers, however, employ microwave cavity resonators which necessitate the use of large electromagnets, limiting their application to dedicated laboratories. For an SOC monitoring device for VRFBs, a small, cost-effective submersible EPR spectrometer, preferably with a permanent magnet, is desirable. The EPR-on-a-Chip (EPRoC) spectrometer miniaturises the complete EPR spectrometer onto a single microchip by utilising the coil of a voltage-controlled oscillator as both microwave source and detector. It is capable of sweeping the frequency while the magnetic field is held constant enabling the use of small permanent magnets. This drastically reduces the experimental complexity of EPR. Hence, the EPRoC fulfils the requirements for an SOC sensor. We, therefore, evaluate the potential for utilisation of an EPRoC dipstick spectrometer as an operando and continuously online monitor for the SOC of VRFBs. Herein, we present quantitative proof-of-principle submersible EPRoC experiments on variably charged vanadium electrolyte solutions. EPR data obtained with a commercial EPR spectrometer are in good agreement with the EPRoC data.
View lessNanoporous gold (npAu) was tested as a catalyst for oxidations of various benzylic sp3-carbon positions in 9H-fluorene derivatives and similar hydrocarbons using tertbutyl hydroperoxide (TBHP) as an oxidant. The silver content in the npAu catalyst had a major influence on the overall conversion: Lower silver amounts (0.53 mol%) led to higher conversions, whereas higher amounts of silver increasingly resulted in the disproportionation of TBHP as a competing reaction. Because residual silver from the bulk alloy was oxidized by TBHP and leached into the solution during the reaction, the Ag content diminished over time. Therefore, the recycling of the catalyst had a positive effect on the conversion after each use. Using electron paramagnetic resonance (EPR) spectroscopy, the formation of radicals from TBHP by npAu was evidenced indicating a radical-based reaction mechanism which was further elucidated by NMR spectroscopic and GC-MS (trace) product analysis. Subsequent oxidations of benzylic sp3-carbon positions gave good to excellent conversions and chemoselectivities featuring npAu as a suitable catalyst for such reactions.
View lessPeople have a need to form and maintain fulfilling social contact, yet they differ with respect to with whom they satisfy the need and how quickly this need is deprived or overly satiated. These social dynamics across relationships and across time are theoretically delineated in the current article. Furthermore, we developed a questionnaire to measure individual differences in three aspects of such social dynamics: (a) Family-friends interdependence, (b) Social deprivation, and (c) Social oversatiation. In a longitudinal study spanning 9 weeks in spring 2020, in total 471 participants (18–75 years, 47% women) answered the newly developed items on social dynamics, questionnaires on social dispositions (e.g., affiliation motive, need to be alone, social anxiety), and questions on personal and indirect contact with family and friends during nationwide contact restrictions related to COVID-19. The results showed that individual differences in Family-friends interdependence, Social deprivation, and Social oversatiation can be measured reliably, validly, and with predictive value for changes in daily contact as contact restrictions were loosened. We discuss potential applications of the Social Dynamics Scale (SDS) for studying social relationships in healthy and clinical populations, and conclude that the brief self-report questionnaire of social dynamics can be useful for situations and samples where direct behavioral observations are not feasible.
View lessInteractions between membranes and biomolecular condensates can give rise to complex phenomena such as wetting transitions, mutual remodeling, and endocytosis. In this study, light-triggered manipulation of condensate engulfment is demonstrated using giant vesicles containing photoswitchable lipids. UV irradiation increases the membrane area, which can be stored in nanotubes. When in contact with a condensate droplet, the UV light triggers rapid condensate endocytosis, which can be reverted by blue light. The affinity of the protein-rich condensates to the membrane and the reversibility of the engulfment processes is quantified from confocal microscopy images. The degree of photo-induced engulfment, whether partial or complete, depends on the vesicle excess area and the relative sizes of vesicles and condensates. Theoretical estimates suggest that utilizing the light-induced excess area to increase the vesicle-condensate adhesion interface is energetically more favorable than the energy gain from folding the membrane into invaginations and tubes. The overall findings demonstrate that membrane-condensate interactions can be easily and quickly modulated via light, providing a versatile system for building platforms to control cellular events and design intelligent drug delivery systems for cell repair.
View lessGlycosaminoglycans (GAGs) are linear and acidic polysaccharides. They are ubiquitous molecules, which are involved in a wide range of biological processes. Despite being structurally simple at first glance, with a repeating backbone of alternating hexuronic acid and hexosamine dimers, GAGs display a highly complex structure, which predominantly results from their heterogeneous sulfation patterns. The commonly applied method for compositional analysis of all GAGs is "disaccharide analysis." In this process, GAGs are enzymatically depolymerized into disaccharides, derivatized with a fluorescent label, and then analysed through liquid chromatography. The limiting factor in the high throughput analysis of GAG disaccharides is the time-consuming liquid chromatography. To address this limitation, we here utilized trapped ion mobility-mass spectrometry (TIM-MS) for the separation of isomeric GAG disaccharides, which reduces the measurement time from hours to a few minutes. A full set of disaccharides comprises twelve structures, with eight possessing isomers. Most disaccharides cannot be differentiated by TIM-MS in underivatized form. Therefore, we developed chemical modifications to reduce sample complexity and enhance differentiability. Quantification is performed using stable isotope labelled standards, which are easily available due to the nature of the performed modifications.
View lessLewis acidic boron compounds are ubiquitous in chemistry due to their numerous applications, yet tuning and optimizing their properties towards different purposes is still a challenging field of research. In this work, the boron Lewis acid B[OTeF3(C6F5)2]3 was synthesized by reaction of the teflate derivative HOTeF3(C6F5)2 with BCl3 or BCl3·SMe2. This new compound presents a remarkably high thermal stability up to 300 °C, as well as one of the most sterically encumbered boron centres known in the literature. Theoretical and experimental methods revealed that B[OTeF3(C6F5)2]3 exhibits a comparable Lewis acidity to that of the well-known B(C6F5)3 and around 85% of the Lewis acidity of the related B(OTeF5)3. The affinity of B[OTeF3(C6F5)2]3 towards pyridine was accessed by Isothermal Titration Calorimetry (ITC) and compared to that of B(OTeF5)3 and B(C6F5)3. The ligand-transfer reactivity of this new boron compound towards different fluorides was demonstrated by the formation of an anionic Au(III) complex and a hypervalent iodine(III) species.
View lessThe molecular IrF5−, IrF6− anions and M[IrF6] (M = Na-Cs) ion pairs were prepared by co-deposition of laser-ablated MF with IrF6 and isolated in solid Ne or Ar matrices. The free anions were obtained by co-deposition of IrF6 with laser-ablated metals (Ir, Pt) as electron sources. The products were characterized in a combined analysis of matrix IR spectroscopy and electronic structure calculations using two-component quasi-relativistic DFT methods accounting for scalar-relativistic and spin-orbit coupling effects as well as multi-reference configuration-interaction approaches with SOC. Inclusion of SOC is crucial in the prediction of spectra and properties of IrF6− and its alkali-metal ion pairs. The observed IR bands and the computations show that the IrF6− anion adopts an Oh structure in a nondegenerate ground state stabilized by SOC effects, and not a distorted D4h structure in a triplet ground state as suggested by scalar-relativistic calculations. The corresponding “closed-shell” M[IrF6] ion pairs with C3v symmetry are stabilized by coordination of an alkali metal ion to three F atoms, and their structural change in the series from M = Na to Cs was proven spectroscopically. There is no evidence for the formation of IrF7, IrF7− or M[IrF7] (M = Na-Cs) ion pairs in our experiments.
View lessThe trifluorosilylarsinidene F3SiAs in the triplet ground state has been generated through the reaction of laser-ablated silicon atoms with AsF3 in cryogenic Ne- and Ar-matrices. The reactions proceed with the initial formation perfluorinated arsasilene FAsSiF2 in the singlet ground state by two As‒F bonds insertion reaction on annealing. The trifluorosilylarsinidene F3SiAs was formed via F-migration reactions of FAsSiF2 under irradiation at UV light (λ = 275 nm). The characterization of FAsSiF2 and F3SiAs by IR matrix-isolation spectroscopy is supported by computations at CCSD(T)-F12/aug-cc-pVTZ and B3LYP/aug-cc-pVTZ levels of theory.
View lessHerein we report a general access to silver(i) perfluoroalcoholates, their structure in the solid state and in solution, and their use as transfer reagents. The silver(i) perfluoroalcoholates are prepared by the reaction of AgF with the corresponding perfluorinated carbonyl compounds in acetonitrile and are stable for a prolonged time at –18 °C. X-Ray analysis of single crystals of perfluoroalcoholate species showed that two Ag(i) centers are bridged by the alcoholate ligands. In acetonitrile solution, Ag[OCF3] forms different structures as indicated by IR spectroscopy. Furthermore, the silver(i) perfluoroalcoholates can be used as easy-to-handle transfer reagents for the synthesis of Cu[OCF3], Cu[OC2F5], [PPh4][Au(CF3)3(OCF3)], and fluorinated alkyl ethers.
View lessTriazaphospholes are potential polydentate ligands due to the presence of both phosphorus and nitrogen donor atoms within the aromatic 5-membered heterocycle. The incorporation of an additional pyridyl-substituent opens up the possibility of a post-synthesis modification via chemoselective and also stepwise alkylation exclusively of the nitrogen atoms. This can be controlled by the choice and by the stoichiometry of the electrophile and allows the targeted synthesis of a variety of novel mono- and dicationic ligands. Reaction with Cu(I)-halides causes the formation of cuprates of the type [CuXn](n-1)-, which enables coordination of the π-acidic phosphorus donor to the negatively charged metal core, which is favored over the coordination by a strongly σ-donating nitrogen atom. The use of cationic triazaphosphole derivatives can be used as a strategy to enforce the coordination of the ligand to an electron rich metal solely via the phosphorus atom. However, there is a subtle balance between the formation of either coordination polymers or dimeric structures, as the substitution pattern on the heterocycle and the nature of the halide have a large influence on the coordination motifs formed.
View lessMehr als 30 Jahre nach der Wende scheint der Deutungskampf um das Ende des DDR-Rundfunks nicht beigelegt zu sein. Einerseits werden die mangelnden Einflussmöglichkeiten Ostdeutscher bei der Gestaltung des Rundfunks nach 1989 kritisiert. Andererseits wird die Eingliederung in das westdeutsche Rundfunksystem als Erfolg gefeiert, wobei die verschiedenen Identifikationsmöglichkeiten hervorgehoben werden, die die neu gegründeten Landessender von Anfang an boten. Dieser Beitrag fragt, wie Ostdeutsche den DDR-Rundfunk und seine Abwicklung heute erinnern. Gestützt auf die Strukturations- und Identitätstheorie von Anthony Giddens und auf der Basis von 37 biographischen Interviews wird ein Spektrum von Deutungen aufgezeigt, die Menschen aus Ostberlin rückblickend mit dem Medienstrukturumbruch verbinden. Die Studie zeigt, dass neben einer Gruppe von Befragten, die den späten DDR-Rundfunk kaum oder gar nicht in ihre Selbsterzählungen eingebunden haben, die Vergegenwärtigung dieser Einrichtung über unterschiedliche Biographien hinweg im Modus einer Selbstvergewisserung stattfindet. Dabei werden Zuordnungen und Abgrenzungen zur DDR-Herkunft vorgenommen. Die DDR-Rundfunkgeschichte wird mit Identität aufgeladen, was zum einen auf die medial dominanten DDR- und Ost-Diskurse zurückzuführen ist, zum anderen auf die verschiedenen (Kollektiv‑)Erfahrungen und Lebensbedingungen der Ostdeutschen nach 1989.
View lessAccurate ensemble forecasts of heavy precipitation in India are vital for many applications and essential for early warning of damaging flood events, especially during the monsoon season. In this study we investigate to what extent Quantile Mapping (QM) and Ensemble Model Output Statistics (EMOS) statistical postprocessing reduce errors in precipitation ensemble forecasts over India, in particular for heavy precipitation. Both methods are applied to day-1 forecasts at 12-km resolution from the 23-member National Centre for Medium Range Weather Forecasting (NCMRWF) global ensemble prediction system (NEPS-G). By construction, QM leads to distributions close to the observed ones, while EMOS optimizes the ensemble spread, and it is not a priori clear which is better suited for practical applications. The methods are therefore compared with respect to several key aspects of the forecasts: local distributions, ensemble spread, and skill for forecasting precipitation amounts and the exceedance of heavy-precipitation thresholds. The evaluation includes rank histograms, Continuous Ranked Probability Skill Scores (CRPSS), Brier Skill Scores (BSS), reliability diagrams, and receiver operating characteristic. EMOS performs best not only with respect to correcting under- or overdispersive ensembles, but also in terms of forecast skill for precipitation amounts and heavy precipitation events, with positive CRPSS and BSS in most regions (both up to about 0.4 in some areas), while QM in many regions performs worse than the raw forecast. QM performs best with respect to the overall local precipitation distributions. Which aspects of the forecasts are most relevant depends to some extent on how the forecasts are used. If the main criteria are the correction of under- or overdispersion, forecast reliability, match between the forecasted distribution for individual days and observations (CRPSS), and the skill in forecasting heavy-precipitation events (BSS), then EMOS is the better choice for postprocessing NEPS-G forecasts for short lead times.
View lessThe photothermal therapeutic effect on tumors located at different subcutaneous depths varies due to the attenuation of light by tissue. Here, based on the wavelength-dependent optical attenuation properties of tissues, the tumor depth is assessed using a multichannel lanthanide nanocomposite. A zeolitic imidazolate framework (ZIF-8)-coated nanocomposite is able to deliver high amounts of the hydrophilic heat shock protein 90 inhibitor epigallocatechin gallate through a hydrogen-bonding network formed by the encapsulated highly polarized polyoxometalate guest. It is superior to both bare and PEGylated ZIF-8 for drug delivery. With the assessment of tumor depth and accumulated amount of nanocomposite by fluorescence, an irradiation prescription can be customized to release sufficient HSP90 inhibitor and generate heat for sensitized photothermal treatment of tumors, which not only ensured therapeutic efficacy but also minimized damage to the surrounding tissues.
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