In this retrospective, single-center, observational study, we compared the clinical characteristics, analyzed the glaucoma development, and the glaucoma surgery requirement mediators in patients with different virus-associated anterior uveitis (VAU). In total, 270 patients (= eyes) with VAU confirmed by positive Goldmann-Witmer coefficients (GWC) for cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), rubella virus (RV), and multiple virus (MV) were included. Clinical records of these patients were analyzed. Demographic constitution, clinical findings, glaucoma development, and surgeries were recorded. The concentrations of 27 immune mediators were measured in 150 samples of aqueous humor. The GWC analysis demonstrated positive results for CMV in 57 (21%), HSV in 77 (29%), VZV in 45 (17%), RV in 77 (29%), and MV in 14 (5%) patients. CMV and RV AU occurred predominantly in younger and male patients, while VZV and HSV AU appeared mainly with the elderly and females (P<0.0001). The clinical features of all viruses revealed many similarities. In total, 52 patients (19%) showed glaucomatous damage and of these, 27 patients (10%) needed a glaucoma surgery. Minimal-invasive glaucoma surgery (MIGS) showed a reliable IOP reduction in the short-term period. In 10 patients (37%), the first surgical intervention failed and a follow-up surgery was required. We conclude that different virus entities in anterior uveitis present specific risks for the development of glaucoma as well as necessary surgery. MIGS can be suggested as first-line-treatment in individual cases, however, the device needs to be carefully chosen by experienced specialists based on the individual needs of the patient. Filtrating glaucoma surgery can be recommended in VAU as an effective therapy to reduce the IOP over a longer period of time.View less
National identity definitions determine who belongs to the national ingroup (e.g., “us Germans”) versus the “foreign” outgroup prone to hostile outgroup bias. We conducted five studies in two countries investigating if viewing the ingroup's national identity as fixed exacerbates the perceived divide between ingroup and outgroup and thus increases anti‐immigrant hostility, while a malleable view blurs the divide and reduces anti‐immigrant hostility. In a Prestudy (58 participants), an Implicit Theory of National Identity Scale was developed. In Studies 1 (154 participants) and 2 (390 participants), our scale predicted individuals’ prejudice and participation rates in a hypothetical referendum and a real petition against immigrants. In Studies 3 (225 participants) and 4 (225 participants), experimental evidence was obtained. Leading participants to believe that the definition of “a true compatriot” changes over time (rather than remaining the same) resulted in lower levels of prejudice and participation rates in an anti‐immigrant petition.View less
Several encouraging pre‐clinical results highlight the melanin‐concentrating hormone receptor 1 (MCHR1) as promising target for anti‐obesity drug development. Currently however, experimentally resolved structures of MCHR1 are not available, which complicates rational drug design campaigns. In this study, we aimed at developing accurate, homologymodel‐based 3D pharmacophores against MCHR1. We show that traditional approaches involving docking of known active small molecules are hindered by the flexibility of binding pocket residues. Instead, we derived three‐dimensional pharmacophores from molecular dynamics simulations by employing our novel open‐source software PyRod. In a retrospective evaluation, the generated 3D pharmacophores were highly predictive returning up to 35 % of active molecules and showing an early enrichment (EF1) of up to 27.6. Furthermore, PyRod pharmacophores demonstrate higher sensitivity than ligand‐based pharmacophores and deliver structural insights, which are key to rational lead optimization.View less
Background: Postoperative anaemia is a frequent surgical complication and in contrast to preoperative anaemia has not been validated in relation to mortality, morbidity and its associated health economic effect. Postoperative anaemia can predispose postoperative delirium through impairment of cerebral oxygenation. The aim of this secondary analysis is to investigate the association of postoperative anaemia in accordance with the sex specific World Health Organization definition of anaemia to postoperative delirium and its impact on the duration of hospital stay.
Methods: A secondary analysis of the prospective multicentric observational CESARO-study was conducted. 800 adult patients undergoing elective surgery were enrolled from various operative disciplines across seven hospitals ranging from university hospitals, district general hospitals to specialist clinics of minimally invasive surgery in Germany. Patients were classified as anaemic according to the World Health Organization parameters, setting the haemoglobin level cut off below 12g/dl for females and below 13g/dl for males. Focus of the investigation were patients with acute anaemia. Patients with present preoperative anaemia or missing haemoglobin measurement were excluded from the sample set. Delirium screening was established postoperatively for at least 24 hours and up to three days, applying the validated Nursing Delirium Screening Scale.
Results: The initial sample set contained 800 patients of which 183 were suitable for analysis in the study. Ninety out of 183 (49.2%) suffered from postoperative anaemia. Ten out of 93 (10.9%) patients without postoperative anaemia developed a postoperative delirium. In the group with postoperative anaemia, 28 (38.4%) out of 90 patients suffered from postoperative delirium (odds ratio 3.949, 95% confidence interval, (1.358-11.480)) after adjustment for NYHA-stadium, severity of surgery, cutting/suture time, duration of anaesthesia, transfusion of packed red cells and sedation status with Richmond Agitation Scale after surgery. Additionally, patients who suffered from postoperative anaemia showed a significantly longer duration of hospitalisation (7.75 vs. 12.42 days, odds ratio = 1.186, 95% confidence interval, 1.083-1.299, after adjustments).
Conclusion: The study results reveal that postoperative anaemia is not only a frequent postsurgical complication with an incidence probability of almost 50%, but could also be associated with a postoperative delirium and a prolonged hospitalisation.View less
This study’s objective was the generation of a standardized geometry of the healthy nasal cavity. An average geometry of the healthy nasal cavity was generated using a statistical shape model based on 25 symptom-free subjects. Airflow within the average geometry and these geometries was calculated using fluid simulations. Integral measures of the nasal resistance, wall shear stresses (WSS) and velocities were calculated as well as cross-sectional areas (CSA). Furthermore, individual WSS and static pressure distributions were mapped onto the average geometry. The average geometry featured an overall more regular shape that resulted in less resistance, reduced WSS and velocities compared to the median of the 25 geometries. Spatial distributions of WSS and pressure of the average geometry agreed well compared to the average distributions of all individual geometries. The minimal CSA of the average geometry was larger than the median of all individual geometries (83.4 vs. 74.7 mm²). The airflow observed within the average geometry of the healthy nasal cavity did not equal the average airflow of the individual geometries. While differences observed for integral measures were notable, the calculated values for the average geometry lay within the distributions of the individual parameters. Spatially resolved parameters differed less prominently.View less
The tight junction (TJ) and the adherens junction (AJ) bridge the paracellular cleft of epithelial and endothelial cells. In addition to their role as protective barriers against bacteria and their toxins they maintain ion homeostasis, cell polarity, and mechano-sensing. Their functional loss leads to pathological changes such as tissue inflammation, ion imbalance, and cancer. To better understand the consequences of such malfunctions, the junctional nanoarchitecture is of great importance since it remains so far largely unresolved, mainly because of major difficulties in dynamically imaging these structures at sufficient resolution and with molecular precision. The rapid development of super-resolution imaging techniques ranging from structured illumination microscopy (SIM), stimulated emission depletion (STED) microscopy, and single molecule localization microscopy (SMLM) has now enabled molecular imaging of biological specimens from cells to tissues with nanometer resolution. Here we summarize these techniques and their application to the dissection of the nanoscale molecular architecture of TJs and AJs. We propose that super-resolution imaging together with advances in genome engineering and functional analyses approaches will create a leap in our understanding of the composition, assembly, and function of TJs and AJs at the nanoscale and, thereby, enable a mechanistic understanding of their dysfunction in disease.View less
Analysis of faecal glucocorticoid metabolites (FGMs) is frequently applied to assess adrenocortical activity in animal conservation and welfare studies. Faecal sample collection is non-invasive and feasible under field conditions. FGM levels are also less prone to circadian rhythms, episodic fluctuations and short acute stressors than glucocorticoid (GC) levels obtained from other matrices, for example blood or saliva. To investigate the suitability of FGM measurement in polar bears (Ursus maritimus), a species listed as Vulnerable by the IUCN (International Union for Conservation of Nature), a cortisol enzyme immunoassay (EIA) was biologically validated by demonstrating a significant increase in FGMs after five zoo-to-zoo transports. In addition to validating the method, the study also documented an average delay of 7 h until the first occurrence of food colorants in the monitored polar bears, which provides essential information for future studies. After validation, the assay was applied to measure FGM concentrations of five polar bears over a 1-year period. Several pre-defined potentially stressful events were recorded in an event log to measure their effect on FGM concentrations. A mixed model analysis revealed significant increases in FGM concentrations after social tension and environmental changes, whereas season and sex had no significant effect. The study demonstrates that the applied cortisol EIA is suitable for measuring FGM levels in polar bears and that using a carefully validated assay for FGM analysis in combination with a detailed sampling protocol can serve as a valuable tool for evaluating mid- to long-term stress in polar bears. FGM levels can be used to monitor stress in captive polar bears in order to optimize housing conditions but also to elucidate stress responses in wild populations for targeted conservation measures.View less
Mass spectrometry enables the in-depth structural elucidation of membrane protein complexes, which is of great interest in structural biology and drug discovery. Recent breakthroughs in this field revealed the need for design rules that allow fine-tuning the properties of detergents in solution and gas phase. Desirable features include protein charge reduction, because it helps to preserve native features of protein complexes during transfer from solution into the vacuum of a mass spectrometer. Addressing this challenge, we here present the first systematic gas-phase study of azobenzene detergents. The utility of gas-phase techniques for monitoring light-driven changes of isomer ratios and molecular properties are investigated in detail. This leads to the first azobenzene detergent that enables the native mass spectrometry analysis of membrane proteins and whose charge-reducing properties can be tuned by irradiation with light. More broadly, the presented work outlines new avenues for the high-throughput characterization of supramolecular systems and opens a new design strategy for detergents in membrane protein research.View less
In this article, we explore the power of shared embodiment for the constitution of an affective community. More specifically, we examine how people afflicted by long-term, arduous experiences of war, migration, and discrimination sensually articulate and, at least temporarily, renegotiate feelings of non/belonging, care, and in/exclusion. Methodologically, we draw on emplaced ethnography and systematic phenomenological go-alongs with a group of elderly migrants, born and raised in different parts of Vietnam, who had arrived in Germany within different legal–political frameworks and who, during the time of our psychological–anthropological research, frequented the same psychotherapeutic clinic. We apply the notion of “affective communities” (Zink in Affective Societies: Key Concepts. Routledge, New York, 2019) to grasp how the group experienced a sensual place of mutual belonging outside the clinic when moving through different public spaces in Berlin as part of their therapy. Particular attention is paid to the participants’ embodied and emplaced memories that were reactivated during these excursions. Shared sensations and spatiality, we argue, made them feel they belonged to an ephemeral community of care that was otherwise hardly imaginable due to their distinct individual biographies, contrasting political attitudes, and ties to different social collectives. In analyzing this affective community, we highlight how significant spatio-sensorial modes of temporal solidification can be in eliciting embodied knowledge that positively contributes to therapeutic processes.View less
Excellent conversion efficiencies of over 20 % and facile cell production have placed hybrid perovskites at the forefront of novel solar cell materials, with CH3NH3PbI3 being an archetypal compound. The question why CH3NH3PbI3 has such extraordinary characteristics, particularly a very efficient power conversion from absorbed light to electrical power, is hotly debated, with ferroelectricity being a promising candidate. This does, however, require the crystal structure to be non‐centrosymmetric and we herein present crystallographic evidence as to how the symmetry breaking occurs on a crystallographic and, therefore, long‐range level. Although the molecular cation CH3NH3+ is intrinsically polar, it is heavily disordered and this cannot be the sole reason for the ferroelectricity. We show that it, nonetheless, plays an important role, as it distorts the neighboring iodide positions from their centrosymmetric positions.View less
We aimed to investigate the prevalence, molecular characteristics and risk factors of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) shedding in horses. A prospective study included three cohorts: (i) farm horses (13 farms, n = 192); (ii) on hospital admission (n = 168) and; (iii) horses hospitalized for ≥72 h re-sampled from cohort (ii) (n = 86). Enriched rectal swabs were plated, ESBL-production was confirmed (Clinical and Laboratory Standards Institute (CLSI)) and genes were identified (polymerase chain reaction (PCR)). Identification and antibiotic susceptibility were determined (Vitek-2). Medical records and owners’ questionnaires were analyzed. Shedding rates increased from 19.6% (n = 33/168) on admission to 77.9% (n = 67/86) during hospitalization (p < 0.0001, odds ratio (OR) = 12.12). Shedding rate in farms was 20.8% (n = 40/192), significantly lower compared to hospitalized horses (p < 0.0001). The main ESBL-E species (n = 192 isolates) were E. coli (59.9%, 115/192), Enterobacter sp. (17.7%, 34/192) and Klebsiella pneumoniae (13.0%, 25/192). The main gene group was CTX-M-1 (56.8%). A significant increase in resistance rates to chloramphenicol, enrofloxacin, gentamicin, nitrofurantoin, and trimethoprim-sulpha was identified during hospitalization. Risk factors for shedding in farms included breed (Arabian, OR = 3.9), sex (stallion, OR = 3.4), and antibiotic treatment (OR = 9.8). Older age was identified as a protective factor (OR = 0.88). We demonstrated an ESBL-E reservoir in equine cohorts, with a significant ESBL-E acquisition, which increases the necessity to implement active surveillance and antibiotic stewardship programs.View less
Diamond films are advanced engineering materials for various industrial applications requiring a coating material with extremely high thermal conductivity and low electrical conductivity. An approach for the synthesis of diamond films via high-speed jet deposition of thermally activated gas has been applied. In this method, spatially separated high-speed flows of methane and hydrogen were thermally activated, and methyl and hydrogen radicals were deposited on heated molybdenum substrates. The morphology and structure of three diamond films were studied, which were synthesized at a heating power of 900, 1700, or 1800 W, methane flow rate of 10 or 30 sccm, hydrogen flow rate of 1500 or 3500 sccm, and duration of the synthesis from 1.5 to 3 h.The morphology and electronic state of the carbon on the surface and in the bulk of the obtained films were analyzed by scanning electron microscopy, Raman scattering, X-ray photoelectron, and near-edge X-ray absorption fine structure spectroscopies. The diamond micro-crystals with a thick oxidized amorphous sp2-carbon coating were grown at a heating power of 900 W and a hydrogen flow rate of 1500 sccm. The quality of the crystals was improved, and the growth rate of the diamond film was increased seven times when the heating power was 1700–1800 W and the methane and hydrogen flow rates were 30 and 3500 sccm, respectively. Defective octahedral diamond crystals of 30 μm in size with a thin sp2-carbon surface layer were synthesized on a Mo substrate heated at 1273 K for 1.5 h. When the synthesis duration was doubled, and the substrate temperature was decreased to 1073 K, the denser film with rhombic-dodecahedron diamond crystals was grown. In this case, the thinnest hydrogenated sp2-carbon coating was detected on the surface of the diamond crystals. View Full-TextView less
Despite extensive research on party system stability, the concept is often reduced to the survival of existing parties. This article argues for introducing programmatic stability as a separate dimension and shows how the combination of party replacement and programmatic instability shapes patterns of party competition. Based on their interaction, the article distinguishes four ideal types: stable systems, systems with empty party labels, systems with ephemeral parties, and general instability. The empirical analysis relies on media data and proposes a new measure of programmatic stability to study its interaction with party replacement in fifteen European countries during the period of the economic crisis. As the article shows, the two dimensions shape the transformation of party systems in northwestern, southern, and eastern Europe. Relying on multidimensional scaling, the article analyzes in detail the cases of the United Kingdom, Romania, Ireland, and Latvia to showcase party competition under different conditions of systemic instability.View less
Cytochrome c oxidase (CcO), a redox-coupled proton pump, catalyzes the reduction of molecular oxygen to water, thereby establishing the transmembrane proton gradient that fuels ATP synthesis. CcO employs two channels for proton uptake, the D- and the K-channel. In contrast to the D-channel, the K-channel does not constitute a continuous pathway of H-bonds for proton conduction and is only active in the reductive phase rendering its proton transport mechanism enigmatic. Theoretical studies have suggested selective hydration changes within the K-channel to become activated and being essential for vectorial proton transport. Here, we unravel a previously unidentified mechanism for transient proton channel activation by combining computational studies with site-directed nano-environmental probing of protonation, structural changes, and water dynamics. We show that electrostatic changes at the binuclear center lead to long-range conformational changes propagating to the K-channel entrance as evidenced by time-resolved fluorescence depolarization experiments and molecular dynamics (MD) simulations. These redox-induced long-range structural rearrangements affect the H-bond network at the K-channel's protein surface as shown by pKa-shift analysis of a local probe in experiment and simulation. Concomitantly, selective channel hydration at the K-channel entrance was revealed by dipolar relaxation studies to be associated with channel opening. We propose that instead of a singular change, it is the intricate interplay of these individual redox-triggered changes in the cause–effect relationship that defines the mechanism for transient proton conduction of the K-channel.View less
Orthohantaviruses are re-emerging rodent-borne pathogens distributed all over the world. Here, we report the isolation of a Puumala orthohantavirus (PUUV) strain from bank voles caught in a highly endemic region around the city Osnabrück, north-west Germany. Coding and non-coding sequences of all three segments (S, M, and L) were determined from original lung tissue, after isolation and after additional passaging in VeroE6 cells and a bank vole-derived kidney cell line. Different single amino acid substitutions were observed in the RNA-dependent RNA polymerase (RdRP) of the two stable PUUV isolates. The PUUV strain from VeroE6 cells showed a lower titer when propagated on bank vole cells compared to VeroE6 cells. Additionally, glycoprotein precursor (GPC)-derived virus-like particles of a German PUUV sequence allowed the generation of monoclonal antibodies that allowed the reliable detection of the isolated PUUV strain in the immunofluorescence assay. In conclusion, this is the first isolation of a PUUV strain from Central Europe and the generation of glycoprotein-specific monoclonal antibodies for this PUUV isolate. The obtained virus isolate and GPC-specific antibodies are instrumental tools for future reservoir host studies.View less
Porphyrin molecules are particularly interesting candidates for spintronic applications due to their bonding flexibility, which allows to modify their properties substantially by the addition or transformation of ligands. Here, we investigate the electronic and magnetic properties of cobalt octaethylporphyrin (CoOEP), deposited on copper substrates with two distinct crystallographic surface orientations, Cu(100) and Cu(111), with X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD). A significant magnetic moment is present in the Co ions of the molecules deposited on Cu(100), but it is completely quenched on Cu(111). Heating the molecules on both substrates to 500 K induces a ring-closure reaction with cobalt tetrabenzoporphyrin (CoTBP) as reaction product. In these molecules, the magnetic moment is quenched on both surfaces. Our XMCD and XAS measurements suggest that the filling of the dz2 orbital leads to a non-integer valence state and causes the quench of the spin moments on all samples except CoOEP/Cu(100), where the molecular conformation induces variations to the ligand field that lift the quench. We further employ density functional theory calculations, supplemented with on-site Coulomb correlations (DFT+U), to study the adsorption of these spin-bearing molecules on the Cu substrates. Our calculations show that charge transfer from the Cu substrates as well as charge redistribution within the Co 3d orbitals lead to the filling of the Co minority spin dz2 orbital, causing a ‘turning off’ of the exchange splitting and quenching of the spin moment at the Co magnetic centers. Our investigations suggest that, by this mechanism, molecule–substrate interactions can be used to control the quenching of the magnetic moments of the adsorbed molecules.View less
For a molecular radical to be stable, the environment needs to be inert. Furthermore, an unpaired electron is less likely to react chemically when it is placed in an extended orbital. Here, we use the tip of a scanning tunneling microscope to abstract one of the pyrrolic hydrogen atoms from phthalocyanine (H2Pc) deposited on a single layer of molybdenum disulfide (MoS2) on Au(111). We show the successful dissociation reaction by current-induced three-level fluctuations reflecting the inequivalent positions of the remaining H atom in the pyrrole center. Tunneling spectroscopy reveals two narrow resonances inside the semiconducting energy gap of MoS2 with their spatial extent resembling the highest occupied molecular orbital (HOMO) of H2Pc. By comparison to simple density functional calculations of the isolated molecule, we show that these correspond to a single occupation of the Coulomb-split highest molecular orbital of HPc. We conclude that the dangling σ bond after N–H bond cleavage is filled by an electron from the delocalized HOMO. The extended nature of the HOMO together with the inert nature of the MoS2 layer favors the stabilization of this radical state.View less
Sylwester Gawinkowski opened discussion of the paper by Javier Aizpurua: How many electrons are transferred by one ultrashort pulse? If you are thinking about applications in electronics, then it seems that this number may be too small. Is simply increasing the pulse energy and therefore significantly increasing the number of such emitted electrons possible?
Direct (photo)electrochemical production of non-fossil fuels from water and CO2 requires water-oxidation catalysis at near-neutral pH in the presence of appropriate anions that serve as proton acceptors. We investigate the largely enigmatic structural role of anions in water oxidation for the prominent cobalt-phosphate catalyst (CoCat), an amorphous and hydrated oxide material. Co3([(P/As)O]4)2·8H2O served, in conjunction with phosphate–arsenate exchange, as a synthetic model system. Its structural transformation was induced by prolonged operation at catalytic potentials and probed by X-ray absorption spectroscopy not only at the metal (Co), but for the first time also at the anion (As) K-edge. For initially isostructural microcrystals, anion exchange determined the amorphization process and final structure. Comparison to amorphous electrodeposited Co oxide revealed that in CoCat, the arsenate binds not only at oxide-layer edges, but also arsenic substitutes cobalt positions within the layered-oxide structure in an unusual AsO6 coordination. Our results show that in water oxidation catalysis at near-neutral pH, anion type and exchange dynamics correlate with the catalyst structure and redox properties.View less
The magnetic properties of adsorbed metalloporphyrin molecules can be altered or tuned by the substrate, additional axial ligands, or changes to the molecules’ macrocycle. These modifications influence the electronic configuration of the fourfold-coordinated central metal ion that is responsible for the metalloporphyrins’ magnetic properties. We report a substantial increase in the effective spin moment obtained from sum-rule analysis of X-ray magnetic circular dichroism for an iron metalloporphyrin molecule on Au(111) through its conversion from iron(II)-octaethylporphyrin to iron(II)-tetrabenzoporphyrin in a surface-assisted ring-closure ligand reaction. Density functional theory calculations with additional strong Coulomb correlation (DFT+U) show that the on-surface reaction alters the conformation of the molecule, increasing its planarity and the ion–surface distance. A spin-Hamiltonian fit of the magnetization as a function of field reveals a substantial increase in the intra-atomic magnetic dipole term (Tz) and a decrease in the magnitude of the easy-plane anisotropy upon ring closure. This consequence of the ring closure demonstrates how new magnetic properties can be obtained from on-surface reactions, resulting here in significant modifications to the magnetic anisotropy of the Fe ion, and sheds light onto the molecule–substrate interaction in these systems.View less