(Acetato-κO)(2,2′-bipyridine-κ2 N,N′)trimethyl­platinum(IV) monohydrate

In the title hydrate, [Pt(CH3)3(CH3COO)(C10H8N2)]·H2O, the PtIV atom exhibits a distorted octa­hedral coordination geometry built up by three methyl ligands in a facial arrangement, a bipyridine ligand and a monodentately bound acetate ligand. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds are observed between the water mol­ecule and the platinum complex, which link the mol­ecules into chains along the c axis

Flow-induced glycocalyx formation and cell alignment of HUVECs compared to iPSC-derived ECs for tissue engineering applications

The relevance of cellular in vitro models highly depends on their ability to mimic the physiological environment of the respective tissue or cell niche. Static culture conditions are often unsuitable, especially for endothelial models, since they completely neglect the physiological surface shear stress and corresponding reactions of endothelial cells (ECs) such as alignment in the direction of flow. Furthermore, formation and maturation of the glycocalyx, the essential polysaccharide layer covering all endothelial surfaces and regulating diverse processes, is highly dependent on applied fluid flow. This fragile but utterly important macromolecular layer is hard to analyze, its importance is often underestimated and accordingly neglected in many endothelial models. Therefore, we exposed human umbilical vein ECs (HUVECs) and human induced pluripotent stem cell-derived ECs (iPSC-ECs) as two relevant EC models in a side-by-side comparison to static and physiological dynamic (6.6 dyn cm−2) culture conditions. Both cell types demonstrated an elongation and alignment along the flow direction, some distinct changes in glycocalyx composition on the surface regarding the main glycosaminoglycan components heparan sulfate, chondroitin sulfate or hyaluronic acid as well as an increased and thereby improved glycocalyx thickness and functionality when cultured under homogeneous fluid flow. Thus, we were able to demonstrate the maturity of the employed iPSC-EC model regarding its ability to sense fluid flow along with the general importance of physiological shear stress for glycocalyx formation. Additionally, we investigated EC monolayer integrity with and without application of surface shear stress, revealing a comparable existence of tight junctions for all conditions and a reorganization of the cytoskeleton upon dynamic culture leading to an increased formation of focal adhesions. We then fabricated cell sheets of EC monolayers after static and dynamic culture via non-enzymatic detachment using thermoresponsive polymer coatings as culture substrates. In a first proof-of-concept we were able to transfer an aligned iPSC-EC sheet to a 3D-printed scaffold thereby making a step in the direction of vascular modelling. We envision these results to be a valuable contribution to improvements of in vitro endothelial models and vascular engineering in the future

(OC-6-33)-(2,2′-Bipyridine-κ2 N,N′)trimeth­yl(2-methyl­sulfanyl-2-thia­zoline-κN)platinum(IV) tetra­fluoridoborate

The asymmetric unit of the title complex, [Pt(CH3)3(C10H8N2)(C4H7NS2)]BF4, contains two crystallographically independent mol­ecules. The PtIV atom in each complex cation exhibits a distorted octa­hedral coordination geometry, built up by three methyl ligands in a facial binding fashion, a bipyridine ligand and a monodentately N-bound 2-methyl­sulfanyl-2-thia­zoline ligand (configuration index: OC-6–33). In the crystal structure, weak inter­molecular C—H⋯F hydrogen bonds are found between the complex cations and BF4 − anions

Development and validation of a sensor prototype for near-infrared imaging of the newborn brain

Imaging brain oxygenation is crucial for preventing brain lesions in preterm infants. Our aim is to build and validate a near-infrared optical tomography (NIROT) sensor for the head of neonates. This sensor, combined with an optoacoustic device, will enable quantitative monitoring of the structural and functional information of the brain. Since the head of preterm infants is small and fragile great care must be taken to produce a comfortable and compact device in which a sufficient number of light sources and detectors can be implemented. Here we demonstrate our first prototype. Heterogeneous silicone phantoms were produced to validate the prototype's data acquisition, data processing, and image reconstruction. Reconstructed optical properties agree well with the target values. The mechanical performance of the new NIROT sensor prototype confirms its suitability for the clinical application

Analyse von notfallmedizinischen Routinedaten aus Präklinik und Klinik

Background: In the 2018 advisory opinion concerning the realignment of healthcare, it is advocated that in order to relieve pressure on emergency departments (ED) prehospital medical emergency services should be given the option to directly transport suitable patients to doctors' offices. Objectives: To determine the prevalence of patients treated by prehospital emergency services that have the potential to be directly allocated to a primary care provider. Materials and methods: Preclinical and clinical data of adult patients who in a 2-month period were transported to the ED of a university hospital by an ambulance were evaluated. To determine a safe and meaningful transport directly to a doctor's office, a stepwise assessment was carried out: patients were categorized on the basis of the prehospital assessment of urgency as "urgent" (contact to doctor necessary within a maximum time of 30 min) and "less urgent" (contact to doctor not necessary within 30 min, maximum 120 min). "Less urgent" patients were further divided and those treated as outpatients were identified. This group was further restricted to cases whose administrative reception in the ED was documented Monday-Friday between 8 am and 7 pm. In addition, these cases were further differentiated with regard to medical content and compared with the triage results in the ED (Manchester Triage, MTS). Results: In all, 1260 patients were brought to the ED by ambulance within the study period (total number of patients treated in this time period n = 11,506); 894 cases had a documented prehospital level of urgency and could therefore be included. Of these n = 477 (53.4%) were categorized as "less urgent"; 317 (66.5%) of these "less urgent" cases were treated as outpatients in the ED, and n = 114 (23.9%) in a time frame potentially suitable for direct transport to doctors' offices, which is 1% of all patients treated in the ED in the time period examined. However, 70 of the cases suitable for doctors' office (63.6% of n = 110 with documented MTS) were rated more urgent in the ED. With regards to prehospital complaints and documented diagnosis we assume employment of a relevant amount of resources in the treatment of these cases. Conclusions: EDs could be relieved from every tenth patient brought in by prehospital emergency services (1% of all patients treated) during normal offices hours by direct allocation to doctors' offices. Regarding patient's safety this process however has to be seen critically as > 60% of these cases were potentially undertriaged. Necessary resources for diagnostics and treatment have to be available in the doctors' offices and known to prehospital emergency services. Primary assignment of patients to doctors' offices by prehospital emergency can only relieve urban EDs to a negligible extent, is potentially dangerous and linked to a tremendous logistic effort

Description and evaluation of the process-based forest model 4C v2.2 at four European forest sites

The process-based model 4C (FORESEE) has been developed over the past 20 years to study climate impacts on forests and is now freely available as an open-source tool. The objective of this paper is to provide a comprehensive description of this 4C version (v2.2) for scientific users of the model and to present an evaluation of 4C at four different forest sites across Europe. The evaluation focuses on forest growth as well as carbon (net ecosystem exchange, gross primary production), water (actual evapotranspiration, soil water content), and heat fluxes (soil temperature) using data from the PROFOUND database. We applied different evaluation metrics and compared the daily, monthly, and annual variability of observed and simulated values. The ability to reproduce forest growth (stem diameter and biomass) differs from site to site and is best for a pine stand in Germany (Peitz, model efficiency ME=0.98). 4C is able to reproduce soil temperature at different depths in Sorø and Hyytiälä with good accuracy (for all soil depths ME > 0.8). The dynamics in simulating carbon and water fluxes are well captured on daily and monthly timescales (0.51 < ME < 0.983) but less so on an annual timescale (ME < 0). This model–data mismatch is possibly due to the accumulation of errors because of processes that are missing or represented in a very general way in 4C but not with enough specific detail to cover strong, site-specific dependencies such as ground vegetation growth. These processes need to be further elaborated to improve the projections of climate change on forests. We conclude that, despite shortcomings, 4C is widely applicable, reliable, and therefore ready to be released to the scientific community to use and further develop the model

An Antibody-Aptamer-Hybrid Lateral Flow Assay for Detection of CXCL9 in Antibody-Mediated Rejection after Kidney Transplantation

Chronic antibody-mediated rejection (AMR) is a key limiting factor for the clinical outcome of a kidney transplantation (Ktx), where early diagnosis and therapeutic intervention is needed. This study describes the identification of the biomarker CXC-motif chemokine ligand (CXCL) 9 as an indicator for AMR and presents a new aptamer-antibody-hybrid lateral flow assay (hybrid-LFA) for detection in urine. Biomarker evaluation included two independent cohorts of kidney transplant recipients (KTRs) from a protocol biopsy program and used subgroup comparisons according to BANFF-classifications. Plasma, urine and biopsy lysate samples were analyzed with a Luminex-based multiplex assay. The CXCL9-specific hybrid-LFA was developed based upon a specific rat antibody immobilized on a nitrocellulose-membrane and the coupling of a CXCL9-binding aptamer to gold nanoparticles. LFA performance was assessed according to receiver operating characteristic (ROC) analysis. Among 15 high-scored biomarkers according to a neural network analysis, significantly higher levels of CXCL9 were found in plasma and urine and biopsy lysates of KTRs with biopsy-proven AMR. The newly developed hybrid-LFA reached a sensitivity and specificity of 71% and an AUC of 0.79 for CXCL9. This point-of-care-test (POCT) improves early diagnosis-making in AMR after Ktx, especially in KTRs with undetermined status of donor-specific HLA-antibodies

Fibroblast growth factor signalling in multiple sclerosis:inhibition of myelination and induction of pro-inflammatory environment by FGF9

Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched ‘pre-myelinating’ MBP+/PLP+ oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients

Age-Dependent TLR3 Expression of the Intestinal Epithelium Contributes to Rotavirus Susceptibility

Rotavirus is a major cause of diarrhea worldwide and exhibits a pronounced small intestinal epithelial cell (IEC) tropism. Both human infants and neonatal mice are highly susceptible, whereas adult individuals remain asymptomatic and shed only low numbers of viral particles. Here we investigated age-dependent mechanisms of the intestinal epithelial innate immune response to rotavirus infection in an oral mouse infection model. Expression of the innate immune receptor for viral dsRNA, Toll-like receptor (Tlr) 3 was low in the epithelium of suckling mice but strongly increased during the postnatal period inversely correlating with rotavirus susceptibility, viral shedding and histological damage. Adult mice deficient in Tlr3 (Tlr3−/−) or the adaptor molecule Trif (TrifLps2/Lps2) exerted significantly higher viral shedding and decreased epithelial expression of proinflammatory and antiviral genes as compared to wild-type animals. In contrast, neonatal mice deficient in Tlr3 or Trif did not display impaired cell stimulation or enhanced rotavirus susceptibility. Using chimeric mice, a major contribution of the non-hematopoietic cell compartment in the Trif-mediated antiviral host response was detected in adult animals. Finally, a significant age-dependent increase of TLR3 expression was also detected in human small intestinal biopsies. Thus, upregulation of epithelial TLR3 expression during infancy might contribute to the age-dependent susceptibility to rotavirus infection