N,N'-dimethylperylene-3,4,9,10-bis(dicarboximide) on alkali halide(001) surfaces

The growth of N,N'-dimethylperylene-3,4,9,10-bis(dicarboximide) (DiMe-PTCDI) on KBr(001) and NaCl(001) surfaces has been studied. Experimental results have been achieved using frequency modulation atomic force microscopy at room temperature under ultra-high vacuum conditions. On both substrates, DiMe-PTCDI forms molecular wires with a width of 10 nm, typically, and a length of up to 600 nm at low coverages. All wires grow along the [110] direction (or [1$\bar{1}$0] direction, respectively) of the alkali halide (001) substrates. There is no wetting layer of molecules: Atomic resolution of the substrates can be achieved between the wires. The wires are mobile on KBr surface but substantially more stable on NaCl. A p(2 x 2) superstructure in brickwall arrangement on the ionic crystal surfaces is proposed based on electrostatic considerations. Calculations and Monte-Carlo simulations using empirical potentials reveal possible growth mechanisms for molecules within the first layer for both substrates, also showing a significantly higher binding energy for NaCl(001). For KBr, the p(2 x 2) superstructure is confirmed by the simulations, for NaCl, a less dense, incommensurate superstructure is predicted.Comment: 5 pages, 5 figure

Enoxaparin therapy for arterial thrombosis in infants with congenital heart disease

Objective: To investigate efficacy and safety of enoxaparin for catheter-related arterial thrombosis in infants with congenital heart disease. Design: Prospective observational study. Setting: Pediatric Intensive Care and Cardiology Unit at the University Children's Hospital of Zurich. Patients: Acohort of 32 infants aged 0-12 months treated with enoxaparin for catheter-related arterial thrombosis from 2002 to 2005. Measurements: Dose requirements of enoxaparin, resolution of thrombosis by Doppler ultrasound, and bleeding complications. Results: Catheter-related arterial thrombosis was located in the iliac/femoral arteries in 31 (97%) infants and aorta in 1 infant, and was related to indwelling catheters and cardiac catheterization in 17 (53%) and 15 (47%) cases, respectively. Newborns required increased doses of enoxaparin to achieve therapeutic anti-FXa levels (mean 1.62 mg/kg per dose) compared with infants aged 2-12 months (mean 1.12 mg/kg per dose; p = 0.0002). Complete resolution of arterial thrombosis occurred in 29 (91%) infants at amean of 23 days after initiation of enoxaparin therapy. Partial or no resolution was observed in 1 (3%) and 2 (6%) infants, respectively, at amean follow-up time of 4.3 months. Bleeding complications occurred in 1 (3%) infant. Conclusion: Enoxaparin is efficient and safe for infants with congenital heart disease and catheter-related arterial thrombosis, possibly representing avalid alternative to the currently recommended unfractionated hepari

Instructing human macrophage polarization by stiffness and glycosaminoglycan functionalization in 3D collagen networks

Dynamic alterations of composition and mechanics of the extracellular matrix (ECM) are suggested to modulate cellular behavior including plasticity of macrophages (MPhs) during wound healing. In this study, engineered 3D fibrillar matrices based on naturally occurring biopolymers (collagen I, glycosaminoglycans (GAGs)) were used to mimic matrix stiffening as well as modification by sulfated and non-sulfated GAGs at different stages of wound healing. Human MPhs were found to sensitively respond to these microenvironmental cues in terms of polarization towards pro-inflammatory or wound healing phenotypes over 6 days in vitro. MPhs exhibited a wound healing phenotype in stiffer matrices as determined by protein and gene expression of relevant cytokines (IL10, IL12, TNF). Presence of sulfated and non-sulfated GAGs inhibited this polarization effect. Furthermore, control experiments on 2D matrices stressed the relevance of using stiffness-controlled 3D matrices, as MPhs showed a reciprocal polarization behavior depending on GAG presence. Hence, the results indicate a strong influence of dimensionality, stiffness, and GAG presence of the biomaterial scaffold on MPh polarization and emphasize the need for matrices closely mimicking the 3D in vivo context with a variable stiffness and GAG composition in in vitro studies

The ABC transporter MsbA adopts the wide inward-open conformation in E. coli cells

Membrane proteins are currently investigated after detergent extraction from native cellular membranes and reconstitution into artificial liposomes or nanodiscs, thereby removing them from their physiological environment. However, to truly understand the biophysical properties of membrane proteins in a physiological environment, they must be investigated within living cells. Here, we used a spin-labeled nanobody to interrogate the conformational cycle of the ABC transporter MsbA by double electron-electron resonance. Unexpectedly, the wide inward-open conformation of MsbA, commonly considered a nonphysiological state, was found to be prominently populated in Escherichia coli cells. Molecular dynamics simulations revealed that extensive lateral portal opening is essential to provide access of its large natural substrate core lipid A to the binding cavity. Our work paves the way to investigate the conformational landscape of membrane proteins in cells

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: Protocol for the DRAIN randomised clinical trial

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH. Methods: DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded

Impact of national holidays and weekends on incidence of acute type A aortic dissection repair

Publisher Copyright: © 2022, The Author(s).Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54–0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68–0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.Peer reviewe

Inbred mouse strains reveal biomarkers that are pro-longevity, antilongevity or role switching.

Traditionally, biomarkers of aging are classified as either pro-longevity or antilongevity. Using longitudinal data sets from the large-scale inbred mouse strain study at the Jackson Laboratory Nathan Shock Center, we describe a protocol to identify two kinds of biomarkers: those with prognostic implication for lifespan and those with longitudinal evidence. Our protocol also identifies biomarkers for which, at first sight, there is conflicting evidence. Conflict resolution is possible by postulating a role switch. In these cases, high biomarker values are, for example, antilongevity in early life and pro-longevity in later life. Role-switching biomarkers correspond to features that must, for example, be minimized early, but maximized later, for optimal longevity. The clear-cut pro-longevity biomarkers we found reflect anti-inflammatory, anti-immunosenescent or anti-anaemic mechanisms, whereas clear-cut antilongevity biomarkers reflect inflammatory mechanisms. Many highly significant blood biomarkers relate to immune system features, indicating a shift from adaptive to innate processes, whereas most role-switching biomarkers relate to blood serum features and whole-body phenotypes. Our biomarker classification approach is applicable to any combination of longitudinal studies with life expectancy data, and it provides insights beyond a simplified scheme of biomarkers for long or short lifespan

Data accuracy, consistency and completeness of the national Swiss cystic fibrosis patient registry: Lessons from an ECFSPR data quality project.

BACKGROUND Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research. METHODS All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with 5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research