Potential energy function for a photo‐switchable lipid molecule

Photo‐switchable lipids are synthetic lipid molecules used in photo‐pharmacology to alter membrane lateral pressure and thus control opening and closing of mechanosensitive ion channels. The molecular picture of how photo‐switchable lipids interact with membranes or ion channels is poorly understood. To facilitate all‐atom simulations that could provide a molecular picture of membranes with photo‐switchable lipids, we derived force field parameters for atomistic computations of the azobenzene‐based fatty acid FAAzo‐4. We implemented a Phyton‐based algorithm to make the optimization of atomic partial charges more efficient. Overall, the parameters we derived give good description of the equilibrium structure, torsional properties, and non‐bonded interactions for the photo‐switchable lipid in its trans and cis intermediate states, and crystal lattice parameters for trans‐FAAzo‐4. These parameters can be extended to all‐atom descriptions of various photo‐switchable lipids that have an azobenzene moiety

Long wavelength optical control of glutamate receptor ion channels using a tetra-ortho-substituted azobenzene derivative

A tetra-ortho-chloro substituted azobenzene unit was incorporated into a photoswitchable tethered ligand for ionotropic glutamate receptors. This compound confers the modified protein with the unusual optical responses of the substituted azo scaffold permitting channel opening with yellow and red light and channel closing with blue light

Towards a nationwide implementation of a standardized nutrition and dietetics terminology in clinical practice: a pre-implementation focus group study including a pretest and using the consolidated framework for implementation research

BACKGROUND & AIMS In order to assure high quality of nutrition and dietetic care as well as research, the implementation of a standardized terminology, such as the World Health Organization (WHO) International Classification of Functioning, Disability and Health for Dietetics (ICF-Dietetics) is indispensable. The aim of this study was to explore the clinical practicability and applicability of the ICF-Dietetics in the field of nutrition and dietetic practice prior to the implementation in order to develop criteria (points to consider) for a targeted implementation strategy. METHODS A focus group study including a pretest of the ICF-Dietetics was conducted. Subsequently, facilitators and barriers for a nationwide implementation of the ICF-Dietetics in clinical nutrition and dietetic practice were identified and linked to interventions (combining theory-based and group-based approach) using the Consolidated Framework of Implementation Research (CFIR) to organize and represent data and summarized in a logic model. RESULTS In the pretest 55 clinical documentations which consisted of 248 different ICF-Dietetics categories were received. In four focus groups with 22 health professionals, 66 relevant higher-level themes and implementation strategy criteria (points to consider) were identified. These themes referred to all five domains of the CFIR, namely intervention characteristics, inner setting, outer setting, characteristics of individuals and implementation process and contained important barriers and facilitators that were linked to six implementation objectives as well as six context requirements and five main actors. CONCLUSIONS This study provides facilitators and barriers to be addressed when implementing the ICF-Dietetics in clinical practice and shows potential interventions based on this analysis. A nationwide implementation was mainly seen as a great advantage for enhancing quality and continuity of care and for providing comparable data. However, it requires further refinements and a multifaceted implementation strategy where the engagement of leadership of institutions plays a crucial role. These results have provided a foundation for a targeted implementation strategy to increase the success, reproducibility and comparability

Perinatal Risk Factors and Later Social, Thought, and Attention Problems after Perinatal Stroke

Objective. Survivors of perinatal stroke may be at risk for behavioral problems. Perinatal risk factors that might increase the likelihood of later behavior problems have not been identified. The goal of this study was to explore whether perinatal factors might contribute to behavior problems after perinatal stroke. Methods. 79 children with unilateral perinatal stroke were studied. Perinatal factors included gender, gestational age, neonatal seizures, instrumented delivery, fetal distress, acute birth problems, birth weight, and time of diagnosis. Subjects with evidence of hypoxic ischemic encephalopathy were excluded. Parents completed the Achenbach Child Behavior Checklist (CBCL) (Achenbach 1985). The CBCL yields T-scores in several symptom scales. We focused on Social, Thought, and Attention Problems scates. Results. Gestational age and the presence of uteroplacental insufficiency were associated with significant differences on the Thought Problems scale; Attention Problems scores approached significance for these variables. Fetal distress, neonatal seizures, or neonatal diagnosis was associated with 25–30% incidence of clinically significant T-scores on Social, Thought, and Attention Problems scales. Conclusions. Several perinatal factors were associated with a high incidence of social, thought, and behavior problems in children with perinatal stroke. These findings may be useful in anticipatory guidance to parents and physicians caring for these children

European studies: Taking stock and looking ahead

This essay is an attempt to generalize experiences of Central and Eastern European universities in the field of European Studies over the past 20 years. The paper follows the logic of business analysis in order to come up with proposals for future action

Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis

Background Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated. Methods High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes. Results TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (−10.2±1.5 versus −5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (−22.3±1.1 versus −9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L. Conclusion Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Objective Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. Design Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. Results Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63–68) and 86% (84–87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37–39) and specificity of 90% (89–91) with 19% needing biopsy. Conclusion Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies

A red-shifted photochromic sulfonylurea for the remote control of pancreatic beta cell function

Azobenzene photoresponsive elements can be installed on sulfonylureas, yielding optical control over pancreatic beta cell function and insulin release. An obstacle to such photopharmacological approaches remains the use of ultraviolet-blue illumination. Herein, we synthesize and test a novel yellow light-activated sulfonylurea based on a heterocyclic azobenzene bearing a push–pull system