Optimization of Mechanosensitive Cross-Talk between Matrix Stiffness and Protein Density: Independent Matrix Properties Regulate Spreading Dynamics of Myocytes.

Cells actively sense differences in topology, matrix elasticity and protein composition of the extracellular microenvironment and adapt their function and morphology. In this study, we focus on the cross-talk between matrix stiffness and protein coating density that regulates morphology and proliferation dynamics of single myocytes. For this, C2C12 myocytes were monitored on L-DOPA functionalized hydrogels of 22 different elasticity and fibronectin density compositions. Static images were recorded and statistically analyzed to determine morphological differences and to identify the optimized extracellular matrix (ECM). Using that information, selected ECMs were used to study the dynamics before and after cell proliferation by statistical comparison of distinct cell states. We observed a fibronectin-density-independent increase of the projected cell area until 12 kPa. Additionally, changes in fibronectin density led to an area that was optimum at about 2.6 µg/cm2, which was confirmed by independent F-actin analysis, revealing a maximum actin-filament-to-cell-area ratio of 7.5%. Proliferation evaluation showed an opposite correlation between cell spreading duration and speed to matrix elasticity and protein density, which did not affect cell-cycle duration. In summary, we identified an optimized ECM composition and found that independent matrix properties regulate distinct cell characteristics.

Optical Ultrastructure of Large Mammalian Hearts Recovers Discordant Alternans by In Silico Data Assimilation.

Understanding and predicting the mechanisms promoting the onset and sustainability of cardiac arrhythmias represent a primary concern in the scientific and medical communities still today. Despite the long-lasting effort in clinical and physico-mathematical research, a critical aspect to be fully characterized and unveiled is represented by spatiotemporal alternans patterns of cardiac excitation. The identification of discordant alternans and higher-order alternating rhythms by advanced data analyses as well as their prediction by reliable mathematical models represents a major avenue of research for a broad and multidisciplinary scientific community. Current limitations concern two primary aspects: 1) robust and general-purpose feature extraction techniques and 2) in silico data assimilation within reliable and predictive mathematical models. Here, we address both aspects. At first, we extend our previous works on Fourier transformation imaging (FFI), applying the technique to whole-ventricle fluorescence optical mapping. Overall, we identify complex spatial patterns of voltage alternans and characterize higher-order rhythms by a frequency-series analysis. Then, we integrate the optical ultrastructure obtained by FFI analysis within a fine-tuned electrophysiological mathematical model of the cardiac action potential. We build up a novel data assimilation procedure demonstrating its reliability in reproducing complex alternans patterns in two-dimensional computational domains. Finally, we prove that the FFI approach applied to both experimental and simulated signals recovers the same information, thus closing the loop between the experiment, data analysis, and numerical simulations.

Meat Reduction in 5 to 8 Years Old Children-A Survey to Investigate the Role of Parental Meat Attachment.

It is by now well established that a plant-based and meatless or reduced-meat diet is an important contribution to a sustainability and healthy diet. This work discusses important determinants for parents of implementing a meat reduced diet for their children. A questionnaire was conducted with 90 parents of children aged 5-8 years living in Germany, where they had to choose one out of three options of a dish, namely meaty, reduced meat and no meat, for their child. The results show that the parent's attachment to meat and the associated attitudes and habits play a crucial role in their meal choice and therefore eating behaviour, including consumed amounts of meat, of their child. Moreover, perceived tastiness, healthiness and balanced serving style, as well as the child's preferences influences the parent's decision. The findings of this work provide valuable insights to the food industry and food producers, health professionals and public health, as it highlights the background, as well as some drivers and barriers for parents choosing a dish with less meat for their children.

Therapeutic Treatment for Abdominal Obesity in Adults.

BACKGROUND: Abdominal obesity, an accumulation of fat in the abdominal region, is a risk factor for several non-communicable diseases. This review aims to identify non-surgical treatment options for abdominal obesity in adults. Interventions with behavioral, dietary, physical activity, or pharmaceutical components were compared to control conditions. METHODS: A systematic literature research for randomized controlled trials was conducted in Medline, Embase, and the Cochrane Central Register of Controlled Trials according to a prespecified and registered protocol (PROSPERO CRD42017057898). RESULTS: Out of 2954 articles, 15 studies with 2918 participants remained after applying inclusion and exclusion criteria. Altogether the programs achieved a -2.65cm (95% confidence interval (CI) [-3.77, -1.53]) reduction in waist circumference (WC), as a measure of abdominal obesity. Eight behavioral interventions reduced WC by -1.88cm (95% CI [-2.55, -1.22]), and six combined interventions with behavioral plus dietary and/or physical activity components by -4.11cm (95% CI [-6.17, -2.05]). The only pharmaceutical trial did not find any effect on WC. CONCLUSION: Overall, the identified interventions showed a moderate effect on WC. One reason may be that in most studies WC was a secondary outcome parameter, while only a small number of interventions primarily targeted abdominal obesity. Further research regarding the treatment of abdominal obesity is urgently needed.

Pharmacokinetics of afatinib, a selective irreversible ErbB family blocker, in patients with advanced solid tumours.

BACKGROUND AND OBJECTIVE: Afatinib is a potent, irreversible, ErbB family blocker in clinical development for the treatment of a variety of solid tumours. This study evaluated the pharmacokinetics of afatinib (10-100 mg once daily) in cancer patients. METHODS: Data from 221 patients with advanced solid tumours in four phase I and one phase II trial were analysed using non-compartmental methods. RESULTS: Within each dose group, the shape of the geometric mean plasma concentration-time profiles after single and multiple doses were comparable. Maximum plasma concentration (C(max)) values were achieved 2-5 h after dosing and thereafter declined at least bi-exponentially. Steady-state plasma concentrations were attained within 8 days after the start of dosing. The geometric mean terminal elimination half-life at steady state was about 37 h. Repeated dosing resulted in a 2.77-fold accumulation based on the area under the plasma concentration-time curve (AUC), and 2.11-fold accumulation based on C(max) values. A slightly more than dose-proportional increase in afatinib exposure was observed. There was moderate intra-individual variability in afatinib trough concentration values (the geometric coefficient of variation (gCV) ranged from 22.2 to 67.5 %). The inter-patient variability in plasma concentrations was moderate to high (e.g. at the 40 mg dose, the gCVs ranged from 35.6 to 221 %). The exposure to afatinib (as measured by AUC and C(max)) correlated with the severity of the most common adverse events of afatinib--diarrhoea and rash. CONCLUSION: The pharmacokinetic profile of afatinib supports a once-daily dosage regimen. As expected for this patient population, the pharmacokinetic parameters of afatinib showed moderate to high inter-patient variability. Afatinib exhibits non-linear pharmacokinetics.