Explore the vast range of titles available.

The present drug-drug interaction study investigates whether single or repeated doses of 240 mg Ginkgo biloba extract EGb 761 ® alter the pharmacokinetics or pharmacodynamics of rivaroxaban in healthy subjects. This was a single-centre, two-period, fixed-sequence trial. In Period 1, rivaroxaban was taken alone. In Period 2, rivaroxaban was given on the first and last of 8 days of EGb 761 ® treatment. Plasma concentrations of rivaroxaban and anti-Factor Xa activity were determined until 48 h after each rivaroxaban intake. The data of forty-one healthy subjects (25 males, 16 females) aged 21–70 years were evaluable. Geometric mean ratios (90% confidence intervals) for rivaroxaban administered concomitantly with a single or multiple doses of EGb 761 ® vs. rivaroxaban administered alone were 97.97 (91.78, 104.58) and 96.78 (90.67, 103.31) for maximum concentration (C max ), 98.55 (94.43, 102.84) and 97.82 (93.73, 102.08) for area under the concentration-time curve (AUC 0-∞ ) of rivaroxaban in plasma (primary endpoints), 98.19 (92.00, 104.80) and 99.78 (93.43, 106.55) for maximum effect (E max ), 99.46 (93.63, 105.66) and 99.12 (93.25, 105.35) for area under the effect curve (AUEC 0-48 ). All 90% confidence intervals were within the prespecified range of 80%–125%. Neither adverse events related to haemorrhages nor clinically significant findings in haematology or coagulation parameters were observed. The treatments were safe and well-tolerated. Single and repeated doses of EGb 761® neither affect plasma concentrations of rivaroxaban nor anti-Factor Xa activity in healthy subjects.

The aim of this in vitro study was to quantify the antibacterial effect of a copper-deposited titanium surface as a model for dental implants on the peri-implantitis-associated strain Porphyromonas gingivalis (DSM 20709). A spark-assisted anodization method in a combined deposition-anodization process was applied to deposit copper on discs made of titanium. This method allows the deposition of different concentrations of copper on the surface by varying the process time. Conventional culturing was used to investigate the adhesion of P. gingivalis onto the discs over 2, 4, and 6 h as well as to study the antibacterial effect of copper released in solution. The viability of the bacterial cells is strongly inhibited on copper-deposited discs and reaches a CFU reduction of 3 log-units after 6 h in comparison to the reference. The copper released in solution causes a reduction of 4 log-units after a 6 h incubation time. With a 6 h incubation time, the CFU count decreases with increasing copper concentrations on the disc (by 2% for the 1.3 µg/disc; 32% for the 5.6 µg/disc; and 34% for the 9.5 µg/disc). However, at a higher copper concentration of 17.7 µg/disc, after 6 h, the decrease in the CFU count is less pronounced than that observed in solution, where a further decrease is observed. In conclusion, copper-functionalized titanium significantly reduces the survival of adhered bacteria and decreases the viable bacterial count in the environment surrounding the titanium. Thus, the area surrounding implants is being protected by copper released from the surface, forming a “safe zone” for improved implant healing.

Objective Fever is a very common adaptive immune response in acute respiratory tract disorders during infancy. Antipyretic / analgesic drugs such as paracetamol (acetaminophen) are widely used to improve the comfort of the child but may cause medically unneeded antipyresis and rare but potentially serious side effects. We assess whether treatment with Pelargonium sidoides extract EPs 7630 reduces the administration of paracetamol in children with acute tonsillopharyngitis (ATP) or acute bronchitis (AB). Design Meta-analysis of randomised, placebo-controlled clinical trials. Methods We searched clinical trial registries (ISRCTN, ClinicalTrials.gov ) and medical literature (MEDLINE, EMBASE), for randomised, placebo-controlled trials investigating the administration of EPs 7630 to children with ATP or AB and reporting the co-administration of paracetamol. Based on the individual participant data of the eligible trials, study populations were characterized according to sex and age, and meta-analyses were performed for cumulative paracetamol use and ability to attend school at treatment end. Results Six trials including a total of 523 children aged 6–10 years (EPs 7630: 265; placebo: 258) and suffering from non-β-hemolytic streptococcal ATP (3 trials) or from AB (3 trials) were identified and eligible. Children received EPs 7630 or placebo for 6 (ATP) or 7 days (AB). Compared to placebo, EPs 7630 reduced the cumulative dose of paracetamol in 5 out of the 6 trials, by an average of 244 mg (Hedges’ g; − 0.28; 95% confidence interval: [− 0.53; − 0.02]; p  < 0.03). At treatment end, 30.2% (EPs 7630) and 74.4% (placebo) of the children were still unable to attend school (risk ratio: 0.43; 95% confidence interval: [0.29; 0.65]; p  < 0.001). Conclusions In children aged 6–10 years with AB or ATP, EPs 7630 alleviated the symptom burden and accelerated recovery. Although EPs 7630 has no known antipyretic effect, concomitant use of paracetamol was reduced.

Steering the EU food system towards a sustainability transformation requires a vast and actionable knowledge base available to a range of public and private actors. Few have captured this complexity by assessing food systems from a multi-dimensional and multi-level perspective, which would include (1) nutrition and diet, environmental and economic outcomes together with social equity dimensions and (2) system interactions across country, EU and global scales. This paper addresses this gap in food systems research and science communication by providing an integrated analytical approach and new ways to communicate this complexity outside science. Based on a transdisciplinary science approach with continuous stakeholder input, the EU Horizon2020 project ‘Metrics, Models and Foresight for European SUStainable Food And Nutrition Security’ (SUSFANS) developed a five-step process: Creating a participatory space; designing a conceptual framework of the EU food system; developing food system performance metrics; designing a modelling toolbox and developing a visualization tool. The Sustainable Food and Nutrition-Visualizer, designed to communicate complex policy change-impacts and trade-off questions, enables an informed debate about trade-offs associated with options for change among food system actors as well as in the policy making arena. The discussion highlights points for further research related to indicator development, reach of assessment models, participatory processes and obstacles in science communication.

While crop models are widely used to assess the change in crop productivity with climate change, their skill in assessing irrigation water demand or the risk of crop failure in large area impact assessments is relatively unknown. The objective of this study is to investigate which aspects of modeling crop water use (reference crop evapotranspiration (ET0), soil water extraction, soil evaporation, soil water balance and root growth) contributes most to the variability in estimates of maize crop water use and the risk of crop failure, and demonstrate the resulting uncertainty in a climate change impact study for Europe. The SIMPLACE crop modeling framework was used to couple the LINTUL5 crop model in factorial combinations of 2-3 different approaches for simulating the 5 aspects of crop water use, resulting in 51 modeling approaches. Using experiments in France and New Zeland, analysis of total sensitivity revealed that ET0 explained the most variability in both irrigated maize water use and rainfed grain yield levels, with soil evaporation also imporatant in the French experiment. In the European impact study, net irrigation requirement differed by 36% between the Penman and Hargreaves ET0 methods in the baseline period. Average EU grain yields were similar between models, but differences approached 1-2 tonnes in parts of France and Southern Europe. EU wide esimates of crop failure in the historical period ranged between 5.4 years for Priestley-Taylor to every 7.9 years for the Penman ET0 methods. While the uncertainty in absolute values between models was significant, estimates of relative changes were similar between models, confirming the utility of crop models in assessing climate change impacts. If ET0 estimates in crop models can be improved, through the use of appropriate methods, uncertainty in irrigation water demand as well as in yield estimates under drought can be reduced.

The recent shift in transport policy towards travel demand management has directed the attention of transport research towards the dynamic processes in travel behaviour; learning and change on the one hand and rhythms and routines on the other. Progress in the understanding of these processes requires from observation or self-reports data over long duration. The survey reported here provides for the first time in 30 years a data source which allows these issues to be addressed. The project Mobidrive, funded by the German Ministry of Research and Education, conducted a six-week continuous travel diary with the aim of analysing the rhythms in the behaviour of the respondents. The paper describes the implementation of this travel diary survey, which was conducted in Karlsruhe and Halle, two German cities of about 270,000 inhabitants each, in the autumn of 1999. A total of 317 persons over 6 years of age in 139 households participated in the main study. The description covers the development of the forms, the design of the survey protocol, the screening experiences (including participation rates) and an assessment of the data quality in terms of item/unit non-response and reporting fatigue. The paper closes with an outlook for the analyses possible with the data set. [PUBLICATION ABSTRACT]

Liver macrophages (LMs) play a central role in acute and chronic liver pathologies. Investigation of these processes in humans as well as the development of diagnostic tools and new therapeutic strategies require in vitro models that closely resemble the in vivo situation. In our study, we sought to gain further insight into the role of LMs in different liver pathologies and into their characteristics after isolation from liver tissue. For this purpose, LMs were characterized in human liver tissue sections using immunohistochemistry and bioinformatic image analysis. Isolated cells were characterized in suspension using FACS analyses and in culture using immunofluorescence staining and laser scanning microscopy as well as functional assays. The majority of our investigated liver tissues were characterized by anti-inflammatory LMs which showed a homogeneous distribution and increased cell numbers in correlation with chronic liver injuries. In contrast, pro-inflammatory LMs appeared as temporary and locally restricted reactions. Detailed characterization of isolated macrophages revealed a complex disease dependent pattern of LMs consisting of pro- and anti-inflammatory macrophages of different origins, regulatory macrophages and monocytes. Our study showed that in most cases the macrophage pattern can be transferred in adherent cultures. The observed exceptions were restricted to LMs with pro-inflammatory characteristics.

This paper applies the Environmental Kuznets Curve (EKC) model to examine the impact of trade openness, foreign direct investment liberalization, the decreasing role of the state, energy consumption and urbanization on per capita emission in countries at various stages of economic development and as a group. For this purpose, a dynamic panel estimation applying the Arellano-Bond's Generalized Method of Moments (GMM) was conducted using the average of five-year observations from 1980-2009. The findings suggest that while trade and Foreign Direct Investment (FDI) are not expected to affect environmental quality, increasing role of the state has a negative and significant impact only in developed countries. Further, the results suggest that energy consumption has a significant impact on all countries regardless of their stage of development, while urbanization affects environmental quality only in the least developed countries.

The global food and agricultural trade network is crucial for food security. Shocks such as those posed by extreme weather events, conflicts, pandemics, and economic crises can test the resilience of the trade network to the sudden interruption of trade flows. Depending on the level of connectivity in the trade network and its structure, such shocks have the potential to propagate through the entire network and can affect countries’ food availability and variety. This paper contributes to the literature on food and agricultural trade networks in two main ways: (1) understanding the global trade network as a complex system that can be affected by and responds to shocks, we define and operationalize its resilience as a multidimensional concept, which is shaped by the interdependencies in the network and their structure; and (2) applying techniques from network analysis to examine the evolution of three dimensions of resilience within the global food and agricultural trade network between 1995 and 2019. The main findings show that, between 1995 and 2007, trade connectivity among countries increased. Overall, this bolstered countries’ and the network's resilience to trade shocks. However, vulnerabilities persisted in terms of ensuring sufficient product variety and quantity. Adding to these vulnerabilities, trade integration stalled in the second half of the series, pointing to a slight tendency towards trade disintegration and potentially lower resilience of countries to trade shocks already in 2019.

The development of in vitro hepatocyte cell culture systems is crucial for investigating drug-induced liver injury (DILI). One prerequisite for monitoring DILI related immunologic reactions is the extension of primary human hepatocyte (PHH) cultures towards the inclusion of macrophages. Therefore, we developed and characterized an autologous co-culture system of PHH and primary human hepatic macrophages (hepM) (CoC1). We compared CoC1 with a co-culture of the same PHH batch + M0 macrophages derived from THP1 cells (CoC2) in order to represent a donor independent macrophage reaction. Then, we treated the mono- and co-cultures with drugs that cause DILI—menadione (MEN, 1 or 10 µM, 3 h), diclofenac (DIC, 0.5 or 5 mM, 6 h), or acetaminophen (APAP, 0.5 or 5 mM, 6 h)—and assessed culture stability, cell activity, macrophage differentiation, cytokine production and cell viability. Without drug treatment, CoC1 was the most stable over a culture time of up to 60 h. Cytokine array analysis revealed a proinflammatory profile of PHH mono-cultures due to isolation stress but showed different influences of hepM and M0 on the cytokine profile in the co-cultures. MEN, DIC and APAP treatment led to donor-dependent signs of cell stress and toxicity. HepM can either promote or reduce the DILI effects donor dependently in CoC1. CoC2 are slightly less sensitive than CoC1 in representing DILI. In summary, we present a new autologous co-culture system that can mimic DILI in a donor-dependent manner. This cellular system could be useful for new drug testing strategies and reducing animal testing.