Highlight report: Launch of a large integrated European in vitro toxicology project: EU-ToxRisk.

The integrated European project, EU-ToxRisk, proudly sees itself as "flagship" exploring new alternative-to-animal approaches to chemical safety evaluation. It promotes mechanism-based toxicity testing and risk assessment according to the principles laid down for toxicology for the twenty-first century. The project was officially launched in January 2016 with a kickoff meeting in Egmond aan Zee, the Netherlands. Over 100 scientists representing academia and industry as well as regulatory authorities attended the inaugural meeting. The project will integrate advances in in vitro and in silico toxicology, read-across methods, and adverse outcome pathways. EU-ToxRisk will continue to make use of the case study strategy deployed in SEURAT-1, a FP7 initiative ended in December 2015. Even though the development of new non-animal methods is one target of EU-ToxRisk, the project puts special emphasis on their acceptance and implementation in regulatory contexts. This €30 million Horizon 2020 project involves 38 European partners and one from the USA. EU-ToxRisk aims at the "development of a new way of risk assessment."Toxicolog

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs--liver, lung, skin, brain--are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing

Researchers’ attitudes to the 3Rs - An upturned hierarchy?

Animal use in biomedical research is generally justified by its potential benefits to the health of humans, or other animals, or the environment. However, ethical acceptability also requires scientists to limit harm to animals in their research. Training in laboratory animal science (LAS) helps scientists to do this by promoting best practice and the 3Rs. This study evaluated scientists’ awareness and application of the 3Rs, and their approach to other ethical issues in animal research. It was based on an online survey of participants in LAS courses held in eight venues in four European countries: Portugal (Porto, Braga), Germany (Munich, Heidelberg), Switzerland (Basel, Lausanne, Zurich), and Denmark (Copenhagen). The survey questions were designed to assess general attitudes to animal use in biomedical research, Replacement alternatives, Reduction and Refinement conflicts, and harm-benefit analysis. The survey was conducted twice: immediately before the course (‘BC’, N = 310) and as a follow-up six months after the course (‘AC’, N = 127). While courses do appear to raise awareness of the 3Rs, they had no measurable effect on the existing low level of belief that animal experimentation can be fully replaced by non-animal methods. Most researchers acknowledged ethical issues with their work and reported that they discussed these with their peers. The level of an animal’s welfare, and especially the prevention of pain, was regarded as the most pressing ethical issue, and as more important than the number of animals used or the use of animals as such. Refinement was considered more feasible than Replacement, as well as more urgent, and was also favoured over Reduction. Respondents in the survey reversed the ‘hierarchy’ of the 3Rs proposed by their architects, Russell and Burch, prioritizing Refinement over Reduction, and Reduction over Replacement. This ordering may conflict with the expectations of the public and regulators.</div

Investigating of Integrated Weed Management in Broomcorn (Sorghum bicolor) Farms in Miyaneh Region

The experiment was carried out as randomized complete block design in factorial with three replications to evaluate of the possibility of integrated weed management in Broomcorn (Sorghum bicolor) yield. Treatments were included herbicides (Foramsulfuron, Bromoxynil+MCPA and 2,4-D+ MCPA), application dose (recommendation dose, 25% less and more than recommended doses for corn farms) and mechanical control (with or without cultivation). The result indicated all factors including herbicides, application doses and cultivation were significantly influenced weeds density and dry weight. The best herbicide in weeds density and dry weight  decreasing percentage was Foramsulfuron treatment. Cultivation treatment was significantly influenced weeds control. The best doses were 25% more recommended dose and recommended dose on weeds density and dry weight  decreasing percentage

The new evidence of Albian – Cenomanian boundary biostratigraphy for first time from Iran

The Sarvak Formation in Tang – e – Chenarbashi with 712 meters thickness encompasses Albian - Cenomanian planktonic foraminifera. In the studied section, surveying the Albian – Cenomanian boundary is indicated that Rotalipora appeninica Zone not be recognized. Paracostellagerina libyca can be to consider as a marker for Albian – Cenomanian boundary, absence of the Albian marker foraminifera permit us to consider the first occurrence of this species as the begining of Cenomanian. Also Favosella voloshinae, Paracostellagerina libyca are report for first time from Iran

Effect of planting patterns of sunflower on yield and extinction coefficient

We studied the effect of different planting patterns and density of sunflower on yield and on extinction coefficient. The experiment was conducted in the field at the Seed and Plant Improvement Institute, Karaj, Iran on a loamy clay. Planting patterns included wide rows, conventional rows, twin rectangular rows and twin zigzag rows. Populations of plants were at 3 levels including 6, 8 and 10 plants per square meter. The results show that different planting patterns sometimes produced higher yield, but not always. Furthermore, equidistant plant distribution at equal plant densities produced a higher radiation interception and extinction coefficient. Moreover, when row spacing was reduced, grain yield increased. The greatest increase in radiation interception and in the extinction coefficient in response to planting patterns and plant densities was observed in twin zigzag rows of 8 plants m–2. Twin zigzag rows of 8 plants m–2 and conventional rows of 8 plants m–2 produced the highest yield

Considering new methodologies in strategies for safety assessment of foods and food ingredients

Toxicology and safety assessment are changing and require new strategies for evaluating risk that are less depending on apical toxicity endpoints in animal models and relying more on knowledge of the mechanism of toxicity. This manuscript describes a number of developments that could contribute to this change and implement this in a stepwise roadmap that can be applied for the evaluation of food and food ingredients. The roadmap was evaluated in four case studies by using literature and existing data. This preliminary evaluation was shown to be useful. However, this experience should be extended by including examples where experimental work needs to be included. To further implement these new insights in toxicology and safety assessment for the area of food and food ingredients, the recommendation is that stakeholders take action in addressing gaps in our knowledge, e.g. with regard to the applicability of the roadmap for mixtures and food matrices. Further development of the threshold of toxicological concern is needed, as well as cooperation with other sectors where similar schemes are under development. Moreover, a more comprehensive evaluation of the roadmap, also including the identification of the need for in vitro experimental work is recommended.publishe

Effect of Acupuncture on Pain and Quality of Life in Patients with Lumbar Spinal Stenosis: A Case Series Study

Lumbar spinal stenosis (LSS) is a major cause of debilitation in adults, and acupuncture is a recommended treatment. We assessed the effect of acupuncture on pain and quality of life in patients with LSS. Twenty-four patients with LSS who had symptoms of neurogenic claudication were randomly selected and underwent 10 sessions of acupuncture. Pain and quality of life were evaluated before and immediately after the intervention and 6 weeks later using a visual analogue scale and Short Form-36 Health Survey. Paired t tests and repeated measure tests were used to analyze the data. The mean age of the patients was 48.2 ± 10.8 years. The mean visual analogue scale scores before and immediately after intervention (7.9 ± 1.3 and 4.3 ± 2.1) were statistically different (p < 0.001), as was the mean score (3.08 ± 2.3) 6 weeks later (p = 0.01). Five aspects of the Short Form-36 Health Survey score were associated with significant improvements immediately after acupuncture (p < 0.05). Comparisons of the scores before and 6 weeks after intervention showed significant improvements in emotions, vitality, general health, bodily pain, and physical well-being. Therefore, acupuncture had a significant short-term effect on pain and quality of life in patients with LSS

Effects of Integrated Weed Management on Forage Corn (Zea mays) in Miyaneh Region, Iran

As factorial experiment based on randomized complete block design with four replications was carried out to evaluate the effects of weed management on yield and components yield of corn silage in Miyaneh region in the summer of 2009. Treatments were cultivation (with and without), herbicides (Foramsulfuron, Nicosulfuron and 2,4-D+MCPA) and without controlling weed as control treatment. The results indicated that application of herbicides significantly influenced weeds dry weight at 1% probability level. The highest and lowest percentage loss of weeds dry weight were related to Foramsulfuron and 2,4-D+MCPA, respectively, which were significantly different from other herbicides (Nicosulfuron). Cultivation was significantly effective on weeds dry weight as compared with non cultivation treatment. The results, also, indicated that cultivation and herbicides significantly affected increasing the biological and grain yields compared to non weeds control treatment. The highest biological and grain yield increase were obtained by 59.1% and 57.2% due to cultivation treatment and by 51.8% and 58.2% due to Foramsulfuron herbicide application, respectively. The lowest biological and grain yield was obtained by application of Nicosulfuron herbicide which was statistically comparable to that of 2,4-D+MCPA herbicide treatment

Effects of Planting Pattern and Density on Yield of Soybean Genotypes under North Khuzestan Conditions

In order to study the effects of planting pattern and plant density on yield of soybean genotypes, an experiment was carried out in Safiabad Agricultural Research Center, Dezful, Iran in 2011. The experimental design was a factorial strip plot based on completely randomized block design with 3 replications. Planting pattern consisted of 3 levels (60 cm with 1 planted row, 75 cm and 90 cm with 2 planted rows) as vertical factor, a factorial of plant density (30, 40 and 50 plant/m2) and genotypes (504, L14 and DPX) was considered as horizontal factors. The means of planting pattern × density showed that the highest number of pods/plant (52.85) belonged to 60 cm with single row of plants and 40 plant m-2. The lowest (28.35) number of pods/plant was observed in 90 cm with double rows planted and 50 plant m-2. The genotypes responded to planting density differently. The highest (4936.11 kg/ha) grain yield belonged to DPX genotype with 50 plants m-2. The lowest (4936.11 kg/ha) grain yield was achieved at L14 genotype with 30 plant m-2. The results of this expriment suggested that planting pattern of 60 cm with single row of plants, 50 plant m-2, DPX and 504 genotypes were probably suitable for this area