The Relevance of In Silico, In Vitro and Non-human Primate Based Approaches to Clinical Research on Major Depressive Disorder.

Major depressive disorder (MDD) is the most severe form of depression and the leading cause of disability worldwide. When considering research approaches aimed at understanding MDD, it is important that their effectiveness is evaluated. Here, we assessed the effectiveness of original studies on MDD by rating their contributions to subsequent medical papers on the subject, and we compared the respective contribution of findings from non-human primate (NHP) studies and from human-based in vitro or in silico research approaches. For each publication, we conducted a quantitative citation analysis and a systematic qualitative analysis of the citations. In the majority of cases, human-based research approaches (both in silico and in vitro) received more citations in subsequent human research papers than did NHP studies. In addition, the human-based approaches were considered to be more relevant to the hypotheses and/or to the methods featured in the citing papers. The results of this study suggest that studies based on in silico and in vitro approaches are taken into account by medical researchers more often than are NHP-based approaches. In addition, these human-based approaches are usually cheaper and less ethically contentious than NHP studies. Therefore, we suggest that the traditional animal-based approach for testing medical hypotheses should be revised, and more opportunities created for further developing human-relevant innovative techniques.

A worldwide survey on the use of animal-derived materials and reagents in scientific experimentation.

The use of cell and tissue-based methods in basic, applied and regulatory science has been increasing exponentially. Animal-derived components, including serum, coating materials, growth factors and antibodies are routinely used in cell/tissue cultures and in general laboratory practices. In addition to ethical issues, the use and production of animal-derived materials and reagents raises many scientific concerns, generally associated with presence of undefined components and batch-to-batch variability, which may compromise experimental reproducibility. On the other hand, non-animal materials and reagents, such as human cells, alternatives to animal sera or non-animal recombinant antibodies, are becoming increasingly available, and their use is encouraged by the EU Directive 2010/63 and the Guidance Document on Good In vitro Method Practices (GIVIMP), published by the Organization for Economic Cooperation and Development (OECD). In an effort to map the current state of use of animal-derived reagents across different sectors and to identify the obstacles possibly hampering the implementation of non-animal derived alternatives, a global online survey addressed to scientists working on in vivo, in vitro, in silico methods, in academia as well as pharmaceutical or cosmetic companies, was conducted with the goal to understand: 1) the most commonly used animal-derived materials and reagents, 2) the main issues associated with the production and use of animal-derived materials and reagents, 3) the current level of knowledge on available non-animal alternative materials and reagents, and 4) what educational and information sources could be most useful or impactful to disseminate knowledge on non-animal alternatives. This paper provides an overview of the survey replies and discusses possible proposals to increase awareness, acceptance and use of non-animal ingredients.

A model for educational simulation of the effect of oxytocin on uterine contractions.

Fetal oxygenation is sometimes compromised due to hyperstimulation of uterine contractions (UC) following labor augmentation with oxytocin. We present a model for educational simulation that incorporates the pharmacokinetic-pharmacodynamic properties of oxytocin, reproducing the effect of this drug on UC features. Six UC tracings were generated, reflecting different relevant situations. Three independent experts identified correctly the simulated situations in all tracings and attributed an average realism score of 9.4 (0-10). The model presented for simulation of the effect of oxytocin on UC provides sufficiently realistic results to be used in healthcare education and can easily be adapted to different patients and educational scenarios.

A model for educational simulation of the evolution of uterine contractions during labor.

Electronic fetal monitoring remains an important tool in labor ward settings, providing continuous information on fetal heart rate and maternal uterine contractions. A prompt detection of abnormalities in these signals is essential for the timely resolution of situations that may put both mother and fetus at risk. Uterine contraction signals provide information that is important to evaluate the onset and progress of labor, as well as the significance of certain fetal heart rate abnormalities. We present a model for educational simulation of the spontaneous evolution of uterine contractions during labor, which combines a previously published signal generator with literature-based pre-programmed scripts for educationally relevant scenarios. This model is an essential component of a high-fidelity simulator of intrapartum emergencies, aimed to improve the competency of healthcare providers. Real and simulated tracings were presented to three independent clinical experts who judged simulated signals to be indistinguishable or negligibly different from real tracings.