Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic "Skin-On-A-Chip" Microfluidic Device.

The efficacy of transdermal absorption of drugs and the irritation or corrosion potential of topically applied formulations are important areas of investigation in pharmaceutical, military and cosmetic research. The aim of the present experiments is to test the role of P-glycoprotein in dermal drug delivery in various ex vivo and in vitro platforms, including a novel microchip technology developed by Pázmány Péter Catholic University. A further question is whether the freezing of excised skin and age have any influence on P-glycoprotein-mediated dermal drug absorption. Two P-glycoprotein substrate model drugs (quinidine and erythromycin) were investigated via topical administration in diffusion cells, a skin-on-a-chip device and transdermal microdialysis in rat skin. The transdermal absorption of both model drugs was reduced by P-glycoprotein inhibition, and both aging and freezing increased the permeability of the tissues. Based on our findings, it is concluded that the process of freezing leads to reduced function of efflux transporters, and increases the porosity of skin. P-glycoprotein has an absorptive orientation in the skin, and topical inhibitors can modify its action. The defensive role of the skin seems to be diminished in aged individuals, partly due to reduced thickness of the dermis. The novel microfluidic microchip seems to be an appropriate tool to investigate dermal drug delivery.

Skin-on-a-Chip Device for Ex Vivo Monitoring of Transdermal Delivery of Drugs-Design, Fabrication, and Testing.

To develop proper drug formulations and to optimize the delivery of their active ingredients through the dermal barrier, the Franz diffusion cell system is the most widely used in vitro/ex vivo technique. However, different providers and manufacturers make various types of this equipment (horizontal, vertical, static, flow-through, smaller and larger chambers, etc.) with high variability and not fully comparable and consistent data. Furthermore, a high amount of test drug formulations and large size of diffusion skin surface and membranes are important requirements for the application of these methods. The aim of our study was to develop a novel Microfluidic Diffusion Chamber device and compare it with the traditional techniques. Here the design, fabrication, and a pilot testing of a microfluidic skin-on-a chip device are described. Based on this chip, further developments can also be implemented for industrial purposes to assist the characterization and optimization of drug formulations, dermal pharmacokinetics, and pharmacodynamic studies. The advantages of our device, beside the low costs, are the small drug and skin consumption, low sample volumes, dynamic arrangement with continuous flow mimicking the dermal circulation, as well as rapid and reproducible results.

Measuring Individual Differences in Decision Biases: Methodological Considerations.

Individual differences in people's susceptibility to heuristics and biases (HB) are often measured by multiple-bias questionnaires consisting of one or a few items for each bias. This research approach relies on the assumptions that (1) different versions of a decision bias task measure are interchangeable as they measure the same cognitive failure; and (2) that some combination of these tasks measures the same underlying construct. Based on these assumptions, in Study 1 we developed two versions of a new decision bias survey for which we modified 13 HB tasks to increase their comparability, construct validity, and the participants' motivation. The analysis of the responses (N = 1279) showed weak internal consistency within the surveys and a great level of discrepancy between the extracted patterns of the underlying factors. To explore these inconsistencies, in Study 2 we used three original examples of HB tasks for each of seven biases. We created three decision bias surveys by allocating one version of each HB task to each survey. The participants' responses (N = 527) showed a similar pattern as in Study 1, questioning the assumption that the different examples of the HB tasks are interchangeable and that they measure the same underlying construct. These results emphasize the need to understand the domain-specificity of cognitive biases as well as the effect of the wording of the cover story and the response mode on bias susceptibility before employing them in multiple-bias questionnaires.

Is it time for studying real-life debiasing? Evaluation of the effectiveness of an analogical intervention technique.

The aim of this study was to initiate the exploration of debiasing methods applicable in real-life settings for achieving lasting improvement in decision making competence regarding multiple decision biases. Here, we tested the potentials of the analogical encoding method for decision debiasing. The advantage of this method is that it can foster the transfer from learning abstract principles to improving behavioral performance. For the purpose of the study, we devised an analogical debiasing technique for 10 biases (covariation detection, insensitivity to sample size, base rate neglect, regression to the mean, outcome bias, sunk cost fallacy, framing effect, anchoring bias, overconfidence bias, planning fallacy) and assessed the susceptibility of the participants (N = 154) to these biases before and 4 weeks after the training. We also compared the effect of the analogical training to the effect of 'awareness training' and a 'no-training' control group. Results suggested improved performance of the analogical training group only on tasks where the violations of statistical principles are measured. The interpretation of these findings require further investigation, yet it is possible that analogical training may be the most effective in the case of learning abstract concepts, such as statistical principles, which are otherwise difficult to master. The study encourages a systematic research of debiasing trainings and the development of intervention assessment methods to measure the endurance of behavior change in decision debiasing.