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Recently, lidocaine topical systems utilizing nonaqueous matrices have been developed and provide efficient lidocaine delivery through the skin, such that lower concentrations of drug provide equivalent or greater drug delivery than drug-in-matrix hydrogel lidocaine patches. This study characterizes drug delivery from a nonaqueous lidocaine topical system with increasing drug load both in vitro and in vivo. Topical systems formulated with either 1.8% or 5.4% lidocaine were applied to healthy volunteers' backs (n = 15) for 12 h in a single-center, open-label, four-treatment, four-period crossover pharmacokinetic study. Subjects were dosed with either three 1.8% systems or one, two, or three 5.4% systems in each period. Blood was collected for up to 48 h, and plasma lidocaine levels were measured with a validated HPLC method. In parallel, human and mouse skin models characterized the in vitro skin permeation profile. The pharmacokinetic profile was linear between one, two, and three lidocaine 5.4% applications. Application of three lidocaine 1.8% systems (108 mg lidocaine) was bioequivalent to one lidocaine 5.4% system (108 mg lidocaine). Both topical systems remained well adhered to the skin and irritation was mild. The 5.4% system had approximately threefold higher skin permeability than the 1.8% system in the mouse and human skin models. The results indicate increasing the drug load by three times results in triple the drug delivery both in vivo and in vitro. The relationship between the in vitro permeation and in vivo absorption correlates and is nonlinear.

Enhanced mixing in microfluidic systems is necessary in many applications such as chemical processing, biological assays, and diagnosis. We are developing a microfluidic system to efficiently mix minute reagents (down to several microliters) using vibration-induced flow (VIF), in which a net flow is generated around a micropillar by applying periodic vibration. In this study, we numerically investigate the enhancement in chaotic mixing using the VIF technique and periodic switching of vibrations. By extending our previous numerical simulation model, we investigate the flow field and trajectories of fluid particles in three-dimensional space. We demonstrate that chaotic advection characteristics can be observed by periodically switching the vibrational direction of a substrate using simple cylindrical pillars. In addition, using an appropriate interval for switching the vibration axes yields better mixing performance. The extent of chaotic advection is evaluated quantitatively using the Lyapunov exponent considering various vibration parameters, such as the vibration amplitude, separation distance between each pillar and pillar shape. The flow field induced by a large-amplitude and sharp-edged wall pillar provides excellent mixing results. Thus, VIF is successfully applied to obtain an efficient mixing strategy with the aid of the chaotic theory. [ABSTRACT FROM AUTHOR]

Purpose: The Japanese healthcare system has designated registered sales clerks to sell over-the-counter (OTC) drugs. Because of this, the AEON HAPYCOM Comprehensive Training Organization implemented an education program to train registered clerks in 2014. The program is unique; it consists of both lectures and hands-on workshop components. We conducted this study as part of a self-evaluation designed to improve the program. Methods: Program participants were asked to respond to an evaluation form upon completion. The form was designed to ascertain student perceptions of the program's components (e.g., themes, lecturers, materials, and the hands-on workshop) as well as its applicability to their practice of selling OTC drugs. Results: We obtained a total of 6,776 responses from 3,388 participants. On average, each of the program's components were rated highly, with the hands-on workshop being rated the highest. There was a weak relationship between the scores for program preparation and its applicability to OTC sales practices. Conclusion: The program (especially the hands-on workshop component) was highly evaluated by participants. However, we determined that enhancements could be made to the hands-on workshop and other mechanisms to encourage participants to prepare before attending the program.

Mixed‐potential‐driven catalysis, in which anodic and cathodic reactions are electrochemically short‐circuited, converts the Gibbs free energy difference into overpotentials that drive both half‐reactions without an external energy input. We developed a theoretical framework that suggests that the catalytic activities of individual catalyst components determine the distribution of the aforementioned driving forces. By short‐circuiting spatially separated electrodes made of Au/C with reduced‐graphene oxide, nitrogen‐doped reduced‐graphene oxide, caged nitrogen‐doped reduced‐graphene oxide, Pt/C, or Pd/C, we demonstrated this framework using glucose oxidation as a model, given its significance in generating high‐value products and its potential in fuel cell technology. A short‐circuit current was detected in the absence of external potentials, demonstrating electron transfer during glucose oxidation. Additionally, by correlating the mixed potential predicted from the polarization curves of each half‐reaction with the mixed potential measured in short‐circuit experiments under the same conditions, we confirmed that the kinetic activity of each catalyst component determines the mixed potential. This, in turn, affects the division of the driving force. Driving force partitioning is a potent tool for enhancing the overall rate of a reaction. Our findings may facilitate the design of not only glucose oxidation catalysts but also other heterogeneous catalysts based on mixed‐potential‐driven reaction mechanisms. [ABSTRACT FROM AUTHOR]

Magnetic resonance image (MRI) is now widely used for imaging follow-up for post coiling brain aneurysms. However, the accuracy on the estimation of residual aneurysm, which is crucial for the retreatment planning, remains to be controversial. The purpose of this study is to evaluate a new post-processing technique that provides improved estimation of the residual aneurysm after coil embolization. One hundred aneurysms on 93 patients who underwent coil embolization for brain aneurysm were evaluated using the 1.5 Tesla time-resolved magnetic resonance angiography (TR-MRA) one year after the treatment. To minimize the inter-observer variability caused by the window level adjustment, an automatic post processing protocol using the full-width at half-maximum (FWHM) value was utilized. The result was then compared with that from the conventional cerebral angiography. Of the 97 aneurysms that underwent both TR-MRA and DSA, 23 (23.7%) showed residual neck / dome during follow-up. After window level adjustment, the size of the parent artery in the TR-MRA was consistent with that in the DSA. The reconstructed Volume Rendering images provided clear contours of the residual aneurysms and contributed to the understanding the configuration of residual aneurysm. The largest and the smallest diameter of the residual aneurysms was larger in the TR-MRA than in the DSA (8.05 vs. 7.72 mm, p = 0.0004; 4.99 vs. 4.19 mm, p = 0.007 respectively). The sensitivity, specificity, and positive and negative predictive values of TR-MRA compared to DSA were 100%, 97%, 73%, and 100%, respectively. Using the FWHM value to optimize the window level adjustment, the size of the residual component observed in the TR-MRA was larger compared to that in the DSA whereas the size of neck and the parent artery showed consistency between the two modalities. This image processing technique can be used as an effective screening tool for evaluating residual component in post-coiling brain aneurysms.

Magnetic resonance image (MRI) is now widely used for imaging follow-up for post coiling brain aneurysms. However, the accuracy on the estimation of residual aneurysm, which is crucial for the retreatment planning, remains to be controversial. The purpose of this study is to evaluate a new post-processing technique that provides improved estimation of the residual aneurysm after coil embolization. One hundred aneurysms on 93 patients who underwent coil embolization for brain aneurysm were evaluated using the 1.5 Tesla time-resolved magnetic resonance angiography (TR-MRA) one year after the treatment. To minimize the inter-observer variability caused by the window level adjustment, an automatic post processing protocol using the full-width at half-maximum (FWHM) value was utilized. The result was then compared with that from the conventional cerebral angiography. Of the 97 aneurysms that underwent both TR-MRA and DSA, 23 (23.7%) showed residual neck / dome during follow-up. After window level adjustment, the size of the parent artery in the TR-MRA was consistent with that in the DSA. The reconstructed Volume Rendering images provided clear contours of the residual aneurysms and contributed to the understanding the configuration of residual aneurysm. The largest and the smallest diameter of the residual aneurysms was larger in the TR-MRA than in the DSA (8.05 vs. 7.72 mm, p = 0.0004; 4.99 vs. 4.19 mm, p = 0.007 respectively). The sensitivity, specificity, and positive and negative predictive values of TR-MRA compared to DSA were 100%, 97%, 73%, and 100%, respectively. Using the FWHM value to optimize the window level adjustment, the size of the residual component observed in the TR-MRA was larger compared to that in the DSA whereas the size of neck and the parent artery showed consistency between the two modalities. This image processing technique can be used as an effective screening tool for evaluating residual component in post-coiling brain aneurysms.

Subliminal information has been suggested to facilitate insight problem solving. The present study examinedwhether subliminal hints may influence not only retention of the goals but also planning of sequential steps required to solve thenine-dot problem. Using continuous flash suppression, participants were subliminally presented with either an image depictingthe entire solution of the problem, the three steps to solve the problem in a sequential order, or an image of the nine dots thatdoes not involve solution of the problem. Participants presented with the entire solution of the problem tended to show bettersolution performance and greater relaxation of constraints than those in the latter two conditions, whose performance failedto significantly differ from each other. These results indicate that subliminal information may be stored as a global and staticvisuo-spatial representation to influence solution but may not involve planning of each step to achieve insight problem solving.