Feasibility of using a depth camera or pressure mat for visual feedback balance training with functional electrical stimulation.

Individuals with incomplete spinal-cord injury/disease are at an increased risk of falling due to their impaired ability to maintain balance. Our research group has developed a closed-loop visual-feedback balance training (VFBT) system coupled with functional electrical stimulation (FES) for rehabilitation of standing balance (FES + VFBT system); however, clinical usage of this system is limited by the use of force plates, which are expensive and not easily accessible. This study aimed to investigate the feasibility of a more affordable and accessible sensor such as a depth camera or pressure mat in place of the force plate. Ten able-bodied participants (7 males, 3 females) performed three sets of four different standing balance exercises using the FES + VFBT system with the force plate. A depth camera and pressure mat collected centre of mass and centre of pressure data passively, respectively. The depth camera showed higher Pearson's correlation (r > 98) and lower root mean squared error (RMSE < 10 mm) than the pressure mat (r > 0.82; RMSE < 4.5 mm) when compared with the force plate overall. Stimulation based on the depth camera showed lower RMSE than that based on the pressure mat relative to the FES + VFBT system. The depth camera shows potential as a replacement sensor to the force plate for providing feedback to the FES + VFBT system.

Integration of a physiologically-based pharmacokinetic model with a whole-body, organ-resolved genome-scale model for characterization of ethanol and acetaldehyde metabolism.

Ethanol is one of the most widely used recreational substances in the world and due to its ubiquitous use, ethanol abuse has been the cause of over 3.3 million deaths each year. In addition to its effects, ethanol's primary metabolite, acetaldehyde, is a carcinogen that can cause symptoms of facial flushing, headaches, and nausea. How strongly ethanol or acetaldehyde affects an individual depends highly on the genetic polymorphisms of certain genes. In particular, the genetic polymorphisms of mitochondrial aldehyde dehydrogenase, ALDH2, play a large role in the metabolism of acetaldehyde. Thus, it is important to characterize how genetic variations can lead to different exposures and responses to ethanol and acetaldehyde. While the pharmacokinetics of ethanol metabolism through alcohol dehydrogenase have been thoroughly explored in previous studies, in this paper, we combined a base physiologically-based pharmacokinetic (PBPK) model with a whole-body genome-scale model (WBM) to gain further insight into the effect of other less explored processes and genetic variations on ethanol metabolism. This combined model was fit to clinical data and used to show the effect of alcohol concentrations, organ damage, ALDH2 enzyme polymorphisms, and ALDH2-inhibiting drug disulfiram on ethanol and acetaldehyde exposure. Through estimating the reaction rates of auxiliary processes with dynamic Flux Balance Analysis, The PBPK-WBM was able to navigate around a lack of kinetic constants traditionally associated with PK modelling and demonstrate the compensatory effects of the body in response to decreased liver enzyme expression. Additionally, the model demonstrated that acetaldehyde exposure increased with higher dosages of disulfiram and decreased ALDH2 efficiency, and that moderate consumption rates of ethanol could lead to unexpected accumulations in acetaldehyde. This modelling framework combines the comprehensive steady-state analyses from genome-scale models with the dynamics of traditional PK models to create a highly personalized form of PBPK modelling that can push the boundaries of precision medicine.