Optimal Schedules in Multitask Motor Learning

Although scheduling multiple tasks in motor learning to maximize long-term retention of performance is of great practical importance in sports training and motor rehabilitation after brain injury, it is unclear how to do so. We propose here a novel theoretical approach that uses optimal control theory and computational models of motor adaptation to determine schedules that maximize long-term retention predictively. Using Pontryagin’s maximum principle, we derived a control law that determines the trial-by-trial task choice that maximizes overall delayed retention for all tasks, as predicted by the state-space model. Simulations of a single session of adaptation with two tasks show that when task interference is high, there exists a threshold in relative task difficulty below which the alternating schedule is optimal. Only for large differences in task difficulties do optimal schedules assign more trials to the harder task. However, over the parameter range tested, alternating schedules yield long-term retention performance that is only slightly inferior to performance given by the true optimal schedules. Our results thus predict that in a large number of learning situations wherein tasks interfere, intermixing tasks with an equal number of trials is an effective strategy in enhancing long-term retention

Immunotherapy for NAFLD and NAFLD-related hepatocellular carcinoma

The progression of non-alcoholic fatty liver disease (NAFLD), the most common liver disease, leads to non-alcoholic steatohepatitis and hepatocellular carcinoma. Despite the increasing incidence and prevalence of NAFLD, its therapeutic and preventive strategies to lower the disease burden is limited. In recent years, immunotherapy, including anti-programmed cell death 1/programmed cell death 1 ligand 1 treatment, has emerged as a potential approach to reach satisfactory modulation for the progression of NAFLD and treatment of NAFLD-related hepatocellular carcinoma. However, the effectiveness of immunotherapy against NAFLD and NAFLD-related hepatocellular carcinoma is in the early phase and it is yet not advanced. In addition, conflicting results are being reported regarding the prognosis of patients with NAFLD-related hepatocellular carcinoma and high expression of programmed cell death 1/programmed cell death 1 ligand 1. Herein, this review will discuss and elucidate the attempts and underlying mechanisms of immunotherapy against NAFLD and NAFLD-related hepatocellular carcinoma

Effects of education on low-phosphate diet and phosphate binder intake to control serum phosphate among maintenance hemodialysis patients: A randomized controlled trial.

Background:For phosphate control, patient education is essential due to the limited clearance of phosphate by dialysis. However, well-designed randomized controlled trials about dietary and phosphate binder education have been scarce. Methods:We enrolled maintenance hemodialysis patients and randomized them into an education group (n = 48) or a control group (n = 22). We assessed the patients' drug compliance and their knowledge about the phosphate binder using a questionnaire. Results:The primary goal was to increase the number of patients who reached a calcium-phosphorus product of lower than 55. In the education group, 36 (75.0%) patients achieved the primary goal, as compared with 16 (72.7%) in the control group (P = 0.430). The education increased the proportion of patients who properly took the phosphate binder (22.9% vs. 3.5%, P = 0.087), but not to statistical significance. Education did not affect the amount of dietary phosphate intake per body weight (education vs. control: -1.18 ± 3.54 vs. -0.88 ± 2.04 mg/kg, P = 0.851). However, the dietary phosphate-to-protein ratio tended to be lower in the education group (-0.64 ± 2.04 vs. 0.65 ± 3.55, P = 0.193). The education on phosphate restriction affected neither the Patient-Generated Subjective Global Assessment score (0.17 ± 4.58 vs. -0.86 ± 3.86, P = 0.363) nor the level of dietary protein intake (-0.03 ± 0.33 vs. -0.09 ± 0.18, P = 0.569). Conclusion:Education did not affect the calcium-phosphate product. Education on the proper timing of phosphate binder intake and the dietary phosphate-to-protein ratio showed marginal efficacy

Mesenchymal Stem Cell-Extracellular Vesicle Therapy for Stroke: Scalable Production and Imaging Biomarker Studies

A major clinical hurdle to translate MSC-derived extracellular vesicles (EVs) is the lack of a method to scale-up the production of EVs with customized therapeutic properties. In this study, we tested whether EV production by a scalable 3D-bioprocessing method is feasible and improves neuroplasticity in animal models of stroke using MRI study. MSCs were cultured in a 3D-spheroid using a micro-patterned well. The EVs were isolated with filter and tangential flow filtration and characterized using electron microscopy, nanoparticle tracking analysis, and small RNA sequencing. Compared to conventional 2D culture, the production-reproduction of EVs (the number/size of particles and EV purity) obtained from 3D platform were more consistent among different lots from the same donor and among different donors. Several microRNAs with molecular functions associated with neurogenesis were upregulated in EVs obtained from 3D platform. EVs induced both neurogenesis and neuritogenesis via microRNAs (especially, miR-27a-3p and miR-132-3p)-mediated actions. EV therapy improved functional recovery on behavioral tests and reduced infarct volume on MRI in stroke models. The dose of MSC-EVs of 1/30 cell dose had similar therapeutic effects. In addition, the EV group had better anatomical and functional connectivity on diffusion tensor imaging and resting-state functional MRI in a mouse stroke model. This study shows that clinical-scale MSC-EV therapeutics are feasible, cost-effective, and improve functional recovery following experimental stroke, with a likely contribution from enhanced neurogenesis and neuroplasticity

The Prevalence of Hepatitis C Virus Infection in Korea: Pooled Analysis

This study evaluated the prevalence of hepatitis C virus (HCV) infections in Korea. Pooled estimates of the anti-HCV positivity were calculated using the data published in 15 reports on the general population and health check-up examinees. The overall pooled estimate of the prevalence of HCV among middle-aged adults (40 yr old and above) was 1.68% (95% confidence interval: 1.51-1.86%) during the year of 1990-2000 among the general population. Most of the published data indicated that the prevalence of anti-HCV increased with age. The anti-HCV positivity was significantly higher in females than in males. Because the risk of HCV exposure in blood recipients has decreased remarkably, the spread of HCV through means other than a transfusion must be prevented

Fast Slot Synchronization for Intercell Asynchronous DS/CDMA Systems

Manuscript received August 4, 2000; revised January 17, 2001; accepted January 17, 2001. The editor coordinating the review of this paper and approving it for publication is Q. Bi.Slot synchronization is a critical step for fast and reliable cell search in intercell asynchronous direct sequence-code division multiple access systems. To increase reliability, observations over a number of slots may be combined. In this paper, combining schemes of multiple observations are studied for slot synchronization. The optimal combining rule is determined based on detection theory. It is found that two known combining schemes correspond to special cases of the optimal combining. These schemes may not work well in typical environments, since the schemes are optimized for specific environments. To improve slot synchronization performance in typical environments, a new combining scheme is proposed in this paper. The performance of the proposed combining scheme as well as other combining schemes is analyzed for Rayleigh fading channels with frequency offset. Numerical analysis shows that the proposed combining scheme significantly outperforms other combining schemes in typical environments.This work was supported by the Brain Korea 21 Project