Quantitative Assessment of Finger Movement Profile in a Visual-Motor Task Based on a Tablet Computer: The Application in Parkinson's Disease.

BACKGROUND/OBJECTIVE: Easily applicable, quantitative assessment of movement is widely needed in various clinical settings, especially in the evaluation of Parkinson's disease (PD). METHODS: We developed a highly repeatable tablet computer-based finger movement assessment system (FMAS) to record finger movement profile in a visual-motor task both in PD (n = 217) and healthy participants (n = 221). RESULTS: We found age-related declines in finger movement performance among the healthy participants but not in PD patients with the FMAS. Significant differences in movement time (MT) and latency/MT ratio but not in latency were observed in PD patients as compared with healthy subjects (P < 0.000). Meanwhile, we identified the latency/MT ratio as the optimal parameter to differentiate PD from age-matched healthy subjects in an age-independent manner (cut-off 1.08 with corresponding AUC = 0.861). In addition, a significant correlation was found between finger movement parameters and the Hoehn and Yahr scale (H-Y scale), UPDRS III score and the duration of the disease in PD patients (P < 0.01). CONCLUSION: It was suggested that the tablet computer-based evaluation of finger movement provided an easily applicable quantitative method to assess the conditions of PD patients.

Functional assessment of CYP3A4 allelic variants on lidocaine metabolism in vitro.

AIM: Human cytochrome P450 3A4 is the most abundant isoform of P450 enzyme in the liver. It plays an important role in the metabolism of wide variety of xenobiotic and endogenous substrates. So far, there are few reports about the functional characterization of CYP3A4 variants in terms of specific substrates. The aim of this study was to systematically investigate the genetic polymorphisms of 23 CYP3A4 alleles and evaluate their catalytic activities on the metabolism of lidocaine in vitro. METHODS AND RESULTS: The wild-type and 22 CYP3A4 variants were expressed in Spodoptera frugiperda 21 insect cells. Then the insect microsomes were incubated with the CYP3A4-specific substrate lidocaine. Reactions were performed with 50-3,000 µM for 60 min at 37°C. Lidocaine and its metabolite monoethylglycinexylidide were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system. Of the 23 CYP3A4 allelic variants tested, 2 variants (CYP3A4*17 and CYP3A4*30) had no detectable enzyme activity; and 5 variants (CYP3A4*2, CYP3A4*5, CYP3A4*9, CYP3A4*16 and CYP3A4*24) showed significantly decreased intrinsic clearance values compared with wild-type CYP3A4*1. CONCLUSION: As the first study of all these CYP3A4 alleles for lidocaine metabolism, our results in vitro assessment may provide novel insights into the allele-specific and substrate-specific activity of CYP3A4 and may also offer a reference to the personalized treatment of lidocaine in a clinical setting.

Assessment of toxicity of tetrahydrofuran on the microbial community in activated sludge.

Activated sludge is widely used to treat industrial wastewater, but its efficiency is affected by a variety of factors, including toxic substances such as tetrahydrofuran (THF). In this study, we examined the toxicity of THF at different concentrations (0-320 mM) on the microbial community in activated sludge. A remarkable dose-dependent decrease in the total organic compound removal rate and culturable bacteria and fungi was observed. At THF concentrations higher than 160 mM, a decrease in pH to 3.0 was observed. The activities of five enzymes (catalase, dehydrogenase, urease, phosphatase and protease) analyzed were all significantly inhibited (p<0.01) at THF concentrations higher than 160 mM, especially dehydrogenase activity, which lost 95.4% of its activity at 320 mM THF. Microbial community analysis by PCR-DGGE revealed a substantial shift in the community structure and a reduction in diversity at a low THF concentration (20mM). These results suggest that THF is much more toxic than reported in the literature, indicating its acute toxicity to microorganisms.