Quantitative Assessment of Gait Bradykinesia in Parkinson’s Disease Using a Portable Gait Rhythmogram

To quantify gait bradykinesia during daily activity in patients with Parkinson's disease (PD), we measured movement-induced accelerations over more than 24h in 50 patients with PD and 17 age-matched normal controls, using a new device, the portable gait rhythmogram. Acceleration values induced by various movements, averaged each 10 min, exhibited a gamma distribution. The mean value of the distribution curve was used as an index of the "amount of overall movement per 24h". Characteristic changes were observed in both the gait cycle and gait acceleration. During hypokinesia, the gait cycle became either faster or slower. A number of patients with marked akinesia/bradykinesia showed a reduced and narrow range of gait acceleration, i.e., a range of floor reaction forces. The results suggest that assessment of the combination of changes in gait cycle and gait acceleration can quantitatively define the severity of gait bradykinesia

A Proposal for New Algorithm that Defines Gait-Induced Acceleration and Gait Cycle in Daily Parkinsonian Gait Disorders

We developed a new device, the portable gait rhythmogram (PGR), to record up to 70 hrs of movement-induced accelerations. Acceleration values induced by various movements, averaged every 10 min, showed gamma distribution, and the mean value of this distribution was used as an index of the amount of overall movements. Furthermore, the PGR algorithm can specify gait-induced accelerations using the pattern-matching method. Analysis of the relationship between gait-induced accelerations and gait cycle duration makes it possible to quantify Parkinson’s disease (PD)-specific pathophysiological mechanisms underlying gait disorders. Patients with PD showed the following disease-specific patterns: (1) reduced amount of overall movements and (2) low amplitude of gait-induced accelerations in the early stages of the disease, which was compensated by fast stepping. Loss of compensation was associated with slow stepping gait, (3) narrow range of gait-induced acceleration amplitude and gait cycle duration, suggesting monotony, and (4) evident motor fluctuations during the day by tracing changes in the above two parameters. Prominent motor fluctuation was associated with frequent switching between slow stepping mode and active mode. These findings suggest that monitoring various movement- and gait-induced accelerations allows the detection of specific changes in PD. We conclude that continuous long-term monitoring of these parameters can provide accurate quantitative assessment of parkinsonian clinical motor signs

The effect of once-yearly zoledronic acid on hip structural and biomechanical properties derived using computed tomography (CT) in Japanese women with osteoporosis

The effects of zoledronic acid on hip structural and biomechanical properties were evaluated in Japanese patients with osteoporosis by computed tomography (CT). The subjects included in this study were a subset of female subjects (zoledronic acid group, 49 subjects; placebo group, 53 subjects) in the phase 3 trial (ZONE study) who were available for multi-detector row CT (MDCT) scanning. Eligible subjects were those diagnosed with primary osteoporosis based on the Diagnostic Criteria for Primary Osteoporosis (2000) by the Japanese Society for Bone and Mineral Research and who had between one and four fractured vertebrae located between the fourth thoracic vertebra and the fourth lumbar vertebra. The subjects received a once-yearly intravenous infusion of zoledronic acid 5 mg or placebo for two years. CT data were obtained at baseline and at 12 and 24 months later and analyzed under blinded conditions. The results demonstrated that once-yearly intravenous infusion of zoledronic acid improved volumetric bone mineral density (vBMD), cortical bone geometry parameters, and CT-derived biomechanical parameters at the femoral neck, intertrochanteric region, and shaft; particularly at the intertrochanteric region, significant improvements in cortical bone geometry parameters and CT-derived biomechanical parameters, compared with those in the placebo group, were detectable early, at 12 months. The present data suggest that zoledronic acid has a possibility to reduce the risk of hip fractures in Japanese patients with osteoporosis

Common Variants in a Novel Gene, FONG on Chromosome 2q33.1 Confer Risk of Osteoporosis in Japanese

Osteoporosis is a common disease characterized by low bone mass, decreased bone quality and increased predisposition to fracture. Genetic factors have been implicated in its etiology; however, the specific genes related to susceptibility to osteoporosis are not entirely known. To detect susceptibility genes for osteoporosis, we conducted a genome-wide association study in Japanese using ∼270,000 SNPs in 1,747 subjects (190 cases and 1,557 controls) followed by multiple levels of replication of the association using a total of ∼5,000 subjects (2,092 cases and 3,114 controls). Through these staged association studies followed by resequencing and linkage disequilibrium mapping, we identified a single nucleotide polymorphism (SNP), rs7605378 associated with osteoporosis. (combined P = 1.51×10−8, odds ratio = 1.25). This SNP is in a previously unknown gene on chromosome 2q33.1, FONG. FONG is predicted to encode a 147 amino-acid protein with a formiminotransferase domain in its N-terminal (FTCD_N domain) and is ubiquitously expressed in various tissues including bone. Our findings would give a new insight into osteoporosis etiology and pathogenesis

Interactive Rhythmic Auditory Stimulation Reinstates Natural 1/f Timing in Gait of Parkinson's Patients

Parkinson's disease (PD) and basal ganglia dysfunction impair movement timing, which leads to gait instability and falls. Parkinsonian gait consists of random, disconnected stride times—rather than the 1/f structure observed in healthy gait—and this randomness of stride times (low fractal scaling) predicts falling. Walking with fixed-tempo Rhythmic Auditory Stimulation (RAS) can improve many aspects of gait timing; however, it lowers fractal scaling (away from healthy 1/f structure) and requires attention. Here we show that interactive rhythmic auditory stimulation reestablishes healthy gait dynamics in PD patients. In the experiment, PD patients and healthy participants walked with a) no auditory stimulation, b) fixed-tempo RAS, and c) interactive rhythmic auditory stimulation. The interactive system used foot sensors and nonlinear oscillators to track and mutually entrain with the human's step timing. Patients consistently synchronized with the interactive system, their fractal scaling returned to levels of healthy participants, and their gait felt more stable to them. Patients and healthy participants rarely synchronized with fixed-tempo RAS, and when they did synchronize their fractal scaling declined from healthy 1/f levels. Five minutes after removing the interactive rhythmic stimulation, the PD patients' gait retained high fractal scaling, suggesting that the interaction stabilized the internal rhythm generating system and reintegrated timing networks. The experiment demonstrates that complex interaction is important in the (re)emergence of 1/f structure in human behavior and that interactive rhythmic auditory stimulation is a promising therapeutic tool for improving gait of PD patients

Surface segregation at the aluminum interface of poly(3-hexylthiophene)/fullerene solar cells

The effects of thermal annealing before and after Al deposition on poly 3-hexylthiophene P3HT6, 6-phenyl-C61 butyric acid methyl ester PCBM blend solar cells were investigated by current density-voltage measurements and x-ray photoelectron spectroscopy XPS . Compared to the preannealed device, the postannealed device exhibited enhanced open-circuit voltage VOC, which is ascribed to the decrease in the reverse saturation current density J0. The XPS measurements demonstrated that P3HT is dominant at the Al interface in the preannealed device while PCBM is instead dominant in the postannealed device. This surface-segregated PCBM formed in the postannealed device can serve as a hole-blocking layer at the Al interface to reduce J0, and therefore improve VOC