Inducing unstable walking conditions through visual and auditory stimuli.

[Purpose] Falls can significantly affect elderly individuals. However, most current methods used to detect and analyze high-risk conditions make use of simulated falling movements for data collection, which may not accurately represent actual falls. The present study aimed to induce natural falls using visual and auditory stimuli to create unstable walking conditions. [Participants and Methods] Two experiments were performed. The first experiment focused on inducing unstable walking using visual stimuli; whereas, the second experiment combined visual and auditory stimuli. To investigate the effects of stimuli on the induction of unstable walking, our results were compared with those of normal walking conditions. In addition, the two experimental conditions were compared to identify the most effective stimuli. [Results] Both experiments revealed a decrease in step length, an increase in step time and width, and an increase in the coefficient of variation of measurements, indicating an induced walking pattern with a higher risk of falls. Furthermore, combining visual and auditory stimuli caused deterioration of inter-limb coordination, as observed through an increased phase coordination index, thus resulting in further instability during walking. [Conclusion] Visual and auditory stimuli induced unstable walking. In particular, the combination of visual and auditory stimuli with a 0.8-s rhythm increased instability.

Evaluation of species differences in the metabolism of the selective NaV1.7 inhibitor DS-1971a, a mixed substrate of cytochrome P450 and aldehyde oxidase.

Nonclinical metabolite profiling of DS-1971a, a potent selective NaV1.7 inhibitor, was performed to predict human metabolites.After the oral administration of radiolabelled DS-1971a, the predominant metabolite in mouse plasma was M4, a monoxide at the pyrimidine ring, while the major metabolites with the first and second highest exposure in monkey plasma were M2, a monoxide at the cyclohexane ring, and M11, a demethylated pyrazole metabolite.Incubation studies with liver cytosolic and microsomal fractions in the absence or presence of NADPH indicated that the metabolising enzyme responsible for M4 formation was aldehyde oxidase (AO), while cytochrome P450s (P450s) were responsible for M2 and M11 formation. These results suggest that DS-1971a is a substrate for both AO and P450.When DS-1971a was incubated with liver S9 fractions and NADPH, the most abundant metabolites were M4 in mice, and M2 and M11 in monkeys, indicating that the results of in vitro incubation studies could provide information reflecting the in vivo plasma metabolite profiles in mice and monkeys. The results obtained from the incubation with the human liver S9 fraction and NADPH suggested that a major circulating metabolite in humans is M1, a regioisomer of M2.

The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid ß Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs.

The reduction of brain amyloid beta (Aß) peptides by anti-Aß antibodies is one of the possible therapies for Alzheimer's disease. We previously reported that the Aß peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aß antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aß antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aß 40, and Aß 42 compared to Aß fibrils. The levels of serum anti-Aß antibodies and plasma Aß peptides increased in both animals and decreased the brain Aß 40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aß antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aß peptides and their toxic effects via clearance of Aß peptides by generated antibodies.

Human pharmacokinetic prediction of UDP-glucuronosyltransferase substrates with an animal scale-up approach.

The aim of the current study was to evaluate the accuracy of allometric scaling methods for drugs metabolized by UDP-glucuronosyltransferases (UGTs), such as ketoprofen, imipramine, lorazepam, levofloxacin, zidovudine, diclofenac, furosemide, raloxifene, gemfibrozil, mycophenolic acid, indomethacin, and telmisartan. Human plasma clearance (CL) predictions were conducted from preclinical in vivo data by using multiple-species allometry with the rule of exponents and single-species allometric scaling (SSS) of mice, rats, monkeys, or dogs. Distribution volume at a steady state (V(ss)) was predicted by multiple-species allometry or SSS of V(ss). Oral plasma clearance (CL(po)) was calculated under the assumption that F(a) × F(g) was equivalent across species. Each of the results was compared with the observed parameter calculated from the clinical data after intravenous or oral administration. Multiple-species allometry and SSS of mice, rats, and dogs resulted in a similar accuracy of CL and CL(po) predictions. Monkeys tended to provide the most accurate predictions of human CL and CL(po). The ability to predict the half-life, which was determined from CL and V(ss) predictions, was more accurate in SSS of rats and monkeys. The in vivo fraction metabolized by glucuronidation (f(m,UGT)) in bile duct-cannulated monkeys was relatively similar to that of humans compared with other animal species, which likely contributed to the highest accuracy of SSS prediction of monkeys. On the basis of the current results, monkeys would be more reliable than other animal species in predicting human pharmacokinetics and f(m,UGT) for drugs metabolized by UGTs.

Carotid intima-media thickness and risk of cardiovascular events in high-risk patients. Results of the Osaka Follow-Up Study for Carotid Atherosclerosis 2 (OSACA2 Study).

BACKGROUND AND PURPOSE: There is epidemiological evidence that increased carotid intima-media thickness (IMT) is a predictor of cardiovascular disease (CVD) events. However, the significance of carotid IMT in high-risk patients in whom risk factors are managed clinically has not been adequately investigated. The purpose of this study was to determine the usefulness of carotid IMT measurement in such patients. METHODS: The study comprised 900 outpatients with cardiovascular risk factors or established atherosclerosis. Carotid IMT was calculated as the mean bilateral IMT of the common carotid artery, bifurcation, and internal carotid artery. Baseline vascular risk factors, medications, and history of CVD were recorded at the time of enrollment. The incidence of CVD events was determined prospectively. RESULTS: During a mean follow-up period of 2.6 years, there were 64 CVD events. The relative risk (RR) of a CVD event increased with increased IMT. Association between CVD events and carotid IMT was significant after adjustment for risk factors and history of CVD, showing an increased risk per IMT tertile from the middle tertile (RR, 2.5; 95% confidence interval [CI]: 1.0-6.3) to the highest (RR, 3.6; 95% CI: 1.4-9.0). When patients with a history of CVD were excluded (n = 574), the predictive value of IMT was significant even after adjustment for risk factors (hazard ratio per 1 SD IMT increase was 1.57 [95% CI: 1.11-2.20]). CONCLUSIONS: Carotid IMT is an independent predictor of vascular events in high-risk patients in whom risk factors are managed clinically.

Polarization imaging of a 3D object by use of on-axis phase-shifting digital holography.

A polarimetric imaging method of a 3D object by use of on-axis phase-shifting digital holography is presented. The polarimetric image results from a combination of two kinds of holographic imaging using orthogonal polarized reference waves. Experimental demonstration of a 3D polarimetric imaging is presented.

Phase-shifting digital holography with a phase difference between orthogonal polarizations.

Phase-shifting digital holography with a phase difference between orthogonal polarizations is proposed. The use of orthogonal polarizations can make it possible to record two phase-shifted holograms simultaneously. By combining the holograms with the distributions of a reference wave and an object wave, the complex field of the object's wavefront can be obtained. Preliminary experimental results are shown to confirm the proposed method.

Traumatic pericardial rupture involved with complication by blunt chest trauma.

A 65-year-old man who had sustained a blunt chest trauma in a traffic accident demonstrated a mass in the left hilum by chest radiography. Emergency surgery demonstrated a rupture of the left-side pericardium with herniation of the heart into the left pleural cavity along with a right ventricular rupture. The tear in the right ventricle was sutured using 4-0 polypropylene with felt and the pericardial rupture was repaired with an expanded polytetrafluoroethylene sheet. A 31-year-old man who had been crushed against a tree while skiing 5 years and 6 months earlier was diagnosed as having severe tricuspid valve regurgitation and tricuspid valve replacement was performed. Large left pericardial defect was found and repaired with an equine pericardial patch. In both cases, a bridging of phrenic nerve was found in the pericardial defect that was regarded as a traumatic rupture.