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Background Zonisamide is one of the anti-parkinsonian agents approved and used in Japan, and it improves motor symptoms and off time in the advanced stage of Parkinson's disease. However, there is no evidence of its efficacy in the early stage of Parkinson's disease. Aim To investigate the effect of zonisamide on the early stage of Parkinson's disease. Methods We consecutively recruited patients with less than 3 years of disease duration who were treated with levodopa/dopa decarboxylase inhibitor only or additional small amounts of dopamine agonists. We evaluated motor severities with the Unified Parkinson's Disease Rating Scale, non-motor severities with the Non-Motor Symptom scale and health-related quality of daily life with the 39 items of the Parkinson's Disease Questionnaire. Patients also evaluated themselves with the Patient Global Impression of Improvement index. Serum zonisamide levels were monitored throughout the study. After the baseline clinical evaluation, patients received 25 mg of open-label zonisamide, and were evaluated for 28 weeks. Results We recruited 13 patients, and 11 patients completed the study. Adjunctive zonisamide significantly improved the Unified Parkinson's Disease Rating Scale part III score and Patient Global Impression of Improvement after the 12th week. The Non-Motor Symptom Scale and summary index of the 39-item Parkinson's Disease Questionnaire showed no significant changes. Mean plasma levels of zonisamide were stable throughout the study. Two patients could not complete because of adverse events. Conclusions Zonisamide can be expected to be safe and beneficial to motor symptoms of Parkinson's disease in the early stage as well as the advanced stage. [ABSTRACT FROM AUTHOR]

[Display omitted] • In situ observation of the cement-based materials under hydraulic pressure with image analyses revealed the volumetric strain development due to hydraulic pressure varied greatly with location, owing to heterogeneous water infiltration in the mortar specimens. • The behavior of strains and the resultant internal damage to a mortar specimen under hydraulic pressure are strongly influenced by hydraulic pressure as a confinement mechanism and water infiltration as a stress-relaxation mechanism. • In situ observation and fluorescent imaging of the small cylindrical mortar specimens showed no visible damage within the spatial resolution (50–172 μm) up to 20 MPa whilst the reduction in Young's modulus suggested the occurrence of microcracks. The influence of hydraulic pressure (max. 20 MPa) on the internal damage of cement-based materials is experimentally studied. In order to observe in situ the internal damage of cement-based materials under hydraulic pressure, a new testing apparatus equipped with an X-ray micro-computed tomography (X-μCT) scanner is developed. The behaviors of water infiltration and strain development are evaluated for mortar specimens with different water-to-cement ratios. Although the internal damage of the mortar specimens under hydraulic pressure was not detected by the X-μCT scanner and fluorescent imaging, the mechanical properties tested after hydraulic pressure loadings were altered, indicative of the occurrence of microcracks (<50 μm) below the resolution of these observation techniques. It is concluded that the internal damage of mortar specimens under hydraulic pressure is strongly influenced by two mechanisms: hydraulic pressure as a mechanism of external confinement and water infiltration as a mechanism of stress relaxation. The volumetric strain development due to hydraulic pressure varies greatly with location, owing to heterogeneous water infiltration in mortar. Therefore, the balance of these two mechanisms must be taken into account to assess the risk of internal damage of cement-based materials under hydraulic pressure. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Cerebrovascular lesions (CVLs) are known to play important roles in the pathophysiology underlying Alzheimer''s disease (AD), especially in elderly AD cases. The present study was conducted to elucidate the relationship between the CVLs and vascular risk factors (VRFs) in elderly Japanese patients with AD. Subjects and methods: The CVLs such as lacunar infarcts, old microbleeds (OMBs), white matter lesions (WMLs), and occlusive vascular lesions on MRI were analyzed in relation to the risk factors in 120 Japanese patients with probable AD. Their mean age was 75.6years. The subjects were divided into two age groups: young-old group (YOG) consisting of 55 cases being younger than 75years and old-old group (OOG) consisting of 65 cases being 75years or older. Results: In overall analysis, 10 cases (8.3%) showed brain atrophy without CVLs on MRI, 46 cases (38.3%) showed WMLs in addition to the brain atrophy, 61 cases (50.8%) showed lacunar lesions, and 3 cases (2.5%) were diagnosed as having a superficial siderosis. Lacunar infarcts and OMBs were more frequently observed in OOG than in YOG, and were also more frequently observed in those with 2 or more VRFs than those with less than 2 VRFs (p<0.05). The WMLs were more pronounced in OOG, and in those with more VRFs. Conclusion: The CVLs including lacunes, WMLs, and OMBs were present more than 90% of elderly Japanese patients with AD. As the severity of CVLs was associated with VRFs and age, VRFs may modify clinical presentation of elderly AD patients. [Copyright &y& Elsevier]

There are three main electrochemical factors affecting the electroosmotic flow in clay soil: the voltage loss at the clay/electrode interface, the type of current carriers in the soil, and the ion composition change in the clay due to voltage application. Appropriate evaluation of these factors is important to cost effectively implement electroosmosis for in situ soil consolidation projects. In this study, three different experimental systems were developed and used to investigate electrochemical reactions occurring in reconstituted and natural marine clay during electroosmotic consolidation. The results of polarization tests show that the voltage loss at the clay/electrode interface is different depending on the combination of the clay material and electrode material. The results of electroosmotic element test also show that electroosmotic dehydration does not increase if large current–voltage value is applied and that an optimal current–voltage value for causing electroosmosis depends on the cohesive soil composition. If the clay contains a lot of oxidizable ions, such as sodium, these ions affect electrophoresis and chemical reactions that occur in the soil. Therefore, the optimal configuration to apply electric current also differs depending on the clay. The results of laboratory-scale electroosmotic dehydration tests, arranged in a realistic in situ layout, are performed to study the relationship between soil dehydration, consolidation, and surface crack generation. [ABSTRACT FROM AUTHOR]

Glass beads were coated with a mixture of mechanoluminescent (ML) paint and epoxy resin in order to visualize particle-level force distribution through an analog granular material. SEM observation and X-ray CT scanning was used to verify that the application of the ML coating on the glass beads was uniform. Load tests were conducted on single columns of coated glass particles to equate luminance to diametrical forces transmitted through the particles and particle contacts. The relationship between loading (force) rate during elastic loading of the coated particles and luminance was determined using a column of beads placed in an axial loading device. Coated glass particles were placed in a transparent plane strain container and subjected to biaxial loading to visualize the load transmission through the analog granular material placed in a regular packing. The anisotropy of chains of load transmission during loading was detectable using this test arrangement. The sum of contact forces at the top container boundary deduced from particle luminance is shown to be in agreement with applied boundary loads. This novel technique holds promise as an alternative approach to visualize and measure load transmission through idealized 2D assemblies of granular material. [ABSTRACT FROM AUTHOR]

Cerebral circulation is known to be protected by the regulatory function against the hypoperfusion that will affect the cognitive function as a result of brain ischemia and energy failure. The regulatory function includes cerebrovascular autoregulation, chemical control, metabolic control, and neurogenic control, and those compensatory mechanisms can be influenced by hypertension, atherosclerosis, cardiac diseases, cerebrovascular diseases and aging. On the other hand, large and/or small infarction, intracranial hemorrhage, subarachnoid hemorrhage, atherosclerosis, amylod angiopathy are also more directly associated with cognitive decline not only in those with vascular cognitive impairment or vascular dementia but also those with Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Abstract: Constitutive activation of the PI3 kinase/Akt pathway is associated with the neoplastic phenotype of a large number of human tumor cells. As the anti-apoptotic role of the PI3 kinase/Akt pathway has been established, we have examined whether specific blockade of this pathway sensitizes tumor cells to DNA-damaging agent-induced cytotoxicity by enhancing apoptotic cell death. Although a PI3 kinase inhibitor, LY294002, by itself does not induce apoptotic cell death, LY294002 selectively and markedly enhances the apoptosis-inducing efficacy of doxorubicin: such an enhanced cell death is only detected in tumor cells in which the PI3 kinase/Akt pathway is constitutively activated, and it is totally dependent on the functional p53 pathway. These results suggest that the combination of a PI3 kinase/Akt pathway inhibitor and doxorubicin provides an efficient chemotherapeutic strategy for the treatment of tumor cells in which the PI3 kinase/Akt pathway is constitutively activated and the p53 pathway is functional. [Copyright &y& Elsevier]

In this study, a new tsunami overflow-seepage-coupled centrifuge experimental system was developed and applied to investigate the concurrent processes, and to elucidate the mechanism, of the instability involving the scour of the mound/sandy seabed, bearing capacity failure and flow of the foundation, and the failure of caisson breakwaters, with high-resolution image analysis. A series of experiments were conducted with and without the effects of the seepage by keeping the same overflow conditions (water volume, overflow velocity, fall height and water depth), and with different mound cross-sections. All of the experiments were conducted under 50 gravities and comprised of 3 series. The first series of experiments targeted the instability of the mounds themselves by constraining the caisson movement (sliding and overturning). The second series of experiments then allowed the caisson movement and clarified how the mound scour would affect the overall stability of the caissons. The third series of experiments examined the effect of a countermeasure on the basis of the results from the two series of experiments. The experimental results first demonstrated that the coupled overflow-seepage actions promoted the development of the mound scour significantly. Notably, the scour front developed in the form of progressive slip failure at the vicinity of caissons, regardless of the mound thickness. This stems from the fact that the development of the mound scour shortened the seepage path around the shoulder area of the mound, enhancing the coupling effect of the overflow and seepage. Indeed, the scour stopped far from the caisson toe in the absence of seepage without affecting the stability of the caissons. By contrast, the scour development due to the coupled overflow-seepage approached the caisson toe and brought about bearing capacity failure of the mound, resulting in the total failure of the caisson breakwater, which otherwise remained stable without the coupling effect. The velocity vectors obtained from the high-resolution image analysis illustrated the series of such concurrent scour/bearing-capacity-failure/flow processes leading to the instability of the breakwater. The influence of placing an embankment as a countermeasure was also examined by employing different bank thickness. It is shown that the stability of the breakwaters was significantly improved with decreasing hydraulic gradient that manifested underneath the caissons due to the embankment effect. These findings will facilitate better assessment and improvement of the stability of caisson breakwaters with rubble mound foundations. [ABSTRACT FROM AUTHOR]