We developed a new measurement method for the isometric knee extensor strength with a hand-held dynamometer (HHD). The purpose of this study was to assess the clinical utility of the new method by ...examining the interrater reliability between male and female rater, validity and simplicity. The subjects were 31 community-dwelling elderly people (9 male, 22 female, mean age 81.6±6.1 years) who were receiving a day-care rehabilitation program. Their isometric knee extensor strength were measured three times by this method and the belt method that fixed a HHD by a belt. The time to finish the measurement was recorded under the condition that the rater was masked. As a result, intraclass correlation coefficient (ICC), which represents interrater reliability between male and female rater, was 0.96. There were no significant differences in the measurement values between this method (male and female rater) and the belt method. ICCs of the belt method were 0.89 in male rater and 0.90 in female rater. The time to finish the measurement by this method was 2 minutes and 12 seconds (± 40 second) on average, which was significantly shorter than the belt method (p<0.05). From these results, the reliability, validity and simplicity for the frail elderly of this new method were considered acceptable.
Abstract
Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) ...fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.
Background
Although tolvaptan is an effective treatment for hepatic edema, there are no established criteria for assessment of the therapeutic effect. The present study evaluates the association ...between body weight change and clinical symptoms to identify an effective indicator of tolvaptan response.
Methods
The study comprised 460 patients. The first data set contained 147 patients with hepatic edema who received tolvaptan in Kagoshima Kouseiren Hospital, a representative institution of this study. From these data, an optimal cutoff value of body weight change, which accurately indicated symptom reduction, was identified. The response rates obtained based on the cutoff value were evaluated by receiver-operating characteristic (ROC) analysis and kappa coefficients. The kappa coefficient was then validated internally using the bootstrap method and externally using the validation data set of 313 patients from four other hospitals.
Results
A cutoff value for body weight loss of 1.5 kg/week produced the largest area under the ROC curve (0.961; sensitivity, 89.8%; specificity, 92.0%) and a high kappa coefficient (0.831). The correlation between symptom reduction and body weight loss of 1.5 kg/week was evaluated internally and externally, and the cutoff value was validated.
Conclusions
The cutoff value of body weight change that most accurately reflected symptom reduction was 1.5 kg/week; this value is expected to be an effective indicator of response to tolvaptan in clinical practice.
Carbon nanoarchitectures derived from biobased building blocks are potential sustainable alternatives to electrode materials generated with petroleum-derived resources. We aim at developing a ...fundamental understanding on the connection between the structure and electrochemical performance of porous carbon nanofiber (PCNF) architectures from the polysaccharide chitosan as a biobased building block. We fabricated a range of PCNF architectures from the chitosan carbon precursor and tailored their structure by varying the amount and molecular weight of the sacrificial pore-forming polymer poly(ethylene oxide). The morphology (high-resolution scanning electron microscopy), carbon structure (X-ray diffraction, transmission electron microscopy), pore network (N2 gas adsorption, small-angle X-ray scattering), and surface/bulk composition (X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy) were studied in detail together with a comprehensive electrochemical analysis on the fabricated electrodes. In supercapacitor devices, the best-performing freestanding electrode had (1) a high accessible surface area (a s,BET ≈ 700 m2 g–1) and hierarchical pore network (micro- and mesopores) providing a fast ion diffusion process, high specific capacitance, and rate capability, (2) surface chemistry allowing a high Coulombic efficiency by avoiding parasitic Faradaic side reactions, and (3) a unique turbostratic carbon nanostructure leading to low charge transfer resistance while keeping good electrical conductivity. This electrode exhibited good stability over 2000 cycles (at 2 A g–1) with high capacitance retention (>80%) and charge efficiency (>90%). In the capacitive deionization (CDI) device, our electrode demonstrated an ultrahigh salt adsorption capacity of 23.6 mg g–1, which is among the state-of-the-art values reported for a biobased carbon. A high charge efficiency (85%) was achieved during the CDI process using low-cost materials, in contrast to similarly performing devices fabricated with expensive ion exchange membranes or petroleum-based carbon precursors. Our results demonstrate that inexpensive chitosan-based materials can be readily transformed in one carbonization step without any aggressive activating chemicals into tailor-made hierarchically ordered state-of-the-art carbon materials for charge storage devices.
Ultrafine porous carbon nanofiber network with ~40 nm fiber diameter is realized for the first time utilizing a biobased polymer as carbon precursor. A simple one-step carbonization procedure is ...applied to convert the electrospun chitosan/poly(ethylene oxide) nanofibers to self-N-doped ultrafine hierarchically porous carbon nanofiber interconnected web. The pore formation process is governed by the immiscible nature of the two polymers and the sacrificial character of poly(ethylene oxide) with low carbon yield at the carbonization temperature (800 °C). The obtained porous scaffold has a high specific surface area (564 m2 g−1), high micro (0.22 cm3 g−1) as well as meso/macropore volume (0.28 cm3 g−1). Structural analysis indicates high graphitic content and the existence of turbostratic carbon typical for carbon fibers derived from otherwise synthetic polymer precursors. X-ray photoelectron spectroscopy confirms the presence of an N-doped structure with dominating graphitic N, together with a smaller amount of pyridinic N. The prepared electrode exhibits good electrochemical performance as a supercapacitor device. The excellent charge storage characteristics are attributed to the unique ultrafine hierarchical nanoarchitecture and the interconnected N-doped carbon structure. This green material holds great promise for the realization of more sustainable high-performance energy storage devices.
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•Chitosan is used to prepare porous carbon nanofiber network for the first time.•Advanced nanoarchitecture is obtained using poly(ethylene oxide) as porogen.•The ultrafine carbon nanofiber web has an advantageous hierarchical pore structure.•A self-N-doped turbostratic carbon structure is realized without additives.•The fabricated electrode exhibits excellent capacitive charge storage performance.
Aim: Experimental studies of human atherogenesis require an appropriate animal model that mimics human physiology and pathology. Because swine physiology is similar to human physiology, we developed ...a hyperlipidemia-induced atherosclerosis model using the recently developed world’s smallest MicrominipigTM. Methods: These animals weigh only 5kg at 3months of age, much smaller than any other miniature pig. We found that the administration of a high-fat/high-cholesterol diet containing at least 0.2% cholesterol without cholic acid for as little as eight weeks induces hypercholesterolemia and subsequent atherosclerosis in these animals. Results: The serum levels of low-density lipoprotein cholesterol(LDL-C) and the percent distribution of cholesterol in the LDL fractions were markedly increased. The hepatic expression of LDL receptor and hydroxymethylglutaryl-CoA reductase was coordinately decreased. The cholesteryl ester transfer protein activity, which plays a role in reverse cholesterol transport, was detected in the serum of the Microminipigs. Niemann-Pick C1-like 1 protein was expressed in both the liver and small intestine; however, hepatic apoB mRNA editing enzyme was not expressed. As in humans, and in contrast to that observed in mice, most of the hepatic lipase activity was localized in the liver. These results suggest that the hyperlipidemia-induced gene expression profile linked to cholesterol homeostasis and atherogenesis is similar in Microminipigs and humans. Conclusion: We conclude that the characteristics of the Microminipig, including its easy handling size, make it an appropriate model for studies of atherosclerosis and related conditions.
Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms ...involving inflammation and the accumulation of amyloid-β (Aβ), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear.
To test our hypothesis that Aβ, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied.
Seven-week-old C57BL/6 male mice were injected with 15 μL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aβ, tau, and p-tau were assessed immunohistochemically over time.
On day 7 after blood injection, Iba-1+ and S100B+ cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3–14, Aβ deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14–28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aβ. Deposits of Aβ, but not tau/p-tau, were phagocytosed by CD163+ macrophages increased by Gc-protein macrophage-activating factor during days 7–28, suggesting different mechanisms of deposition and regulation between Aβ and tau/p-tau.
Deposition and regulation differ between Aβ and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed.
•Cerebral microbleeds due to brain injury may be a factor in Alzheimer's disease.•We imitated cerebral microbleeds by blood microinjection into the brains of mice.•The mechanism of accumulation of amyloid may be different from that of tau and p-tau.•We find amyloid-β is accumulated by inflammatory changes occurred by the injection.•The accumulation of tau / p-tau may be associated with hem by injecting blood.
The southern Izu‐Bonin arc is the volcanic representation of Pacific Ocean lithosphere subduction beneath the oceanic crust of the Philippine Sea plate. We present new geochemical data including ...high‐precision Pb isotopic measurements from the 700 km length of this intraoceanic arc. An aim of this study is to link the along‐arc characteristics with variations in the subducting Pacific crust. Chemical variations have been previously recognized along the northern section of the arc as a southward decrease in 87Sr/86Sr and increase in 206Pb/204Pb. This trend continues into the southern arc as far as 27.5°N. An overall correlation between 87Sr/86Sr and fluid‐mobile element enrichment between 35 and 27.5°N implies a contribution of a slab‐derived fluid, mainly from altered oceanic crust and pelagic sediment. However, the observation that volcanoes plot systematically closer to the Northern Hemisphere Reference Line (NHRL) with increasing 206Pb/204Pb indicates that a component other than pelagic sediment and ocean crust plays a key role toward the south. South of 27.5°N, the along‐arc isotopic trend changes dramatically, with 87Sr/86Sr increasing southward from 27.5°N and the 206Pb/204Pb becoming highly radiogenic (∼19.6). This isotopic signature requires involvement of a component with high 206Pb/204Pb and low Δ8/4. Volcaniclastic sediments originating from HIMU oceanic islands on the subducting Pacific Plate are possible candidates to introduce such a component into the mantle wedge. This is consistent with the sedimentary section of ODP Site 801, located outboard of the Mariana arc which has >40% mass of HIMU volcaniclastics. An aqueous fluid, not melt, has played a major role in the source magma compositions in the 27.5–25°N segment. South of 25°N the isotopic characteristics again change significantly. 143Nd/144Nd decreases down to 0.51280, but the high 206Pb/204Pb and low Δ8/4 signatures are retained. The remarkable Th enrichment associated with low 143Nd/144Nd, Δ8/4, and Δ7/4 suggests that melting a mixture of HIMU volcaniclastics and pelagic sediment is responsible for the geochemical characteristics of this most southerly section.
Anthocyanidins are the aglycon nucleuses of anthocyanins, which are reddish pigments widely spread in colored fruits and vegetables. To investigate their anti-cancer effect, induction of apoptosis ...was tested in human promyelocytic leukemia cells (HL-60), which is a valid model for testing antileukemic or general antitumoral compounds. Of six anthocyanidins representing the aglycons of most of anthocyanins, only those with an ortho-dihydroxyphenyl structure on the B-ring induce apoptosis, suggesting that the ortho-dihydroxyphenyl structure of anthocyanidins may contribute to the induction of apoptosis. Delphinidin, the most potent inducer, causes apoptosis in a time- and dose-dependent manner. The efficacious induction of apoptosis was observed at 100 micro M for 6 h. Concomitant with the apoptosis, delphinidin stimulates JNK pathway activation including JNK phosphorylation and c-jun gene expression, and activates caspase-3. Antioxidants including N-acetyl-L-cysteine (NAC) and catalase effectively block delphinidin-induced JNK phosphorylation, caspase-3 activation, and DNA fragmentation. Moreover, anthocyanidins directly cause HL-60 cells to generate intracellular hydrogen peroxide. Thus, anthocyanidins may trigger an apoptotic death program through an oxidative stress-involved JNK signaling pathway. The induction of apoptosis by anthocyanins may be the pivotal mechanism by which its chemopreventive action against cancer is based.
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