Comparison of the Berg Balance Scale and Fullerton Advanced Balance Scale to predict falls in community-dwelling adults.

[Purpose] The purpose of this study was to investigate and compare the predictive properties of Berg Balance Scale and Fullerton Advanced Balance Scales, in a group of independently-functioning community dwelling older adults. [Subjects and Methods] Ninety-seven community-dwelling older adults (male=39, female=58) who were capable of walking independently on assessment were included in this study. A binary logistic regression analysis of the Berg Balance Scale and Fullerton Advanced Balance Scale scores was used to investigate a predictive model for fall risk. A receiver operating characteristic analysis was conducted for each, to determine the cut-off for optimal levels of sensitivity and specificity. [Results] The overall prediction success rate was 89.7%; the total Berg Balance Scale and Fullerton Advanced Balance Scale scores were significant in predicting fall risk. Receiver operating characteristic analysis determined that a cut-off score of 40 out of 56 on the Berg Balance Scale produced the highest sensitivity (0.82) and specificity (0.67), and a cut-off score of 22 out of 40 on the Fullerton Advanced Balance Scale produced the highest sensitivity (0.85) and specificity (0.65) in predicting faller status. [Conclusion] The Berg Balance Scale and Fullerton Advanced Balance Scales can predict fall risk, when used for independently-functioning community-dwelling older adults.

Comparison of the psychometric properties of two balance scales in children with cerebral palsy.

[Purpose] The purpose of this study was to compare the item difficulty degree between the Pediatric Balance Scale and Fullerton Advanced Balance scale for children with cerebral palsy. [Subjects and Methods] Forty children with cerebral palsy (male=17, female=23) voluntarily participated in the study. Item difficulty was expressed in the Rasch analysis using a logit value, with a higher value indicative of increasing item difficulty. [Results] Among the 24 items of the combined Pediatric Balance Scale and Fullerton Advanced Balance scale, the most difficult item was "Walk with head turns", whereas, the easiest item was "Sitting with back unsupported and feet supported on the floor". Among the 14 items of the Pediatric Balance Scale, 9 items (item 1, 2, 3, 4, 5, 6, 7, 11, and 12) had negative logit values, whereas for the Fullerton Advanced Balance scale, only 1 item (item 1) had a negative logit value. [Conclusion] The Fullerton Advanced Balance scale is a more appropriate tool to assess balance ability than the Pediatric Balance Scale in in a group of higher functioning children with cerebral palsy.

Potential neuroprotective flavonoid-based inhibitors of CDK5/p25 from Rhus parviflora.

Rhus parviflora (Anacardiaceae) is an indigenous medicinal shrub found in South Asia with flavonoid rich edible fruit. This study examined flavonoid derivatives of R. parviflora fruit with CDK5/p25 inhibition activity. Evaluation by in vitro assay and docking simulations for CDK5/p25 revealed that the aurones, sulfuretin (1) and aureusidin (2), the aurone glycoside, aureusidin-6-O-ß-D-glucopyranoside (3) and hovetrichoside C (4), the flavonoid glycoside, quercetin-3-O-ß-D-galactopyranoside (5), and the biflavonoid, cupressuflavone (6), had the potential to inhibit CDK5/p25, which could be useful in the treatment of neurodegenerative disorders such as Alzheimer's disease. Compound2 showed the significant in vitro inhibition capacity (IC50 value of 4.81 µM) as well as binding affinity with docking energy of -8.73 (kcal/mol) for active sites CYS83 and GLN130 of CDK5/p25 enzyme in comparison to reference compound R-roscovitine.

Effects of peptides derived from BACE1 catalytic domain on APP processing.

One of the hallmarks of Alzheimer's disease (AD) is the deposition of beta-amyloid (Abeta) peptides in neuritic plaques. Abeta peptides are derived from sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. beta-APP cleaving enzyme-1 (BACE1) has been shown to be the major beta-secretase and is a primary therapeutic target for AD. We report here novel BACE1 inhibitory peptidomimetics, which are derived from catalytic domains of BACE1 themselves, instead of APP cleavage sites and are structurally modified by myristoylation in N-terminus for efficient cell permeability. The peptides not only inhibited the formation of APPbeta (a soluble N-terminal fragment of APP cleaved by beta-secretase), but also significantly reduced Abeta40 production. Our results suggest a new approach for identifying inhibitory agents for the treatment of AD.

Apoptosis induced by ID6105, a new anthracycline (11-hydroxyaclacinomycin X, Hyrubicin), and its anti-tumor effects on experimental tumor models.

A new anthracycline ID6105 (11-hydroxyaclacinomycin X, Hyrubicin), which has potent antitumor activities against a broad range of cancer cell lines, was produced by hybrid biosynthetic approach. We investigated ID6105-induced apoptosis and in vivo efficacy on experimental tumors, and also defined its optimal dosing schedule. From PARP cleavage assay and caspase-3 activation assay, we found that ID6105 can induce apoptosis in tumor cells and its ability was superior to doxorubicin. In human tumor xenograft models, ID6105 showed greater antitumor effects on SW620 and NCI-H23 than doxorubicin. The 1 mg/kg of ID6105 treatment reduced size of tumor by 93% in NCI-H23 model whereas doxorubicin (2 mg/kg) showed only 39% inhibition rate. In SW620 model, 0.3 mg/kg of ID6105 proved to be comparable to 2 mg/kg of doxorubicin. Testing with several dosing schedule such as qd10, qd5, and q4d3, we decided intravenous qd5 treatment was an optimal schedule as a dose regimen of ID6105. In conclusion, ID6105 is a potent apoptosis-inducing anthracycline and effective in treatment of tumors with qd5 dosing schedule.

Inhibition of BETA2/NeuroD by Id2.

Id (Inhibitor of Differentiation) proteins belong to a family of transcriptional modulators that are characterized by a helix loop helix (HLH) region but lack the basic amino acid domain. Id proteins are known to interact with basic helix-loop-helix (bHLH) transcription factors and function as their negative regulators. The negative role of Id proteins has been well demonstrated in muscle development and some in neuronal cells. In this study, we investigated the effect of Id on the function of BETA2/NeuroD, a bHLH transcription factor responsible for neuron and endocrine cell specific gene expression. cDNAs of several Id isoforms were isolated by yeast two-hybrid system using the bHLH domain of E47, a ubiquitous bHLH partner as a bait. Id proteins expressed in COS M6 cells, were found in both cytosolic and nuclear fractions. Electrophoretic mobility shift assay showed that coexpression of Id2 proteins inhibited BETA2/ NeuroD binding to its target sequence, E-box. Id2 inhibited E-box mediated gene expression in a dose dependent manner in BETA2/NeuroD expressing HIT cells. Id coexpressed with BETA2/NeuroD in HeLa cells, inhibited the stimulatory activity of BETA2/NeuroD. These results suggest that Id proteins may negatively regulate tissue specific gene expression induced by BETA2/NeuroD in neuroendocrine cells and the inhibitory role of Id proteins during differentiation may be conserved in various tissues.

Synthesis and anticancer activity of geldanamycin derivatives derived from biosynthetically generated metabolites.

A new series of geldanamycin derivatives were synthesized using a semi-synthetic approach involving genetically engineered biosynthetic intermediates. These analogues were then evaluated for anti-proliferation activity in human cancer cell lines, SK-Br3 and SK-Ov3. Most of the synthesized compounds exhibited potent in vitro anti-proliferation activity toward both cell lines. Such compounds potently inhibited the expression of the Hsp90 client protein ErbB2.