DNA methylation of microRNA genes in multiple myeloma

DNA methylation is one of the heritable epigenetic modifications, leading to repressed gene expressions and consequent phenotypic alterations without changing the DNA sequence. MicroRNA (miRNA) is a novel class of short non-coding RNA molecules regulating a wide range of cellular functions through translational repression of their target genes. Recently, epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM). This article presents a brief overview of the pathogenesis of MM, the role of DNA methylation in cancer biology, methods of DNA methylation analysis, miRNA biology and dysregulation of miRNAs in MM and summaries the current data on the role of DNA methylation of tumor-suppressive miRNAs in MM.postprin

Systematic review of the nonsurgical management of atlantoaxial rotatory fixation in childhood

OBJECTIVE: Atlantoaxial rotatory fixation (AARF) is an acquired fixed abnormality of C1–2 joint rotation associated with torticollis in childhood. If the condition is left uncorrected, patients are at risk for developing C1–2 fusion with permanent limitation in the cervical range of movement, cosmetic deformity, and impact on quality of life. The management of AARF and the modality of nonsurgical treatment are poorly defined in both primary care and specialized care settings, and the optimal strategy is not clear. This systematic review aims to examine the available evidence to answer key questions relating to the nonsurgical management of AARF. METHODS: A systematic review was performed using the following databases: PubMed, MEDLINE, Healthcare Management Information Consortium (HMIC), EMCare, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), British Nursing Index (BNI), and Allied and Complementary Medicine Database (AMED). Search criteria were created and checked independently among the authors. All articles with a radiological diagnosis of AARF and primary outcome data that met the study inclusion criteria were included and analyzed by the authors. RESULTS: Search results did not yield any level I evidence such as a meta-analysis or randomized controlled trial. The initial search yielded 724 articles, 228 of which were screened following application of the core exclusion criteria. A total of 37 studies met the full criteria for inclusion in this review, consisting of 4 prospective studies and 33 retrospective case reviews. No articles directly compared outcomes between modalities of nonsurgical management. Six studies compared the outcome of AARF based on duration of symptoms before initiation of treatment. Comparative analysis of studies was hindered by the wide variety of treatment modalities described and the heterogeneity of outcome data. CONCLUSIONS: The authors did not identify any level I evidence comparing different nonsurgical management approaches for AARF. There were few prospective studies, and most studies were uncontrolled, nonrandomized case series. Favorable outcomes were often reported regardless of treatment methods, with early treatment of AARF tending to yield better outcomes independent of the treatment modality. There is a lack of high-quality data, and further research is required to determine the optimal nonsurgical treatment strategy

An EEG-based perceptual function integration network for application to drowsy driving

© 2015 Elsevier B.V. All rights reserved. Drowsy driving is among the most critical causes of fatal crashes. Thus, the development of an effective algorithm for detecting a driver's cognitive state demands immediate attention. For decades, studies have observed clear evidence using electroencephalography that the brain's rhythmic activities fluctuate from alertness to drowsiness. Recognition of this physiological signal is the major consideration of neural engineering for designing a feasible countermeasure. This study proposed a perceptual function integration system which used spectral features from multiple independent brain sources for application to recognize the driver's vigilance state. The analysis of brain spectral dynamics demonstrated physiological evidenced that the activities of the multiple cortical sources were highly related to the changes of the vigilance state. The system performances showed a robust and improved accuracy as much as 88% higher than any of results performed by a single-source approach

A unified constitutive model for asymmetric tension and compression creep-ageing behaviour of naturally aged Al-Cu-Li alloy

A set of unified constitutive equations is presented that predict the asymmetric tension and compression creep behaviour and recently observed double primary creep of pre-stretched/naturally aged aluminium-cooper-lithium alloy AA2050-T34. The evolution of the primary micro- and macro-variables related to the precipitation hardening and creep deformation of the alloy during creep age forming (CAF) are analysed and modelled. Equations for the yield strength evolution of the alloy, including an initial reversion and subsequent strengthening, are proposed based on a theory of concurrent dissolution, re-nucleation and growth of precipitates during artificial ageing. We present new observations of so-called double primary creep during the CAF process. This phenomenon is then predicted by introducing effects of interacting microstructures, including evolving precipitates, diffusing solutes and dislocations, into the sinh-law creep model. In addition, concepts of threshold creep stress σth and a microstructure-dependant creep variable H, which behave differently under different external stress directions, are proposed and incorporated into the creep model. This enables prediction of the asymmetric tension and compression creep-ageing behaviour of the alloy. Quantitative transmission electron microscopy (TEM) and related small-angle X-ray scattering (SAXS) analysis have been carried out for selected creep-aged samples to assist the development and calibration of the constitutive model. A good agreement has been achieved between the experimental results and the model. The model has the potential to be applied to creep age forming of other heat-treatable aluminium alloys

Identifying changes in EEG information transfer during drowsy driving by transfer entropy

© 2015 Huang, Pal, Chuang and Lin. Drowsy driving is a major cause of automobile accidents. Previous studies used neuroimaging based approaches such as analysis of electroencephalogram (EEG) activities to understand the brain dynamics of different cortical regions during drowsy driving. However, the coupling between brain regions responding to this vigilance change is still unclear. To have a comprehensive understanding of neural mechanisms underlying drowsy driving, in this study we use transfer entropy, a model-free measure of effective connectivity based on information theory. We investigate the pattern of information transfer between brain regions when the vigilance level, which is derived from the driving performance, changes from alertness to drowsiness. Results show that the couplings between pairs of frontal, central, and parietal areas increased at the intermediate level of vigilance, which suggests that an enhancement of the cortico-cortical interaction is necessary to maintain the task performance and prevent behavioral lapses. Additionally, the occipital-related connectivity magnitudes monotonically decreases as the vigilance level declines, which further supports the cortical gating of sensory stimuli during drowsiness. Neurophysiological evidence of mutual relationships between brain regions measured by transfer entropy might enhance the understanding of cortico-cortical communication during drowsy driving

Lycopene inhibits cell migration and invasion and upregulates Nm23-H1 in a highly invasive hepatocarcinoma, SK-Hep-1 cells

[[abstract]]The carotenoid lycopene has been associated with decreased risks of several types of cancer, such as prostate cancer and hepatoma. Tumor metastasis is the most important cause of cancer death. Although lycopene was shown to inhibit metastasis, the mechanism underlying this action is not well understood. Here, we tested the possibility that lycopene may inhibit cancer cell metastasis by upregulating the expression of nm23-H1, a metastasis suppressor gene, in SK-Hep-1 cells, a highly invasive hepatoma cell line, and we determined migration and invasion activities and the expression of nm23-H1 protein and mRNA. We showed that lycopene inhibited SK-Hep-1 migration and invasion in a bell-shaped manner, with the highest effect at 5 ?mol/L (91 and 63% inhibition for migration and invasion, respectively; P < 0.05). At the same test level (10 ?mol/L), lycopene was much more effective than ?-carotene in reducing cell invasion (by 870%). In contrast to the effects on migration and invasion, lycopene enhanced nm23-H1 expression at both the protein and mRNA levels; the effects were also bell shaped, and at 5 ?mol/L, lycopene enhanced nm23-H1 protein and mRNA expressions by 220 ? 33 and 153 ? 22% (P < 0.01), respectively. These bell-shaped effects of lycopene may be related to autoxidation of lycopene at elevated concentrations (10 ?mol/L). Significant correlations existed between nm23-H1 protein expression and migration (r2 = 0.78, P < 0.001) and between nm23-H1 protein expression and invasion (r2 = 0.84, P < 0.001) in lycopene-treated SK-Hep-1 cells. We conclude that lycopene has significant antimigration and anti-invasion activity, and that this effect is associated with its induction of nm23-H1 expression

Lycopene inhibits experimental metastasis of human hepatoma SK-Hep-1 cells in athymic nude mice

[[abstract]]Lycopene has been shown to inhibit tumor metastasis in vitro, but it is unclear whether lycopene is antimetastatic in vivo. Here, nude mice were orally supplemented 2 times per week for 12 wk with a low or high dose of lycopene [1 or 20 mg/kg body weight (BW)] or with β-carotene (20 mg/kg BW). Two weeks after the beginning of supplementation, mice were injected once with human hepatoma SK-Hep-1 cells via the tail vein. Plasma levels of matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) increased gradually in tumor-injected mice (tumor controls) following tumor injection but were markedly lowered by lycopene or β-carotene supplementation. Ten weeks after tumor injection, mice were killed and tumor metastasis was found to be confined to the lungs. Compared with the tumor controls, high-lycopene supplementation lowered the mean number of tumors from 14 ± 8 to 3 ± 5 (P < 0.05) and decreased tumor cross-sectional areas by 62% (P < 0.05). High-lycopene supplementation also decreased the positive rate of proliferating cellular nuclear antigen (PCNA), the level of VEGF, and protein expressions of PCNA, MMP-9, and VEGF in lung tissues. However, high-lycopene increased the protein expression of nm23-H1 (an antimetastatic gene) by 133% (P < 0.001). For most variables measured, effects of lycopene were dose dependent and the effect of β-carotene was between those of high-dose and low-dose lycopene. These results show that lycopene supplementation reduces experimental tumor metastasis in vivo and suggest that such an action is associated with attenuation of tumor invasion, proliferation, and angiogenesis

Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor k B and stimulatory protein 1

[[abstract]]Abstract The carotenoid lycopene has been associated with decreased risks of several types of cancer, such as hepatoma. Although lycopene has been shown to inhibit metastasis, its mechanism of action is poorly understood. Here, we used SK-Hep-1 cells (from a human hepatoma) to test whether lycopene exerts its anti-invasion activity via down-regulation of the expression of matrix metalloproteinase (MMP)-9, an important enzyme in the degradation of basement membrane in cancer invasion. The activity and expressions of MMP-9 protein and mRNA were detected by gelatin zymography, Western blotting and RT-PCR, respectively. The binding abilities of nuclear factor-kappa B (NF-κB), activator protein-1 and stimulatory protein-1 (Sp1) to the binding sites in the MMP-9 promoter were measured by the electrophoretic mobility shift assay. We showed that lycopene (1–10 μM) significantly inhibited SK-Hep-1 invasion (P<.05) and that this effect correlated with the inhibition of MMP-9 at the levels of enzyme activity (r2=.94, P<.001), protein expression (r2=.80, P=.007) and mRNA expression (r2=.94, P<.001). Lycopene also significantly inhibited the binding abilities of NF-κB and Sp1 and decreased, to some extent, the expression of insulin-like growth factor-1 receptor (IGF-1R) and the intracellular level of reactive oxygen species (P<.05). The antioxidant effect of lycopene appeared to play a minor role in its inhibition of MMP-9 and invasion activity of SK-Hep-1 cells because coincubation of cells with lycopene plus hydrogen peroxide abolished the antioxidant effect but did not significantly affect the anti-invasion ability of lycopene. Thus, lycopene decreases the invasive ability of SK-Hep-1 cells by inhibiting MMP-9 expression and suppressing the binding activity of NF-κB and Sp1. These effects of lycopene may be related to the down-regulation of IGF-1R, while the antioxidant activity of lycopene appears to play a minor role

Developing an EEG-based on-line closed-loop lapse detection and mitigation system

© 2014 Wang, Huang, Wei, Huang, Ko, Lin, Cheng and Jung. In America, 60% of adults reported that they have driven a motor vehicle while feeling drowsy, and at least 15-20% of fatal car accidents are fatigue-related. This study translates previous laboratory-oriented neurophysiological research to design, develop, and test an On-line Closed-loop Lapse Detection and Mitigation (OCLDM) System featuring a mobile wireless dry-sensor EEG headgear and a cell-phone based real-time EEG processing platform. Eleven subjects participated in an event-related lane-keeping task, in which they were instructed to manipulate a randomly deviated, fixed-speed cruising car on a 4-lane highway. This was simulated in a 1st person view with an 8-screen and 8-projector immersive virtual-reality environment. When the subjects experienced lapses or failed to respond to events during the experiment, auditory warning was delivered to rectify the performance decrements. However, the arousing auditory signals were not always effective. The EEG spectra exhibited statistically significant differences between effective and ineffective arousing signals, suggesting that EEG spectra could be used as a countermeasure of the efficacy of arousing signals. In this on-line pilot study, the proposed OCLDM System was able to continuously detect EEG signatures of fatigue, deliver arousing warning to subjects suffering momentary cognitive lapses, and assess the efficacy of the warning in near real-time to rectify cognitive lapses. The on-line testing results of the OCLDM System validated the efficacy of the arousing signals in improving subjects' response times to the subsequent lane-departure events. This study may lead to a practical on-line lapse detection and mitigation system in real-world environments

Knowledge-based identification of sleep stages based on two forehead electroencephalogram channels

© 2014 Huang, Lin, Ko, Liu, Su and Lin. Sleep quality is important, especially given the considerable number of sleep-related pathologies. The distribution of sleep stages is a highly effective and objective way of quantifying sleep quality. As a standard multi-channel recording used in the study of sleep, polysomnography (PSG) is a widely used diagnostic scheme in sleep medicine. However, the standard process of sleep clinical test, including PSG recording and manual scoring, is complex, uncomfortable, and time-consuming. This process is difficult to implement when taking the whole PSG measurements at home for general healthcare purposes. This work presents a novel sleep stage classification system, based on features from the two forehead EEG channels FP1 and FP2. By recording EEG from forehead, where there is no hair, the proposed system can monitor physiological changes during sleep in a more practical way than previous systems. Through a headband or self-adhesive technology, the necessary sensors can be applied easily by users at home. Analysis results demonstrate that classification performance of the proposed system overcomes the individual differences between different participants in terms of automatically classifying sleep stages. Additionally, the proposed sleep stage classification system can identify kernel sleep features extracted from forehead EEG, which are closely related with sleep clinician's expert knowledge. Moreover, forehead EEG features are classified into five sleep stages by using the relevance vector machine. In a leave-one-subject-out cross validation analysis, we found our system to correctly classify five sleep stages at an average accuracy of 76.7 ± 4.0 (SD) % [average kappa 0.68 ± 0.06 (SD)]. Importantly, the proposed sleep stage classification system using forehead EEG features is a viable alternative for measuring EEG signals at home easily and conveniently to evaluate sleep quality reliably, ultimately improving public healthcare