335 research outputs found

    Behavioral characteristics of chinese adolescents with dyslexia: The use of teachers' behavior checklist in Hong Kong

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    T2 Values of Posterior Horns of Knee Menisci in Asymptomatic Subjects

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    [[abstract]]Purpose: The magnetic resonance (MR) T2 value of cartilage is a reliable indicator of tissue properties and therefore may be used as an objective diagnostic tool in early meniscal degeneration. The purpose of this study was to investigate age, gender, location, and zonal differences in MR T2 value of the posterior horns of knee menisci in asymptomatic subjects. Methods: Sixty asymptomatic volunteers (30 men and 30 women) were enrolled and divided into three different age groups: 20–34, 35–49 and 50–70 years. The inclusion criteria were BMI<30 kg/cm2, normalized Western Ontario and McMaster Universities (WOMAC) pain score of zero, and no evidence of meniscal and ligamentous abnormalities on routine knee MR imaging. The T2 values were measured on images acquired with a T2-weighted fat-suppressed turbo spin-echo sequence at 3T. Results: The mean T2 values in both medial and lateral menisci for the 20–34, 35–49, and 50–70 age groups were 9.94 msec±0.94, 10.73 msec±1.55, and 12.36 msec±2.27, respectively, for women and 9.17 msec±0.74, 9.64 msec±0.67, and 10.95 msec±1.33, respectively, for men. The T2 values were significantly higher in the 50–70 age group than the 20–34 age group (P<0.001) and in women than in men (P = 0.001, 0.004, and 0.049 for each respective age group). T2 values were significantly higher in medial menisci than in lateral menisci only in women age 50–70 (3.33 msec, P = 0.006) and in the white zone and red/white zone of the 50–70 and 35–49 age groups than that of the 20–34 age group (2.47, 1.02; 2.77, 1.16 msec, respectively, all P<0.01). Conclusion: The MR T2 values of the posterior meniscal horns increase with increasing age in women and are higher in women than in men. The age-related rise of T2 values appears to be more severe in medial menisci than in lateral menisci. Differences exist in the white zone and red/white zone.[[incitationindex]]SCI[[booktype]]電子

    Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity

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    The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/ or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and Cterminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn136 in V1 (T138N mutation) inconjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N139INN sequence, which ablates the overlapping Asn141-Asn142-Ser-Ser potential N-linked glycosylation sequons inV1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu593, Trp596 and Lys601. The 136 and/or 142glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a setting of NAb selection

    Effect of prolonged HAART on oral colonization with Candida and candidiasis

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    BACKGROUND: Progressive cell-mediated immunodeficiency with decrease of CD4+ lymphocyte count to less than or equal to 200 cells/mm(3 )is a major risk factor for colonization with Candida species and development of candidiasis. Oropharyngeal candidiasis may occur in up to 90% of human immunodeficiency virus (HIV)-infected patients during the course of the disease. This study is to determine the effect of prolonged highly active antiretroviral therapy (HAART) on oropharyngeal colonization with Candida species and oral candidiasis. METHODS: A prospective, longitudinal follow-up study in HIV-infected patients receiving HAART. RESULTS: The mean CD4+ count increased from 232.5 to 316 cells/mm(3 )and the proportion of patients whose CD4+ count less than 200 cells/mm(3 )decreased from 50.0% to 28.9% (p = 0.0003) in patients receiving HAART for at least 2 years. The prevalence of oral candidiasis decreased from 10.6% to 2.1% (p = 0.004). The decrease in Candida colonization was less impressive, falling from 57.8% to 46.5 % (p = 0.06). Of the 142 patients enrolled in at least two surveys, 48 (33.8%) remained colonized with Candida and 42 (29.6%) remained negative. In the remaining 52 patients, 34 switched from culture positive to negative, and an increase in CD4+ lymphocytes was noted in 91.2% of them. Among the 18 patients who switched from culture negative to positive, 61.1% also demonstrated an increase in CD4+ lymphocyte count (p = 0.01). CONCLUSION: These findings indicate that HAART is highly effective in decreasing oral candidiasis in association with a rise in CD4+ lymphocyte counts, but only marginally effective in eliminating Candida from the oropharynx

    Type III Secretion System Genes of Dickeya dadantii 3937 Are Induced by Plant Phenolic Acids

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    Background: Dickeya dadantii is a broad-host range phytopathogen. D. dadantii 3937 (Ech3937) possesses a type III secretion system (T3SS), a major virulence factor secretion system in many Gram-negative pathogens of plants and animals. In Ech3937, the T3SS is regulated by two major regulatory pathways, HrpX/HrpY-HrpS-HrpL and GacS/GacA-rsmB-RsmA pathways. Although the plant apoplast environment, low pH, low temperature, and absence of complex nitrogen sources in media have been associated with the induction of T3SS genes of phytobacteria, no specific inducer has yet been identified. Methodology/Principal Findings: In this work, we identified two novel plant phenolic compounds, o-coumaric acid (OCA) and t-cinnamic acid (TCA), that induced the expression of T3SS genes dspE (a T3SS effector), hrpA (a structural protein of the T3SS pilus), and hrpN (a T3SS harpin) in vitro. Assays by qRT-PCR showed higher amounts of mRNA of hrpL (a T3SS alternative sigma factor) and rsmB (an untranslated regulatory RNA), but not hrpS (a s 54-enhancer binding protein) of Ech3937 when these two plant compounds were supplemented into minimal medium (MM). However, promoter activity assays using flow cytometry showed similar promoter activities of hrpN in rsmB mutant Ech148 grown in MM and MM supplemented with these phenolic compounds. Compared with MM alone, only slightly higher promoter activities of hrpL were observed in bacterial cells grown in MM supplemented with OCA/TCA. Conclusion/Significance: The induction of T3SS expression by OCA and TCA is moderated through the rsmB-Rsm

    Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation

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    BACKGROUND: Mycoplasmas are the smallest microorganisms capable of self-replication. Our previous studies show that some mycoplasmas are able to induce malignant transformation of host mammalian cells. This malignant transformation is a multistage process with the early infection, reversible and irreversible stages, and similar to human tumor development in nature. The purpose of this study is to explore mechanisms for this malignant transformation. METHODS: To better understand mechanisms for this unique process, we examined gene expression profiles of C3H cells at different stages of the mycoplasma-induced transformation using cDNA microarray technology. A total of 1185 genes involved in oncogenesis, apoptosis, cell growth, cell-cycle regulation, DNA repair, etc. were examined. Differences in the expression of these genes were compared and analyzed using the computer software AtlasImage. RESULTS: Among 1185 genes screened, 135 had aberrant expression at the early infection stage, 252 at the reversible stage and 184 at the irreversible stage. At the early infection stage, genes with increased expression (92 genes) were twice more than those with decreased expression (42 genes). The global gene expression at the reversible stage appeared to be more volatile than that at any other stages but still resembled the profile at the early infection stage. The expression profile at the irreversible stage shows a unique pattern of a wide range of expression levels and an increased number of expressing genes, especially the cancer-related genes. Oncogenes and tumor suppressors are a group of molecules that showed significant changes in expression during the transformation. The majority of these changes occurred in the reversible and irreversible stages. A prolonged infection by mycoplasmas lead to the expression of more cancer related genes at the irreversible stage. CONCLUSION: The results indicate that the expression profiles correspond with the phenotypic features of the cells in the mycoplasma induced transformation process. The early mycoplasma infection stage shares a common phenomenon with many other acute infections, genes with increased expression significantly outnumbering those with decreased expression. The reversible stage is a transition stage between benignancy and malignancy at the molecular level. Aberrant expression of oncogenes and tumor repressors plays a key role in mycoplasma-induced malignant transformation

    Utilization of IκB–EGFP Chimeric Gene as an Indicator to Identify Microbial Metabolites with NF-κB Inhibitor Activity

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    NF-κB regulates several important expressions, such as cytokine release, anti-apoptosis, adhesion molecule expression, and cell cycle processing. Several NF-κB inhibitors have been discovered as an anti-tumor or anti-inflammatory drug. The activity of NF-κB transcription factor is negatively regulated by IκB binding. In this study, IκB assay system was established and IκB–EGFP fusion protein was used as an indicator to monitor the effects of substances on the IκB degradation. The results indicated that the chosen hydroquinone could inhibit the IκB degradation and cause the cell de-attachment from the bottom of culture plate. In addition, this system could also monitor the IκB degradation of microbial metabolite of natural mixtures of propolis. Thus, the IκB assay system may be a good system for drug discovery related to microbial metabolite

    Using principal component analysis to develop a single-parameter screening tool for metabolic syndrome

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    Abstract Background Metabolic syndrome (MS) is an important current public health problem faced worldwide. To prevent an "epidemic" of this syndrome, it is important to develop an easy single-parameter screening technique (such as waist circumference (WC) determination recommended by the International Diabetes Federation). Previous studies proved that age is a chief factor corresponding to central obesity. We intended to present a new index based on the linear combination of body mass index, and age, which could enhance the area under the receiver operating characteristic curves (AUCs) for assessing the risk of MS. Methods The labour law of the Association of Labor Standard Law, Taiwan, states that employers and employees are respectively obligated to offer and receive routine health examination periodically. Secondary data analysis and subject's biomarkers among five high-tech factories were used in this study between 2007 and 2008 in northern Taiwan. The subjects included 4712 males and 4196 females. The first principal component score (FPCS) and equal-weighted average (EWA) were determined by statistical analysis. Results Most of the metabolic and clinical characteristics were significantly higher in males than in females, except high-density lipoprotein cholesterol level. The older group (>45 years) had significantly lower values for height and high-density lipoprotein cholesterol level than the younger group. The AUCs of FPCS and EWA were significantly larger than those of WC and waist-to-height ratio. The low specificities of EWA and FPCS were compensated for by their substantially high sensitivities. FPCS ≥ 0.914 (15.4%) and EWA ≥ 8.8 (6.3%) were found to be the most prevalent cut off points in males and females, respectively. Conclusions The Bureau of Health Promotion, Department of Health, Taiwan, had recommended the use of WC ≥ 90 cm for males and ≥ 80 cm for females as singular criteria for the determination of central obesity instead of multiple parameters. The present investigation suggests that FPCS or EWA is a good predictor of MS among the Taiwanese. However, the use of FPCS is not computationally feasible in practice. Therefore, we suggest that EWA be used in clinical practice as a simple parameter for the identification of those at risk of MS.</p

    Vascular disrupting agents in clinical development

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    Growth of human tumours depends on the supply of oxygen and nutrients via the surrounding vasculature. Therefore tumour vasculature is an attractive target for anticancer therapy. Apart from angiogenesis inhibitors that compromise the formation of new blood vessels, a second class of specific anticancer drugs has been developed. These so-called vascular disrupting agents (VDAs) target the established tumour vasculature and cause an acute and pronounced shutdown of blood vessels resulting in an almost complete stop of blood flow, ultimately leading to selective tumour necrosis. As a number of VDAs are now being tested in clinical studies, we will discuss their mechanism of action and the results obtained in preclinical studies. Also data from clinical studies will be reviewed and some considerations with regard to the future development are given

    Biomechanical comparison of a new stand-alone anterior lumbar interbody fusion cage with established fixation techniques – a three-dimensional finite element analysis

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    <p>Abstract</p> <p>Background</p> <p>Initial promise of a stand-alone interbody fusion cage to treat chronic back pain and restore disc height has not been realized. In some instances, a posterior spinal fixation has been used to enhance stability and increase fusion rate. In this manuscript, a new stand-alone cage is compared with conventional fixation methods based on the finite element analysis, with a focus on investigating cage-bone interface mechanics and stress distribution on the adjacent tissues.</p> <p>Methods</p> <p>Three trapezoid 8° interbody fusion cage models (dual paralleled cages, a single large cage, or a two-part cage consisting of a trapezoid box and threaded cylinder) were created with or without pedicle screws fixation to investigate the relative importance of the screws on the spinal segmental response. The contact stress on the facet joint, slip displacement of the cage on the endplate, and rotational angle of the upper vertebra were measured under different loading conditions.</p> <p>Results</p> <p>Simulation results demonstrated less facet stress and slip displacement with the maximal contact on the cage-bone interface. A stand-alone two-part cage had good slip behavior under compression, flexion, extension, lateral bending and torsion, as compared with the other two interbody cages, even with the additional posterior fixation. However, the two-part cage had the lowest rotational angles under flexion and torsion, but had no differences under extension and lateral bending.</p> <p>Conclusion</p> <p>The biomechanical benefit of a stand-alone two-part fusion cage can be justified. This device provided the stability required for interbody fusion, which supports clinical trials of the cage as an alternative to circumferential fixations.</p
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