Assessing trends and predictors of tuberculosis in Taiwan

<p>Abstract</p> <p>Background</p> <p>Variety of environmental and individual factors can cause tuberculosis (TB) incidence change. The purpose of this study was to assess the characteristics of TB trends in the period 2004 - 2008 in Taiwan by month, year, gender, age, temperature, seasonality, and aborigines.</p> <p>Methods</p> <p>The generalized regression models were used to examine the potential predictors for the monthly TB incidence in regional and national scales.</p> <p>Results</p> <p>We found that (<it>i</it>) in Taiwan the average TB incidence was 68 per 100,000 population with mortality rate of 0.036 person^-1yr^-1, (<it>ii</it>) the highest TB incidence rate was found in eastern Taiwan (116 per 100,000 population) with the largest proportion of TB relapse cases (8.17%), (<it>iii</it>) seasonality, aborigines, gender, and age had a consistent and dominant role in constructing TB incidence patterns in Taiwan, and (<it>iv</it>) gender, time trend, and 2-month lag maximum temperature showed strong association with TB trends in aboriginal subpopulations.</p> <p>Conclusions</p> <p>The proposed Poisson regression model is capable of forecasting patterns of TB incidence at regional and national scales. This study suggested that assessment of TB trends in eastern Taiwan presents an important opportunity for understanding the time-series dynamics and control of TB infections, given that this is the typical host demography in regions where these infections remain major public health problems.</p

The influence of single model ensemble on the simulated extratropical interannual variability

This study compares the interannual variance of boreal winter near-surface temperature (DJF T2m) with and without performing single model ensemble (SME) in seasonal hindcasts (DEMETER, ENSEMBLES, and NCEP CFSv2) and historical climate simulations (CMIP5). The results demonstrate that the extratropical temperature variability is significantly reduced after performing SME even though the signal in the tropical Pacific remains strong. Cancellation between positive and negative perturbations simulated by individual model members, of both tropical and extratropical origins, leads to the under-simulation. The atmospheric circulation induced by tropical Pacific sea surface temperature is not well represented in global climate models and the simulation is further deteriorated by SME, leading to an unrealistically weak interannual variance of simulated winter temperature in North America. Similar effect was also found in North Eurasia where winter temperature is strongly influenced by atmospheric internal variability and its interaction with land and ice/snow in the middle-high latitudes. The SME procedure should be avoided when evaluating the model performance in simulating the higher-order long-term statistics (such as variance). Variance of individual models should be calculated first and then averaged among members. Models used in seasonal forecast and long-term climate simulation already have good capability in simulating the long-term statistics of stochastic processes in the extratropics, although the capability in accurately simulating the temporal variation is still poor

A Lamping U-Shaped Fiber Biosensor Detector for MicroRNA

This study presents a U-shaped optical fiber developed for a facile application of microRNA detection. It is fabricated by the lamping process and packaged in a quartz tube to eliminate human negligence. In addition, silanization and electrostatic self-assembly are employed to bind gold nanoparticles and miRNA-133a probe onto the silicon dioxide of the fiber surface. For Mahlavu of hepatocellular carcinoma (HCC), detection is determined by the wavelength shift and transmission loss of a U-shaped optical fiber biosensor. The spectral sensitivity of wavelength and their coefficient of determination are found at &minus;218.319 nm/ ng/mL and 0.839, respectively. Concurrently, the sensitivity of transmission loss and their coefficient of determination are found at 162.394 dB/ ng/mL and 0.984, respectively. A method for estimating the limit of detection of Mahlavu is at 0.0133 ng/mL. The results show that the proposed U-shaped biosensor is highly specific to miRNA-133a and possesses good sensitivity to variations in specimen concentration. As such, it could be of substantial value in microRNA detection

Correction: Notch Ligand Delta-Like 4-Pretreated Dendritic Cells Alleviate Allergic Airway Responses by Enhancing IL-10 Production.

[This corrects the article DOI: 10.1371/journal.pone.0063613.]

Development of a highly sensitive glycan microarray for quantifying AFP-L3 for early prediction of hepatitis B virus-related hepatocellular carcinoma.

The α-fetoprotein fraction L3 (AFP-L3), which is synthesized by malignant cells and incorporates a fucosylated oligosaccharide, has been investigated as a diagnostic and prognostic marker for hepatocellular carcinoma (HCC). Quantification of AFP-L3 by conventional enzyme-linked immunosorbent assay (ELISA) has not always produced reliable results for serum samples with low AFP, and thus we evaluated the clinical utility of quantifying AFP-L3 using a new and highly sensitive glycan microarray assay. Sera from 9 patients with chronic hepatitis B and 32 patients with hepatitis B virus (HBV)-related HCC were tested for AFP-L3 level using the glycan microarray. Additionally, we compared receiver operator characteristic curves for the ELISA and glycan microarray methods for determination of the AFP-L3: AFP-L1 ratio in patient samples. This ratio was calculated for 8 HCC patients who underwent transarterial embolization therapy pre- or post-treatment with AFP-L3. Glycan microarrays showed that the AFP-L3 ratio of HBV-related HCC patients was significantly higher than that measured for chronic hepatitis B patients. Overall parameters for estimating AFP-L3% in HCC samples were as follows: sensitivity, 53.13%; specificity, 88.89%; and area under the curve, 0.75. The elevated AFP-L3% in the 8 patients with HBV-related HCC was strongly associated with HCC progression. Following one month of transarterial embolization therapy, the relative mean AFP-L3% decreased significantly. In addition, we compared Fut8 gene expression between paired tumor and non-tumor tissues from 24 patients with HBV-related HCC. The Fut8 mRNA expression was significantly increased in tumorous tissues in these patients than that in non-tumor tissue controls. Higher expression of Fut8 mRNA in tumorous tissues in these patients was associated with poor differentiation than well and moderate differentiation. Our results describe a new glycan microarray for the sensitive and rapid quantification of fucosylated AFP; this method is potentially applicable to screening changes in AFP-L3 level for assessment of HCC progression

Notch Ligand Delta-Like 4-Pretreated Dendritic Cells Alleviate Allergic Airway Responses by Enhancing IL-10 Production

<div><p>The Notch pathway plays a role in the processes of cell proliferation, differentiation, and apoptosis, which affect the development and function of various organs. Dendritic cells (DCs), as professional antigen-presenting cells (APCs), induce T cell activation and promote T cell differentiation by antigen stimulation. Research has shown that Notch ligand delta-like 4 (Dll4) in APCs is associated with stimulation of a Th1-type response. However, the regulatory roles of Dll4 in the activation and function of DCs have yet to be clearly elucidated. In this study, we demonstrated that activation of Dll4-pretreated bone marrow-derived DCs by performing ovalbumin (OVA) stimulation expressed a high level of interleukin (IL)-10 without diminishing IL-12 production. By contrast, the proinflammatory cytokines, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, decreased in Dll4-pretreated DCs by performing either lipopolysaccharide (LPS) or OVA stimulation. Compared to fully mature DCs, lower levels of MHC class II CD40 and higher levels of CD80 and CD86 molecules were expressed in these semi-mature like DCs. Dll4 Notch signaling also enhanced Notch ligand mRNA expression of Dll1, Dll4, and Jagged1 in DCs. Dll4-modified DCs exhibited a reduced capacity to stimulate the proliferation of OVA-specific CD4⁺ T cells, but actively promoted large amounts of IL-10 production in these activated T cells. Furthermore, immunomodulatory effects of Dll4-modified DCs were examined in an established asthmatic animal model. After adoptive transfer of OVA-pulsed plus Dll4-pretreated DCs in OVA-immunized mice, OVA challenge induced lower OVA-specific immunoglobulin E (IgE) and higher IgG_2a antibody production, lower eotaxin, keratinocyte-derived chemokine (KC), IL-5, and IL-13 release in bronchial alveolar lavage fluid, attenuated airway hyper-responsiveness, and promoted higher IL-10 and interferon (IFN)-γ production in the spleen. In summary, our findings elucidate the new role of Dll4 in the phenotype and function of DCs and provide a novel approach for manipulating T cell-driven deleterious immune diseases.</p></div

Interleukin-10 expression is upregulated following ovalbumin stimulation in Dll4-pretreated dendritic cells.

<p>(A) Cytotoxicity effect of Dll4 on dendritic cells. On Day 4 of culture, bone marrow-derived dendritic cells (DCs) were treated with 1 and 5 µg/mL of Dll4 for 48 h, then cultured with or without 100 µg/mL ovalbumin (OVA) for an additional 24 h. Cell viability was detected using an MTT assay. Untreated DCs were pulsed with OVA or medium alone as the controls. (B) Interleukin (IL)-10 and IL-12 mRNA expression and (C) protein levels from various doses of Dll4-pretreated DCs with OVA stimulation. On Day 4 of culture, bone marrow-derived DCs were treated with medium or various concentrations of Dll4 (1 and 5 µg/mL) for 48 h and then activated by OVA (100 µg/mL) stimulation for an additional 5 or 24 h. Untreated immature DCs served as the control group (DC). Transcripts and protein production of IL-10 and IL-12 were measured using a quantitative real-time RT-PCR and ELISA, respectively. Results from 3 independent experiments are shown and expressed as the mean ± SEM. ** <i>p</i><0.01, *** <i>p</i><0.001 compared to OVA-treated DCs (OVA group).</p