Japanese encephalitis virus envelope protein mitigates TNF-alpha mRNA expression in RAW264.7 cells

[[abstract]]Japanese encephalitis virus (JEV) is known as an important mosquito-borne human pathogen that causes Japanese encephalitis and may lead to lethal effect. Since monocyte has been demonstrated to play transmissible role for JEV, rare study is reported to clarify the effect of JEV envelope (JEVE) protein on monocyte. This study intends to investigate the effects of JEVE protein inside monocyte. Notably, significant decreased expression of tumour necrosis factor (TNF)-alpha mRNA in RAW264.7 cells transfected with pEGFP-JEVE was observed as compared to those cells transfected with pEGFP. Increased p21(Waf1/Cip1) protein was observed in both pEGFP and pEGFP-JEVE transfected RAW264.7 cells. However, increased p53 protein was only detected in pEGFP-transfected cells but not pEGFP-JEVE transfected cells as well as the result that no increased expression of nuclear factor-kB was observed in pEGFP-JEVE transfected cells. These experimental results indicate the effects of JEVE protein in alleviating TNF-alpha mRNA expression that is associated with the increased p53-independent p21(Waf1/Cip1) expression and provide an explanation in the role of JEV transmission through monocyte

Integration of environmental considerations in quality function deployment by using fuzzy logic

[[abstract]]Recently, resource optimization (energy and material) and environmental issues in the life-cycle context are taken very seriously by both the general public and government agencies. These activities urge governments and companies alike to set up environmental friendly production technologies, which aim to avoid harmful emissions into air, water and soil. However, these Eco-designed products have not been achieved a favorable position in the marketplace as expected even though they appear to be more environmental friendly and economical. This may be due that they are focused solely on environmental impact analysis without regard for customer needs and cost considerations. In this research, an Eco-quality function deployment (Eco-QFD) is developed to aid a product design team in considering environmental concerns since QFD is a proven quality systems tool to achieve total customer satisfaction. A fuzzy group method is applied to Eco-QFD for product development planning to reduce the vagueness and uncertainty in a group decision-making process. This fuzzy multi-objective model not only considers the overall customer satisfaction but also encourages enterprises to produce an environmentally friendly product. With an interactive approach, the optimal balance between environmental acceptability and overall customer satisfaction can be obtained. Finally, a case study illustrating the application of the proposed model is also provided. (C) 2008 Elsevier Ltd. All rights reserved

Transglutaminase inhibitor cystamine alleviates the abnormality in liver from NZB/W F1 mice

[[abstract]]Increased hepatic abnormality has been observed in patients with systemic lupus erythematosus (SLE) and contributes to the elevated apoptosis that results in severe disease activity. Since cystamine has been demonstrated to be beneficial for NZB/NV F1 mice, this study investigates the effects of cystamine on various inflammatory and stress-related proteins in liver from NZB/W F I mice. Nephelometric analyses and immunoblots were conducted to detect aspartate aminotransferase (AST), alanine aminotransferase (ALT), C-reactive protein (CRP), p53, p21, Gadd45, heat shock protein 70 (HSP70) and cyclooxygenase-2 (COX-2). AST and ALT were reduced in NZB/W F1 mice that were given cystamine and CRP, p53, p21, Gadd45, HSP70 and COX-2 proteins in the liver were reduced in NZB/W F1 mice that were treated with cystamine. Moreover, cystamine has no obvious effect on BALB/c mice. These findings suggest that cystamine reduces the inflammation in liver of NZB/W F1 mice and provide a clue in treatment of SLE with liver abnormality. (c) 2007 Elsevier B.V. All rights reserved

Beneficial effects of treatment with cystamine on brain in NZB/W F1 mice

[[abstract]]The involvement of the central nervous system (CNS) or neuropsychosis has been reported in patients with systemic lupus erythematosus (SLE) and considered a major cause of long-standing functional impairment and mortality. However, little is known in the improvement of the brain abnormality in SLE.To investigate the effect and mechanism of cystamine on brain in SLE, NZB/W F1 mice were used as the animal model. Gel zymography, caspase-3 activity assay and Western blots were performed to elucidate the effect of cystamine. Significant reduction of matrix metalloproteinases (MMP)-9/MMP-2 ratio and urokinase-type plasminogen activator (uPA) expression was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Significant increase of heat-shock protein (HSP)-70 and HSP27 was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Additionally, significant reduction of mitochondrial dependent apoptosis was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group by increasing BCL-2 and reducing caspase-9, Bad, and Apaf-1 expression. Moreover, increased phosphorylated p65 (NF-kappa B) protein was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group. These experimental results firstly demonstrated the beneficial effects of cystamine on brain in NZB/W F1 mice and suggested the therapeutic potential in patients with neuropsychiatric SLE (NP-SLE). (c) 2008 Elsevier B.V. All rights reserved

Efficient simulation of the spatial transmission dynamics of influenza

Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies over-estimated the within-country rate of spatial spread of pandemic influenza. As large spatially resolved data sets are constructed, the need for efficient simulation code with which to investigate the spatial patterns of the pandemic becomes clear. Here, we present a significant improvement to the efficiency of an individual based stochastic disease simulation framework commonly used in multiple previous studies. We quantify the efficiency of the revised algorithm and present an alternative parameterization of the model in terms of the basic reproductive number. We apply the model to the population of Taiwan and demonstrate how the location of the initial seed can influence spatial incidence profiles and the overall spread of the epidemic. Differences in incidence are driven by the relative connectivity of alternate seed locations. The ability to perform efficient simulation allows us to run a batch of simulations and take account of their average in real time. The averaged data are stable and can be used to differentiate spreading patterns that are not readily seen by only conducting a few runs. © 2010 Tsai et al.published_or_final_versio

Health literacy, health status, and healthcare utilization of Taiwanese adults: results from a national survey

Abstract Background Low health literacy is considered a worldwide health threat. The purpose of this study is to assess the prevalence and socio-demographic covariates of low health literacy in Taiwanese adults and to investigate the relationships between health literacy and health status and health care utilization. Methods A national survey of 1493 adults was conducted in 2008. Health literacy was measured using the Mandarin Health Literacy Scale. Health status was measured based on self-rated physical and mental health. Health care utilization was measured based on self-reported outpatient clinic visits, emergency room visits, and hospitalizations. Results Approximately thirty percent of adults were found to have low (inadequate or marginal) health literacy. They tended to be older, have fewer years of schooling, lower household income, and reside in less populated areas. Inadequate health literacy was associated with poorer mental health (OR, 0.57; 95% CI, 0.35-0.91). No association was found between health literacy and health care utilization even after adjusting for other covariates. Conclusions Low (inadequate and marginal) health literacy is prevalent in Taiwan. High prevalence of low health literacy is not necessarily indicative of the need for interventions. Systematic efforts to evaluate the impact of low health literacy on health outcomes in other countries would help to illuminate features of health care delivery and financing systems that may mitigate the adverse health effects of low health literacy.http://deepblue.lib.umich.edu/bitstream/2027.42/78252/1/1471-2458-10-614.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78252/2/1471-2458-10-614.pdfPeer Reviewe

Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively

Household out-of-pocket medical expenditures and national health insurance in Taiwan: income and regional inequality

BACKGROUND: Unequal geographical distribution of medical care resources and insufficient healthcare coverage have been two long-standing problems with Taiwan's public health system. The implementation of National Health Insurance (NHI) attempted to mitigate the inequality in health care use. This study examines the degree to which Taiwan's National Health Insurance (NHI) has reduced out-of-pocket medical expenditures in households in different regions and varying levels of income. METHODS: Data used in this study were drawn from the 1994 and 1996 Surveys of Family Income and Expenditure. We pooled the data from 1994 and 1996 and included a year dummy variable (NHI), equal to 1 if the household data came from 1996 in order to assess the impact of NHI on household out-of-pocket medical care expenditures shortly after its implementation in 1995. RESULTS: An individual who was older, female, married, unemployed, better educated, richer, head of a larger family household, or living in the central and eastern areas was more likely to have greater household out-of-pocket medical expenditures. NHI was found to have effectively reduced household out-of-pocket medical expenditures by 23.08%, particularly for more affluent households. With the implementation of NHI, lower and middle income quintiles had smaller decreases in out-of-pocket medical expenditure. NHI was also found to have reduced household out-of-pocket medical expenditures more for households in eastern Taiwan. CONCLUSION: Although NHI was established to create free medical care for all, further effort is needed to reduce the medical costs for certain disadvantaged groups, particularly the poor and aborigines, if equality is to be achieved

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

HypertenGene: extracting key hypertension genes from biomedical literature with position and automatically-generated template features

<p>Abstract</p> <p>Background</p> <p>The genetic factors leading to hypertension have been extensively studied, and large numbers of research papers have been published on the subject. One of hypertension researchers' primary research tasks is to locate key hypertension-related genes in abstracts. However, gathering such information with existing tools is not easy: (1) Searching for articles often returns far too many hits to browse through. (2) The search results do not highlight the hypertension-related genes discovered in the abstract. (3) Even though some text mining services mark up gene names in the abstract, the key genes investigated in a paper are still not distinguished from other genes. To facilitate the information gathering process for hypertension researchers, one solution would be to extract the key hypertension-related genes in each abstract. Three major tasks are involved in the construction of this system: (1) gene and hypertension named entity recognition, (2) section categorization, and (3) gene-hypertension relation extraction.</p> <p>Results</p> <p>We first compare the retrieval performance achieved by individually adding template features and position features to the baseline system. Then, the combination of both is examined. We found that using position features can almost double the original AUC score (0.8140vs.0.4936) of the baseline system. However, adding template features only results in marginal improvement (0.0197). Including both improves AUC to 0.8184, indicating that these two sets of features are complementary, and do not have overlapping effects. We then examine the performance in a different domain--diabetes, and the result shows a satisfactory AUC of 0.83.</p> <p>Conclusion</p> <p>Our approach successfully exploits template features to recognize true hypertension-related gene mentions and position features to distinguish key genes from other related genes. Templates are automatically generated and checked by biologists to minimize labor costs. Our approach integrates the advantages of machine learning models and pattern matching. To the best of our knowledge, this the first systematic study of extracting hypertension-related genes and the first attempt to create a hypertension-gene relation corpus based on the GAD database. Furthermore, our paper proposes and tests novel features for extracting key hypertension genes, such as relative position, section, and template features, which could also be applied to key-gene extraction for other diseases.</p