244 research outputs found

    An analysis of the debate between economic gobalization and regionalization based on Rawlsā€™s theory of justice

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    Driven by globalization, international economic integration has become unavoidable. Within this broader trend, two distinctive modes of international regime building can be identified globalism and regionalism. Globalism, illustrated using the case of the World Trade Organization (WTO), pushes forward global economic integration using established norms. In contrast, regionalism involves gradual expansion of regional integration mechanisms based on interests of member states. This study assesses these two development modes with justice as a concept of moral rightness. To this effect, Rawlsā€™s theory of justice is applied to evaluate standards of justice in international regimes. Based on Rawlsā€™s two principles of justice, three assessment criteria are developed: (1) equal qualification principle, (2) equal opportunity principle, and (3) difference principle. These criteria are applied for comparative analysis of justice in the development of global and regional regimes in order to develop a model for international regimes that is consistent with the concept of justice. A comparison of (1) qualifications for membership; (2) fairness of decision making mechanisms, and (3) institutionalization of differential treatment shows that justice in global regimes is superior to that in regional regimes. In other words, in terms of the philosophy of moral rightness, states should pursue integration based on the principles of globalism

    Efficacy of Mammographic Evaluation of Breast Cancer in Women Less Than 40 Years of Age: Experience from a Single Medical Center in Taiwan

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    Background/PurposeMammography is the standard imaging modality for breast cancer diagnosis. However, the value of mammographic diagnosis in breast cancer patients aged less than 40 years old has not been well assessed. The goal of our study was to determine the diagnostic efficacy of mammography for the detection of breast cancer in women under 40 years of age in a single medical center in Taiwan.MethodsOf 1766 women diagnosed with breast cancer in one medical center between 1999 and 2005, 227 (12.9%) who were younger than 40 years of age were enrolled, and 105 of these 227 patients had pre-biopsy mammograms available for analysis. The sensitivities for mammography at first (prospective) and second (retrospective) readings and for corresponding ultrasound were calculated. The distribution of different breast composition between the mammographic true-positive (TP) and false-negative (FN) lesions at the first and second readings was analyzed.ResultsOf the 105 patients, 104 presented with a palpable mass and the other one was asymptomatic. There were 109 pathologically proven breast cancers from the 105 patients; 92 of 109 cancerous lesions were detected at the first mammographic reading (sensitivity 84.4%), and the most common mammographic sign was microcalcifications (40.2%). The second reading detected seven additional cancers (99 of 109 lesions; sensitivity 90.8%). There was no significant difference between mammographic TP and FN lesions for the different breast composition on first and second readings. Ninety patients also had ultrasound available for correlation with 94 cancers diagnosed from them. The diagnostic sensitivity of ultrasound was 94.7% (89 of 94 lesions).ConclusionMammography has an acceptable sensitivity for the detection of breast cancer in women aged less than 40 years, regardless of different breast composition. Breast ultrasound can offer a higher sensitivity for such a population

    Evaluation of the diagnostic performance of infrared imaging of the breast: a preliminary study

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    <p>Abstract</p> <p>Background</p> <p>The study was conducted to investigate the diagnostic performance of infrared (IR) imaging of the breast using an interpretive model derived from a scoring system.</p> <p>Methods</p> <p>The study was approved by the Institutional Review Board of our hospital. A total of 276 women (mean age = 50.8 years, SD 11.8) with suspicious findings on mammograms or ultrasound received IR imaging of the breast before excisional biopsy. The interpreting radiologists scored the lesions using a scoring system that combines five IR signs. The ROC (receiver operating characteristic) curve and AUC (area under the ROC curve) were analyzed by the univariate logistic regression model for each IR sign and an age-adjusted multivariate logistic regression model including 5 IR signs. The cut-off values and corresponding sensitivity, specificity, Youden's Index (Index = sensitivity+specificity-1), positive predictive value (PPV), negative predictive value (NPV) were estimated from the age-adjusted multivariate model. The most optimal cut-off value was determined by the one with highest Youden's Index.</p> <p>Results</p> <p>For the univariate model, the AUC of the ROC curve from five IR signs ranged from 0.557 to 0.701, and the AUC of the ROC from the age-adjusted multivariate model was 0.828. From the ROC derived from the multivariate model, the sensitivity of the most optimal cut-off value would be 72.4% with the corresponding specificity 76.6% (Youden's Index = 0.49), PPV 81.3% and NPV 66.4%.</p> <p>Conclusions</p> <p>We established an interpretive age-adjusted multivariate model for IR imaging of the breast. The cut-off values and the corresponding sensitivity and specificity can be inferred from the model in a subpopulation for diagnostic purpose.</p> <p>Trial Registration</p> <p>NCT00166998.</p

    The Observation for Ocular Surface Diseases in Respiratory Care Center in One Regional Teaching Hospital in Southern Taiwan

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    Abstract: Purpose: To discover the incidence of ocular surface diseases in the RCC in one region hospital in southern Taiwan. Methods: A prospective study was performed from January 2014 to May 2014. We recorded the causes of admission, eyelid position, abnormal findings of the conjunctiva and cornea. Besides, we also collected data about age, sex, sedation score, the intubation or not, the ventilator setting, date of admission, endotracheal tube or tracheostomy used et al. Results: Total 30 patients were examined in RCC. The mean age of the patients was 60.5 years (range 32-82). 18 patients were male and 12 were female. 24 patients had been sedated or non-sedated with various ventilators. 6 patients were in T-piece trial. 22 patients had tube intubation and 8 patients had received tracheostomy. Mean stay time was 20.5 days. The percent of ocular surface diseases were 33.3% (10/30), and lagophthalmos was observed about 33.3% due to sedation. 23.3% (7/30) patients had conjunctival problems and 26.6% (8/30) had keratopathy. We found that 80% (8/10) patients with lagophthalmos had eye disorders. The endotracheal tube intubation group had a relatively higher incidence of ocular surface diseases (7/22ļ¼›32%). If the sedation score lower than 8, 26 % patients may have eye diseases. Conclusion: The incidence of ocular surface diseases is closely related to heavy sedation or muscle relaxants. The assessment of eyelid position in relation to the ocular surface disease is the most important observation required in RCC. How to set up the routine protocol for eye care for the staff in ICU becomes valuable and serious today. We must keep in mind that prevention is always better than cure

    Schwann Cell Migration Induced by Earthworm Extract via Activation of PAs and MMP2/9 Mediated through ERK1/2 and p38

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    The earthworm, which has stasis removal and wound-healing functions, is a widely used Chinese herbal medicine in China. Schwann cell migration is critical for the regeneration of injured nerves. Schwann cells provide an essentially supportive activity for neuron regeneration. However, the molecular migration mechanisms induced by earthworms in Schwann cells remain unclear. Here, we investigate the roles of MAPK (ERK1/2, JNK and p38) pathways for earthworm-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in Schwann cells. Moreover, earthworm induced phosphorylation of ERK1/2 and p38, but not JNK, activate the downstream signaling expression of PAs and MMPs in a time-dependent manner. Earthworm-stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with U0126 and SB203580, resulting in migration and uPA-related signal pathway inhibition. The results were confirmed using small interfering ERK1/2 and p38 RNA. These results demonstrated that earthworms can stimulate Schwann cell migration and up-regulate PAs and MMP2/9 expression mediated through the MAPK pathways, ERK1/2 and p38. Taken together, our data suggests the MAPKs (ERK1/2, p38)-, PAs (uPA, tPA)-, MMP (MMP2, MMP9) signaling pathway of Schwann cells regulated by earthworms might play a major role in Schwann cell migration and nerve regeneration

    FLJ10540 is associated with tumor progression in nasopharyngeal carcinomas and contributes to nasopharyngeal cell proliferation, and metastasis via osteopontin/CD44 pathway

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    BACKGROUND: Nasopharyngeal carcinoma (NPC) is well-known for its highly metastatic characteristics, but little is known of its molecular mechanisms. New biomarkers that predict clinical outcome, in particular the ability of the primary tumor to develop metastatic tumors are urgently needed. The aim of this study is to investigate the role of FLJ10540 in human NPC development. METHODS: A bioinformatics approach was used to explore the potentially important regulatory genes involved in the growth/metastasis control of NPC. FLJ10540 was chosen for this study. Two co-expression strategies from NPC microarray were employed to identify the relationship between FLJ10540 and osteopontin. Quantitative-RT-PCR, immunoblotting, and immunohistochemistry analysis were used to investigate the mRNA and protein expression profiles of FLJ10540 and osteopontin in the normal and NPC tissues to confirm microarray results. TW01 and Hone1 NPC cells with overexpression FLJ10540 or siRNA to repress endogenous FLJ10540 were generated by stable transfection to further elucidate the molecular mechanisms of FLJ10540-elicited cell growth and metastasis under osteopontin stimulation. RESULTS: We found that osteopontin expression exhibited a positive correlation with FLJ10540 in NPC microarray. We also demonstrated comprehensively that FLJ10540 and osteopontin were not only overexpressed in NPC specimens, but also significantly correlated with advanced tumor and lymph node-metastasis stages, and had a poor 5-year survival rate, respectively. Stimulation of NPC parental cells with osteopontin results in an increase in FLJ10540 mRNA and protein expressions. Functionally, FLJ10540 transfectant alone, or stimulated with osteopontin, exhibited fast growth and increased metastasis as compared to vehicle control with or without osteopontin stimulation. Conversely, knockdown of FLJ10540 by siRNA results in the suppression of NPC cell growth and motility. Treatment with anti-CD44 antibodies in NPC parental cells not only resulted in a decrease of FLJ10540 protein, but also affected the abilities of FLJ10540-elicited cell growth and motility in osteopontin stimulated-NPC cells. CONCLUSIONS: These findings suggest that FLJ10540 may be critical regulator of disease progression in NPC, and the underlying mechanism may involve in the osteopontin/CD44 pathway

    Association of combination antiretroviral therapy with risk of neurological diseases in patients with HIV/AIDS in Taiwan: a nested case-control study

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    Heterogeneous neurocognitive impairment remains an important issue, even in the era of combination antiretroviral therapy (cART), with an incidence ranging from 15% to 65%. Although ART drugs with higher penetration scores to the central nervous system (CNS) show better HIV replication control in the CNS, the association between CNS penetration effectiveness (CPE) scores and neurocognitive impairment remains inconclusive. To explore whether ART exposure is associated with the risk of neurological diseases among patients with HIV/AIDS, this study in Taiwan involved 2,571 patients with neurological diseases and 10,284 matched, randomly selected patients without neurological diseases between 2010 and 2017. A conditional logistic regression model was used in this study. The parameters for ART exposure included ART usage, timing of exposure, cumulative defined daily dose (DDD), adherence, and cumulative CPE score. Incident cases of neurological diseases, including CNS infections, cognitive disorders, vasculopathy, and peripheral neuropathy, were obtained from the National Health Insurance Research Database in Taiwan. Odds ratios (ORs) for the risk of neurological diseases were conducted using a multivariate conditional logistic regression model. Patients with a history of past exposure (OR: 1.68, 95% confidence interval [CI]:1.22ā€“2.32), low cumulative DDDs (&lt; 2,500) (OR: 1.28, 95% CI: 1.15ā€“1.42), low adherence (0 &lt; adherence (ADH) ā‰¤ 0.8) (OR: 1.46, 95% CI: 1.30ā€“1.64), or high cumulative CPE scores (&gt;14) (OR: 1.34, 95% CI: 1.14ā€“1.57) had a high risk of neurological diseases. When stratified by classes of ART drugs, patients with low cumulative DDDs or low adherence had a high risk of neurological diseases, including NRTIs, PIs, NNRTIs, INSTIs, and multi-drug tablets. Subgroup analyses also suggested that patients with low cumulative DDDs or low adherence had a high risk of neurological diseases when they had high cumulative CPE scores. Patients with high cumulative DDDs or medication adherence were protected against neurological diseases only when they had low cumulative CPE scores (ā‰¤ 14). Patients may be at risk for neurological diseases when they have low cumulative DDDs, low adherence, or usage with high cumulative CPE scores. Continuous usage and low cumulative CPE scores of ART drugs may benefit neurocognitive health in patients with HIV/AIDS

    Amyloid-Beta (AĪ²) D7H Mutation Increases Oligomeric AĪ²42 and Alters Properties of AĪ²-Zinc/Copper Assemblies

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    Amyloid precursor protein (APP) mutations associated with familial Alzheimer's disease (AD) usually lead to increases in amyloid Ī²-protein (AĪ²) levels or aggregation. Here, we identified a novel APP mutation, located within the AĪ² sequence (AĪ²D7H), in a Taiwanese family with early onset AD and explored the pathogenicity of this mutation. Cellular and biochemical analysis reveal that this mutation increased AĪ² production, AĪ²42/40 ratio and prolonged AĪ²42 oligomer state with higher neurotoxicity. Because the D7H mutant AĪ² has an additional metal ion-coordinating residue, histidine, we speculate that this mutation may promote susceptibility of AĪ² to ion. When co-incubated with Zn2+ or Cu2+, AĪ²D7H aggregated into low molecular weight oligomers. Together, the D7H mutation could contribute to AD pathology through a ā€œdouble punchā€ effect on elevating both AĪ² production and oligomerization. Although the pathogenic nature of this mutation needs further confirmation, our findings suggest that the AĪ² N-terminal region potentially modulates APP processing and AĪ² aggregation, and further provides a genetic indication of the importance of Zn2+ and Cu2+ in the etiology of AD

    Epsteinā€“Barr Virus DNase (BGLF5) induces genomic instability in human epithelial cells

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    Epsteinā€“Barr Virus (EBV) DNase (BGLF5) is an alkaline nuclease and has been suggested to be important in the viral life cycle. However, its effect on host cells remains unknown. Serological and histopathological studies implied that EBV DNase seems to be correlated with carcinogenesis. Therefore, we investigate the effect of EBV DNase on epithelial cells. Here, we report that expression of EBV DNase induces increased formation of micronucleus, an indicator of genomic instability, in human epithelial cells. We also demonstrate, using Ī³H2AX formation and comet assay, that EBV DNase induces DNA damage. Furthermore, using host cell reactivation assay, we find that EBV DNase expression repressed damaged DNA repair in various epithelial cells. Western blot and quantitative PCR analyses reveal that expression of repair-related genes is reduced significantly in cells expressing EBV DNase. Host shut-off mutants eliminate shut-off expression of repair genes and repress damaged DNA repair, suggesting that shut-off function of BGLF5 contributes to repression of DNA repair. In addition, EBV DNase caused chromosomal aberrations and increased the microsatellite instability (MSI) and frequency of genetic mutation in human epithelial cells. Together, we propose that EBV DNase induces genomic instability in epithelial cells, which may be through induction of DNA damage and also repression of DNA repair, subsequently increases MSI and genetic mutations, and may contribute consequently to the carcinogenesis of human epithelial cells
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