905 research outputs found
The global strategy for women's, children's and adolesents' health (2016-2030) : a roadmap based on evidence and country experience
Lessons of Defeat and Success: Taiwan’s 2012 Elections in Comparative Perspective
In early 2011, the Kuomintang (KMT, Guomindang) government appeared to be in danger of losing power in the upcoming presidential elections. The DPP had recovered sufficiently from its disastrous electoral performance in 2008 to pose a real challenge to Ma Ying-jeou (Ma Yingjiu) and had matched the KMT’s vote share in mid-term local elections. Ma also faced the challenge of an independent presidential candidate, James Soong (Song Chuyu), who had come a close second in 2000 and now threatened to divide the pro KMT vote. Nevertheless, the KMT was able to win reduced majorities in both the presidential and legislative elections in January 2012. This article seeks to explain how the KMT was able to hold on to power by comparing the campaign with earlier national-level elections. We are interested in identifying the degree to which the Democratic Progressive Party (DPP, Minjindang) learnt from its electoral setbacks in 2008 and whether the KMT employed a similar campaign strategy to the one that had been so effective in returning it to power in 2008. Our analysis relies of an examination of campaign propaganda and campaign strategies as well as participant observation and survey data from 2012 and earlier contests
Effects of an in-frame deletion of the 6k gene locus from the genome of Ross River virus
The alphaviral 6k gene region encodes the two structural proteins 6K protein and, due to a ribosomal frameshift event, the transframe protein (TF). Here, we characterized the role of the 6k proteins in the arthritogenic alphavirus Ross River virus (RRV) in infected cells and in mice, using a novel 6k in-frame deletion mutant. Comprehensive microscopic analysis revealed that the 6k proteins were predominantly localized at the endoplasmic reticulum of RRV-infected cells. RRV virions that lack the 6k proteins
6K and TF [RRV-(6K)] were more vulnerable to changes in pH, and the corresponding virus had increased sensitivity to a higher temperature. While the 6k deletion did not reduce RRV particle production in BHK-21 cells, it affected virion release from the host cell. Subsequent in vivo studies demonstrated that RRV-(6K) caused a milder disease than wild-type virus, with viral titers being reduced in infected mice. Immunization of mice with RRV-(6K) resulted in a reduced viral load and accelerated
viral elimination upon secondary infection with wild-type RRV or another alphavirus, chikungunya virus (CHIKV). Our results show that the 6k proteins may contribute to alphaviral disease manifestations and suggest that manipulation of the 6k gene may be a potential strategy to facilitate viral vaccine development
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Hypokalemia, Its Contributing Factors and Renal Outcomes in Patients with Chronic Kidney Disease
Background: In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated. Design, Participants & Measurements 2500 participants with CKD stage 1–4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used. Results: The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m2. Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03–3.22) in sK 5 mEq/L conferred 1.6-fold (95% CI,1.09–2.34) increased risk of ESRD compared with sK = 4.5–5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range. Conclusion: In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes
Sr-Nd-Pb-Hf isotope results from ODP Leg 187: Evidence for mantle dynamics of the Australian-Antarctic Discordance and origin of the Indian MORB source
New high precision PIMMS Hf and Pb isotope data for 14–28 Ma basalts recovered during ODP Leg 187 are compared with zero-age dredge samples from the Australian-Antarctic Discordance (AAD). These new data show that combined Nd-Hf isotope systematics can be used as an effective discriminant between Indian and Pacific MORB source mantle domains. In particular, Indian mantle is displaced to lower εNd and higher εHf ratios compared to Pacific mantle. As with Pb isotope plots, there is almost no overlap between the two mantle types in Nd-Hf isotope space. On the basis of our new Nd-Hf isotope data, we demonstrate that Pacific MORB-source mantle was present near the eastern margin of the AAD from as early as 28 Ma, its boundary with Indian MORB-source mantle coinciding with the eastern edge of a basin-wide arcuate depth anomaly that is centered on the AAD. This observation rules out models requiring rapid migration of Pacific MORB mantle into the Indian Ocean basin since separation of Australia from Antarctica. Although temporal variations in isotopic composition can be discerned relative to the fracture zone boundary of the modern AAD at 127°E, the distribution of different compositional groups appears to have remained much the same relative to the position of the residual depth anomaly for the past 30 m.y. Thus significant lateral flow of mantle along the ridge axis toward the interface appears unlikely. Instead, the dynamics that maintain both the residual depth anomaly and the isotopic boundary between Indian and Pacific mantle are due to eastward migration of the Australian and Antarctic plates over a stagnated, but slowly upwelling, slab oriented roughly orthogonal to the ridge axis. Temporal and spatial variations in the compositions of Indian MORB basalts within the AAD can be explained by progressive displacement of shallower Indian MORB-source mantle by deeper mantle having a higher εHf composition ascending ahead of the upwelling slab. Models for the origin of the distinctive composition of the Indian MORB-source based on recycling of a heterogeneous enriched component that consist of ancient altered ocean crust plus<10% pelagic sediment are inconsistent with Nd-Hf isotope systematics. Instead, the data can be explained by a model in which Indian mantle includes a significant proportion of material that was processed in the mantle wedge above a subduction zone and was subsequently mixed back into unprocessed upper mantle
PNPLA3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease
The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity.METHODS:Medline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I 2 statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses.RESULTS:Among 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients.CONCLUSIONS:PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD
Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients
Pseudoxanthoma elasticum (PXE) is a heritable disease caused by ABCC6 deficiency. Patients develop ectopic calcification in skin, eyes and vascular tissues. ABCC6, primarily found in liver and kidneys, mediates the cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a potent inhibitor of calcification. PXE patients and Abcc6 mice display reduced PPi levels in plasma and peripheral tissues. PXE is currently incurable, although some palliative treatments exist. In recent years, we have successfully developed therapeutic methodologies to compensate the PPi deficit in animal models and humans. Here, we inadvertently discovered that modulating dietary PPi can also be an effective approach to reducing calcification in Abcc6 mice. Our findings were prompted by a change in institutional rodent diet. The new chow was enriched in PPi, which increased plasma PPi, and significantly reduced mineralization in Abcc6 mice. We also found that dietary PPi is readily absorbed in humans. Our results suggest that the consumption of food naturally or artificially enriched in PPi represents a possible intervention to mitigate calcification progression in PXE, that dietary preferences of patients may explain PXE heterogeneous manifestations and that animal chow has the potential to influence data reproducibility
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