Systematic review and meta-analysis of chronic kidney disease as predictor of atrial fibrillation recurrence following catheter ablation

Background: Recent observational studies have shown that patients with chronic kidney disease (CKD) have higher risk of atrial fibrillation (AF) recurrence and, therefore, the value of catheter ablation therapy in patients with CKD has been doubted. The purpose of this meta-analysis was to systematically analyze the effect of CKD on recurrence of AF following catheter ablation.Methods: PubMed and Cochrane clinical trials databases were searched until August 2012. Of the 1966 initially identified studies, 4 observational studies with 1379 patients were analyzed.Results: The meta-analysis of these studies showed that CKD was associated with higher AF recurrence rate following single catheter ablation (HR = 1.96, 95% CI 1.35–2.85, p = 0.0004) while there were significant differences between individual trials (p = 0.07 and I2 = 58%). Sensitivity analysis suggested that this outcome was stable. A subgroup analysis showed that CKD has higher recurrent risk in patients with 100% paroxysmal AF (HR = 2.45, 95% CI 1.28–4.70, p = 0.007) than in patients with non 100% paroxysmal AF (HR = 1.65, 95% CI 1.15–2.36, p = 0.006).Conclusions: CKD was associated with higher AF recurrence rate following single catheter ablation. In addition, patients with 100% paroxysmal AF have higher risk than patients with non 100% paroxysmal AF that merits special consideration when evaluating patients for catheter-based AF ablation. Given that the CKD prevalence is rapidly increasing, there is an imperative need for better risk stratification of catheter ablation candidates.

Cardiac abnormalities after induction of endoplasmic reticulum stress are associated with mitochondrial dysfunction and connexin43 expression

The endoplasmic reticulum (ER) is responsible for protein synthesis and calcium storage. ER stress, reflected by protein unfolding and calcium handling abnormalities, has been studied as a pathogenic factor in cardiovascular diseases. The aim of this study is to examine the effects of ER stress on mechanical and electrophysiological functions in the heart and explore the underlying molecular mechanisms. A total of 30 rats were randomly divided into control, ER stress inducer (tunicamycin[TN]) and ER stress inhibitor (tunicamycin+4-phenylbutyric acid [4-PBA]) groups. ER stress induction led to significantly systolic and diastolic dysfunction as reflected by maximal increasing/decreasing rate of left intraventricular pressure (±dp/dt), left ventricular peaksystolic pressure(LVSP) and LV end-diastolic pressure(LVEDP). Epicardial mapping performed in vivo revealed reduced conduction velocity and increased conduction heterogeneity associated with the development of spontaneous ventricular tachycardia. Masson’s trichrome staining revealed marked fibrosis in the myocardial interstitial and sub-pericardial regions, and thickened epicardium. Western blot analysis revealed increased pro-fibrotic factor transforming growth factor-β1 (TGF-β1), decreased mitochondrial biogenesis protein peroxlsome proliferator-activated receptor-γ coactlvator-1α （PGC-1a）, and decreased mitochondrial fusion protein mitofusin-2 (MFN2). These changes were associated with mitochondria dysfunction and connexin 43(CX43)translocation to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA. Our study shows that ER stress induction can produce cardiac electrical and mechanism dysfunction as well as structural remodelling. Mitochondrial function alterations are contributed by CX43 transposition to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA

MicroRNA-96 Promotes Schistosomiasis Hepatic Fibrosis in Mice by Suppressing Smad7

Infection with Schistosoma causes aberrant expression of host microRNAs (miRNAs), and normalizing the levels of dysregulated miRNAs can attenuate pathology. Here, we show that the host miRNA, miR-96, is markedly upregulated during the progression of hepatic schistosomiasis. We demonstrate that elevation of miR-96 induces hepatic fibrosis in infected mice by suppressing the expression of its target gene, Smad7. We show that infection with Schistosoma induces the expression of transforming growth factor beta1 (TGF-beta1), which in turn upregulates the expression of miR-96 through SMAD2/3-DROSHA-mediated post-transcriptional regulation. Furthermore, inhibition of miR-96 with recombinant adeno-associated virus 8 (rAAV8)-mediated delivery of Tough Decoy RNAs in mice attenuated hepatic fibrosis and prevented lethality following schistosome infection. Taken together, our data highlight the potential for rAAV8-mediated inhibition of miR-96 as a therapeutic strategy to treat hepatic schistosomiasis

Low-Dose Recombinant Adeno-Associated Virus-Mediated Inhibition of Vascular Endothelial Growth Factor Can Treat Neovascular Pathologies Without Inducing Retinal Vasculitis

The wet form of age-related macular degeneration is characterized by neovascular pathologies that, if untreated, can result in edemas followed by rapid vision loss. Inhibition of vascular endothelial growth factor (VEGF) has been used to successfully treat neovascular pathologies of the eye. Nonetheless, some patients require frequent intravitreal injections of anti-VEGF drugs, increasing the burden and risk of complications from the procedure to affected individuals. Recombinant adeno-associated virus (rAAV)-mediated expression of anti-VEGF proteins is an attractive alternative to reduce risk and burden to patients. However, controversy remains as to the safety of prolonged VEGF inhibition in the eye. Here, we show that two out of four rAAV serotypes tested by intravitreal delivery to express the anti-VEGF drug conbercept lead to a dose-dependent vascular sheathing pathology that is characterized by immune cell infiltrates, reminiscent of vasculitis in humans. We show that this pathology is accompanied by increased expression in vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1), both of which promote extravasation of immune cells from the vasculature. While formation of the vascular sheathing pathology is prevented in immunodeficient Rag-1 mice that lack B and T cells, increased expression of VACM1 and ICAM1 still occurs, indicating that inhibition of VEGF function leads to expression changes in cell adhesion molecules that promote extravasation of immune cells. Importantly, a 10-fold lower dose of one of the vectors that cause a vascular sheathing pathology is still able to reduce edemas resulting from choroidal neovascularization without causing any vascular sheathing pathology and only a minimal increase in VCAM1 expression. The data suggest that treatments of neovascular eye pathologies with rAAV-mediated expression of anti VEGF drugs can be developed safely. However, viral load needs to be adjusted to the tropisms of the serotype and the expression pattern of the promoter

Influence of Restrainer Piers on the Seismic Performance of Long Bridges with Equal-Height Piers

Pounding may occur between the main girders under the action of strong earthquakes, so as between main girders and abutments. This causes excessive longitudinal displacement of the main girder and unseating damage to bridges. Because long bridges in mountainous areas with high intensity are easy to unseat, the authors studied the influence of restrainer piers, expansion joint spacings (EJSs), and the span on the seismic performance of long bridges. The ABAQUS finite element software was used to simulate a bridge dynamic analysis model considering the elastoplasticity of the pounding effect of the pier and the beam. By inputting El-Centro, Northbridge, and Taft seismic waves, the time-history analysis of the seismic response of long bridges was carried out. The results indicated that a reasonable number of restrainer piers, an appropriate EJS, and a span could effectively reduce the maximum relative displacement of pier-beams. This behavior will improve the seismic performance of bridge structures. Moreover, for a 24-span equal-height beam bridge, the optimum seismic effect was obtained when 3 restrainer piers, an EJS of 70 mm, and a 50 m span were used

Characteristics and Influencing Factors of Spatial Differentiation of Urban Black and Odorous Waters in China

The pollution problem caused by urban black and odorous waters has received much attention from the Chinese government. Our research aims at systematically identifying the characteristics and the influential factors of spatial differentiation of urban black and odorous waters across China. The research, based on the data of 2100 black and odorous waters in China, was conducted with the spatial analysis tool of ArcGIS. We found that the amount of Chinese urban black and odorous waters varied in spatial distribution, which was an agglomerated type with significant agglomeration. The kernel density was characterized by independent single kernel centers with ribbon-like and sporadic distributions of subcenters. The cold and hot spots showed a gradient distribution pattern of cold in the southwest and hot in the central east. These spatial distribution characteristics could be attributed to the following core factors, total wastewater discharge, length of urban drainage pipelines, municipal solid waste collection, daily urban sewage treatment capacity, and investment in urban pollution treatment of wastewater. The findings reveal the current geospatial distribution of black and odorous waters pollution and provide reference for the Chinese government to treat the pollution from several key points. Lastly, it is suggested that the Chinese government should establish joint control, joint prevention, and joint treatment mechanisms in the black and odorous waters areas and improve the safety standards of the whole water environment, so as to promote the treatment and elimination of urban black and odorous waters