BackgroundProspective studies that have examined the association between dietary magnesium intake and serum magnesium concentrations and the risk of cardiovascular disease (CVD) events have reported conflicting findings. We undertook a meta-analysis to evaluate the association between dietary magnesium intake and serum magnesium concentrations and the risk of total CVD events.Methodology/Principal FindingsWe performed systematic searches on MEDLINE, EMBASE, and OVID up to February 1, 2012 without limits. Categorical, linear, and nonlinear, dose-response, heterogeneity, publication bias, subgroup, and meta-regression analysis were performed. The analysis included 532,979 participants from 19 studies (11 studies on dietary magnesium intake, 6 studies on serum magnesium concentrations, and 2 studies on both) with 19,926 CVD events. The pooled relative risks of total CVD events for the highest vs. lowest category of dietary magnesium intake and serum magnesium concentrations were 0.85 (95% confidence interval 0.78 to 0.92) and 0.77 (0.66 to 0.87), respectively. In linear dose-response analysis, only serum magnesium concentrations ranging from 1.44 to 1.8 mEq/L were significantly associated with total CVD events risk (0.91, 0.85 to 0.97) per 0.1 mEq/L (Pnonlinearity = 0.465). However, significant inverse associations emerged in nonlinear models for dietary magnesium intake (Pnonlinearity = 0.024). The greatest risk reduction occurred when intake increased from 150 to 400 mg/d. There was no evidence of publication bias.Conclusions/SignificanceThere is a statistically significant nonlinear inverse association between dietary magnesium intake and total CVD events risk. Serum magnesium concentrations are linearly and inversely associated with the risk of total CVD events.

Bis-(-)-nor-meptazinols (bis-(-)-nor-MEPs) 5 were designed and synthesized by connecting two (-)-nor-MEP monomers with alkylene linkers of different lengths via the secondary amino groups. Their acetylcholinesterase (AChE) inhibitory activities were more greatly influenced by the length of the alkylene chain than butyrylcholinesterase (BChE) inhibition. The most potent nonamethylene-tethered dimer 5h exhibited low-nanomolar IC 50 values for both ChEs, having a 10 000-fold and 1500-fold increase in inhibition of AChE and BChE compared with (-)-MEP. Molecular docking elucidated that 5h simultaneously bound to the catalytic and peripheral sites in AChE via hydrophobic interactions with Trp86 and Trp286. In comparison, it folded in the large aliphatic cavity of BChE because of the absence of peripheral site and the enlargement of the active site. Furthermore, 5h and 5i markedly prevented the AChE-induced Abeta aggregation with IC 50 values of 16.6 and 5.8 microM, similar to that of propidium (IC 50 = 12.8 microM), which suggests promising disease-modifying agents for the treatment of AD patients.

Obesity plays an important role in the pathogenesis of atrial fibrillation (AF). Recently, rather than general fat distribution, epicardial adipose tissue (EAT) gains a growing concern. EAT is the local adipose deposition between myocardium and pericardium. Accumulated evidence revealed several distinguishing characteristics of EAT. It lies contiguously with the myocardium and could infiltration into myocardium, actively secrets cytokines and adipokines mediating inflammation or remodeling, and contains abundant ganglionated plexi. Clinical research also found EAT may be an independent risk factor of AF. Volume or thickness of EAT measured on CT or MRI could be applied as a predictor of presence, severity, and recurrence of AF. Some drugs, like antidiabetic drugs and lipid-lowing drugs, show ability to reduce EAT. Additional surgical ablation of EAT was also proved that it could improve outcome of pulmonary vein isolation for AF. In present review, we summarize recent epidemic, biological, and clinical findings about EAT and its possible role in AF. K E Y W O R D S atrial fibrillation, epicardial adipose tissue, mechanisms, therapies 1 2 THE LINK BETWEEN AF, OBESITY, AND ADIPOSE TISSUE Obesity and AFObesity is an already recognized risk factor of AF. 5,6 It is usually assessed by several indicators, such as body mass index (BMI), waist circumference, waist to hip ratio, and body fat rate. Compared with nonobese people, obese individuals possess higher probability (49%) of suffering AF, which may be associated with atrial enlargement, ventricular diastolic dysfunction, and ectopic fat depot increase. 5 Furthermore, previous literature showed that every 5 kg/m 2 increase in BMI could increase about 10-30% higher risks of AF, and also indicated that every 1 kg/m 2 reduction in BMI was associated with a significant 7% reduction in the risk of AF. 7 These pieces of evidence support that obesity is closely associated with AF occurrence. However, in general, the indicators to measure obesity, such as BMI, are relatively rough to reflect excess adipose; and individuals with similar BMI may have different risks of AF. More precise measurements are needed to predict the occurrence and development of AF.