The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Background: Human ␥-glutamyltranspeptidase 1 (hGGT1) is a key enzyme in cysteine metabolism and several diseases. Results: We obtained the high resolution crystal structure of hGGT1. Conclusion:The structure reveals the molecular basis for differences between the human and bacterial enzymes in autoprocessing and catalytic activity. Significance: The structure provides a template for the structure-based design of therapeutic inhibitors of hGGT1.

Methyl cinnamate, an active component of Zanthoxylum armatum , is a widely used natural flavor compound with antimicrobial and tyrosinase inhibitor activities. However, the underlying bioactivity and molecular mechanisms of methyl cinnamate on adipocyte function and metabolism remain unclear. The aim of this study was to investigate the inhibitory effect of methyl cinnamate on adipogenesis in 3T3-L1 preadipocytes. Methyl cinnamate markedly suppressed triglyceride accumulation associated with down-regulation of adipogenic transcription factor expression, including sterol regulatory element binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, methyl cinnamate-inhibited PPARγ activity and adipocyte differentiation were partially reversed by the PPARγ agonist troglitazone. Furthermore, methyl cinnamate stimulated Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and phospho-AMP-activated protein kinase (AMPK) expression during adipogenesis. This study first revealed methyl cinnamate has antiadipogenic activity through mechanisms mediated, in part, by the CaMKK2-AMPK signaling pathway in 3T3-L1 cells.

Background-Identification of critical atrial substrates in patients with nonparoxysmal atrial fibrillation (AF) failing to respond to pulmonary vein isolation is important. This study investigated the signal characteristics, substrate nature, and ablation results of rotors during AF. Methods and Results-In total, 53 patients (age=55±8), 31 with persistent AF and 22 with long-lasting AF, underwent pulmonary vein isolation and substrate modification of complex fractionated atrial electrograms. Small-radius-reentrant rotors were identified from signal analyses of the dominant frequency and fractionation interval and nonlinear analyses (newly developed, beat-to-beat nonlinear measurement of the repetitiveness of the electrogram morphology >6 seconds). In 15% of the patients, activation maps demonstrated occurrences of rotor-like small-radius reentrant circuits (n=9; 1.1 per patient; cycle length=110±21 ms; diameter=11±6 mm) with fibrillation occurring outside these areas. Rotors were identified by conventional point-by-point mapping and signal analyses and were subsequently eradicated by catheter ablation in these patients. Persistent AF for <1 year, a smaller left atrial size, substrates with higher mean voltages and shorter total activation durations predicted a higher incidence of rotors (all P<0.05). In the multivariable model, areas of reentrant circuits exhibited a higher dominant frequency, kurtosis, and higher degree of a beat-to-beat electrogram similarity than areas without or outside the rotors (all P<0.05). Conclusions-Rotor-like re-entry with fibrillatory conduction was found in a limited number of patients with nonparoxysmal AF after pulmonary vein isolation. Those areas were characterized by rapid repetitive activity with a high degree of electrogram similarity. Methods Patient CharacteristicsWe enrolled 53 patients (55±8 years) with symptomatic drug-refractory nonparoxysmal AF who underwent radiofrequency ablation guided by NavX system (St Jude Medical Inc, MN). The study cohort included 31 patients (58%) with persistent AF (duration <1 year but >7 days) and 22 patients (42%) with long-lasting persistent AF (duration of ≥1 year; Table 1). All patients presented with incessant AF in the beginning of the procedure. The patients were excluded from the study if they were in sinus rhythm or had spontaneous termination of AF before the PVI. Electrophysiological StudyAn electrophysiological study and catheter ablation in the fasting state were performed in each patient after informed consent was obtained. All antiarrhythmic drugs, except amiodarone, were discontinued for ≥5 half-lives before the start of the procedure. Overall, 19 patients (36%) were treated with amiodarone before the procedure because of symptomatic AF, but no patients received that drug during the electrophysiological procedure. Electroanatomic mapping was performed in all patients. The details of the mapping have been described in other previous studies. 10,11 Signal Acquisition and Linear AnalysisDuring AF, point-by-point mapping was ...

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