Cold weather is correlated with a higher incidence of AAD and AMI.

BackgroundMuch remains to be known about the mechanisms by which O2-dependent host defenses mediate broad antimicrobial activity.Methodology/Principal FindingsWe show herein that reactive nitrogen species (RNS) generated by inducible nitric oxide (NO) synthase (iNOS) account for the anti-Burkholderia mallei activity of IFNγ-primed macrophages. Inducible NOS-mediated intracellular killing may represent direct bactericidal activity, because B. mallei showed an exquisite sensitivity to NO generated chemically. Exposure of B. mallei to sublethal concentrations of NO upregulated transcription of [Fe-S] cluster repair genes, while damaging the enzymatic activity of the [Fe-S] protein aconitase. To test whether [Fe-S] clusters are critical targets for RNS-dependent killing of B. mallei, a mutation was constructed in the NO-induced, [Fe-S] cluster repair regulator iscR. Not only was the iscR mutant hypersusceptible to iNOS-mediated killing, but its aconitase pool was readily oxidized by NO donors as compared to wild-type controls. Although killed by authentic H2O2, which also oxidizes [Fe-S] clusters, B. mallei appear to be resilient to NADPH oxidase-mediated cytotoxicity. The poor respiratory burst elicited by this bacterium likely explains why the NADPH oxidase is nonessential to the killing of B. mallei while it is still confined within phagosomes.Conclusions/SignificanceCollectively, these findings have revealed a disparate role for NADPH oxidase and iNOS in the innate macrophage response against the strict aerobe B. mallei. To the best of our knowledge, this is the first instance in which disruption of [Fe-S] clusters is demonstrated as cause of the bactericidal activity of NO congeners.

BackgroundIn patients undergoing surgical interventions under general anesthesia, obstructive sleep apnea syndrome (OSA) can cause serious perioperative cardiovascular or respiratory complications leading to fatal consequences, even sudden death. In this study we test the hypothesis that morbidly obese patients diagnosed by a polysomnography test and using continuous positive airway pressure (CPAP) therapy have fewer and less severe perioperative complications and a shorter hospital stay than patients who have a medical history that meets at least three STOP-Bang criteria and are not using CPAP therapy.MethodsPostoperative hospital stay and pulmonary complications were analyzed in three groups of morbidly obese patients undergoing bariatric surgery (Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy) between January 2009 and November 2013 (n = 693). Group A comprised 99 patients who were preoperatively diagnosed with OSA based on polysomnography results. These patients used CPAP therapy before and after surgery. Group B consisted of 182 patients who met at least three STOP-Bang criteria but who were not diagnosed with OSA based on polysomnography results. These patients did not use CPAP. Group C, the reference group, comprised 412 patients who scored one to two items on the STOP-Bang.ResultsDuring the perioperative period, Group B patients had a significantly (p < 0.001) higher cumulative rate of pulmonary complications, worse oxygen saturation, respiratory rates, and increased length of stay in hospital. There was also two cases of sudden death in this group.ConclusionBased on these results, we conclude that patients meeting at least three STOP-BANG criteria have higher postoperative complications and an increased length of hospital stay than patients using CPAP.

In the current practice of AVR, persistent postoperative LBBB and RBBB occur infrequently (∼ 5% of cases), a percentage less than half of that in current transcatheter aortic valve implantation procedures. Given the adverse effects of LBBB, the lower prevalence of procedure-induced LBBB in AVR should be taken into account while deciding which valve replacement procedure is chosen for a patient.

ISRCTN90330260.