Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

<p>Abstract</p> <p>Background</p> <p>Catabolite repression control (CRC) is an important global control system in <it>Pseudomonas </it>that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in <it>Pseudomonas </it>spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in <it>Pseudomonas </it>spp. the Crc regulon has remained largely unexplored.</p> <p>Results</p> <p>In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced <it>Pseudomonas </it>genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits.</p> <p>Conclusions</p> <p>Catabolite repression control regulates a broad spectrum of genes in <it>Pseudomonas</it>. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how <it>Pseudomonas </it>bacteria integrate nutritional status cues with the regulation of traits that are of ecological, industrial and clinical importance.</p

Nonantithrombotic Medical Options in Acute Coronary Syndromes: Old Agents and New Lines on the Horizon

Acute coronary syndromes (ACS) constitute a spectrum of clinical presentations ranging from unstable angina and non-ST-segment elevation myocardial infarction to ST-segment myocardial infarction. Myocardial ischemia in this context occurs as a result of an abrupt decrease in coronary blood flow and resultant imbalance in the myocardial oxygen supply-demand relationship. Coronary blood flow is further compromised by other mechanisms that increase coronary vascular resistance or reduce coronary driving pressure. The goals of treatment are to decrease myocardial oxygen demand, increase coronary blood flow and oxygen supply, and limit myocardial injury. Treatments are generally divided into “disease-modifying” agents or interventions that improve hard clinical outcomes and other strategies that can reduce ischemia. In addition to traditional drugs such as beta-blockers and inhibitors of the reninangiotensin-aldosterone system, newer agents have expanded the number of molecular pathways targeted for treatment of ACS. Ranolazine, trimetazidine, nicorandil, and ivabradine are medications that have been shown to reduce myocardial ischemia through diverse mechanisms and have been tested in limited fashion in patients with ACS. Attenuating the no-reflow phenomenon and reducing the injury compounded by acute reperfusion after a period of coronary occlusion are active areas of research. Additionally, interventions aimed at ischemic pre- and post-conditioning may be useful means by which to limit myocardial infarct size. Trials are also underway to examine altered metabolic and oxygen-related pathways in ACS. This review will discuss traditional and newer anti-ischemic therapies for patients with ACS, exclusive of revascularization, anti-thrombotic agents, and the use of high-intensity statins

The ω-3 fatty acids for Prevention of Post-Operative Atrial Fibrillation trial—rationale and design

Postoperative atrial fibrillation/flutter (PoAF) commonly complicates cardiac surgery, occurring in 25% to 60% of patients. Postoperative atrial fibrillation/flutter is associated with significant morbidity, higher long-term mortality, and increased health care costs. Novel preventive therapies are clearly needed. In experiments and short-term trials, seafood-derived long-chain ω-3 polyunsaturated fatty acids (PUFAs) influence several risk factors that might reduce risk of PoAF. A few small and generally underpowered trials have evaluated effects of ω-3-PUFAs supplementation on PoAF with mixed results. The OPERA trial is an appropriately powered, investigator-initiated, randomized, double-blind, placebo-controlled, multinational trial to determine whether perioperative oral ω-3-PUFAs reduces occurrence of PoAF in patients undergoing cardiac surgery. Additional aims include evaluation of resource use, biologic pathways and mechanisms, postoperative cognitive decline, and safety. Broad inclusion criteria encompass a “real-world” population of outpatients and inpatients scheduled for cardiac surgery. Treatment comprises a total preoperative loading dose of 8 to 10 g of ω-3-PUFAs or placebo divided over 2 to 5 days, followed by 2 g/d until hospital discharge or postoperative day 10, whichever comes first. Based on anticipated 30% event rate in controls, total enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to detect 25% reduction in PoAF. The OPERA trial will provide invaluable evidence to inform biologic pathways; proof of concept that ω-3-PUFAs influence cardiac arrhythmias; and potential regulatory standards and clinical use of this simple, inexpensive, and low-risk intervention to prevent PoAF

Yield of Downstream Tests After Exercise Treadmill Testing A Prospective Cohort Study

ObjectivesThe purpose of this study was to estimate the frequency and results of downstream testing after exercise treadmill tests (ETTs).BackgroundThe utility of additional diagnostic testing after ETT is not well characterized.MethodsWe followed consecutive individuals without known coronary artery disease referred for clinical ETT at a large medical center. We measured the frequency and results of downstream imaging tests and invasive angiography within 6 months of ETT and the combined endpoint of survival free from cardiovascular death, myocardial infarction, and coronary revascularization.ResultsAmong 3,656 consecutive subjects who were followed for a mean of 2.5 ± 1.1 years, 332 (9.0%) underwent noninvasive imaging and 84 (2.3%) were referred directly to invasive angiography after ETT. The combined endpoint occurred in 76 (2.2%) patients. The annual incidence of the combined endpoint after negative, inconclusive, and positive ETT was 0.2%, 1.3%, and 12.4%, respectively (p < 0.001). Rapid recovery of electrocardiography (ECG) changes during ETT was associated with negative downstream test results and excellent prognosis, whereas typical angina despite negative ECG was associated with positive downstream tests and adverse prognosis (p < 0.001). Younger age, female sex, higher metabolic equivalents of task achieved, and rapid recovery of ECG changes were predictors of negative downstream tests.ConclusionsAmong patients referred for additional testing after ETT, the lowest yield was observed among individuals with rapid recovery of ECG changes or negative ETT, whereas the highest yield was observed among those with typical angina despite negative ECG or a positive ETT. These findings may be used to identify patients who are most and least likely to benefit from additional testing

Impact of a Simple Inexpensive Quality Assurance Effort on Physician's Choice of Thrombolytic Agents and Door-to-Needle Time: Implication for Costs of Management

The objective of this study were to assess the impact of a quality assurance effort on the door-to-needle time and the choice of thrombolytic agent for the management of acute myocardial infarction in the emergency department. The study design involved a prospective collection of data on a series of consecutive patients who received a thrombolytic agent for a presumed acute myocardial infarction. The study was carried out in the emergency department of a major university urban tertiary care center. A total of 349 patients were studied from September 1989 to March 1994. The quality assurance program began in 1989 and included chart review of all patients receiving thrombolytic therapy, with special attention to all patients with door-to-needle times >60 minutes to identify causes for delay. Feedback was directed to pharmacy, nursing, and physician staff. Biannual reports were distributed throughout the hospital and the emergency department. Nursing-specific feedback led to the development of protocols for all aspects of the delivery of thrombolytic agents. The choice of thrombolytic agent was not dictated by the protocol, but the physician staff was continuously updated on the results of the latest clinical trials comparing one thrombolytic agent with another. The mean age was 58 years for men and 67 years for women in this cohort consisting of 78% men and 22% women. Thirty-seven percent of the myocardial infarctions were in an anterior location and 56% were in an inferior location. The median duration of chest pain before presentation to the emergency department was 120 minutes. Hospital mortality was 3%. Median door-to-needle time fell from 46 (1989–1991) to 36 (1992–1994) minutes, P 60 minutes decreased from 35% (1989–1991) to 16% (1992–1994) minutes, P < 0.0001. Corresponding with the ISIS-3 report, there was a significant increase in the proportion of patients receiving streptokinase over the first 3 years of the study (P < 0.0001), which changed to a trend toward increased utilization of tissue plasminogen activator with the GUSTO report in the final 6 months of the study. In conclusion, a quality assurance program led to a significant reduction in the door-to-needle time, and recent megatrials were found to influence the choice of thrombolytic agent used.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48037/1/11239_2004_Article_145367.pd

Presentation, Diagnosis, and Outcomes of Acute Aortic Dissection: 17-Year Trends From the International Registry of Acute Aortic Dissection

none17siDiagnosis, treatment, and outcomes of acute aortic dissection (AAS) are changing.openPape, Linda A; Awais, Mazen; Woznicki, Elise M; Suzuki, Toru; Trimarchi, Santi; Evangelista, Arturo; Myrmel, Truls; Larsen, Magnus; Harris, Kevin M; Greason, Kevin; Di Eusanio, Marco; Bossone, Eduardo; Montgomery, Daniel G; Eagle, Kim A; Nienaber, Christoph A; Isselbacher, Eric M; O'Gara, PatrickPape, Linda A; Awais, Mazen; Woznicki, Elise M; Suzuki, Toru; Trimarchi, Santi; Evangelista, Arturo; Myrmel, Truls; Larsen, Magnus; Harris, Kevin M; Greason, Kevin; Di Eusanio, Marco; Bossone, Eduardo; Montgomery, Daniel G; Eagle, Kim A; Nienaber, Christoph A; Isselbacher, Eric M; O'Gara, Patric

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits