Genomic and Transcriptomic Insights into Salinity Tolerance-Based Niche Differentiation of Synechococcus Clades in Estuarine and Coastal Waters.

Cluster 5 Synechococcus is one of the most important primary producers on earth. However, ecotypes of this genus exhibit complex geographical distributions, and the genetic basis of niche partitioning is still not fully understood. Here, we report distinct distributions of subcluster 5.1 (SC5.1) and subcluster 5.2 (SC5.2) Synechococcus in estuarine waters, and we reveal that salinity is the main factor determining their distribution. Clade III (belonging to SC5.1) and CB4 (belonging to SC5.2) are dominant clades in the study region, with different ecological distributions. We further conducted physiological, genomic, and transcriptomic studies of Synechococcus strains YX04-3 and HK05, which are affiliated with clade III and CB4, respectively. Laboratory tests showed that HK05 could grow at low salinity (13 ppt), whereas the growth of YX04-3 was suppressed when salinity decreased to 13 ppt. Genomic and transcriptomic analysis suggested that euryhaline clade CB4 is capable of dealing with a sudden drop of salinity by releasing compatible solutes through mechanosensitive channels that are coded by the mscL gene, decreasing biosynthesis of organic osmolytes, and increasing expression of heat shock proteins and high light-inducible proteins to protect photosystem. Furthermore, CB4 strain HK05 exhibited a higher growth rate when growing at low salinity than at high salinity. This is likely achieved by reducing its biosynthesis of organic osmolyte activity and increasing its photosynthetic activity at low salinity, which allowed it to enhance the assimilation of inorganic carbon and nitrogen. Together, these results provide new insights regarding the ecological distribution of SC5.2 and SC5.1 ecotypes and their underlying molecular mechanisms. IMPORTANCE Synechococcus is a group of unicellular Cyanobacteria that are widely distributed in global aquatic ecosystems. Salinity is a factor that affects the distribution of microorganisms in estuarine and coastal environments. In this study, we studied the distribution pattern of Synechococcus community along the salinity gradient in a subtropical estuary. By using omic methods, we unveiled genetic traits that determine the niche partitioning of euryhaline and strictly marine Synechococcus. We also explored the strategies employed by euryhaline Synechococcus to cope with a sudden drop of salinity, and revealed possible mechanisms for the higher growth rate of euryhaline Synechococcus in low salinity conditions. This study provides new insight into the genetic basis of niche partitioning of Synechococcus clades.

Distinct metabolic strategies of the dominant heterotrophic bacterial groups associated with marine Synechococcus.

The marine Synechococcus is a major primary producer in the global oceans. It is phylogenetically highly diverse, and its major phylogenetic lineages display clear spatial segregation among different marine environments. Here, we showed that the composition of the associated bacterial communities was related to the geographic origin of the different Synechococcus strains, and it was stable during long-term lab incubation. Of all the Synechococcus cultures investigated, the Rhodobacteraceae had a relatively high abundance and was the core bacterial family of the associated bacterial communities. In contrast, the Flavobacteriaceae were only abundant in the cultures collected from the South China Sea (which is warm and oligotrophic), whereas those of the Alteromonadaceae were abundant in the cultures from the coastal waters off Hong Kong and Xiamen. We also found that the Rhodobacteraceae had more ABC transporters and utilized a wider spectrum of carbon sources than did the Flavobacteriaceae and Alteromonadaceae. Moreover, the Alteromonadaceae had more transporters for importing phosphate and amino acids, but fewer transporters for importing oligosaccharides, polyol, and lipid, than the Flavobacteriaceae. Furthermore, metagenomic analysis demonstrated that bacteria involved in nitrate-ammonification prevailed in all the cultures. These results imply that networks formed by phytoplankton and heterotrophic bacteria might vary across habitats, and that different dominant bacterial groups play different roles in the phycosphere. This study provides new insight into the unique interactive and interdependent bond between phytoplankton and their associated microbiome, which may enhance our understanding of carbon and nutrient cycling in marine environments.

Aspirin resistance and adverse clinical events in patients with coronary artery disease.

PURPOSE: We sought to determine the clinical significance of aspirin resistance measured by a point-of-care assay in stable patients with coronary artery disease (CAD). METHODS: We used the VerifyNow Aspirin (Accumetrics Inc, San Diego, Calif) to determine aspirin responsiveness of 468 stable CAD patients on aspirin 80 to 325 mg daily for > or =4 weeks. Aspirin resistance was defined as an Aspirin Reaction Unit > or =550. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), unstable angina requiring hospitalization, stroke, and transient ischemic attack. RESULTS: Aspirin resistance was noted in 128 (27.4%) patients. After a mean follow-up of 379+/-200 days, patients with aspirin resistance were at increased risk of the composite outcome compared to patients who were aspirin-sensitive (15.6% vs 5.3%, hazard ratio [HR] 3.12, 95% confidence intervals [CI], 1.65-5.91, P < .001). Cox proportional hazard regression modeling identified aspirin resistance, diabetes, prior MI, and a low hemoglobin to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 2.46, 95% CI, 1.27-4.76, P = .007). CONCLUSIONS: Aspirin resistance, defined by an aggregation-based rapid platelet function assay, is associated with an increased risk of adverse clinical outcomes in stable patients with CAD.

Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease.

AIM: The use of low-dose aspirin to prevent cardiovascular disease events is well established. However, the incidence and predictors of upper gastrointestinal bleeding (UGIB) with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users. METHODS: A total of 991 patients with coronary artery disease (CAD) on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB. RESULTS: UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension (OR = 4.6, 95%CI 1.5-14.7, P = 0.009), history of peptic ulceration (OR = 3.1, 95%CI 1.1-9.0, P = 0.039), tertiary education (OR = 3.08, 95%CI 1.1-9.0, P = 0.039) and higher lean body mass (P = 0.016) were independent factors associated with UGIB. Use of nitrate did not reduce UGIB. CONCLUSION: The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy.

Prediction of aortic augmentation index using radial pulse transmission-wave analysis.

OBJECTIVE: Current arterial transfer functions have low capability in predicting aortic augmentation index (AIx) from radial pulse contour (RPC), because of the difficulty in accurately identifying the merging point (inflection point) in the derived aortic pulse contour (APC). We hypothesize that the formation time between each characteristic wave in APC is about one-third of ejection duration (ED/3). We sought to assess the accuracy of ED/3 in identifying the merging point in APC as compared to the conventional differential method. In addition, we sought to derive the AIx from RPC based on an arterial transfer function and the ED/3 method. METHODS: APC and RPC sequences were measured digitally and simultaneously in 60 subjects (37 males; aged 60 +/- 10 years). An ensemble-averaged RPC-to-APC transfer function was determined from 30 randomly selected subjects and was used to derive APC sequences in the 30 additional subjects. The accuracy of AIx predicted from RPC was determined. RESULTS: In patients with a clearly identifiable merging point in APC, the ED/3 method identified the merging point of measured APC within 1.97 +/- 0.60 ms of that identified by the conventional differential method, with identical AIx. The AIx and merging point of derived APC using the ED/3 method were also within 0.22 +/- 1.01% and 1.81 +/- 1.64 ms, respectively, of those of the measured APC using the conventional differential method. The accuracy of the predicted AIx was independent of age, sex, body-mass index and presence of hypertension. CONCLUSION: In a quiet resting state, the ED/3 is an alternative method for identifying the merging point in APC. In conjunction with transfer-function technique, AIx can be derived accurately from RPC.

A randomized, double-blind, placebo-controlled trial of abciximab for prevention of in-stent restenosis in diabetic patients after coronary stenting: results of the ASIAD (Abciximab in Stenting Inhibits restenosis Among Diabetics) Trial.

OBJECTIVES: Coronary stenting is associated with a high incidence of restenosis in patients with diabetes mellitus. Recent data suggest that diabetic patients treated with abciximab have a lower rate of target vessel revascularization (TVR). We sought to investigate whether abciximab can reduce in-stent restenosis after coronary stenting in diabetic patients. METHODS: In this prospective double-blind trial, we randomly assigned 254 patients with type 2 diabetes mellitus undergoing nonurgent coronary stenting to receive abciximab with an initial heparin bolus of 50 U/kg (n = 128) or placebo with an initial heparin bolus of 70 U/kg (n = 126). All patients received aspirin and clopidogrel before the procedure. The primary endpoint was angiographic restenosis by quantitative coronary angiography at 6 months. The secondary endpoint was death, myocardial infarction (MI), or target lesion revascularization (TLR) at 6 months. RESULTS: The clinical, angiographic, and procedural characteristics were matched between the 2 groups. Angiographic follow-up was completed in 226 patients (90%). Angiographic restenosis occurred in 29.1% of the abciximab group, and 24% of the placebo group (p = 0.30). The rates of the secondary endpoint were similar between the 2 groups (23.4% in the abciximab group versus 22.2% in the placebo group; p = 0.88). TLR was performed on 36 (18.4%) lesions in 29 (23.4%) patients of the abciximab group, and 26 (13.6%) lesions in 23 (18.3%) patients of the placebo groups, respectively (p = 0.21 and 0.35, respectively). CONCLUSIONS: Abciximab does not reduce angiographic restenosis or TLR in type 2 diabetic patients undergoing nonurgent coronary stenting.

Relation of aspirin resistance to coronary flow reserve in patients undergoing elective percutaneous coronary intervention.

Previous studies have shown that more complete platelet inhibition improves the coronary flow reserve (CFR), a measure of microvascular integrity, in patients undergoing percutaneous coronary intervention (PCI). We hypothesized that patients with aspirin resistance would have impaired CFR after elective PCI. We used VerifyNow Aspirin to determine the response to aspirin in 117 consecutive patients who underwent elective single-lesion PCI. The assay results are expressed quantitatively in Aspirin Reaction Units based on the degree of platelet aggregation. All patients received a 300-mg loading dose of clopidogrel >12 hours before and a 75-mg maintenance dose the morning of PCI. CFR was estimated using the Thrombolysis In Myocardial Infarction frame count method. Of the 117 patients, 22 (18.8%) were aspirin resistant. The clinical, angiographic, and procedural characteristics of the aspirin-sensitive and -resistant patients were balanced. All patients underwent successful PCI with <50% residual diameter stenosis and Thrombolysis In Myocardial Infarction grade 3 flow after PCI. Aspirin-resistant patients had a lower CFR than the aspirin-sensitive patients (1.42 +/- 0.35 vs 1.80 +/- 0.64, p = 0.018). Univariate correlates of CFR included the Aspirin Reaction Unit (r = -0.227, p = 0.014) and post-PCI creatine kinase-MB elevation (p = 0.048). Multivariate linear regression analysis revealed the Aspirin Reaction Unit to be the only independent determinant of CFR after PCI (r2 = 0.051, p = 0.014). Thus, aspirin resistance was associated with impaired CFR in patients who underwent elective PCI, implicating insufficient aspirin-induced platelet inhibition as a cause of microvascular dysfunction by distal atherothrombotic embolization and/or spasm.

Low-dose aspirin increases aspirin resistance in patients with coronary artery disease.

PURPOSE: We sought to investigate the association of aspirin dose and aspirin resistance in stable coronary artery disease patients measured by a point-of-care assay. METHODS: We studied 468 consecutive stable coronary artery disease patients in a referral cardiac center who were taking aspirin 80 to 325 mg daily for > or =4 weeks. The VerifyNow Aspirin (Ultegra RPFA-ASA, Accumetrics Inc, San Diego, Calif) was used to determine aspirin responsiveness. An aspirin reaction unit (ARU) > or =550 indicates the absence of aspirin-induced platelet dysfunction, based on correlation with epinephrine-induced light transmission aggregometry. Demographic and clinical data were collected to analyze the predictors of aspirin resistance. RESULTS: Aspirin resistance was noted in 128 (27.4%) patients. Univariate predictors of aspirin resistance include elderly (P = 0.002), women (P <0.001), anemia (P <0.001), renal insufficiency (P = 0.009) and aspirin dose < or =100 mg (P = 0.004). Multivariate analysis revealed hemoglobin (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.51 to 0.69; P <0.001) and aspirin dose < or =100 mg (OR 2.23; 95% CI 1.12 to 4.44; P = 0.022) to be independent predictors of aspirin resistance. Daily aspirin dose < or = 100 mg was associated with increased prevalence of aspirin resistance compared with 150 mg and 300 mg daily (30.2% vs 16.7% vs 0%, P = 0.0062). CONCLUSION: A 100 mg or less daily dose of aspirin, which may have lower side effects, is associated with a higher incidence of aspirin resistance in patients with coronary artery disease. Prospective randomized studies are warranted to elucidate the optimal aspirin dosage for preventing ischemic complications of atherothrombotic disease.

Concomitant coronary and subclavian steal caused by ipsilateral subclavian artery stenosis and arteriovenous fistula in a hemodialysis patient.

Patients with chronic renal failure, because of concomitant conventional cardiovascular and uremia-associated risk factors, are at risk of developing diffuse and accelerated atherosclerosis involving both the coronary and peripheral territories. We report an end-stage renal failure patient with a history of coronary artery bypass surgery who developed both angina and dizziness during hemodialysis via a left forearm arteriovenous fistula. Magnetic resonance imaging diagnosed the presence of significant subclavian artery stenosis. The patient then underwent successful percutaneous stenting of the left subclavian artery. His angina and dizziness symptoms resolved subsequently.

Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment.

OBJECTIVES: We sought to investigate the effect of aspirin resistance on the incidence of myonecrosis after non-urgent percutaneous coronary intervention (PCI) among patients pretreated with clopidogrel. BACKGROUND: Oral antiplatelet therapy using aspirin and a thienopyridine is the standard of care for preventing thrombotic complications of PCI. The effect of aspirin resistance on the outcomes of patients undergoing PCI is unknown. METHODS: We used the Ultegra Rapid Platelet Function Assay-ASA (Accumetrics Inc., San Diego, California) to determine aspirin responsiveness of 151 patients scheduled for non-urgent PCI. All patients received a 300-mg loading dose of clopidogrel >12 h before and a 75-mg maintenance dose in the morning of the PCI. The incidence of myonecrosis was measured by creatine kinase-myocardial band (CK-MB) and by troponin I (TnI) elevations after PCI. RESULTS: A total of 29 (19.2%) patients were noted to be aspirin-resistant. There was a significantly higher incidence of female subjects in the aspirin-resistant versus aspirin-sensitive groups. The incidence of any CK-MB elevation was 51.7% in aspirin-resistant patients and 24.6% in aspirin-sensitive patients (p = 0.006). Elevation of TnI was observed in 65.5% of aspirin-resistant patients and 38.5% of aspirin-sensitive patients (p = 0.012). Multivariate analysis revealed aspirin resistance (odds ratio [OR] 2.9; 95% confidence interval [CI] 1.2 to 6.9; p = 0.015) and bifurcation lesion (OR 2.8; 95% CI 1.3 to 6.0; p = 0.007) to be independent predictors of CK-MB elevation after PCI. CONCLUSIONS: Despite adequate pretreatment with clopidogrel, patients with aspirin resistance as measured by a point-of-care assay have an increased risk of myonecrosis following non-urgent PCI.

Safety and feasibility of the use of a distal filter protection device in percutaneous revascularization of small coronary arteries.

The FilterWire EX is one of the filter protection devices developed as alternatives to balloon occlusion system for percutaneous coronary intervention. Its use has been recommended in vessels between 3.5 and 5.5 mm in diameter and no data are available on its use in smaller vessels. We evaluated the safety and feasibility of using FilterWire EX in native coronary arteries smaller than 3.5 mm. We successfully deployed and retrieved the FilterWire EX in 49 coronary arteries with a mean vessel diameter of 2.62 +/- 0.45 mm at device deployment. Reversible vasospasm was observed in 24 (50%) vessels, coronary flow was temporarily reduced in 22 (44.9%), and distal embolization was noted in 2 (4%). There was no vessel dissection induced by the device. These data suggest that it is safe and feasible to use the FilterWire EX in small coronary arteries.

Percutaneous recanalization of chronic subclavian artery occlusion using optical coherence reflectometry-guided radiofrequency ablation guidewire.

Subclavian artery lesion that is associated with low complication rate could be treated by percutaneous intervention effectively. However, the success of endovascular therapy for occlusive lesion may be limited by failure to cross with a guidewire. We describe the use of a system using optical coherence reflectometry for navigation and radiofrequency ablation to enable wire passage through subclavian artery occlusion that could not be crossed by conventional guidewires.

Initial experience and safety in the treatment of chronic total coronary occlusions with a new optical coherent reflectometry-guided radiofrequency ablation guidewire.

The Safe-Cross wire system, which has optical coherence reflectometry technology for navigating and radiofrequency energy provided at its tip for crossing chronic total occlusions (CTOs), provides a promising means to treat hard, organized CTOs. Using this system, we report on a 60% success rate in patients who had long-standing coronary CTOs that had > or =1 failed attempt using conventional percutaneous coronary intervention.

Recanalization of chronic and long occlusive in-stent restenosis using optical coherence reflectometry-guided radiofrequency ablation guidewire.

Chronic total occlusions remain a challenge to interventionalists due to failure of crossing or perforation by strong wires. We describe the use of a system using optical coherence reflectometry for navigation and radiofrequency ablation to enable wire passage through occlusions that could not be crossed by conventional guidewires.

Stable and optimal anticoagulation is achieved with a single dose of intravenous enoxaparin in patients undergoing percutaneous coronary intervention.

This study assessed the pharmacokinetics, safety and efficacy of intravenous enoxaparin in patients undergoing percutaneous coronary intervention (PCI). Sixty consecutive patients [(age, 62 11 years; female, 16%; diabetes, 18%; hypertension, 53%; prior myocardial infarction (MI), 43%] undergoing PCI (stable angina, 89%; stent, 92%; two-vessel disease, 23%; B2/C lesions, 45%) were administered intravenous enoxaparin 1 mg/kg for procedural anticoagulation. Blood samples for anti-Xa level and activated partial thromboplastin time (aPTT) were assayed from the first 20 patients before and after enoxaparin administration at the following intervals: 5, 30, 60, 90, 120, 150, 180, 210, 240, 360 and 480 minutes. Activated clotting time was assessed 5 minutes after enoxaparin administration. Bleeding complications were classified according to Thrombolysis In Myocardial Infarction (TIMI) criteria. All patients were monitored for adverse clinical events at clinic visit 4 8 weeks after hospital discharge. No TIMI major or minor bleedings occurred during hospitalization for the PCI (median stay post-PCI = 1 day). One patient (2%) developed a non-Q wave MI after the PCI and before hospital discharge. There was no death or urgent revascularization up to clinical follow-up. The peak anti-Xa level was 1.30 0.18 IU/ml (range, 1.03 1.69 IU/ml). The minimum anti-Xa level was 0.55 IU/ml 4 hours after enoxaparin. Thus, the use of intravenous enoxaparin in patients undergoing PCI is associated with a low incidence of ischemic and bleeding complications. A stable therapeutic anticoagulant effect is provided without the need for monitoring within 4 hours of enoxaparin administration.