Abstract: Dissolved organic matter (DOM) is an intermediate between organic carbon formed by primary producers and carbon dioxide (CO2) produced through respiration, making it a key component of the carbon cycle in aquatic ecosystems. Its composition influences the routes of mineralization. Here, we evaluate DOM composition as a function of time and depth in Lake Mendota, a highly productive eutrophic lake that stratifies in warm months and is located in Madison, Wisconsin, USA. Dissolved organic carbon concentrations and optical properties are presented for 73 samples collected at a single location at varying depths within the water column from June to November. A subset of samples is analyzed by Fourier transform‐ion cyclotron resonance mass spectrometry (FT‐ICR MS) to investigate DOM composition at the molecular level. Temporally, increases in more oxidized formulas are observed in both the epilimnion and hypolimnion. At the surface, correlations between DOM formulas and both chlorophyll concentrations and light intensity show that photochemical reactions contribute to DOM oxidation. In the hypolimnion, redox conditions and interactions with sediments likely influence temporal compositional change. Our results show DOM composition varies with depth with more highly oxidized formulas identified deeper in the water column. However, DOM composition varies more temporally than by location within the water column. This work has implications for climate change as DOM photooxidation in lakes represents an understudied flux of CO2 to the atmosphere. Additionally, lake eutrophication is increasing due to warming temperatures and this data set yields detailed molecular information about DOM composition and processing in such lakes.

Coastal wetlands are vulnerable to sea level rise with unknown consequences for mercury (Hg) cycling, particularly the potential for exacerbating neurotoxic methylmercury (MeHg) production and bioaccumulation in food webs. Here, the effect of sea level rise on MeHg formation in the Florida Everglades was evaluated by incubating peat cores from a freshwater wetland for 0-20 days in the laboratory at five salinity conditions (0.16-6.0 parts-per-thousand; 0.20-454 mg L-1 sulfate (SO42-)) to simulate the onset of sea level rise within coastal margins. Isotopically enriched inorganic mercury (201Hg(II)) was used to track MeHg formation and peat-porewater partitioning. In all five salinity treatments, porewaters became anoxic within 1 day and became progressively enriched in dissolved organic matter (DOM) of greater aromatic composition over the 20 days compared to ambient conditions. In the four highest salinity treatments, SO42- concentrations decreased and sulfide concentrations increased over time due to microbial dissimilatory SO42- reduction that was concurrent with 201Hg(II) methylation. Importantly, elevated salinity resulted in a greater proportion of produced Me201Hg observed in porewaters as opposed to bound to peat, interpreted to be due to the complexation of MeHg with aromatic DOM released from peat. The findings highlight the potential for enhanced production and mobilization of MeHg in coastal wetlands of the Florida Everglades due to the onset of saltwater intrusion.

Methylmercury (MeHg) production is controlled by the bioavailability of inorganic divalent mercury (Hg(II)_i ) and Hg-methylation capacity of the microbial community (conferred by the hgcAB gene cluster). However, the relative importance of these factors and their interaction in the environment remain poorly understood. Here, metagenomic sequencing and a full-factorial MeHg formation experiment were conducted across a wetland sulfate gradient with different microbial communities and pore water chemistries. From this experiment, the relative importance of each factor on MeHg formation was isolated. Hg(II)_i bioavailability correlated with the dissolved organic matter composition, while the microbial Hg-methylation capacity correlated with the abundance of hgcA genes. MeHg formation responded synergistically to both factors. Notably, hgcA sequences were from diverse taxonomic groups, none of which contained genes for dissimilatory sulfate reduction. This work expands our understanding of the geochemical and microbial constraints on MeHg formation in situ and provides an experimental framework for further mechanistic studies.

Background

Obesity is a common source of artifact on conventional SPECT myocardial perfusion imaging (MPI). We evaluated image quality and diagnostic performance of high-efficiency (HE) cadmium-zinc-telluride parallel-hole SPECT MPI for coronary artery disease (CAD) in obese patients.

Methods and results

118 consecutive obese patients at three centers (BMI 43.6 ± 8.9 kg·m(-2), range 35-79.7 kg·m(-2)) had upright/supine HE-SPECT and invasive coronary angiography > 6 months (n = 67) or low likelihood of CAD (n = 51). Stress quantitative total perfusion deficit (TPD) for upright (U-TPD), supine (S-TPD), and combined acquisitions (C-TPD) was assessed. Image quality (IQ; 5 = excellent; < 3 nondiagnostic) was compared among BMI 35-39.9 (n = 58), 40-44.9 (n = 24) and ≥45 (n = 36) groups. ROC curve area for CAD detection (≥50% stenosis) for U-TPD, S-TPD, and C-TPD were 0.80, 0.80, and 0.87, respectively. Sensitivity/specificity was 82%/57% for U-TPD, 74%/71% for S-TPD, and 80%/82% for C-TPD. C-TPD had highest specificity (P = .02). C-TPD normalcy rate was higher than U-TPD (88% vs 75%, P = .02). Mean IQ was similar among BMI 35-39.9, 40-44.9 and ≥45 groups [4.6 vs 4.4 vs 4.5, respectively (P = .6)]. No patient had a nondiagnostic stress scan.

Conclusions

In obese patients, HE-SPECT MPI with dedicated parallel-hole collimation demonstrated high image quality, normalcy rate, and diagnostic accuracy for CAD by quantitative analysis of combined upright/supine acquisitions.

Background Patients who undergo percutaneous coronary intervention (PCI) are at increased risk for recurrent cardiovascular events despite aggressive medical therapy. Methods and Results This post hoc analysis focused on the subset of patients with prior PCI enrolled in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), a multicenter, randomized, double-blind, placebo-controlled trial of icosapent ethyl versus placebo. Icosapent ethyl was added to statins in patients with low-density lipoprotein cholesterol <100 mg/dL and fasting triglycerides 135-499 mg/dL. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. There were 8179 patients randomized in REDUCE-IT followed for a median of 4.9 years, and 3408 (41.7%) of them had a prior PCI with a median follow-up of 4.8 years. These patients were randomized a median of 2.9 years (11 days to 30.7 years) after PCI. Among patients treated with icosapent ethyl versus placebo, there was a 34% reduction in the primary composite end point (hazard ratio [HR], 0.66; 95% CI, 0.58-0.76; P<0.001; number needed to treat^{4.8 years}=12) and a 34% reduction in the key secondary composite end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR, 0.66; 95% CI, 0.56-0.79; P<0.001; NNT^{4.8 years}=19) versus placebo. Similarly, large reductions occurred in total coronary revascularizations and revascularization subtypes. There was also a 39% reduction in total events (rate ratio, 0.61; 95% CI, 0.52-0.72; P<0.001). Conclusions Among patients treated with statins with elevated triglycerides and a history of prior PCI, icosapent ethyl substantially reduced the risk of recurrent events during an average of ~5 years of follow-up with a number needed to treat of only 12. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Background

Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations.

Methods

REDUCE-IT (The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL), controlled low-density lipoprotein (41-100 mg/dL), and either established cardiovascular disease or diabetes plus other risk factors to receive icosapent ethyl 4 g/d or placebo. The primary and key secondary composite end points were significantly reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.

Results

A total of 8179 randomly assigned patients were followed for 4.9 years (median). First revascularizations were reduced to 9.2% (22.5/1000 patient-years) with icosapent ethyl versus 13.3% (33.7/1000 patient-years) with placebo (hazard ratio, 0.66 [95% CI, 0.58-0.76]; P<0.0001; number needed to treat for 4.9 years=24); similar reductions were observed in total (first and subsequent) revascularizations (negative binomial rate ratio, 0.64 [95% CI, 0.56-0.74]; P<0.0001), and across elective, urgent, and emergent revascularizations. Icosapent ethyl significantly reduced percutaneous coronary intervention (hazard ratio, 0.68 [95% CI, 0.59-0.79]; P<0.0001) and coronary artery bypass grafting (hazard ratio, 0.61 [95% CI, 0.45-0.81]; P=0.0005).

Conclusions

Icosapent ethyl reduced the need for first and subsequent coronary revascularizations in statin-treated patients with elevated triglycerides and increased cardiovascular risk. To our knowledge, icosapent ethyl is the first non-low-density lipoprotein-lowering treatment that has been shown to reduce coronary artery bypass grafting in a blinded, randomized trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.