Sex-related differences in contemporary biomarkers for heart failure:a review

The use of circulating biomarkers for heart failure (HF) is engrained in contemporary cardiovascular practice and provides objective information about various pathophysiological pathways associated with HF syndrome. However, biomarker profiles differ considerably among women and men. For instance, in the general population, markers of cardiac stretch (natriuretic peptides) and fibrosis (galectin-3) are higher in women, whereas markers of cardiac injury (cardiac troponins) and inflammation (sST2) are higher in men. Such differences may reflect sex-specific pathogenic processes associated with HF risk, but may also arise as a result of differences in sex hormone profiles and fat distribution. From a clinical perspective, sex-related differences in biomarker levels may affect the objectivity of biomarkers in HF management because what is considered to be 'normal' in one sex may not be so in the other. The objectives of this review are, therefore: (i) to examine the sex-specific dynamics of clinically relevant HF biomarkers in the general population, as well as in HF patients; (ii) to discuss the overlap between sex-related and obesity-related effects, and (iii) to identify knowledge gaps to stimulate research on sex-related differences in HF

Long‐term Cardiovascular Risks Associated With an Elevated Heart Rate: The Framingham Heart Study

Background: Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow‐up. Methods and Results: Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P=0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P<0.0001). Higher heart rate was also associated with higher all‐cause (HR 1.17, 95% CI 1.11 to 1.24, P<0.0001) and cardiovascular mortality (HR 1.18, 95% CI 1.04 to 1.33, P=0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P=0.001). Conclusions: Individuals with a higher heart rate are at elevated long‐term risk for cardiovascular events, in particular, heart failure, and all‐cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation

Cervical spinal cord dimensions and clinical outcomes in adults with Klippel-Feil syndrome: A comparison with matched controls.

Study Design Retrospective case–control study. Objectives To confirm the fact that spinal cord dimensions are smaller in adults with Klippel-Feil syndrome (KFS) than in pediatric patients with KFS and to compare the clinical characteristics and outcomes of neurologic complications in patients with KFS with matched controls. Methods We performed an independent 1:2 case–control retrospective radiographic and chart review of a consecutive series of adults with KFS who underwent surgical intervention. The control group consisted of consecutive non-KFS surgical patients. Patients were matched in 1:2 case–control manner. Their charts were reviewed and the clinical characteristics were compared. Axial T2-weighted magnetic resonance imaging (MRI) was used to measure the anteroposterior and mediolateral axial spinal cord and spinal canal at the operative levels and measurements were compared. Results A total of 22 patients with KFS and 44 controls were identified. The KFS group had a tendency of more myeloradiculopathy, and the control group had a tendency toward more radiculopathy. Both tendencies, however, were not significantly different. MRIs of 10 patients from the KFS group and 22 controls were available. There was no difference in the area of both spinal cord and canal at the operative levels. Conclusion Contrary to the finding in previous reports on pediatric patients, there were no differences between KFS and well-matched control groups in terms of age of onset, presentation, revision rate, complication rate, surgical outcome, and cross-sectional spinal cord and canal dimensions at the operative level

Galectin-3 Activation and Inhibition in Heart Failure and Cardiovascular Disease:An Update

Galectin-3 is a versatile protein orchestrating several physiological and pathophysiological processes in the human body. In the last decade, considerable interest in galectin-3 has emerged because of its potential role as a biotarget. Galectin-3 is differentially expressed depending on the tissue type, however its expression can be induced under conditions of tissue injury or stress. Galectin-3 overexpression and secretion is associated with several diseases and is extensively studied in the context of fibrosis, heart failure, atherosclerosis and diabetes mellitus. Monomeric (extracellular) galectin-3 usually undergoes further "activation" which significantly broadens the spectrum of biological activity mainly by modifying its carbohydrate-binding properties. Self-interactions of this protein appear to play a crucial role in regulating the extracellular activities of this protein, however there is limited and controversial data on the mechanisms involved. We therefore summarize (recent) literature in this area and describe galectin-3 from a binding perspective providing novel insights into mechanisms by which galectin-3 is known to be "activated" and how such activation may be regulated in pathophysiological scenarios

Metabolite Profiles During Oral Glucose Challenge

To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m2) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P ≤ 0.0005 for all). Amino acids, β-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in β-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state

Host-linked soil viral ecology along a permafrost thaw gradient

Climate change threatens to release abundant carbon that is sequestered at high latitudes, but the constraints on microbial metabolisms that mediate the release of methane and carbon dioxide are poorly understood1,2,3,4,5,6,7. The role of viruses, which are known to affect microbial dynamics, metabolism and biogeochemistry in the oceans8,9,10, remains largely unexplored in soil. Here, we aimed to investigate how viruses influence microbial ecology and carbon metabolism in peatland soils along a permafrost thaw gradient in Sweden. We recovered 1,907 viral populations (genomes and large genome fragments) from 197 bulk soil and size-fractionated metagenomes, 58% of which were detected in metatranscriptomes and presumed to be active. In silico predictions linked 35% of the viruses to microbial host populations, highlighting likely viral predators of key carbon-cycling microorganisms, including methanogens and methanotrophs. Lineage-specific virus/host ratios varied, suggesting that viral infection dynamics may differentially impact microbial responses to a changing climate. Virus-encoded glycoside hydrolases, including an endomannanase with confirmed functional activity, indicated that viruses influence complex carbon degradation and that viral abundances were significant predictors of methane dynamics. These findings suggest that viruses may impact ecosystem function in climate-critical, terrestrial habitats and identify multiple potential viral contributions to soil carbon cycling

Harnessing the Power of Genomics to Secure the Future of Seafood

Best use of scientific knowledge is required to maintain the fundamental role of seafood in human nutrition. While it is acknowledged that genomic-based methods allow the collection of powerful data, their value to inform fisheries management, aquaculture, and biosecurity applications remains underestimated. We review genomic applications of relevance to the sustainable management of seafood resources, illustrate the benefits of, and identify barriers to their integration. We conclude that the value of genomic information towards securing the future of seafood does not need to be further demonstrated. Instead, we need immediate efforts to remove structural roadblocks and focus on ways that support integration of genomic-informed methods into management and production practices. We propose solutions to pave the way forward.Peer reviewe

The Sloan Digital Sky Survey Reverberation Mapping project : composite lags at z ≤ 1

Funding: STFC grant ST/M001296/1 (KH).We present composite broad-line region (BLR) reverberation mapping lag measurements for Hα, Hβ, He II λ4686, and Mg II for a sample of 144, z ≲ 1 quasars from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project. Using only the 32-epoch spectroscopic light curves in the first six-month season of SDSS-RM observations, we compile correlation function measurements for individual objects and then coadd them to allow the measurement of the average lags for our sample at mean redshifts of 0.4 (for Hα) and ∼0.65 (for the other lines). At similar quasar luminosities and redshifts, the sample-averaged lag decreases in the order of Mg II, Hα, Hβ, and He II. This decrease in lags is accompanied by an increase in the mean line width of the four lines, and is roughly consistent with the virialized motion for BLR gas in photoionization equilibrium. These are among the first RM measurements of stratified BLR structure at z > 0.3. Dividing our sample by luminosity, Hα shows clear evidence of increasing lags with luminosity, consistent with the expectation from the measured BLR size-luminosity relation based on Hβ. The other three lines do not show a clear luminosity trend in their average lags due to the limited dynamic range of luminosity probed and the poor average correlation signals in the divided samples, a situation that will be improved with the incorporation of additional photometric and spectroscopic data from SDSS-RM. We discuss the utility and caveats of composite lag measurements for large statistical quasar samples with reverberation mapping dataPostprintPeer reviewe

Cardiovascular disease related circulating biomarkers and cancer incidence and mortality:is there an association?

Aims Recent studies suggest an association between cardiovascular disease (CVD) and cancer incidence/mortality, but the pathophysiological mechanisms underlying these associations are unclear. We aimed to examine biomarkers previously associated with CVD and study their association with incident cancer and cancer-related death in a prospective cohort study. Methods and results We used a proteomic platform to measure 71 cardiovascular biomarkers among 5032 participants in the Framingham Heart Study who were free of cancer at baseline. We used multivariable-adjusted Cox models to examine the association of circulating protein biomarkers with risk of cancer incidence and mortality. To account for multiple testing, we set a 2-sided false discovery rat