Background We evaluated whether cardiac troponin T (cTnT) measured with a new highly sensitive assay was associated with incident coronary heart disease (CHD), mortality, and hospitalization for heart failure (HF) in a general population of participants in the Atherosclerosis Risk in Communities (ARIC) Study. Methods and Results Associations between increasing cTnT levels and CHD, mortality, and HF hospitalization were evaluated using Cox proportional-hazards models adjusted for traditional CHD risk factors, kidney function, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro–B-type natriuretic peptide (NT-proBNP) in 9,698 participants aged 54–74 years who at baseline were free from CHD and stroke (and HF in the HF analysis). Measurable cTnT levels (≥0.003 μg/L) were detected in 66.5% of individuals. In fully adjusted models, compared with participants with undetectable levels, those with cTnT levels in the highest category (≥0.014 μg/L, 7.4% of the ARIC population) had significantly increased risk for CHD (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.81–2.89), fatal CHD (HR 7.59, 95% CI 3.78–15.25), total mortality (HR 3.96, 95% CI 3.21–4.88), and HF (HR 5.95, 95% CI 4.47–7.92). Even minimally elevated cTnT (≥0.003 μg/L) was associated with increased risk for mortality and HF (p<0.05). Adding cTnT to traditional risk factors improved risk prediction parameters; the improvements were similar to those with NT-proBNP and better than that with the addition of hs-CRP. Conclusions cTnT detectable with a highly sensitive assay was associated with incident CHD, mortality, and HF in individuals from a general population without known CHD/stroke.

GnRH neurons form the final common pathway for central control of reproduction, with regulation achieved by changing the pattern of GnRH pulses. To help elucidate the neurobiological mechanisms underlying pulsatile GnRH release, we generated transgenic mice in which the green fluorescent protein (GFP) reporter was genetically targeted to GnRH neurons. The expression of GFP allowed identification of 84-94% of immunofluorescently-detected GnRH neurons. Conversely, over 99.5% of GFP-expressing neurons contained immunologically detectable GnRH peptide. In hypothalamic slices, GnRH neurons could be visualized with fluorescence, allowing for identification of individual GnRH neurons for patch-clamp recording and subsequent morphological analysis. Whole-cell current-clamp recordings revealed that all GnRH neurons studied (n = 23) fire spontaneous action potentials. Both spontaneous firing (n = 9) and action potentials induced by injection of depolarizing current (n = 17) were eliminated by tetrodotoxin, indicating that voltage-dependent sodium channels are involved in generating action potentials in these cells. Direct intracellular morphological assessment of GnRH dendritic morphology revealed GnRH neurons have slightly more extensive dendrites than previously reported. GnRH-GFP transgenic mice represent a new model for the study of GnRH neuron structure and function, and their use should greatly increase our understanding of this important neuroendocrine system.

Despite quite modest effect sizes, findings suggest that students' abilities to effectively manage affective states may be subject to some minor fluctuation across the undergraduate educational continuum. However, whether these observed declines constitute meaningful, clinically relevant changes remains unclear.

Background The enhanced sensitivity of cardiac troponin T (cTnT) assays calls for its use as a prognostic marker in chronic heart failure, as an accurate and early marker of myocyte damage, and as a sensitive indicator of acute episodes in chronic disease. To facilitate these applications and inform required benchmarks, we estimated the variability in cTnT measurements, the sources of this variability, and the stability of cTnT using samples stored at −70 °C. Methods and Results Stored samples from the Atherosclerosis Risk in Communities Study (ARIC) study (1996–1998) and ARIC Carotid MRI study participants (2005–06) were assayed in 2009–10 to examine variability in cTnT attributable to laboratory (replicates after freeze thaw, n=29), processing (blind replicates from same blood draw, n = 87), short- (n = 40) and long-term biological variation (repeat visit, n = 38), and degradation in frozen storage (n = 10,870). The Elecsys Troponin T (Roche Diagnostics, Indianapolis, IN) was used to assay cTnT on an automated Cobas e411 analyzer. The lower limit of detection was 3 ng/L. Approximately 1/4th to 1/3rd of the participants had values below the detection limit. The paired correlation for all other comparisons exceeded 0.93 (except for samples drawn 8 years apart = 0.36). The coefficients of variation for individual sources of variation in cTnT were as follows: laboratory 2.1% in those with heart failure (HF) and 11.2% in those without HF; processing 18.3%; biological at six weeks 16.6%, and at eight years 48.4%. The reference change value at 6 weeks was 68.5% and would require 4 samples to determine homeostatic set point within ± 25%. Only modest degradation was detected in stored frozen samples for an average of 8 years. Conclusions cTnT is detectable in approximately 70% of community-dwelling men and women aged 53 to 75 years. The laboratory reliability was high: the reliability coefficient (r) was 0.99 in those with heart failure and 0.94 in those without heart failure. The intra-individual (biologic) variability was low on repeat testing after 6 weeks (r=0.94), and increased for measurements taken 8 years apart (R=0.36). Troponin T is stable in storage at −70° C and the variability in cTnT values attributable to one freeze-thaw cycle is of small magnitude.