Low serum cortisol predicts early death following acute myocardial infarction

<b>Objective</b>: Low serum cortisol concentrations have been associated with adverse prognosis in critical illness of diverse aetiology. We aimed to determine whether low serum cortisol concentrations are associated with adverse prognosis in patients with acute myocardial infarction. <b>Design</b>: Nested case-control study. <b>Setting</b>: Prospective cohort study of consecutive patients admitted with acute myocardial infarction to 9 Scottish hospitals. <b>Patients</b>: 100 patients who survived 30 days (controls) and 100 patients who died within 30 days (cases). <b>Measurements and Main Results</b>: Admission cortisol concentrations were lower in patients who died than those who survived (median 1,189 versus 1,355 nmol/L, p<0.001). A cortisol concentration in the bottom quartile (<1,136 nmol/L) was a strong predictor of death within 30 days, and remained so after adjustment for age and cardiac troponin concentration (adjusted OR 8.78, 95% CI 3.09-24.96, p<0.001). <b>Conclusions</b>: Patients who mount a lesser cortisol stress response to acute myocardial infarction have a poorer early prognosis

Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease

Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease

Nature, predictor, and outcomes of motivation trajectories during a professional training program

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