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Micromembranes were assembled by sequentially chemisorbing polyanions and polycations on miniature (5 x 10(-4) cm2) enzyme electrodes. The sequential chemisorption process allowed the simultaneous tailoring of their sensitivity, dynamic range, drift, and selectivity. When assembled on tips of 250-microm-diameter gold wires coated with redox polymer-"wired" glucose oxidase, they allowed tailoring of the glucose electrodes for > 2 nA/mM sensitivity; 0-30 mM dynamic range; drift of < or =5% per 24 h at 37 degrees C at 15 mM glucose concentration; and < or =5% current increment by the combination of 0.1 mM ascorbate, 0.2 mM acetaminophen, and 0.5 mM urate. The membranes also retained transition metal ions that bound to and damaged the redox polymer "wiring" the enzyme. The electrodes were tested in the jugular veins and in the intrascapular subcutaneous region of anaesthetized and heparinized nondiabetic Sprague-Dawley rats, in which rapid changes of glycemia were forced by intravenous injections of glucose and insulin. After one-point in vivo calibration of the electrodes, all of the 152 data points were clinically accurate when it was assumed that after insulin injection the glycemia in the subcutaneous fluid lags by 9 min behind that of blood withdrawn from the insulin-injected vein.

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BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

Reactive oxygen species that attack DNA are continuously generated in living cells. Both the guanosine (G) mole fraction and its distribution should affect the stability of genomes and their parts to oxidation. At a lesser G content, genomes should be more oxidation resistant or "ennobled". Oxidant scavenging by G's in nonessential parts of introns and intergenic domains should decrease G oxidation in the essential exons. To determine whether genomes are indeed ennobled and whether oxidant-scavenging domains exist in genomes, the relative rates of guanosine oxidation in average exons, introns, and intergenic domains were estimated. Comparison among genomes indicated that average exons are ennobled in the genomes of Caenorhabditis (worm), Arabidopsis (plant), Saccharomyces (yeast), Schizosaccharomyces (yeast), and Plasmodium (malaria parasite), and that average introns and intergenic domains are ennobled in these genomes and in the genome of Drosophila (fly). The exon oxidation rates estimated for these genomes were less than the rate for the hypothetical "standard" genome, with a 0.25 mole fraction of uniformly distributed G. For Plasmodium the rate was half of that estimated for the standard genome. Average exons were not ennobled in the human or fly genomes; their G distributions were comparable to that in the standard genome. Instead, their exons were situated between introns and intergenic domains that could protect them by oxidant scavenging, the G's of their introns and intergenic domains outnumbering those of their exons 50-fold in humans and 4-fold in flies. The G distribution in the Encephalitozoon (parasite) genome was not protective relative to that of the standard genome.