Differences in resting potentials that may arise as a consequence of age-related repression of potassium channels would likely exacerbate differences in drug action that affect closed state inactivation, in comparing flecainide and mexiletine effects in the proband. Additionally, flecainide, but not mexiletine, has been reported to inhibit IKr potassium channels for which HERG forms the principal a subunit. This effect might be tolerated in treatment of adult LQT-3 mutation EX 527 carriers but it might offset the effects of flecainide on F1473C mutant channel activity in the mutation carrier due to his age and genetic background. Finally, the genetic background of the newborn must be considered. The patient carrying the F1473C mutation was also found to carry a common polymorphism KCNH2. This polymorphism has been studied extensively and found to affect HERG channel function, but there is no clear consensus on whether the altered function favors QT prolongation, shortening, or a combination of the two depending on physiological conditions such as heart rate. Importantly, the mother of the proband, homozygous for K897T KCNH2 was unaffected. Thus, it is possible that alteration in repolarization CT99021 reserve via K897T HERG channels, while insufficient to affect electrical activity in the mother, may contribute to QT prolongation and, again to distinction in flecainide��s activity due to this drug��s effects on the IKr channel. This is likely to be the case as the K897T KCNH2 has been reported to be a genetic modifier of latent LQTS in a carrier of K897T KCNH2 and a another low-penetrant KCNH2 mutation. Sodium channel kinetics were modeled in the context of a Markov model based on previous work of Clancy et al, and described in detail in Methods S1. The Markov model is then inserted into a human ventricular action potential model and paced with twice threshold stimuli at a variety of pacing intervals to examine the cellular consequence of the mutation. The beneficial health effects related to consumption of whole grain, fish or fish oil supplements and polyphenol rich foods such as berries are well documented. However, the synergistic effects of these foods on lipid and glucose metabolism in persons at risk for type 2 diabetes have not yet been investigated. In epidemiological studies the intake of whole grain has been associated with lower risk of obesity, insulin resistance, elevated fasting glucose and the incidence of diabetes. Rye bread induces post-prandially lower insulin response than wheat independently of the fiber content. Additionally, a twelve-week consumption of low insulin response diet has been shown to enhance early insulin secretion in persons with metabolic syndrome. This diet also modulated gene expression profile of abdominal subcutaneous tissue by down-regulating genes involved in insulin signaling and apoptosis. However, while the rye bread and pasta diet did not alter the lipidomic profile of plasma, the high insulin response diet led to increased concentrations of proinflammatory lysophosphatidylcholines.