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There is a large interindividual variability in dexmedetomidine dose requirements for sedation of patients in intensive care units (ICU). Cytochrome P450 2A6 (CYP2A6) mediates an important route of dexmedetomidine metabolism, and genetic variation in CYP2A6 affects the clearance of other substrate drugs. We examined whether CYP2A6 genotypes affect(More)
There is evidence that stress and glucocorticoids alter drug self-administration and mesolimbic dopamine (DA) activity in preclinical models. The primary purpose of this study was to test the hypothesis that glucocorticoids are associated with psychostimulant reinforcement and DA release in humans. In total, 16 healthy adults, ages 18-27 years, underwent(More)
BACKGROUND A common polymorphism in the catechol-O-methyltransferase gene involves a valine to methionine mutation that results in a threefold to fourfold decrease in enzyme activity. This polymorphism has been associated with altered mu-opioid receptor binding potential and prefrontal cognitive performance, as well as risk for several neuropsychiatric(More)
Acute exercise results in transient change in redox balance. High concentrations of reactive oxygen species (ROS) can lead to oxidative damage to macromolecules. However, moderate periodic increases in ROS, such as experienced with habitual exercise, may activate signal transduction pathways which stimulate increases in endogenous antioxidant systems. This(More)
Replication fidelity of RNA virus genomes is constrained by the opposing necessities of generating sufficient diversity for adaptation and maintaining genetic stability, but it is unclear how the largest viral RNA genomes have evolved and are maintained under these constraints. A coronavirus (CoV) nonstructural protein, nsp14, contains conserved active-site(More)
Description This package contains functions to classify monitor wear and nonwear time intervals in accelerometer data collected to assess physical activity in free-living condition. The package also contains functions to make plot for accelerometer data, and to obtain the summary of daily monitor wear time and the mean of monitor wear time during valid(More)
The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We(More)
SUMMARY 9 This paper presents a case study in longitudinal data analysis where the goal is to estimate the eecacy of a new drug for treatment of a severe chronic constipation. Data consist of long sequences of binary 11 outcomes (relief=no relief) on each of a large number of patients randomized to treatment (low and high dose) or placebo. Data(More)
BACKGROUND The effect of dietary calcium (Ca) on fecal fat excretion in lactose maldigestion is not known. OBJECTIVE To investigate the effect of dairy and non-dairy dietary Ca on fecal fat excretion in lactose digesters and maldigesters during moderate energy restriction. DESIGN A randomized cross-over trial comparing the effect of 500 mg versus 1500(More)