Longitudinal evaluation of iron status during pregnancy: a prospective cohort study in a high-resource setting.

Background: Iron deficiency affects a large proportion of pregnant women worldwide, with potentially serious consequences for perinatal and infant outcomes, but well-powered, comprehensive analyses of longitudinal iron status during pregnancy are scarce.

Objectives: This study aimed to evaluate the longitudinal changes in iron biomarkers across pregnancy and prevalence of iron deficiency in primiparous women in a high-resource setting and propose early pregnancy iron status cutoffs that predict iron deficiency in the third trimester.

Methods: In a prospective cohort of primiparous women with low-risk, singleton pregnancies in Ireland, iron [ferritin, soluble transferrin receptors (sTfR), total body iron (TBI)] and inflammatory markers (C-reactive protein, α-glycoprotein) were measured at 3 study visits: 15, 20, and 33 wk of gestation.

Parkinsonism disrupts neuronal modulation in the pre-supplementary motor area during movement preparation.

Multiple studies suggest that Parkinson's disease (PD) is associated with changes in neuronal activity throughout the basal ganglia-thalamocortical motor circuit. There are limited electrophysiological data, however, describing how parkinsonism impacts neuronal activity in the pre-supplementary motor area (pre-SMA), an area in medial frontal cortex involved in movement planning and motor control. In this study, single unit activity was recorded in the pre-SMA of two non-human primates during a visually cued reaching task in both the naive and parkinsonian state using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism.

The Impact of a Creativity Camp Intervention on Depression and Well-Being in Adolescents.

Depression is a serious public health problem that often emerges during adolescence. Many adolescents do not respond to standard treatments, necessitating the development of novel interventions. We conducted a preliminary study to assess the impact of a novel creative arts intervention on depression and well-being in adolescents.

Slow-wave sleep dysfunction in mild parkinsonism is associated with excessive beta and reduced delta oscillations in motor cortex.

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson's disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8-35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however.

Excessive cortical beta oscillations are associated with slow-wave sleep dysfunction in mild parkinsonism.

Increasing evidence associates slow-wave sleep (SWS) dysfunction with neurodegeneration. Using a within-subject design in the nonhuman primate model of Parkinson's disease (PD), we found that reduced SWS quantity in mild parkinsonism was accompanied by elevated beta and reduced delta power during SWS in the motor cortex. Our findings support excessive beta oscillations as a mechanism for SWS dysfunction and will inform development of neuromodulation therapies for enhancing SWS in PD.

Phenotypic Variation in Growth and Gene Expression Under Different Photoperiods in Allopatric Populations of the Copepod .

Daylength is a major environmental condition that varies seasonally and predictably along a latitudinal cline, where higher latitudes exhibit greater ranges in total daylengths. Generally, the circadian clock acts as a network of genes whose expression dynamics are known to control daily rhythms in response to daylength, and it enables the control of many physiological processes such as growth and development. While well studied in many model animals, the influence of daylength variation on phenotypic evolution is poorly examined in marine species.

Ecology and Evolution of Phenotypic Plasticity in the Penis and Cirri of Barnacles.

Most barnacles are sessile, simultaneous hermaphrodites that reproduce by copulation. This is achieved through the extension of a muscular penis, famous for being the proportionally largest in the animal kingdom. The penis is a long cylindrical or conical organ, composed of a series of folded rings, allowing it to stretch to great lengths.

Population pharmacokinetics of rosuvastatin: implications of renal impairment, race, and dyslipidaemia.

Objectives: To build the structural model of pharmacokinetics for rosuvastatin and evaluate the impact of demographic characteristics including renal function on its pharmacokinetic parameters.

Methods: A population pharmacokinetic analysis of rosuvastatin in healthy volunteers, subjects with dyslipidaemia, and renal failure patients was performed using non-linear mixed-effects modelling and a two-compartment pharmacokinetic model with simultaneous first- and zero-order absorption. Demographic covariates, dyslipidaemic state and renal function were evaluated for their impact on pharmacokinetic parameters by step-wise additions or deletions using the likelihood ratio test.

The effect of a combination antacid preparation containing aluminium hydroxide and magnesium hydroxide on rosuvastatin pharmacokinetics.

Objective: Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used for the treatment of dyslipidaemia, may be co-administered with antacids in clinical practice. This trial assessed the effect of simultaneous and separated administration of an antacid preparation containing aluminium hydroxide 220 mg/5 mL and magnesium hydroxide 195 mg/5 mL (co-magaldrox 195/220) on the pharmacokinetics of rosuvastatin.

Research Design And Methods: A randomised, open-label, three-way crossover trial was performed.

Case for the establishment of a code of ethics to govern the frivolous use of forensic biomechanical testimony to resolve legal issues involving alleged work-related musculoskeletal disorders.

If the legal system is to be an effective means for resolving issues of medical causation, then it is imperative that scientific evidence be presented ethically, fairly, and objectively. This is especially true for cases involving alleged occupational illness and injury. In particular, for a number of years, the railroad industry has been plagued by such allegations, being forced to defend numerous baseless lawsuits claiming work-related musculoskeletal disorders (WMSDs).

Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment.

Background: Systemic exposure to rosuvastatin had been observed to be approximately 2-fold higher in Japanese subjects living in Japan compared with white subjects in Western Europe or the United States. The organic anion transporting polypeptide 1B1 contributes to the hepatic uptake of rosuvastatin. Polymorphisms in the SLCO1B1 gene can lead to reduced transport function in vitro (T 521>C).

Effect of rosuvastatin on warfarin pharmacodynamics and pharmacokinetics.

The effect of rosuvastatin on warfarin pharmacodynamics and pharmacokinetics was assessed in 2 trials. In trial A (a randomized, double-blind, 2-period crossover study), 18 healthy volunteers were given rosuvastatin 40 mg or placebo on demand (o.d.

Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine.

Background: Cyclosporine (INN, ciclosporin) increases the systemic exposure of all statins. Therefore rosuvastatin pharmacokinetic parameters were assessed in an open-label trial involving stable heart transplant recipients (> or =6 months after transplant) on an antirejection regimen including cyclosporine. Rosuvastatin has been shown to be a substrate for the human liver transporter organic anion transporting polypeptide C (OATP-C).

The effect of gemfibrozil on the pharmacokinetics of rosuvastatin.

Background: Coadministration of statins and gemfibrozil is associated with an increased risk for myopathy, which may be due in part to a pharmacokinetic interaction. Therefore the effect of gemfibrozil on rosuvastatin pharmacokinetics was assessed in healthy volunteers. Rosuvastatin has been shown to be a substrate for the human hepatic uptake transporter organic anion transporter 2 (OATP2).

Rosuvastatin improves the atherogenic and atheroprotective lipid profiles in patients with hypertriglyceridemia.

Background: We examined the effects of rosuvastatin treatment on triglyceride levels and lipid measures in a parallel-group multicenter trial (4522IL/0035) in patients with hypertriglyceridemia (Fredrickson Type IIb or IV).

Methods: After a 6-week dietary lead-in period while on a National Cholesterol Education Program step I diet, 156 patients with fasting triglyceride levels >/= 300 and < 800 mg/dl were randomized to 6 weeks of double-blinded treatment: once-daily rosuvastatin of 5, 10, 20, 40 or 80 mg or placebo. The primary end point was mean percentage change from baseline in total serum triglyceride levels at week 6 as determined by analysis of variance.

The effect of rosuvastatin on oestrogen & progestin pharmacokinetics in healthy women taking an oral contraceptive.

Aims: To assess the effect of rosuvastatin on oestrogen and progestin pharmacokinetics in women taking a commonly prescribed combination oral contraceptive steroid (OCS); the effect on endogenous hormones and the lipid profile was also assessed.

Methods: This open-label, nonrandomised trial consisted of 2 sequential menstrual cycles. Eighteen healthy female volunteers received OCS (Ortho Tri-Cyclen) on Days 1-21 and placebo OCS on Days 22-28 of Cycles A and B Rosuvastatin 40 mg was also given on Days 1-21 of Cycle B.

A review and assessment of potential sources of ethnic differences in drug responsiveness.

The International Conference on Harmonization (ICH) E5 guidelines were developed to provide a general framework for evaluating the potential impact of ethnic factors on the acceptability of foreign clinical data, with the underlying objective to facilitate global drug development and registration. It is well recognized that all drugs exhibit significant inter-subject variability in pharmacokinetics and pharmacologic response and that such differences vary considerably among individual drugs and depend on a variety of factors. One such potential factor involves ethnicity.

An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers.

Background: Rosuvastatin and fenofibrate are lipid-regulating agents with different modes of action. Patients with dyslipidemia who have not achieved treatment targets with monotherapy may benefit from the combination of these agents.

Objective: The effect of coadministration of rosuvastatin and fenofibrate on the steady-state pharmacokinetics of rosuvastatin and fenofibric acid (the active metabolite of fenofibrate) was assessed in healthy volunteers.

Effect of itraconazole on the pharmacokinetics of rosuvastatin.

Background: Rosuvastatin is a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Itraconazole, an inhibitor of cytochrome P450 (CYP) 3A4 and the transport protein P-glycoprotein, is known to interact with other HMG-CoA reductase inhibitors. The current trials aimed to examine in vivo the effect of itraconazole on the pharmacokinetics of rosuvastatin.

The effect of erythromycin on the pharmacokinetics of rosuvastatin.

Rationale Objective: To examine in vivo the effect of erythromycin on the pharmacokinetics of rosuvastatin [an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase]. Erythromycin is a potent inhibitor of CYP3A4 that markedly increases circulating levels of some other HMG-CoA reductase inhibitors.

Methods: In this randomised, double-blind, two-way cross-over, placebo-controlled trial 14 healthy volunteers were given 500 mg erythromycin or placebo four times daily for 7 days.

Pharmacokinetics and pharmacodynamics of rosuvastatin in subjects with hepatic impairment.

Objective: To assess the effect of chronic hepatic impairment on rosuvastatin disposition, pharmacodynamic activity and tolerability.

Methods: This was an open-label, non-randomised, parallel-group trial. Six subjects were enrolled in each of three hepatic-function strata: Child-Pugh class A (CP-A, mild impairment), Child-Pugh class B (CP-B, moderate impairment) and normal hepatic function; the latter two strata were age, weight, race, sex and smoking history matched.

Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects.

Aims: To examine in vivo the effect of ketoconazole on the pharmacokinetics of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor.

Methods: This was a randomized, double-blind, two-way crossover, placebo-controlled trial. Healthy male volunteers (n = 14) received ketoconazole 200 mg or placebo twice daily for 7 days, and rosuvastatin 80 mg was coadministered on day 4 of dosing.

Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease.

The lipid-lowering effects of rosuvastatin and atorvastatin were determined across their dose ranges in a 6-week, randomized, double-blind trial. Three hundred seventy-four hypercholesterolemic patients with fasting low-density lipoprotein (LDL) cholesterol > or =160 but <250 mg/dl (> or =4.14 but <6.

No effect of rosuvastatin on the pharmacokinetics of digoxin in healthy volunteers.

The effect of rosuvastatin on the pharmacokinetics of digoxin was assessed in 18 healthy male volunteers in this double-blind, randomized, two-way crossover trial. Volunteers were dosed with rosuvastatin (40 mg once daily) or placebo to steady state before being given a single dose of digoxin 0.5 mg.

The effect of fluconazole on the pharmacokinetics of rosuvastatin.

Objective: To examine the effect of fluconazole, a potent inhibitor of CYP2C9 and CYP2C19, on the pharmacokinetics of rosuvastatin in healthy volunteers. Significantly increased plasma concentrations of fluvastatin have been observed following co-administration with fluconazole.

Methods: This was a randomised, double-blind, two-way crossover, placebo-controlled trial.