The panel recommends that all patients with PCOS be screened for IGT with a 2-h oral glucose tolerance test. A few members of the AES board recommend alternatively screening women with PCOS for IGT and type 2 DM using an oral glucose tolerance test only in patients with a body mass index of 30 kg/m2 or greater or in lean patients with additional risk factors. Patients with normal glucose tolerance should be rescreened at least once every 2 yr, or more frequently if additional risk factors are identified. Those with IGT should be screened annually for development of type 2 DM. PCOS patients with IGT should be treated with intensive lifestyle modification and weight loss and considered for treatment with insulin-sensitizing agents.
Some actions of insulin are mediated by inositolphosphoglycan mediators. Deficient release of a putative D-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) mediator may contribute to insulin resistance in women with polycystic ovary syndrome (PCOS). Previously we demonstrated that oral DCI supplementation improved ovulation and metabolic parameters in women with PCOS. However, whether oral DCI mediates an increase in the release of the DCI-IPG mediator and an improvement in insulin sensitivity in women with PCOS is unknown. We conducted a randomized controlled trial of DCI supplementation vs. placebo in 11 women with PCOS who were assessed at two-time points, 6 weeks apart. Plasma DCI, DCI-IPG release during OGTT (AUCDCI-IPG) and insulin sensitivity (Si) by FSIVGTT were assessed at baseline and end-of-study. The study was terminated early due to a sudden unavailability of the study drug. However, in all subjects without regard to treatment assignment, there was a positive correlation between the change in AUCDCI-IPG / AUCInsulin ratio and the change in Si during the 6-week period (r=0.69, p=0.02), which remained significant after adjustment for BMI (p=0.022), and after further adjustment for BMI and treatment allocation (p=0.0261). This suggests that in women with PCOS, increased glucose-stimulated DCI-IPG release is significantly correlated with improved insulin sensitivity. The significant relationship between DCI-IPG release and insulin sensitivity suggests that the DCI-IPG mediator may be a target for therapeutic interventions in PCOS.
Objectives. To develop, implement, and assess a learner-centered approach to teaching a third-year pharmacotherapy course in a doctor of pharmacy (PharmD) program. Methods. The pharmacotherapy course was restructured according to the learner-centered approach. The Motivated Strategies for Learning Questionnaire (MSLQ) was administered to students before and after taking the course, and changes in MSLQ subscales from baseline were evaluated. Students' response to the learner-centered approach and characteristics associated with MSLQ scores were also evaluated.Results. Compared to baseline, students' intrinsic goal orientation control of learning beliefs, selfefficacy, critical thinking, and metacognitive self-regulation improved after taking the course. Students responded positively to the learner-centered approach. Additionally, students with a clinical practice career orientation or who prepared frequently for classes scored higher on several MSLQ domains. Conclusions. The learner-centered approach was effective in promoting several domains of motivation and learning strategies in a third-year pharmacotherapy course.Keywords: learner-centered teaching, pharmacotherapy, motivation, learning, Motivated Strategies for Learning Questionnaire, therapeutics INTRODUCTIONGiven the rapid development of new technology and drugs, doctor of pharmacy (PharmD) students must be motivated to become lifelong learners rather than allowed to learn ''just what is necessary to pass the test'' if they are to provide quality care to their future patients.1 Numerous factors influence student motivation. While some research findings suggest that as students progress in their curriculum, they become more intrinsically motivated (ie, they are more interested in increasing understanding and achieving competence), 2 others suggest that during their first year, PharmD students' motivation shifts from a mastery orientation (defined as a ''desire to develop competence'' 3 ) to academic alienation (defined as ''no desire to develop or demonstrate competence'' 3 ). 1 In large classes, teacher attitudes and behavior, course structure, intrinsic factors, learning environment, and course content influence motivation. 4 However, whether specific education strategies affect students' motivation has not been studied extensively.Learner-centered teaching is an approach in which students have control over the learning process.5 With the learner-centered approach, instructors function as facilitators of learning rather than lecturers. In this way, ''teachers do less telling; students do more discovering. '' 5 The roles of the teacher in the learner-centered approach are to design the course such that it creates a climate for optimal learning; model the appropriate expected behavior for the students; encourage students to learn from and with each other; and provide more feedback throughout the process.5 Usually a menu of optional activities or assignments is presented to the students. In this way, the learner-centered method also gives students more...
The bridging mechanism of antithrombin inhibition of thrombin is a dominant mechanism contributing a massive ∼2500-fold acceleration in the reaction rate and is also a key reason for the clinical usage of heparin. Our recent study of the antithrombin-activating properties of a carboxylic acid-based polymer, poly(acrylic acid) (PAA), demonstrated a surprisingly high acceleration in thrombin inhibition (Monien, B. H.; Desai, U. R. J. Med. Chem. 2005, 48, 1269. To better understand this interesting phenomenon, we have studied the mechanism of PAAdependent acceleration in antithrombin inhibition of thrombin. Competitive binding studies with low-affinity heparin and a heparin tetrasaccharide suggest that PAA binds antithrombin in both the pentasaccharide-and the extended heparin-binding sites, and these results are corroborated by molecular modeling. The salt-dependence of the K D of the PAA-antithrombin interaction shows the formation of five ionic interactions. In contrast, the contribution of nonionic forces is miniscule, resulting in an interaction that is significantly weaker than that observed for heparins. A bell-shaped profile of the observed rate constant for antithrombin inhibition of thrombin as a function of PAA concentration was observed, suggesting that inhibition proceeds through the "bridging" mechanism. The knowledge gained in this mechanistic study highlights important rules for the rational design of orally available heparin mimics.
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