P08 Comparing study in self-motivation learning： PBL vs LBL

In order to clarify which teaching form encourages student＇ s self-motivation learning ability better, we did a comparison experiment between problem-based learning （PBL）and lecture-based learning （LBL） in a 3rd year course in basic pharmacology. Of 224 students who participated （124 PBL, 100 LBL） in pharmacology course, the experimental group was divided into 6 teams（20 - 21 students for each team with one tutor）using PBL method with 7 clinical cases discussion while o.ther 100 students held in the same lecture-based format as the traditional LBL course as a control group. In 224 students, 50.4% using PBL method self-directed learning ability had increased compared with 35.3% in LBL teaching mode. The test score indicated that students using LBL teaching method scored overall higher than those using PBL mode, especially at objective items, this result was significant.. iy different（P =0.009）. However, as far as subjective items are concerned, students accepted PBL mode showed their superior advantages over the LBL ones. Similarly, the result was significantly different（ P =0.001 ）. On the whole, PBL method supported by appropriate technology and teachers, has allowed our students to analyze authentic situations as a doctor status and the active learning ability by self-motivation study will be undoubtedly beneficial for their becoming life-long learners and excellent doctors in the future.     

Comprehensive care for the child with upper extremity limb deficiency

Children with limb deficiencies/amputations are best managed by a multidisciplinary team comprised of physicians specializing in their care, prosthetists, and therapists. For a successful functional outcome, the rehabilitation team will need to consider the goals of the child and parents as they select appropriate components that will aid and not overwhelm the child. The prosthesis will need to accommodate growth and development and withstand the rigors of use during play. The child will benefit from a team approach to introduce, train, and problem-solve the process of prosthetic restoration. We examine strategies for decision making for children with upper extremity limb deletions that will allow appropriate component selection to ensure the prosthesis will be accepted and improve function for the child.     

The anticoagulant mechanism of action of heparin in contact-activated plasma: inhibition of factor X activation

The effects of heparin on the activation of blood coagulation factors IX and X in contact-activated plasma were determined in the present study. In the presence and absence of 0.5 U/mL heparin, the amounts of factor IX that were cleaved 30 minutes after the addition of calcium and phospholipid to plasma exposed to glass (ie, contact activated) were essentially identical. In the absence of heparin, however, the plasma clotting time was between three and four minutes, while in the presence of heparin, the clotting time was approximately 40 minutes. More factor IXa was inhibited by antithrombin III in the presence of heparin than in its absence, but factor IXa levels sufficient for factor X activation appeared to be present in the heparinized plasma. Neither an increase in factor Xa nor a decrease in factor X was detected, however, in heparinized plasma. We conclude that the step in the intrinsic pathway of coagulation that is inhibited in the presence of heparin is at the level of factor X activation.     

DNA adducts, mutant frequencies and mutation spectra in lambda lacZ transgenic mice treated with N-nitrosodimethylamine

Groups of lambda lacZ transgenic mice were treated i.p. with N- nitrosodimethylamine (NDMA) as single doses of 5 mg/kg or 10 mg/kg or as 10 daily doses of 1 mg/kg and changes in DNA N7- or O6-methylguanine or the repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT) were followed for up to 14 days in various tissues. Adduct induction in the liver exceeded by at least one order of magnitude than observed in the next nearest target tissue (lung), and was approximately linearly related to dose, except for O6-methylguanine after the first dose of 1 mg/kg which was lower than expected. Substantial induction of lambda lacZ mutagenesis was observed only in the liver, where the mutant frequency was already maximal within 7 days after 5 mg/kg NDMA and remained unchanged thereafter up to 49 days. Small but marginally significant increases in mutant frequency were consistently observed in the spleen after all three modes of treatment. A lack of proportionality between mutation induction and the administered dose or the corresponding adduct levels was observed, probably reflecting the importance of toxicity-related cell proliferation caused by NDMA at higher doses. Twenty eight days after a dose of 10 mg/kg (causing a 3.6- fold increase in mutant frequency), NDMA was found to increase the frequency of GC-->AT mutations (with a concomitant shift of their preferential location from CpG sites to GpG sites), which made up approximately 60% of the induced mutations. Surprisingly, NDMA also caused a significant increase in deletions of a few (up to 11) base- pairs (22%).      

Profiling Patients’ Healthcare Needs to Support Integrated, Person-Centered Models for Long-Term Disease Management (Profile): Research Design

Background:This article presents the design of PROFILe, a studyinvestigating which (bio)medical and non-(bio)medical patient characteristicsshould guide more tailored chronic care. Based on this insight, the project aimsto develop and validate ‘patient profiles’ that can be used inpractice to determine optimal treatment strategies for subgroups of chronicallyill with similar healthcare needs and preferences.Methods/Design:PROFILe is a practice-based research comprising fourphases. The project focuses on patients with type 2 diabetes. During the firststudy phase, patient profiles are drafted based on a systematic literatureresearch, latent class growth modeling, and expert collaboration. In phase 2,the profiles are validated from a clinical, patient-related and statisticalperspective. Phase 3 involves a discrete choice experiment to gain insight intothe patient preferences that exist per profile. In phase 4, the results from allanalyses are integrated and recommendations formulated on which patientcharacteristics should guide tailored chronic care.Discussion:PROFILe is an innovative study which uses a uniquelyholistic approach to assess the healthcare needs and preferences of chronicallyill. The patient profiles resulting from this project must be tested in practiceto investigate the effects of tailored management on patient experience,population health and costs.     

A novel hypomorphic Looptail allele at the planar cell polarity Vangl2 gene

Vangl2 forms part of the planar cell polarity signalling pathway and is the gene defective in the Looptail (Lp) mouse mutant. Two previously described alleles, Lp and Lp^m1Jus, segregate in a semi‐dominant fashion, with heterozygotes displaying the looped‐tail appearance, while homozygotes show the neural tube defect called craniorachischisis. Here, we report a novel experimentally induced allele, Lp^m2Jus, that carries a missense mutation, R259L, in Vangl2. This mutation was specific to the Lp phenotype and absent from both parental strains and 28 other inbred strains. Notably, this mutation segregates in a recessive manner with all heterozygotes appearing normal and 47% of homozygotes showing a looped‐tail. Homozygous Lp^m2Jus embryos showed spina bifida in 12%. Lp^m2Jus genetically interacts with Lp with 77% of compound heterozygotes displaying craniorachischisis. Vangl2^R259L behaved like the wild‐type allele in overexpression and morpholino knockdown/rescue assays in zebrafish embryos. These data suggest that Lp^m2Jus represents a new hypomorphic allele of Lp. Developmental Dynamics 240:839–849, 2011. © 2011 Wiley‐Liss, Inc.     

The two‐process model of sleep regulation: a reappraisal

In the last three decades the two‐process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time‐courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN‐lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non‐pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short‐term, use‐dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24‐h cycle.