The clarion call for a third wave in medical education to optimise healthcare in the twenty-first century.

During the years preceding 1910, the education and training of physicians (doctors) -to-be was based mainly on a master-apprentice model; the primary focus then was on the teaching and development of clinical skills. In 1910, however, Abraham Flexner submitted a highly influential report to the American medical authorities: in it, he recommended that all medical schools should be university-based and that, importantly, medical practice should have a scientific basis strongly underpinned by the basic medical sciences. The recommendation provided the impetus for the design of medical education that begins with a pre-clinical phase to provide the strong scientific foundation for the clinical phase that follows. During the clinical phase, student learning will focus primarily on the clinical sciences relating to the diagnosis, treatment and management of patient care. Thus, two key 'pillars' (the basic sciences and the clinical sciences) of medical education were established; this two pillar model of medical education persisted for many decades thereafter and remained so till today. However, in order to optimise delivery of health care this must be viewed as an 'eco-system' taking into account the practice setting both present and future. The authors will attempt to provide a background to the changing trends in medical education and the changing practice environment, due primarily to the disruptive forces of change in this article.

Impact of faculty development programs for positive behavioural changes among teachers: a case study.

PURPOSE: Faculty development (FD) is essential to prepare faculty members to become effective teachers to meet the challenges in medical education. Despite the growth of FD programmes, most evaluations were often conducted using short questionnaires to assess participants' satisfaction immediately after they attended a programme. Consequently, there were calls for more rigorous evaluations based on observed changes in participants' behaviours. Hence, this study aims to explore how the FD workshops run by the Centre for Medical Education, Yong Loo Lin School of Medicine, National University of Singapore have impacted behavioural changes in the educators. METHODS: We followed up with the educators at least half a year after they have attended the workshops. With limited literature as reference, we initiated a small-scale case-study research design involving semi-structured interviews with six educators which was triangulated with three focus group discussions with their students. This allowed us to explore behavioural changes among the educators as well as evaluate the feasibility of this research methodology. RESULTS: We identified three emerging categories among the educators: ignorance to awareness, from intuition to confirmation and expansion, and from individualism to community of practice. CONCLUSION: Although FD have placed much emphasis on teaching and learning approaches, we found that the teacher-student interaction or human character components (passionate, willing to sacrifice, are open to feedback) in becoming a good educator are lacking in our FD workshops.

Teaching of medical pharmacology: the need to nurture the early development of desired attitudes for safe and rational drug prescribing.

Pharmacology, as a basic medical science discipline, provides the scientific basis of therapeutics, i.e. the scientific foundation for safe and rational prescribing of drugs. The public, lay media, and the medical profession have raised serious concerns over the high incidence of errors of drug prescribing which compromise patient safety, including death of some patients, attributed mainly to inadequate teaching of medical pharmacology and, consequently, to medical graduates lacking skills in safe and effective drug prescribing. There is also overwhelming evidence that the pervasive and prevalent doctor-drug industry relationships have a strong influence over the prescribing habits and drug education of doctors. The British Pharmacological Society and American Association of Medical Colleges have crafted some insightful guidelines, including the learning of desired attitudes, for designing a medical pharmacology curriculum aimed at enhancing patient safety. This article will critically review the major issues relating to errors of drug prescribing, including the need to nurture the early development of desired attitudes which foster safe and rational drug prescribing. A simple educational approach, using a task analysis of drug prescribing, is applied to identify desired attitudes which should be incorporated into a basic pharmacology course for medical students in the twenty-first century.

Problem-based learning: a strategic learning system design for the education of healthcare professionals in the 21st century.

Problem-based learning (PBL) was first implemented by McMaster University medical school in 1969 as a radical, innovative, and alternative pathway to learning in medical education, thus setting a new educational trend. PBL has now spread widely across the globe and beyond the healthcare disciplines, and has prevailed for almost four decades. PBL is essentially a strategic learning system design, which combines several complementary educational principles for the delivery of instruction. PBL is specifically aimed at enhancing and optimizing the educational outcomes of learner-centered, collaborative, contextual, integrated, self-directed, and reflective learning. The design and delivery of instruction in PBL involve peer teaching and learning in small groups through the social construction of knowledge using a real-life problem case to trigger the learning process. Therefore, PBL represents a major shift in the educational paradigm from the traditional teacher-directed (teacher-centered) instruction to student-centered (learner-centered) learning. PBL is firmly underpinned by several educational theories, but problems are often encountered in practice that can affect learning outcomes. Educators contemplating implementing PBL in their institutions should have a clear understanding of its basic tenets, its practice and its philosophy, as well as the issues, challenges, and opportunities associated with its implementation. Special attention should be paid to the training and selection of PBL tutors who have a critical role in the PBL process. Furthermore, a significant change in the mindsets of both students and teachers are required for the successful implementation of PBL. Thus, effective training programs for students and teachers must precede its implementation. PBL is a highly resource-intensive learning strategy and the returns on investment (i.e. the actual versus expected learning outcomes) should be carefully and critically appraised in the decision-making process. Implementation of PBL can be a daunting task and will require detailed and careful planning, together with a significant commitment on the part of educators given the responsibility to implement PBL in an institution. PBL can offer a more holistic, value-added, and quality education to energize student learning in the healthcare professions in the 21st century. Successful implementation of PBL can therefore help to nurture in students the development of desired "habits of mind, behavior, and action" to become the competent, caring, and ethical healthcare professionals of the 21st century. Thus, PBL can contribute to the improvement of the healthcare of a nation by healthcare professionals, but we need to do it right.

Globalization of problem-based learning (PBL): cross-cultural implications.

Problem-based learning (PBL) is essentially a learning system design that incorporates several educational strategies to optimize student-centered learning outcomes beyond just knowledge acquisition. PBL was implemented almost four decades ago as an innovative and alternative pathway to learning in medical education in McMaster University Medical School. Since then, PBL has spread widely across the world and has now been adopted globally, including in much of Asia. The globalization of PBL has important cross-cultural implications. Delivery of instruction in PBL involves active peer teaching-learning in an open communication style. Consequently, this may pose an apparent serious conflict with the Asian communication style generally dominated by a cultural reticence. However, evidence available, especially from the PBL experience of some senior Korean medical students doing an elective in the University of Toronto Medical School and the cross-cultural PBL experience initiated by Kaohsiung Medical University, strongly suggests creating a conducive and supportive learning environment for students learning in a PBL setting can overcome the perceived cultural barriers; that is, nurture matters more than culture in the learning environment. Karaoke is very much an Asian initiative. The Karaoke culture and philosophy provide a useful lesson on how to create a conducive and supportive environment to encourage, enhance and motivate group activity. Some key attributes associated with Asian culture are in fact consistent with, and aligned to, some of the basic tenets of PBL, including the congruence between the Asian emphasis on group before individual interest, and the collaborative small group learning design used in PBL. Although there are great expectations of the educational outcomes students can acquire from PBL, the available evidence supports the contention the actual educational outcomes acquired from PBL do not really match the expected educational outcomes commonly intended and specified for a PBL program. Proficiency in the English language can pose serious problems for some Asian medical schools, which choose to use English as the language for discussion in PBL tutorials. A novel approach that can be applied to overcome this problem is to allow students to engage in discussions using both their native language as well as English, a highly successful practice implemented by the University of Airlangga, Surabaya, Indonesia. As PBL is a highly resource-intensive pedagogy, Asian medical educators need to have a clear understanding of the PBL process, philosophy and practice in order to be able to optimize the educational outcomes that can be derived from a PBL curriculum.

Addressing the needs and priorities of medical teachers through a collaborative intensive faculty development programme.

Faculty development in medical education is crucial for developing and sustaining quality education in medical schools. However, examples of successful intensive programmes based on experiential and collaborative learning are generally lacking in the literature. The Medical Education Unit of National University of Singapore conducted a three-day intensive programme on core competences in medical education. This paper highlights the process of programme development, programme structure, challenges faced and strategies adopted. It also describes the approach taken to educational programme evaluation along with the results. The programme structure was based on experiential and collaborative learning models. Participants contributed to all activities and emerged as facilitators and learners to gain first-hand experience of the complex educational processes. Each individual session was sequential with a brief plenary, demonstration, practicum and reflection. Pre-programme needs assessment showed that even the experienced teachers perceived a need to further improve their educational competencies.

Medical education in Southeast Asia: emerging issues, challenges and opportunities.

CONTEXT: Medical education in Southeast Asian countries is undergoing rapid changes, with the realignment of medical schools' curricula to meet national needs and priorities, the adoption of and experimentation with innovations, and greater emphasis on staff development initiatives. The Medical Education Unit of the National University of Singapore undertook a project to compile the educational processes taking place in these medical schools. METHOD: This was a process-focused initiative. We developed a custom-made questionnaire that emphasised narrative description. We compiled profiles of 30 selected medical schools in the Southeast Asian region and, after editing and review, published these profiles. This report summarises the key findings from the project. FINDINGS: Medical schools in Southeast Asia are in a dynamic state. Schools are gradually adopting student-centred learning approaches, including problem-based learning. Many schools offer their students early clinical training, opportunities for out-of-hospital postings, and student-selected electives. Multiple-choice questions and oral examinations are almost universally used in student assessment. Portfolios and self- and peer-assessments are seldom used. Major challenges faced by the schools involve shortages of qualified staff and financial constraints. Major goals for the future include the implementation of student-centred learning, the revamping of the assessment process, and staff training. CONCLUSIONS: This is a compilation of self-reported profiles of selected medical schools where we encouraged self-reflection and analysis. As with other surveys, there could be potential self-selection bias. Nevertheless, the profiles of these selected schools provide a broad overview of the status of medical schools in Southeast Asia.

Three-finger alpha-neurotoxins and the nicotinic acetylcholine receptor, forty years on.

The discovery, about forty years ago, of alpha-bungarotoxin, a three-finger alpha-neurotoxin from Bungarus multicinctus venom, enabled the isolation of the nicotinic acetylcholine receptor (nAChR), making it one of the most thoroughly characterized receptors today. Since then, the sites of interaction between alpha-neurotoxins and nAChRs have largely been delineated, revealing the remarkable plasticity of the three-finger toxin fold that has optimally evolved to utilize different combinations of functional groups to generate a panoply of target specificities to discern subtle differences between nAChR subtypes. New facets in toxinology have now broadened the scope for the use of alpha-neurotoxins in scientific discovery. For instance, the development of short, combinatorial library-derived, synthetic peptides that bind with sub-nanomolar affinity to alpha-bungarotoxin and prevent its interaction with muscle nAChRs has led to the in vivo neutralization of experimental alpha-bungarotoxin envenomation, while the successful introduction of pharmatopes bearing "alpha-bungarotoxin-sensitive sites" into toxin-insensitive nAChRs has permitted the use of various alpha-neurotoxin tags to localize and characterize new receptor subtypes. More ambitious strategies can now be envisaged for engineering rationally designed novel activities on three-finger toxin scaffolds to generate lead peptides of therapeutic value that target the nicotinic pharmacopoeia. This review details the progress made towards achieving this goal.

Characterization of the rat isolated retractor penis muscle as a model for the study of nitrergic transmission.

INTRODUCTION: The anococcygeus and retractor penis muscles are part of the erectile machinery in male rodents. The rat anococcygeus muscle is a widely used smooth muscle preparation for the study of the effects of test substances on adrenergic, nitrergic, and cholinergic transmission. There is, however, little information available on the process of autonomic transmission in the rat retractor penis muscle, although its autonomic innervation has generally been assumed to be similar to that of the anococcygeus muscle because of the contiguous nature of the two muscles. The present study investigated the involvement of nitrergic transmission in mediating relaxant responses of the rat retractor penis muscle to electrical field stimulation. METHODS: The retractor penis muscle was isolated from Sprague-Dawley rats and mounted in Krebs solution. Phentolamine (5 microM) was added to the bath to block the adrenergic responses of the muscle, which was then precontracted with carbachol (10 microM). RESULTS: Electrical field stimulation (20-30 V, 1 ms pulse width, at 0.5-20 Hz for 10 s) of the carbachol precontracted muscle elicited frequency-dependent relaxant responses (0.9-68%). Tetrodotoxin (1 microM), N(G)-nitro-L-arginine (L-NOARG) (50 microM), N(G)-nitro-L-arginine methylester (L-NAME) (100 microM), and haemoglobin (100 microM) inhibited these relaxant responses by 99.3%, 93.9%, 86.9%, and 77.5%, respectively. L-Arginine (250 microM) (but not its D-isomer) reversed the blockade produced by L-NOARG (72.7%) and L-NAME (81.5%). DISCUSSION: Our results provide clear evidence that the inhibitory (relaxant) responses of the rat retractor penis muscle to electrical field stimulation are mediated by nitric oxide involving the L-arginine-nitric oxide synthase-nitric oxide pathway. The rat retractor penis muscle is a versatile preparation that can replace the cumbersome preparations from the pig, ox, and horse, hitherto used as pharmacological models for the study of the retractor penis muscle.

Autonomic effects of some scorpion venoms and toxins.

1. The autonomic effects of venoms and toxins from several species of scorpions, including the Indian red scorpion Mesobuthus tamulus, the Chinese scorpion Buthus martensi Karsch and the Israeli scorpion Leiurus quinquestriatus quinquestriatus, all belonging to Buthidae, and the Asian black scorpions Heterometrus longimanus and Heterometrus spinifer, belonging to Scorpionidae, are reviewed. 2. The effects of the venoms of M. tamulus and L. q. quinquestriatus on noradrenergic and nitrergic transmission in the rat isolated anococcygeus muscle revealed that both venoms mediated their pharmacological effects via a prejunctional mechanism involving the activation of voltage-sensitive sodium channels with consequent release of neurotransmitters that mediate target organ responses, similar to the effects mediated by other alpha-scorpion toxins. 3. Two new toxins, Makatoxin I and Bukatoxin, were purified to homogeneity from the venom of B. martensi Karsch. Determination of their complete amino acid sequences confirmed that both toxins belonged to the class of alpha-scorpion toxins. The effects of both toxins on noradrenergic and nitrergic transmission in the rat anococcygeus muscle provided firm evidence that their pharmacological actions also closely resembled those mediated by other alpha-scorpion toxins on neuronal voltage-sensitive sodium channels. 4. The venoms of H. longimanus and H. spinifer were found to have high concentrations of noradrenaline (1.8 +/- 0.3 mmol/L) and relatively high concentrations of acetylcholine (79.8 +/- 1.7 micromol/L) together with noradrenaline (146.7 +/- 19.8 micromol/L), respectively, which can account for their potent direct cholinergic and noradrenergic agonist actions in the rat anococcygeus muscle. 5. Our studies confirmed that the rat anococcygeus muscle is an excellent nerve-smooth muscle preparation for investigating the effects of bioactive agents on noradrenergic and nitrergic transmission, as well as the direct agonist actions of these agents on post-synaptic alpha-adrenoceptors and M3 muscarinic cholinoceptors. Although many studies, including our own, have documented that scorpion venoms and toxins mediate their primary effects via a prejunctional mechanism that leads to the marked release of various autonomic neurotransmitters, our studies have shown that there are exceptions to this generally accepted phenomenon. In particular, we have provided firm evidence to show that the venoms from H. longimanus and H. spinifer do not have such a prejunctional site of action but, instead, the venoms mediate their autonomic effects through direct agonist actions on post-junctional muscarinic M3 cholinoceptors and alpha-adrenoceptors.

Candoxin, a novel toxin from Bungarus candidus, is a reversible antagonist of muscle (alphabetagammadelta ) but a poorly reversible antagonist of neuronal alpha 7 nicotinic acetylcholine receptors.

In contrast to most short and long chain curaremimetic neurotoxins that produce virtually irreversible neuromuscular blockade in isolated nerve-muscle preparations, candoxin, a novel three-finger toxin from the Malayan krait Bungarus candidus, produced postjunctional neuromuscular blockade that was readily and completely reversible. Nanomolar concentrations of candoxin (IC(50) = approximately 10 nm) also blocked acetylcholine-evoked currents in oocyte-expressed rat muscle (alphabetagammadelta) nicotinic acetylcholine receptors in a reversible manner. In contrast, it produced a poorly reversible block (IC(50) = approximately 50 nm) of rat neuronal alpha7 receptors, clearly showing diverse functional profiles for the two nicotinic receptor subsets. Interestingly, candoxin lacks the helix-like segment cyclized by the fifth disulfide bridge at the tip of the middle loop of long chain neurotoxins, reported to be critical for binding to alpha7 receptors. However, its solution NMR structure showed the presence of some functionally invariant residues involved in the interaction of both short and long chain neurotoxins to muscle (alphabetagammadelta) and long chain neurotoxins to alpha7 receptors. Candoxin is therefore a novel toxin that shares a common scaffold with long chain alpha-neurotoxins but possibly utilizes additional functional determinants that assist in recognizing neuronal alpha7 receptors.

Biochemical and pharmacological characterization of the venom of the black scorpion Heterometrus spinifer.

The sting of the black scorpion Heterometrus spinifer, which can cause intense localized pain, has not been reported to produce lethal cardiovascular complications, which are well known to result from scorpion envenomation as a consequence of a massive release of catecholamines. Therefore, we have undertaken a biochemical and pharmacological characterization of the venom of H. spinifer. Pharmacologically, the venom (0.125 microL/mL) produced a marked, reversible contracture in the chick biventer cervicis muscle that was blocked by d-tubocurarine (2 microM) but not by tetrodotoxin (5 microM) and omega-conotoxin GVIA (3 microM). The anticholinesterase neostigmine (1 microM) potentiated the contracture by 5.3-fold. An ultra-filtrate fraction of MW < 3000 (F3K) of the venom produced a similar contracture in the biventer muscle, whereas the retentate of MW > 3000 did not. In the rat anococcygeus muscle, the venom produced a contractile response that was partially (37.4 +/- 1.6%) blocked by atropine (5 microM); phentolamine (5 microM) blocked the remaining response. Tetrodotoxin (5 microM) did not block the contractile response of the venom on the anococcygeus muscle. Electrospray ionization-mass spectrometry/mass spectrometry confirmed the presence of high concentrations of acetylcholine (79.8 +/- 1.7 microM) and norepinephrine (146.7 +/- 19.8 microM) in H. spinifer venom, which can fully account for the observed cholinergic and adrenergic effects. In contrast to scorpion venoms that selectively target neuronal ion channels in mediating transmitter release, our data show that H. spinifer venom does not possess such activity, which likely explains the apparent lack of lethality of black scorpion envenomation.