SUMMARY1. A comparison has been made between the electrical properties of excised 'outside-out' patches and whole-cell membranes of GH3 cells using the patch-pipette technique.2. Despite a complicated surface morphology, which includes numerous microvilli, ruffles and blebs, high-resistance seals (typically > 101l Q) were consistently formed between patch pipettes and GH3 cell membranes.3. When the internal solution contained 120 mM-CsF, outward currents through K channels were blocked and large Na channel currents were consistently observed in the whole-cell recording mode. Using the same solutions, single Na channel currents were readily observed in outside-out patches. Averaging patch currents yielded macroscopic currents showing the same voltage-dependent kinetics as those observed for the whole-cell membrane.4. The current vs. voltage and inactivation time constant vs. voltage relationships for the Na channel shifted towards more negative potentials (25 mV or more) within approximately 30 min after going into the whole-cell recording mode. These same relationships could be measured for outside-out patches and their positions along the voltage axis coincided with the asymptotic values measured in the whole-cell mode.5. When the internal solution contained 120 mM-N-methylglucamine fluoride and the external solution contained 150 mM-Tris chloride, no ionic channel currents could be observed either for whole-cell or outside-out patch membranes. Under these conditions, displacement currents induced by tetraphenyl borate (TPB) were recorded in both types of membranes. The total charge moved showed a sigmoidal dependence upon the applied voltage for both whole-cell and outside-out patch membranes. The charge vs. voltage relationship showed a shift along the voltage axis similar to that observed for Na channels except that the magnitude of the shift was larger. A shift in this relationship was also observed for excised patches but the observable * Present address:
An abrupt loss of effectiveness of the presumed carriers, nonactin and valinomycin, in mediating ion conductance occurred at the same temperature as the membrane fluidity, judged visually, was lost. By contrast, the effects of the presumed channel-former, gramicidin, were the same on solid and liquid membranes. Taken together, these findings imply that freezing the membrane primarily reduces the mobility of these antibiotics with little effect on their solubility.
A B S T R A C T The electrical properties of "inward" rectifying egg cell membranes of the starfish Mediastera aequalis have been studied in the presence of K+-TI + mixtures. When the ratio of the external concentrations of these ions is changed while their sum is kept constant, both the conductance and the zero-current membrane potential go through a minimum, showing clear discrepancies from theoretical results based on conventional electrodiffusion models (e.g., Goldman's equation). By contrast, when the ratio of the two concentrations is fixed and their sum varied, the potential follows an ideal Nernst slope, consistent with Goldman's equation. The membrane conductance which, according to previous studies on similar membranes, is to be viewed as a function of the displacement of the membrane potential from its resting value AV, shows marked differences between the cases in which K + or T1 ÷ are the predominant ions: when K ÷ is the predominant permeant ion in solution, the addition of small amounts of T1 + inhibits the current, while corresponding blocking effects of K + on the current are not observed when TI + is the predominant permeant ion. Also, the time course of the conductance during voltage clamp is different in the two cases, being much faster in T1 + than in K ÷ solution for comparable values of AV. Most of the above features are accounted for by a model in which it is assumed that the ionic channels have external binding sites for cations and that their permeability properties depend on the species of the cation bound (K + or TI ÷ in the present experiments).
Formative assessments are systematically designed instructional interventions to assess and provide feedback on students' strengths and weaknesses in the course of teaching and learning. Despite their known benefits to student attitudes and learning, medical school curricula have been slow to integrate such assessments into the curriculum. This study investigates how performance on two different modes of formative assessment relate to each other and to performance on summative assessments in an integrated, medical-school environment. Two types of formative assessment were administered to 146 first-year medical students each week over 8 weeks: a timed, closed-book component to assess factual recall and image recognition, and an un-timed, open-book component to assess higher order reasoning including the ability to identify and access appropriate resources and to integrate and apply knowledge. Analogous summative assessments were administered in the ninth week. Models relating formative and summative assessment performance were tested using Structural Equation Modeling. Two latent variables underlying achievement on formative and summative assessments could be identified; a "formative-assessment factor" and a "summative-assessment factor," with the former predicting the latter. A latent variable underlying achievement on open-book formative assessments was highly predictive of achievement on both open- and closed-book summative assessments, whereas a latent variable underlying closed-book assessments only predicted performance on the closed-book summative assessment. Formative assessments can be used as effective predictive tools of summative performance in medical school. Open-book, un-timed assessments of higher order processes appeared to be better predictors of overall summative performance than closed-book, timed assessments of factual recall and image recognition.
Through relatively short training interventions, PALMs produce large and durable improvements in trainees' abilities to accurately and fluently interpret clinical signs and tests, helping to bridge the gap between novice and expert clinicians.
Our fully integrated, spiral, pre-clerkship curriculum built on repeating interdisciplinary blocks and longitudinal threads has yielded encouraging results as well as some specific innovations that other schools or individual teachers may find valuable to adapt for use in their own settings.
Background:Medical students are expected to master the ability to interpret histopathologic images, a difficult and time-consuming process. A major problem is the issue of transferring information learned from one example of a particular pathology to a new example. Recent advances in cognitive science have identified new approaches to address this problem.Methods:We adapted a new approach for enhancing pattern recognition of basic pathologic processes in skin histopathology images that utilizes perceptual learning techniques, allowing learners to see relevant structure in novel cases along with adaptive learning algorithms that space and sequence different categories (e.g. diagnoses) that appear during a learning session based on each learner's accuracy and response time (RT). We developed a perceptual and adaptive learning module (PALM) that utilized 261 unique images of cell injury, inflammation, neoplasia, or normal histology at low and high magnification. Accuracy and RT were tracked and integrated into a “Score” that reflected students rapid recognition of the pathologies and pre- and post-tests were given to assess the effectiveness.Results:Accuracy, RT and Scores significantly improved from the pre- to post-test with Scores showing much greater improvement than accuracy alone. Delayed post-tests with previously unseen cases, given after 6-7 weeks, showed a decline in accuracy relative to the post-test for 1st-year students, but not significantly so for 2nd-year students. However, the delayed post-test scores maintained a significant and large improvement relative to those of the pre-test for both 1st and 2nd year students suggesting good retention of pattern recognition. Student evaluations were very favorable.Conclusion:A web-based learning module based on the principles of cognitive science showed an evidence for improved recognition of histopathology patterns by medical students.
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