Uncovering students' misconceptions by assessment of their written questions.

BACKGROUND: Misconceptions are ideas that are inconsistent with current scientific views. They are difficult to detect and refractory to change. Misconceptions can negatively influence how new concepts in science are learned, but are rarely measured in biomedical courses. Early identification of misconceptions is of critical relevance for effective teaching, but presents a difficult task for teachers as they tend to either over- or underestimate students' prior knowledge. A systematic appreciation of the existing misconceptions is desirable. This explorative study was performed to determine whether written questions generated by students can be used to uncover their misconceptions. METHODS: During a small-group work (SGW) session on Tumour Pathology in a (bio)medical bachelor course on General Pathology, students were asked to write down a question about the topic. This concerned a deepening question on disease mechanisms and not mere factual knowledge. Three independent expert pathologists determined whether the content of the questions was compatible with a misconception. Consensus was reached in all cases. Study outcomes were to determine whether misconceptions can be identified in students' written questions, and if so, to measure the frequency of misconceptions that can be encountered, and finally, to determine if the presence of such misconceptions is negatively associated with the students' course formal examination score. A subgroup analysis was performed according to gender and discipline. RESULTS: A total of 242 students participated in the SGW sessions, of whom 221 (91 %) formulated a question. Thirty-six questions did not meet the inclusion criteria. Of the 185 questions rated, 11 % (n = 20) was compatible with a misconception. Misconceptions were only found in medical students' questions, not in biomedical science students' questions. Formal examination score on Tumour Pathology was 5.0 (SD 2.0) in the group with misconceptions and 6.7 (SD 2.4) in the group without misconceptions (p = 0.003). CONCLUSIONS: This study demonstrates that misconceptions can be uncovered in students' written questions. The occurrence of these misconceptions was negatively associated with the formal examination score. Identification of misconceptions creates an opportunity to repair them during the remaining course sessions, in advance of the formal examination.

Explicit feedback to enhance the effect of an interim assessment: a cross-over study on learning effect and gender difference.

In a previous study we demonstrated by a prospective controlled design that an interim assessment during an ongoing small group work (SGW) session resulted in a higher score in the course examination. As this reflects the so-called testing effect, which is supposed to be enhanced by feedback, we investigated whether feedback following an interim assessment would have an effect on the score of the course exam, and whether the effect is influenced by the gender of the student. During a General Pathology bachelor course all 386 (bio) medical students took an interim assessment on the topics cell damage (first week) and tumour pathology (fourth week). The intervention consisted of immediate detailed oral feedback on the content of the questions of the interim assessment by the tutor, including the rationale of the correct and incorrect answers. It concerned a prospective randomized study using a cross-over design. Outcome measures were: (1) the difference in the normalized scores (1-10) of the course examination multiple choice questions related to the two topics, (2) effect of gender, and (3) gender-specific scores on formal examination. The effect of feedback was estimated as half the difference in the outcome between the two conditions. Mixed-model analysis was used whereby the SGW group was taken as the study target. The scores of the questions on cell damage amounted to 7.70 (SD 1.59) in the group without and 7.78 (SD 1.39) in the group with feedback, and 6.73 (SD 1.51) and 6.77 (SD 1.60), respectively, for those on tumour pathology. No statistically significant effect of feedback was found: 0.02 on a scale of 1-10 (95 % CI: -0.20; 0.25). There were no significant interactions of feedback with gender. Female students scored 0.43 points higher on the formal examination in comparison with their male colleagues. No additional effect of immediate explicit feedback following an interim assessment during an SGW session in an ongoing bachelor course could be demonstrated in this prospective randomized controlled study. Gender analysis revealed a higher performance of female students on the formal examination, which could not be explained by the effect of feedback in the current study. In this particular learning environment, SGW, explicit feedback may have little added value to the interactive learning that includes implicit feedback.

Amyloid beta induces cellular relocalization and production of agrin and glypican-1.

The major component of senile plaques and vascular amyloid in Alzheimer's disease (AD) brains is the amyloid beta protein (Abeta). Besides Abeta, several other proteins have been identified in these lesions, in particular heparan sulfate proteoglycans (HSPG). However, it is still unclear, what causes the excessive accumulation of HSPG in AD brains. Therefore, we investigated if Abeta may influence production and expression of two major Abeta-associated HSPG species, agrin and glypican-1. When human brain pericytes (HBP) were cultured in the presence of Abeta, protein and mRNA expression of both agrin and glypican-1 were increased and more radioactive sulfate was incorporated in the glycosaminoglycan fraction of Abeta-treated HBP. Furthermore, after Abeta treatment, these HSPG were found in association with the amyloid fibrils attached to the cell membrane, in contrast to the intracellular agrin and glypican-1 staining observed in untreated cells. We conclude that Abeta can modulate the cellular expression of agrin and glypican-1, which may contribute to the accumulation of these HSPG in AD lesions.

Expression pattern of apoptosis-related markers in Huntington's disease.

Inappropriate apoptosis has been implicated in the mechanism of neuronal death in Huntington's disease (HD). In this study, we report the expression of apoptotic markers in HD caudate nucleus (grades 1-4) and compare this with controls without neurological disease. Terminal transferase-mediated biotinylated-UTP nick end-labeling (TUNEL)-positive cells were detected in both control and HD brains. However, typical apoptotic cells were present only in HD, especially in grade 3 and 4 specimens. Expression of the pro-apoptotic protein Bax was increased in HD brains compared to controls, demonstrating a cytoplasmic expression pattern in predominantly shrunken and dark neurons, which were most frequently seen in grades 2 and 3. Control brains displayed weak perinuclear expression of the anti-apoptotic protein Bcl-2, whereas in HD brains Bcl-2 immunoreactivity was markedly enhanced, especially in severely affected grade 4 brains, and was observed in both healthy neurons and dark neurons. Caspase-3, an executioner protease, was only found in four HD brains of different grades and was not expressed in controls. A strong neuronal and glial expression of poly(ADP-ribose) polymerase (PARP)-immunoreactivity was observed in HD brains. These data strongly suggest the involvement of apoptosis in HD. The exact apoptotic pathway occurring in HD neurodegeneration remains yet unclear. However, the presence of late apoptotic events, such as enhanced PARP expression and many TUNEL-positive cells accompanied with weak caspase-3 immunoreactivity in severely affected HD brains, suggests that caspase-mediated neuronal death only plays a minor role in HD.

Creatine protects against 3-nitropropionic acid-induced cell death in murine corticostriatal slice cultures.

In murine corticostriatal slice cultures, we studied the protective effects of the bioenergetic compound creatine on neuronal cell death induced by the mitochondrial toxin 3-nitropropionic acid (3-NP). 3-NP caused a dose-dependent neuronal degeneration accompanied by an increased lactate dehydrogenase (LDH) activity in the cell culture medium. An increased ratio of lactate to pyruvate concentration in the medium suggested that metabolic activity shifted to anaerobic energy metabolism. These effects were predominantly observed in the 24-h recovery period after 3-NP exposure. Creatine protected against 3-NP neurotoxicity: LDH activity was reduced and aerobic respiration of pyruvate was stimulated, which resulted in lower lactate levels and less cell death. In both striatum and cortex, apoptosis in 3-NP-exposed slices was demonstrated by increased activation of the pro-apoptotic protein caspase-3 and by numerous cells exhibiting DNA fragmentation detected by the terminal transferase-mediated biotinylated-UTP nick end-labeling (TUNEL) technique. Creatine administration to the 3-NP-exposed corticostriatal slices resulted in a reduced number of TUNEL-positive cells in the recovery period. However, in the striatum, an unexpected increase of both TUNEL-positive cells and caspase-3-immunostained cells was observed in the exposure phase in the presence of creatine. In the recovery phase, caspase-3-immunostaining decreased to basal levels in both striatum and cortex. These findings suggest that 3-NP-induced neuronal degeneration in corticostriatal slices results from apoptosis that in the cortex can be prevented by creatine, while in the more vulnerable striatal cells it may lead to an accelerated and increased execution of apoptotic cell death, preventing further necrosis-related damage in this region.

3-Nitropropionic acid induces cell death and mitochondrial dysfunction in rat corticostriatal slice cultures.

Exposure of organotypic rat corticostriatal slice cultures to the mitochondrial toxin 3-nitropropionic acid (3-NP) resulted in concentration-dependent loss of cresylviolet-stained cells and increase of lactate dehydrogenase and lactate efflux into the culture medium, indicators for cell death and metabolic activity in the slices, respectively. The involvement of apoptosis in these slices was suggested by using the terminal transferase-mediated biotinylated-UTP nick end-labeling (TUNEL) technique, and immunohistochemistry for the apoptosis-related markers Bax and Bcl-2. In 3-NP-exposed slices, TUNEL-positive cells were observed in both the striatum and the cortex but in different forms: striatal neurons were either diffusely stained or showed nuclear fragmentation, cortical neurons only exhibiting nuclear fragmentation. In 3-NP-exposed slices, the pro-apoptotic protein Bax was abundantly expressed, whereas the anti-apoptotic protein Bcl-2 was not expressed in striatal neurons. We suggest that both apoptosis and necrosis are involved in the 3-NP-treated slices, apoptosis as well as necrosis in the striatum and apoptosis in the cortex.