Two strategies to intensify evidence-based medicine education of undergraduate students: a randomised controlled trial

<p><b>INTRODUCTION</b>Undergraduate evidence-based practice (EBP) is usually taught through standalone courses and workshops away from clinical practice. This study compared the effects of 2 clinically integrated educational strategies on final year medical students.</p><p><b>MATERIALS AND METHODS</b>Final year medical students rotating to the general medicine service for a 2-week internship were randomly assigned to participate in a weekly EBP-structured case conference focusing on students' primary care patients (Group A, n = 47), or to receive a weekly didactic lecture about EBP (Group B, n = 47). The teaching effects of these 2 interventions were evaluated by a validated instrument for assessment of EBP related knowledge (EBP-K), attitude (EBP-A), personal application (EBP-P), and anticipated future use (EBP-F) on the first and last days of rotation.</p><p><b>RESULTS</b>All scores improved significantly after the 2-week EBM-teaching for both groups. When compared to Group B, students in Group A had significantly higher post-intervention scores of EBP-K (21.2 ± 3.5 vs 19.0 ± 4.6; ie. 57.8 ± 72.9% vs 29.1 ± 39.1%; P <0.01) and EBP-P (18.7 ± 4.3 vs 15.3 ± 3.9; ie. 28.5 ± 25.5 % vs 14.1 ± 18.7 %; P <0.001). In contrast, the scores of EBP-A and EBP-F were similar between the 2 groups.</p><p><b>CONCLUSION</b>Structured case conference, when compared to the didactic lectures, significantly improved EBP-K and EBP-P for final year medical students.</p>

Neocartilage from human mesenchymal stem cells in alginate: implied timing of transplantation.

Previous reports have demonstrated the suitability of alginate microencapsulation for chondrogenesis of human mesenchymal stem cells (MSCs) in vitro. This study examined the MSCs-alginate constructs that were transplanted beneath the dorsal skin of nude mice for 8 weeks after a variety of in vitro culture periods. The in vitro culture had great effects on gross morphology and histological characteristics of transplants. The integrity of alginate of transplants increased as the in vitro culture period increased. Transplants were characterized by an opaque and yellowish color, fair burnish, a firm to elastic texture, but without any evidence of calcification spots. Histological findings agreed with the clinical determination of hyaline cartilage, characterized by isolated cells with basophilic ground substance positive in Safranin-O staining and collagen type II immunohistochemistry. Transplants with exposure to TGF-beta1 for more than 2 weeks before transplantation, lost burnish, were flexible in texture, and had an increased formation of calcification spots. Accordingly, 1-week exposure to TGF-beta1 in vitro before transplantation is appropriate for neocartilage formation of human MSCs in alginate. These findings suggested that regeneration using cell therapy or tissue engineering should assist in ascertaining the optimal timing of transplantation.

Gene expression profiles of early adipogenesis in human mesenchymal stem cells.

Bone marrow-derived human mesenchymal stem cells (hMSCs) give rise to adipocytes in response to a medium containing dexamethasone, isobutylmethylxanthine, and insulin. A cDNA microarray was applied to analyze the gene expression profiles between the cells at day 0 and at day 3 of incubation in the adipogenic medium, when the cells began to express PPARgamma2, a transcription factor of adipogenesis. Several genes that were regulated during this time period were then confirmed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Interestingly, several genes identified previously as markers of lineage-specific differentiations other than adipocyte were regulated during adipogenesis. We totally identified 82 genes that were differentially induced by fivefold or greater, and 31 genes that were differentially suppressed by twofold or more. Among them, 55 genes were not previously examined to associate with adipogenesis or have not been determined in hMSCs, therefore, these data provide novel information on the genes involved in adipogenesis of hMSCs.

Immortalization without neoplastic transformation of human mesenchymal stem cells by transduction with HPV16 E6/E7 genes.

hMSCs derived from bone marrow are useful as a species-specific cell culture system for studying cell lineage differentiation and tissue remodeling. However, hMSCs usually have a short in vitro life span due to replicative senescence. We therefore used a high dose of retroviral vector LXSN-16E6E7 to transduce hMSCs of an aging donor and obtained an actively proliferating cell line, designated KP-hMSCs, which expressed HPV16 E6/E7 mRNA. Whereas parental hMSCs ceased to grow after 30 PDs, KP-hMSCs could be propagated beyond 100 PDs. With culture procedures to avoid selection pressure and crowded cell growth, KP-hMSCs showed no signs of neoplastic transformation as examined by soft-agar anchorage-independent growth and NOD-SCID mouse tumorigenicity assays. KP-hMSCs gave similar cytofluorimetric profiles of 31 CD markers to those of the parental primary hMSCs, except with some morphologic changes and expansion of an originally very minor CD34(dim)CD38(+)CD50+ cell population. Upon exposure to specific stimulating conditions in vitro, KP-hMSCs could respond and differentiate along the mesenchymal (bone, fat and cartilage) and nonmesenchymal (neuron) cell lineages. Our results indicated that hMSCs could be immortalized by transduction with HPV16 E6/E7, maintained without neoplastic transformation by careful culture procedures and thus useful for stem cell research and clinical application.

Inhibitory effects of bromocriptine on corticosterone secretion in male rats.

Bromocriptine, a dopamine D2 receptor agonist, is widely used for treating prolactinoma, Parkinson's disease and galactorrhea. However, the influence of bromocriptine on the endocrine system, especially adrenal function, is not clear. The present study was aimed to investigate the effects of bromocriptine on corticosterone production in rats. Male rats were treated or not treated by bromocriptine (5 mg/kg, s.c.) twice per day for 2 days before decapitation. The adrenal zona fasciculata-reticularis cells were prepared and incubated with adrenocorticotropic hormone (ACTH), forskolin (an adenylyl cyclase activator), 8-bromo-adenosine 3':5' cyclic monophosphate (8-Br-cAMP, a membrane-permeable analogue of cAMP), and steroidogenic precursors including 25-OH-cholesterol and pregnenolone. The concentrations of prolactin, corticosterone and pregnenolone in the plasma and/or medium were measured by radioimmunoassay (RIA). The protein expression of cytochrome P450 side-chain cleavage (P450scc) enzyme and steroidogenic acute regulatory protein (StAR) was analyzed by Western blotting. Administration of bromocriptine in vivo resulted in a decrease in the levels of plasma prolactin and corticosterone. Basal--and ACTH--as well as forskolin-stimulated corticosterone secretion by zona fasciculata-reticularis cells was also lower in bromocriptine-treated rats than in control animals. The decreased production of corticosterone in zona fasciculata-reticularis cells could be reversed by administration of 8-Br-cAMP. The corticosterone and pregnenolone release induced by 25-OH-cholesterol in zona fasciculata-reticularis cells was reduced by administration of bromocriptine. The protein expression of both StAR protein and P450scc in zona fasciculata-reticularis cells was inhibited in the bromocriptine-treated group. Administration of bromocriptine in vitro reduced the release of corticosterone stimulated by ACTH and forskolin in rat zona fasciculata-reticularis cells. These results suggested that bromocriptine caused adrenal dysfunction through inhibition of ACTH action and of the activity of adenylyl cyclase, and impaired the early steps of corticosterone biosynthesis.