ABSTRACT
CONTEXT: Calls for medical curriculum reform and increased student diversity in the USA have seen mixed success: performance outcomes following curriculum revisions have been inconsistent and national matriculation of under-represented minority (URM) students has not met aspirations. Published innovations in curricula, academic support and pipeline programmes usually describe isolated interventions that fail to affect curriculum-level outcomes. METHODS: United States Medical Licensing Examination (USMLE) Step 1 performance and graduation rates were analysed for three classes of medical students before (matriculated 1995-1997, n=517) and after (matriculated 2003-2005, n=597) implementing broad-based reforms in our education system. The changes in pipeline recruitment and preparation programmes, instructional methods, assessment systems, academic support and board preparation were based on sound educational principles and best practices. RESULTS: Post-reform classes were diverse with respect to ethnicity (25.8% URM students), gender (51.8% female), and Medical College Admissions Test (MCAT) score (range 20-40; 24.1% scored ≤ 25). Mean±standard deviation MCAT scores were minimally changed (from 27.2±4.7 to 27.8±3.6). The Step 1 failure rate decreased by 69.3% and mean score increased by 14.0 points (effect size: d=0.67) overall. Improvements were greater among women (failure rate decreased by 78.9%, mean score increased by 15.6 points; d=0.76) and URM students (failure rate decreased by 76.5%, mean score increased by 14.6 points; d=0.74), especially African-American students (failure rate decreased by 93.6%, mean score increased by 20.8 points; d=1.12). Step 1 scores increased across the entire MCAT range. Four- and 5-year graduation rates increased by 7.1% and 5.8%, respectively. CONCLUSIONS: The effect sizes in these performance improvements surpassed those previously reported for isolated interventions in curriculum and student support. This success is likely to have resulted from the broad-based, mutually reinforcing nature of reforms in multiple components of the education system. The results suggest that a narrow reductionist view of educational programme reform is less likely to result in improved educational outcomes than a system perspective that addresses the coordinated functioning of multiple aspects of the academic enterprise.
Subject(s)
Curriculum , Education, Medical/methods , Education, Medical/organization & administration , Educational Measurement/methods , Educational Status , Female , Humans , Male , Organizational Innovation , Schools, Medical , TexasABSTRACT
Establishment of an in vitro model of human cholinergic neurons would be highly desirable for understanding and developing treatment for Alzheimer's and motoneuron diseases. Previously we reported that the combination of basic fibroblast growth factor (bFGF), heparin, and laminin directs human fetal neural stem cells to form cholinergic neurons. One problem, however, is that long-term in vitro survival of these cells is low. Our goal for this study was to determine whether astrocytes or their secreted factors enhance differentiation and survival of cholinergic neurons under long-term differentiation conditions. We demonstrate here that astrocytes or astrocyte conditioned media did not enhance cholinergic differentiation but did increase the long-term survival of differentiated human neural stem cells, particularly cholinergic neurons. We further show that astrocytes protected long-term-differentiated cells from apoptotic cell death, which is at least partially mediated by astrocyte-secreted bFGF. Our findings indicate that long-term survival of human stem cell-derived cholinergic neurons requires trophic factors from nonneuronal cells. This data may provide insights into the development of an in vitro model of long-term cultured human cholinergic neurons useful for understanding of the mechanisms of cholinergic differentiation and developing treatments for neurological diseases.
Subject(s)
Astrocytes/physiology , Cell Differentiation/physiology , Choline O-Acetyltransferase/metabolism , Embryonic Stem Cells/physiology , Neurons/physiology , Animals , Animals, Newborn , Astrocytes/chemistry , Bromodeoxyuridine/metabolism , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cell Survival/physiology , Cells, Cultured , Culture Media, Conditioned/pharmacology , Embryonic Stem Cells/drug effects , Enzyme-Linked Immunosorbent Assay/methods , Fetus , Fibroblast Growth Factor 2/pharmacology , Humans , In Situ Nick-End Labeling/methods , L-Lactate Dehydrogenase/metabolism , Nerve Tissue Proteins/metabolism , Neurons/drug effects , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
A neuroprotective factor is shown to be present in mammalian serum. This factor is identified by Western blotting to be serum albumin. The serum factor and albumin both protected cultured spinal cord neurons against the toxicity of glutamate. The inability of K252a, a blocker of the high affinity tyrosine kinase receptor for members of the nerve growth factor family, to block the neuroprotective effect of the serum factor established that the serum factor is not a member of the nerve growth factor family. Post-injury injection of albumin intravenously or into the site of injury immediately after injury both improved significantly locomotor function according to Basso-Beattie-Bresnahan assessment and spontaneous locomotor activity recorded with a photobeam activity system. Albumin has multiple mechanisms whereby it may be neuroprotective, and it is a potentially useful agent for treating neurotraumas.
