RESUMEN
At the Edward Via College of Osteopathic Medicine (VCOM), students are taught through a systems-based block education process organized according to separate organ systems. The block education lectures provide instruction on these various organ systems and their associated diseases and potential for diagnosis and treatment. A curricular initiative implemented at VCOM incorporates International Classification of Diseases, 10th Revision (ICD-10) codes into the preclinical curriculum to enhance student learning and recall of basic science information and to prepare them for patient encounters during clinical rotations. In constructing this curricular initiative, diseases and procedures mentioned in all lectures during the first 2 years were evaluated and matched with their corresponding ICD-10 diagnostic and procedural codes to illustrate to students how this information would be used in a clinical setting. Of 994 lectures with 36,105 slides, 4331 opportunities to associate ICD-10 codes were identified. Information was given to instructors to update their future lectures. This initiative aims to enhance the preclinical educational experience and prepare preclinical students for documenting patient care. After students have been fully exposed to this new learning component, a study is planned to analyze the effects of the curriculum.
Asunto(s)
Curriculum , Educación Médica/métodos , Clasificación Internacional de Enfermedades , Medicina Osteopática/educación , Aprendizaje Basado en Problemas , HumanosRESUMEN
Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Non-specific maternal immune stimulation with Freund's complete adjuvant (FCA) or interferon gamma (IFNgamma) has been associated with protection against birth malformations. Using a diabetic mouse model, late-gestation fetal heart and great vessel morphology were analyzed. Four groups of mice were used: non-diabetic females as a control group, hyperglycemic females induced by streptozotocin as a diabetic group, and diabetic females injected either with FCA or IFNgamma. At day 17 of gestation, females were euthanized and one fetus was arbitrarily selected per litter for fixation and sectioning. Treatment-induced changes in cardiac development were assessed from digital images of serial sections taken at standardized levels in the thorax. One-way parametric and non-parametric ANOVA and ordinal logistic regression were performed to compare the difference among groups (P<0.05). Maternal hyperglycemia altered morphology of the late-gestation fetal mouse heart by causing ventricular chamber dilation, sectional myocardial reduction, and an increase in transversal aortic area. FCA protected the fetal heart from cavitary dilation in diabetic mothers. FCA and IFNgamma protected the fetal heart against reduction of myocardial area, and ascending thoracic aorta dilation. Consequences of late gestation heart chamber dilation and myocardial reduction are not yet known. Maternal immune stimulation partially protected against these developmental defects by mechanisms that remain unclear.
Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/inmunología , Cardiopatías Congénitas/etiología , Cardiopatías Congénitas/inmunología , Ventrículos Cardíacos/patología , Intercambio Materno-Fetal/inmunología , Embarazo en Diabéticas , Animales , Aorta Torácica/embriología , Aorta Torácica/patología , Cardiomiopatía Hipertrófica/inmunología , Cardiomiopatía Hipertrófica/patología , Cardiomiopatía Hipertrófica/prevención & control , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Adyuvante de Freund/farmacología , Cardiopatías Congénitas/prevención & control , Ventrículos Cardíacos/embriología , Hiperglucemia/complicaciones , Sistema Inmunológico , Interferón gamma/farmacología , Ratones , Ratones Endogámicos ICR , EmbarazoRESUMEN
BACKGROUND: Methylnitrosourea (MNU), an alkylating agent derived from creatinine metabolism, is cytotoxic, genotoxic, and mutagenic. Mid-gestational exposure to MNU leads to distal limb defects in mice. Previous studies have shown that nonspecific maternal immune stimulation protects against MNU-induced teratogenesis. A role for immune-mediated placental improvement in this effect remains uncertain. METHODS: The immune system of timed-pregnant C57BL/6N and CD-1 mice was stimulated by GD 7 intraperitoneal (IP) injection with the cytokine interferon-gamma (IFN-gamma). A teratogenic dose of MNU was then administered by IP injection on the morning of GD 9 to disrupt distal limb formation. Fetal limb length, body length, digital deformities, and placental integrity were evaluated on GD 14. RESULTS: The incidence of syndactyly, polydactyly, and interdigital webbing in MNU-exposed mice was decreased by maternal IFN-gamma treatment. In C57BL/6N mice, these defects were reduced by 47, 100, and 63%, respectively, as compared to previous reports on CD-1 mice, by 39, 71, and 20%, respectively. Administration of IFN-gamma significantly diminished MNU-induced endothelial and trophoblast placental damage in both strains of mice. CONCLUSIONS: These findings support a possible link between maternal immunity, placental integrity, and fetal distal limb development. Further, these results suggest that IFN-gamma might act through placental improvement to indirectly protect against MNU-induced fetal limb malformations.
Asunto(s)
Anomalías Inducidas por Medicamentos/prevención & control , Adyuvantes Inmunológicos/uso terapéutico , Interferón gamma/uso terapéutico , Metilnitrosourea/toxicidad , Placenta/inmunología , Teratógenos/toxicidad , Anomalías Inducidas por Medicamentos/embriología , Anomalías Inducidas por Medicamentos/etiología , Anomalías Inducidas por Medicamentos/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Células Endoteliales/efectos de los fármacos , Células Endoteliales/inmunología , Células Endoteliales/patología , Femenino , Edad Gestacional , Sistema Inmunológico/efectos de los fármacos , Inyecciones Intraperitoneales , Interferón gamma/administración & dosificación , Interferón gamma/inmunología , Deformidades Congénitas de las Extremidades Inferiores/inducido químicamente , Deformidades Congénitas de las Extremidades Inferiores/inmunología , Deformidades Congénitas de las Extremidades Inferiores/prevención & control , Intercambio Materno-Fetal , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Embarazo , Distribución Aleatoria , Factores de Tiempo , Trofoblastos/efectos de los fármacos , Trofoblastos/inmunología , Trofoblastos/patologíaRESUMEN
BACKGROUND: Methylnitrosourea (MNU) is a potent carcinogen and teratogen that is associated with central nervous system, craniofacial, skeletal, ocular, and appendicular birth defects following transplacental exposure at critical time points during development, and preliminary studies have suggested that nonspecific maternal immunostimulation may offer protection against development of these birth defects. METHODS: Our study examined morphologic alterations in fetal limb and digital development and placental integrity following maternal exposure to MNU on GD 9 in CD-1 mice, and characterized the improvement in placental integrity and abrogation of fetal defects following maternal immune stimulation with interferon-gamma (IFN-gamma) on GD 7. RESULTS: Fetal limbs were significantly shortened (p < 0.0001) and incidence of limb and digital defects (syndactyly, polydactyly, oligodactyly, clubbing, and webbing) was dramatically increased following mid-gestational maternal MNU exposure. Maternal immune stimulation with IFN-gamma on GD 7 lessened incidence of fetal limb shortening and maldevelopment on GD 12 and 14. Further, disruption of placental spongiotrophoblast integrity, increased cell death in placental trophoblasts with increased intercellular spaces in the spongiotrophoblast layer and minimal inflammation, and increased loss of fetal labyrinthine endothelial cells from MNU-exposed dams suggested that MNU-induced placental breakdown may contribute to fetal limb and digital maldevelopment. MNU + IFN-gamma was associated with diminished cell death within all layers of the placenta, especially in the labyrinthine layer. CONCLUSIONS: These data verify improved distal limb development in MNU-exposed mice as a result of maternal IFN-gamma administration, and suggest a link between placental integrity and proper fetal development.