Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring.
Recent innovations in palliative care education for medical students represent varied settings, learner levels, instructors, educational modalities, and palliative care topics. Future curricula should continue to incorporate interdisciplinary faculty. Studies could be improved by integrating longitudinal curricula and longer-term outcomes; collaborating across institutions; using validated measures; and assessing higher-level outcomes including skills, behaviors, and impact on patient care.
Fundamental to understanding more generalizable concepts; e.g., bacterial pathogenesis 2. Important implication in understanding burden of disease; e.g., epidemiologic features of prevalent infection 3. Evergreen (i.e., known to be true or at least "verified" in a rigorous manner); e.g., clinical manifestations of specific infection, role of immune system in disease presentation 4. Foundational building blocks for understanding next level of core knowledge; e.g., immunologic response to class of pathogens 5. Not simply an easily searchable fact; e.g., size of TB genome 6. Regarded as important subject area by both basic science and clinical experts; e.g., TB 7. Utilized on a regular basis by practicing primary care physician or general specialist; e.g., recognizing at risk populations 8. Explicable; building on prior knowledge; e.g., immune reconstitution inflammatory response with TB & HIV Rx 9. Deliverable as an illness script; e.g., symptoms plus signs leading to the diagnosis of a specific illness 10. Frequently misunderstood in clinical practice; e.g., optimal duration of antibiotic therapy is known 11. Led to the uncovering of big ideas; e.g., bacterial genetics and antimicrobial resistance 12. Counterintuitive; the host response causes much of the morbidity attributable to infectious diseases Supplemental digital content for Chen SF, Deitz J, Batten JN, et al. A multi-institution collaboration to define core content and design flexible curricular components for a foundational medical school course: Implications for national curriculum reform. Acad Med.
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