Publications

Male neonate brains are more susceptible to the effects of perinatal asphyxia resulting in hypoxia and ischemia (HI)-related brain injury. The relative resistance of female neonatal brains to adverse consequences of HI suggests that there are sex-specific mechanisms that afford females greater neuroprotection and/or facilitates recovery post-HI. We hypothesized that HI preferentially induces estrogen receptor α (ERα) expression in female neonatal hippocampi and that ERα is coupled to Src family kinase (SFK) activation that in turn augments phosphorylation of the TrkB and thereby results in decreased apoptosis. After inducing the Vannucci's HI model on P9 (C57BL/6J) mice, female and male ERα wild-type (ERα(+/+)) or ERα null mutant (ERα(-/-)) mice received vehicle control or the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF). Hippocampi were collected for analysis of mRNA of ERα and BDNF, protein levels of ERα, p-TrkB, p-src, and cleaved caspase 3 (c-caspase-3) post-HI. Our results demonstrate that: (1) HI differentially induces ERα expression in the hippocampus of the female versus male neonate, (2) src and TrkB phosphorylation post-HI is greater in females than in males after 7,8-DHF therapy, (3) src and TrkB phosphorylation post-HI depend on the presence of ERα, and (4) TrkB agonist therapy decreases the c-caspase-3 only in ERα(+/+) female mice hippocampus. Together, these observations provide evidence that female-specific induction of ERα expression confers neuroprotection with TrkB agonist therapy via SFK activation and account for improved functional outcomes in female neonates post-HI.

BACKGROUND

An estimated 6,000 to 18,000 additional hospice and palliative medicine (HPM) physicians are needed in the United States. A source could be the military graduate medical education system where 15% of U.S. medical residents are trained. A community-based hospice and palliative care organization created a one-week rotation for military residents including participation in interdisciplinary group visits at patients' homes, facilities, and an inpatient hospice unit.

OBJECTIVE

Our goal was to evaluate the effectiveness of a one-week community HPM rotation for military medical residents.

METHODS

A mixed-methods, multi-stakeholder perspective program evaluation model was used for program years 2011 to 2013. Data were managed and analyzed using Microsoft Excel and Atlas.ti. Participants in the rotation were residents training at two local military hospitals. Program evaluation data were collected from residents, military program liaisons, and hospice clinical preceptors. Quantitative data included pre- and post-tests based on Accreditation Council for Graduate Medical Education competencies completed by residents. Qualitative data included resident essays and semi-structured interviews with hospice preceptors and military program liaisons.

RESULTS

Quantitative and qualitative data suggested that the rotation increased military residents' knowledge, attitudes, and comfort level with HPM. Quantitative analysis of test scores indicated improvements from pre- to post-tests in each of five areas of learning. Qualitative data indicated the rotation created a greater appreciation for the overall importance of HPM and increased understanding of eligibility and methods for pain and symptom management.

CONCLUSIONS

A one-week community hospice rotation for medical military residents impacts participant's knowledge of and attitudes toward HPM.

Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior "cranial" NCC form craniofacial bone, whereas solely posterior "trunk" NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages.