Neonatal Hypoxia-Ischemia alters Brain-Derived Contactin-2-Positive Extracellular Vesicles in the Mouse Plasma.

Neonatal encephalopathy (NE) impairs white matter development and results in long-term neurodevelopmental deficits. Leveraging prior findings of altered neuronal proteins carried by brain-derived extracellular vesicles (EVs) that are marked by a neural-specific cell surface glycoprotein Contactin-2 (CNTN2) in NE infants, the present study aimed to determine the correlation between brain and circulating CNTN2+-EVs and whether NE alters circulating CNTN2+-EV levels in mice. Brain tissue and plasma were collected from postnatal day (P)7, 10, 11, 15 mice to determine the baseline CNTN2 correlation between these two compartments (n = 4-7/time point/sex). NE was induced in P10 pups. Brain and plasma samples were collected at 1, 3, 6, 24, and 120 h (n = 4-8/time point/sex). CNTN2 from brain tissue and plasma EVs were quantified using ELISA. ANOVA and linear regression analyses were used to evaluate changes and correlations between brain and plasma CNTN2+-EVs. In baseline experiments, CNTN2 in brain tissue and plasma EVs peaked at P10 with no sex-difference. Brain and plasma CNTN2+-EV showed a positive correlation across early postnatal ages. NE pups showed an elevated CNTN2 in brain tissue and EVs at 1 h and only in brain tissue at 24 h. NE also abolished the positive plasma-brain correlation. The findings establish a link for central CNTN2 and its release into circulation during early postnatal life. The immediate elevation and release of CNTN2 following NE highlight a potential molecular response shortly after a brain injurious event. Our findings further support the utility of circulating brain-derived EVs as a possible bioindicator of NE.

Pediatric End-of-Life Care Skills Workshop: A Novel, Deliberate Practice Approach.

INTRODUCTION: Pediatric end of life (EOL) care skills are a high acuity, low occurrence skill set required by pediatric clinicians. Gaps in education and competence for this specialized care can lead to suboptimal patient care and clinician distress when caring for dying patients and their families. METHODS: A half-day workshop using a deliberate practice approach was designed by an inter-professional workgroup including bereaved parent consultants. Pediatric fellows (neonatal-perinatal medicine, critical care, hematology oncology, blood and marrow transplant) and advanced practice providers learned and practiced EOL skills in a safe simulation environment with instruction from interprofessional facilitators and standardized patients. Participant perceived competence (self-efficacy) was measured before, immediately-post, and 3 months post workshop. RESULTS: There were 28 first-time (of 34 total) participants in 4 pilot workshops. Participants reported significantly increased self-efficacy post-workshop for 6 of 9 ratings, which was sustained 3 months afterwards. Most (92%, n = 22 of 24 respondents) reported incorporating the workshop training into clinical practice at 3-month follow-up. CONCLUSIONS: With early success of the pilot workshops, future iterative work includes expanding workshops to earlier, interprofessional learners and collecting validity evidence for a competency-based performance checklist tool. A project website (https://z.umn.edu/PECS) was developed for local and collaborative efforts.