No abstract

The zebrafish enteric nervous system (ENS), like those of all other vertebrate species, is principally derived from the vagal neural crest. The developmental controls that govern the specification and patterning of the ENS are not well understood. To identify genes required for the formation of the vertebrate ENS, we preformed a genetic screen in zebrafish. We isolated the lessen (lsn) mutation that has a significant reduction in the number of ENS neurons as well as defects in other cranial neural crest derived structures. We show that the lsn gene encodes a zebrafish orthologue of Trap100, one of the subunits of the TRAP/mediator transcriptional regulation complex. A point mutation in trap100 causes a premature stop codon that truncates the protein, causing a loss of function. Antisense-mediated knockdown of trap100 causes an identical phenotype to lsn. During development trap100 is expressed in a dynamic tissue-specific expression pattern consistent with its function in ENS and jaw cartilage development. Analysis of neural crest markers revealed that the initial specification and migration of the neural crest is unaffected in lsn mutants. Phosphohistone H3 immunocytochemistry revealed that there is a significant reduction in proliferation of ENS precursors in lsn mutants. Using cell transplantation studies, we demonstrate that lsn/trap100 acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest derived cartilages secondarily. Furthermore, we show that endoderm is essential for ENS development. These studies demonstrate that lsn/trap100 is not required for initial steps of cranial neural crest development and migration, but is essential for later proliferation of ENS precursors in the intestine.

PD was definitive therapy for the majority of neonates included in this study who were referred for surgical evaluation of SIP. Our data point to trends in being able to identify infants with SIP who are at risk for salvage laparotomy following PD, and thus, adverse nutritional outcomes. Larger, prospective studies are needed to further evaluate this specific patient population and identify those patients who are likely to succeed with PD following the diagnosis of SIP.

Necrotizing enterocolitis (NEC) is a devastating disease of prematurity with significant morbidity and mortality. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. The presence of probiotic and commensal bacteria within the gut has been shown to mature the intestinal defense system through a variety of mechanisms. We have shown that commensal and probiotic bacteria can promote intestinal host defenses by reducing apoptotic signaling, blocking inflammatory signaling, and maturing barrier function in immature intestinal epithelia. Future studies aimed at elucidating the mechanisms by which probiotic and commensal bacteria exert their effects will be critical to developing effective preventive therapies for NEC.

Background Repeated exposure to pediatric emergency scenarios improves technical skills, but it is unclear whether repeated exposure to specific cases affects medical decision making in varied cases. Objective We sought to determine whether repeated exposure to 1 scenario would translate to improved performance and decision making in varied scenarios. Methods Senior pediatrics residents participated in 3 scenarios with scripted debriefing. Residents were randomized to repeated practice (RP) scenarios or mixed (MIX) scenarios. RP residents completed pulseless electrical activity (PEA) with different stems (Case 1, 2, 3). MIX residents completed PEA (Case 1), seizure (Case 2), and ventricular tachycardia (Case 3) scenarios. Four months later, participants returned to complete 3 more cases: PEA (Case 4), seizure (Case 5), and critical coarctation (Case 6). Results Twenty-three residents participated in the study and were randomized to either the RP or the MIX group. The RP group showed statistically significant improvement in time to start chest compressions, whereas the MIX group showed no improvement. Use of a backboard improved significantly in Case 4 for the RP group but not for the MIX group. Similarly, time to check glucose in the seizure scenario was significantly better in the MIX group that had previous exposure to a seizure scenario. No differences in performance were noted between groups in Case 6, which was new to both groups. Conclusions Results of this study indicate that whereas repeated exposure may improve decision-making skills in similar scenarios, it may not translate to improved medical decision making in other scenarios.