Paraventricular (PVN) and supraoptic nuclei of the hypothalamus maintain homeostasis by modulating pituitary hormonal output. PVN and supraoptic nuclei contain five major cell types: oxytocin-, vasopressin-, CRH-, somatostatin-, and TRH-secreting neurons. Sim1, Arnt2, and Otp genes are essential for terminal differentiation of these neurons. One of their common downstream genes, Brn2, is necessary for oxytocin, vasopressin, and CRH cell differentiation. Here we show that Sim2, a paralog of Sim1, contributes to the expression of Trh and Ss genes in the dorsal preoptic area, anterior-periventricular nucleus, and PVN. Sim2 expression overlaps with Trh-and Ss-expressing cells, and Sim2 mutants contain reduced numbers of Trh and Ss cells. Genetically, Sim1 acts upstream of Sim2 and partially compensates for the loss of Sim2. Comparative expression studies at the anterior hypothalamus at early stages reveal that there are separate pools of Trh cells with distinctive molecular codes defined by Sim1 and Sim2 expression. Together with previous reports, our results demonstrate that Sim1 and Otp utilize two common downstream genes, Brn2 and Sim2, to mediate distinctive sets of neuroendocrine hormone gene expression. (Molecular Endocrinology 18: 1251-1262, 2004)

These findings do not support the use of perioperative low-dose ketamine to decrease opioid use in children with scoliosis undergoing posterior spinal fusion.

Ketorolac does not increase the incidence of developing a pseudoarthrosis when used as an adjunct for postoperative analgesia following a PSFI for AIS using segmental spinal instrumentation and iliac crest bone graft. The differences seen here compared with adults may be due to the greater healing potential in these young patients. We recommend utilization of ketorolac after surgery to supplement pain management when necessary.