No abstract

In this paper we have investigated the developmental-genetic steps that shape the entero-endocrine system of Drosophila melanogaster from the embryo to the adult. The process starts in the endoderm of the early embryo where precursors of endocrine cells and enterocytes of the larval midgut, as well as progenitors of the adult midgut, are specified by a Notch signaling-dependent mechanism. In a second step that occurs during the late larval period, enterocytes and endocrine cells of a transient pupal midgut are selected from within the clusters of adult midgut progenitors. As in the embryo, activation of the Notch pathway triggers enterocyte differentiation, and inhibits cells from further proliferation or choosing the endocrine fate. The third step of entero-endocrine cell development takes place at a mid-pupal stage. Before this time point, the epithelial layer destined to become the adult midgut is devoid of endocrine cells. However, precursors of the intestinal midgut stem cells (pISCs) are already present. After an initial phase of symmetric divisions which causes an increase in their own population size, pISCs start to spin off cells that become postmitotic and express the endocrine fate marker, Prospero. Activation of Notch in pISCs forces these cells into an enterocyte fate. Loss of Notch function causes an increase in the proliferatory activity of pISCs, as well as a higher ratio of Prospero-positive cells.

This large study of CBTs demonstrates the value of preoperatively determining tumor dimensions and how far the tumor is located from the base of the skull. DTBOS and tumor volume, when used in combination with the Shamblin grade, better predict bleeding and cranial nerve injury risk. Furthermore, surgical resection before expansion toward the base of the skull reduces complications as every 1-cm decrease in the distance to the skull base results in 1.8 times increase in >250 mL of blood loss and 1.5 times increased risk of cranial nerve injury.

At 5 years, endo-first and open-first revascularization strategies had equivalent LS rates and AFS in patients with critical limb ischemia when properly selected. A patient-centered approach with close surveillance improves long-term outcomes for both open and endo approaches.