Supplementary Material for: Involvement of the Orexin System in Adrenal Sympathetic Regulation

Orexin (hypocretin) is a neuropeptide secreted from hypothalamic neurons that is known to be activated during motivated behaviors and active waking. Presently, our knowledge of orexin is mainly limited to the central nervous system, and the involvement of the orexin system in peripheral tissues has received little attention. In the present study, we analyzed the existence of the orexin system in the adrenal medulla, which is part of the sympathetic nervous system. Orexin and its receptors are expressed in the bovine adrenal medulla. Orexins stimulated intracellular calcium changes and epinephrine release from cultured bovine adrenal medullary cells. Applied orexin decreased expression of prepro-orexin, orexin receptor-1 and orexin receptor-2, suggesting negative feedback regulation in the adrenal gland. Our results indicate involvement of the orexin system in the sympathetic regulation of the adrenal medulla

Supplementary Material for: Natural History of Small Gastric Subepithelial Lesions Less than 20 mm: A Multicenter Retrospective Observational Study (NUTSHELL20 Study)

Background and Aim: Small gastric subepithelial lesions (SELs) are sometimes encountered in daily esophagogastroduodenoscopy (EGD) practice, but whether once-annual or twice-annual endoscopy can provide sufficient follow-up remains unclear. Because follow-up based on small-SEL characteristics is important, this study clarified the natural history of gastric SELs less than 20 mm. Methods: This retrospective multicenter observation study conducted at 24 Japanese hospitals during April 2000 to March 2020 examined small gastric SELs of ≤20 mm diameter. The primary outcome was the rate of size increase of those SELs detected using EGD, with growth times assessed irrespective of SEL pathological diagnoses. Results: We examined 824 cases with tumors of 1–5 mm diameter in 298 (36.2%) cases, 6–10 mm in 344 (41.7%) cases, 11–15 mm in 112 (13.6%) cases, and 16–20 mm in 70 (8.50%) cases. An increase of small gastric SELs was observed in 70/824 patients (8.5%). The SELs larger than 6 mm increased, even after 10 years. No-change and increasing groups had no significantly different malignant findings at diagnosis. In cases of gastrointestinal stromal tumors (GISTs), internal cystic change in endoscopic ultrasound (EUS) is a risk factor for an increased tumor size. The predictive tumor growth cutoff size at initial diagnosis was 13.5 mm. Conclusions: Small gastric SELs less than 20 mm have an approximately 8.5% chance of increase. Predictive markers for GIST growth are tumor size ≥13.5 mm and internal cystic change in EUS