C. elegans worms hatching in the absence of food show growth arrest during the first larval stage (L1). While much has been learned about the later diapause, dauer, which worms enter under adverse conditions, much less is known about the mechanisms governing L1 arrest. Here we show that worms lacking activity of the asna-1 gene arrest growth reversibly at the L1 stage even when food is abundant. asna-1 encodes an ATPase that functions nonautonomously to regulate growth. asna-1 is expressed in a restricted set of sensory neurons and in insulin-producing intestinal cells. asna-1 mutants are reduced in insulin secretion while overexpression of asna-1 mimics the effects of insulin overexpression. Human ASNA1 is highly expressed in pancreatic beta cells, but not in other pancreatic endocrine cell types, and regulates insulin secretion in cultured cells. We propose that ASNA1 is an evolutionarily conserved modulator of insulin signaling.

Objectives Opioids are commonly prescribed post-surgery. We investigated the proportion of patients who were prescribed any opioids 6–12 months after two common surgeries – laparoscopic cholecystectomy and gastric by-pass (GBP) surgery. A secondary aim was to examine risk factors prior to surgery associated with the prescription of any opioids after surgery. Methods We performed a retrospective observational study on data from medical records from patients who underwent cholecystectomy (n=297) or GBP (n=93) in 2018 in the Region of Västerbotten, Sweden. Data on prescriptions for opioids and other drugs were collected from the patients` medical records. Results There were 109 patients (28%) who were prescribed opioids after discharge from surgery but only 20 patients (5%) who still received opioid prescriptions 6–12 months after surgery. All 20 of these patients had also been prescribed opioids within three months before surgery, most commonly for back and joint pain. Only 1 out of 56 patients who were prescribed opioids preoperatively due to gallbladder pain still received prescriptions for opioids 6–12 months after surgery. Although opioid use in the early postoperative period was more common among patients who underwent cholecystectomy, the patients who underwent GBP were more prone to be “long-term” users of opioids. In the patients who were prescribed opioids within three months prior to surgery, 8 out of 13 patients who underwent GBP and 12 of the 96 patients who underwent cholecystectomy were still prescribed opioids 6–12 months after surgery (OR 11.2; 95% CI 3.1–39.9, p=0,0002). Affective disorders were common among “long-term” users of opioids and prior benzodiazepine and amitriptyline use were significantly associated with “long-term” opioid use. Conclusions The proportion of patients that used opioids 6–12 months after cholecystectomy or GBP was low. Patients with preoperative opioid-use experienced a significantly higher risk of “long-term” opioid use when undergoing GBP compared to cholecystectomy. The indication for being prescribed opioids in the “long-term” were mostly unrelated to surgery. No patient who was naïve to opioids prior surgery was prescribed opioids 6–12 months after surgery. Although opioids are commonly prescribed in the preoperative and in the early postoperative period to patients with gallbladder disease, there is a low risk that these prescriptions will lead to long-term opioid use. The reasons for being prescribed opioids in the long-term are often due to causes not related to surgery.