Ykt6 functionally overlaps with vacuolar and exocytic R-SNAREs in the yeast Saccharomyces cerevisiae.

The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex forms a 4-helix coiled-coil bundle consisting of 16 layers of interacting side chains upon membrane fusion. The central layer (layer 0) is highly conserved and comprises three glutamines (Q) and one arginine (R), and thus SNAREs are classified into Qa-, Qb-, Qc-, and R-SNAREs. Homotypic vacuolar fusion in Saccharomyces cerevisiae requires the SNAREs Vam3 (Qa), Vti1 (Qb), Vam7 (Qc), and Nyv1 (R). However, the yeast strain lacking NYV1 (nyv1Δ) shows no vacuole fragmentation, whereas the vam3Δ and vam7Δ strains display fragmented vacuoles. Here, we provide genetic evidence that the R-SNAREs Ykt6 and Nyv1 are functionally redundant in vacuole homotypic fusion in vivo using a newly isolated ykt6 mutant. We observed the ykt6-104 mutant showed no defect in vacuole morphology, but the ykt6-104 nyv1Δ double mutant had highly fragmented vacuoles. Furthermore, we show the defect in homotypic vacuole fusion caused by the vam7-Q284R mutation was compensated by the nyv1-R192Q or ykt6-R165Q mutations, which maintained the 3Q:1R ratio in the layer 0 of the SNARE complex, indicating that Nyv1 is exchangeable with Ykt6 in the vacuole SNARE complex. Unexpectedly, we found Ykt6 assembled with exocytic Q-SNAREs when the intrinsic exocytic R-SNAREs Snc1 and its paralog Snc2 lose their ability to assemble into the exocytic SNARE complex. These results suggest that Ykt6 may serve as a backup when other R-SNAREs become dysfunctional and that this flexible assembly of SNARE complexes may help cells maintain the robustness of the vesicular transport network.

Superiority trial comparing intraoperative wound irrigation with aqueous 10% povidone-iodine to saline for the purpose of reducing surgical site infection after elective gastrointestinal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Surgical site infection (SSI) is one of the most common complications after gastrointestinal surgery, with a reported incidence of approximately 10%-25%, which is higher than the rates after other types of surgery. Intraoperative wound irrigation (IOWI) is a simple intervention for SSI prevention, and recent studies have reported that IOWI with aqueous povidone-iodine (PVP-I) is significantly more effective at reducing the incidence of SSI than saline. However, the evidence level of previous trials evaluating the efficacy of aqueous PVP-I solution for preventing SSI has been low. METHODS AND ANALYSES: We propose a single-institute, prospective, randomised, blinded-endpoint trial to assess the superiority of IOWI with aqueous 10% PVP-I solution compared with normal saline for reducing SSI in clean-contaminated wounds after elective gastrointestinal surgery. In the study group, IOWI with 40 mL of aqueous 10% PVP-I solution is performed for 1 min before skin suture, and in the control group, IOWI with 100 mL of saline is performed for 1 min before skin suture. We hypothesise that IOWI with aqueous 10% PVP-I solution will achieve a 50% reduction in the incidence of SSIs. The target number of cases is set at 950. The primary outcome is the incidence of incisional SSI up to postoperative day 30 and will be analysed in the modified intention-to-treat set. ETHICS AND DISSEMINATION: This trial was designed and is being conducted by Saitama Medical Center, Jichi Medical University, with approval from the Bioethics Committee for Clinical Research, Saitama Medical Center, Jichi Medical University. Participant recruitment began in June 2019. The final results will be reported in international peer-reviewed journals immediately after trial completion. TRIAL REGISTRATION NUMBER: UMIN000036889.

Risk factors and management of stoma-related obstruction after laparoscopic colorectal surgery with diverting ileostomy.

BACKGROUND: Stoma-related obstruction (SRO) is defined as small bowel obstruction occurring around the limbs of diverting ileostomy (DI). This study was aimed to investigate the incidence, risk factors, and management of SRO after laparoscopic colorectal surgery with DI creation. METHODS: This study included 155 patients who underwent laparoscopic colorectal surgery with DI creation for rectal cancer (n = 138), ulcerative colitis (UC) (n = 14), and familial adenomatous polyposis (FAP) (n = 3) between 2011 and 2019. Univariate and multivariate analyses were performed to identify the risk factors of SRO. RESULTS: The incidence of SRO was 7.7% (n = 12), and it was significantly lower (P < 0.01) in patients with lower anterior resection or intersphincteric resection (4.3%) than in those with ileal-pouch anal anastomosis (IPAA) (35.2%). The multivariate analysis revealed that IPAA was independently associated with the development of SRO (P = 0.001; odds ratio, 9.4; 95% confidence interval, 2.5-35.4). Eleven of 12 patients (92%) with SRO required trans-stomal tube decompression, and 8 of those (67%) underwent early stoma closure. CONCLUSION: IPAA was an independent risk factor of SRO in laparoscopic colorectal surgery with DI creation. Early stoma closure was needed in most cases of SRO.

Intussusception secondary to descending colon lipoma presenting with simultaneous acute appendicitis.

We report a patient with a descending colon lipoma presenting with hematochezia who developed intussusception, which was simultaneously accompanied by acute appendicitis. A 43-year-old man presented with hematochezia. Colonoscopy revealed a submucosal tumor with a reddish surface in the descending colon. A solid mass with fat density value measuring 5 cm in diameter was observed in the descending colon on CT. While awaiting elective resection, the patient developed lower abdominal pain. CT demonstrated antegrade colo-colonic intussusception in the descending colon. Simultaneously, the appendix was inflamed with a high density intraluminal lesion suspected to be a fecalith. The diagnosis of simultaneous intussusception and acute appendicitis was made. Appendectomy and partial resection of the descending colon was performed. Histopathological examination was consistent with descending colon lipoma and acute appendicitis. The mechanism for developing hematochezia and the risk for development of colo-colonic intussusception due to large colon lipoma and acute appendicitis were highlighted.

Evaluation of lasting high levels of CRP among the patients with metabolic syndrome.

"Low-grade" systemic inflammation is common findings in patients with metabolic syndrome (MetS). When we assessed 256 MetS patients, we found eight patients who presented high levels of C-reactive protein (CRP) which are between 40 and 15 mg/L for more than 3 years. They have not satisfied any criteria of inflammatory diseases such as rheumatoid arthritis and the area of visceral fat estimated by computed tomography was more than 200 cm(2). All the other MetS patients of visceral fat over 200 cm(2) presented low levels of CRP which are less than 10 mg/L. Insulin resistance and ultrasound study of carotid plaques showed no differences between high and low levels of CRP patients. There are a series of MetS patients who show high levels of CRP without clinical symptoms of inflammatory diseases. High levels of CRP merely cannot be explained by visceral fat area, insulin resistance, or carotid plaques.