Regulators of G-protein signaling (RGS) proteins are GTPaseactivating proteins (GAPs) that bind to G␣ subunits and attenuate G protein signaling, but where these events occur in the cell is not yet established. Here we investigated, by immunofluorescence labeling and deconvolution analysis, the site at which endogenous G␣-interacting protein (GAIP) (RGS19) binds to G␣i3-YFP and its fate after activation of ␦-opioid receptor (DOR). In the absence of agonist, GAIP is spatially segregated from G␣i3 and DOR in clathrin-coated domains (CCPs) of the cell membrane (PM), whereas G␣i3-YPF and DOR are located in non-clathrin-coated microdomains of the PM. Upon addition of agonist, G␣i3 partially colocalizes with GAIP in CCPs at the PM. When endocytosis is blocked by expression of a dynamin mutant [dyn(K44A)], there is a striking overlap in the distribution of DOR and G␣i3-YFP with GAIP in CCPs. Moreover, G␣i3-YFP and GAIP form a coprecipitable complex. Our results support a model whereby, after agonist addition, DOR and G␣i3 move together into CCPs where G␣i3 and GAIP meet and turn off G protein signaling. Subsequently, G␣i3 returns to non-clathrin-coated microdomains of the PM, GAIP remains stably associated with CCPs, and DOR is internalized via clathrin-coated vesicles. This constitutes a novel mechanism for regulation of G␣ signaling through spatial segregation of a GAP in clathrin-coated pits.

The addition of self-administered nitrous oxide offered significant benefits in the area of patient discomfort during flexible sigmoidoscopy. The availability of this agent is useful in clinical practice and may enhance compliance with a screening programme.

Background: Current guidelines suggest that patients should undergo colonoscopy after CT confirmed acute diverticulitis to outrule colorectal cancer (CRC). The aim of this study was to determine if flexible sigmoidoscopy (FS) could be a viable alternative to full colonoscopy following acute sigmoid diverticulitis.Methods: A retrospective study of 271 patients was performed who were diagnosed with acute sigmoid diverticulitis by CT and subsequently underwent full colonoscopy. Medical records, CT reports, endoscopy reports, and histopathological reports were reviewed.Results: Sigmoid diverticulosis was confirmed on colonoscopy in all patients. No colorectal malignancies were detected. Adenomatous polyps were found in 16 (5.9%) patients, of which three had polyps detected beyond the sigmoid colon. The overall proportion of abnormalities found beyond the sigmoid colon was 1.1% (n=3). Conclusion:The detection of CRC cancer in patients undergoing full colonoscopy following an episode of acute sigmoid diverticulitis is rare. Despite this, current guidelines still advocate for endoscopy due to the potentially serious consequences of a missed malignancy. However, given that the area of concern in these cases is the sigmoid colon, FS may be a feasible means of outruling malignancy in the absence of red flag features that would necessitate a full colonoscopy. Our results support this approach, with no CRC detected and a polyp detection rate equivalent to that of the general population. This offers numerous advantages to a full colonoscopy for the patient and health service by being a quicker, cheaper, safer procedure without the need for full bowel preparation or IV sedation.

No abstract

Pilonidal sinus disease (PSD) is a chronic inflammatory condition of the skin and subcutaneous tissue that typically arises from hair follicles in the natal cleft of the sacrococcygeal region [1]. The aetiology is debated but theorised to be a result of either the obstruction and subsequent inflammation of hair follicles, or acquired from hair penetrating through the skin into subcutaneous tissue [1,2]. This results in infection, abscess formation, chronic discharge and pain [2]. It is a common problem affecting 26/100,000 of the general population, with an incidence of 1.1% in young adult males [1,3]. It is a troublesome disease for patients, with negative impact on quality of life, mood, employment and self-image [4]. It also results in a significant burden for the healthcare service, with high rates of recurrence and readmission following surgery [5].