The role of kinetic context in apparent biased agonism at GPCRs

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism

CT mimics of peritoneal carcinomatosis

Peritoneal carcinomatosis is a term used to describe widespread metastases of cancerous tumors in the peritoneal cavity. It is most common in carcinomas of the gastrointestinal tract (GIT) and ovaries, and must be considered to be the main diagnosis even when the primary is not known. A wide variety of disease processes mimic peritoneal carcinomatosis. Precise diagnosis based on imaging alone is often difficult and very often the final diagnosis is only obtained after appropriate histopathology or microbiology

Case Report-Inguinoscrotal ureteral hernia diagnosed on micturating cystourethrography

The presence of a ureter within an inguinal hernia is an extremely rare entity, usually discovered incidentally during herniorrhaphy and may pose a surgical risk. Early preoperative diagnosis is crucial to guide proper surgical approach and to preserve renal function

CT features, mimics and atypical presentations of gastrointestinal stromal tumor (GIST)

The term stromal tumor was coined in 1983 by Clark and Mazur for smooth muscle neoplasm of the gastrointestinal tract (GIT). Gastrointestinal stromal tumors (GIST) are nonepithelial tumors arising from the interstitial cells of Cajal, which express KIT protein-CD117 on immunohistochemistry. GIST can arise anywhere in the GIT, including the mesentery, omentum, and retroperitoneum

Case report: Benign porta hepatic schwannoma

Schwannoma is a myelin sheath tumor that can occur almost anywhere in the body. The most common locations are the central nervous system, extremities, neck, mediastinum and retroperitoneum. Benign schwannomas in the porta hepatis are extremely rare and radiologically are diagnosed as either enlarged lymph nodes or bowel masses, such as gastrointestinal stromal tumors. In this location they usually produce symptoms by compressing adjacent structures and often present with obstructive jaundice. The preoperative diagnosis can be extremely difficult

AUTOMATIC SEGMENTATION OF LUMEN INTIMA LAYER IN TRANSVERSE MODE ULTRASOUND IMAGES

We propose an elliptical active disc technique for the segmentation of common carotid artery lumen intima layer from transverse mode ultrasound images. The segmentation and subsequent outlining problem is posed as one of optimization of a local energy function with respect to the five degrees-of-freedom that characterize the elliptical active disc. Gradient descent technique is used to find the minimum of the energy function with respect to the five parameters that describe the disc. In addition, we use Green's theorem to optimize the computation of the partial derivatives. For automatic initialization of the active disc, we use the normalized cross-correlation technique. We report results of experimental validation on SPLab, Brno university database, which contains 971 transverse mode ultrasound images of the carotid artery. We achieve accurate carotid artery lumen intima detection in 97.63% of cases. In addition, for lumen intima layer segmentation we achieve an average Dice index of 94.83%

Automatic Segmentation of Lumen Intima Layer in Transverse Mode Ultrasound Images

We propose an elliptical active disc technique for the segmentation of common carotid artery lumen intima layer from transverse mode ultrasound images. The segmentation and subsequent outlining problem is posed as one of optimization of a local energy function with respect to the five degrees-of-freedom that characterize the elliptical active disc. Gradient descent technique is used to find the minimum of the energy function with respect to the five parameters that describe the disc. In addition, we use Green's theorem to optimize the computation of the partial derivatives. For automatic initialization of the active disc, we use the normalized crosscorrelation technique. We report results of experimental validation on SPLab, Brno university database, which contains 971 transverse mode ultrasound images of the carotid artery. We achieve accurate carotid artery lumen intima detection in 97.63 of cases. In addition, for lumen intima layer segmentation we achieve an average Dice index of 94.83. © 2018 IEEE