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G protein–coupled receptors (GPCRs) are the largest family of cell surface receptors and signal through the proximal effectors, G proteins and β-arrestins, to influence nearly every biological process. The G protein and β-arrestin signaling pathways have largely been considered separable; however, direct interactions between Gα proteins and β-arrestins have been described that appear to be part of a distinct GPCR signaling pathway. Within these complexes, Gαi/o, but not other Gα protein subtypes, directly interacts with β-arrestin, regardless of the canonical Gα protein that is coupled to the GPCR. Here, we report that the endogenous biased chemokine agonists of CXCR3 (CXCL9, CXCL10, and CXCL11), together with two small-molecule biased agonists, differentially formed Gαi:β-arrestin complexes. Formation of the Gαi:β-arrestin complexes did not correlate well with either G protein activation or β-arrestin recruitment. β-arrestin biosensors demonstrated that ligands that promoted Gαi:β-arrestin complex formation generated similar β-arrestin conformations. We also found that Gαi:β-arrestin complexes did not couple to the mitogen-activated protein kinase ERK, as is observed with other receptors such as the V2 vasopressin receptor, but did couple with the clathrin adaptor protein AP-2, which suggests context-dependent signaling by these complexes. These findings reinforce the notion that Gαi:β-arrestin complex formation is a distinct GPCR signaling pathway and enhance our understanding of the spectrum of biased agonism. A complex to complicate chemokine signaling: G protein–coupled receptors (GPCRs) represent about 30% of the targets of FDA-approved drugs. GPCRs signal through two pathways that are considered separable: one dependent on direct activation of heterotrimeric G proteins and the other on the recruitment of β-arrestin proteins. Building on their previous work, Zheng et al. showed that some, but not all, of the endogenous agonists of the chemokine receptor CXCR3 induced the formation of a Gαi:β-arrestin complex, which was independent of the relative extent of activation of either G protein or β-arrestin signaling pathways. Signaling downstream of the Gαi:β-arrestin complex was different from that stimulated by β-arrestin alone. Together, these data add to the evidence of crosstalk between G proteins and β-arrestins and may have implications for the development of GPCR-targeting drugs. [ABSTRACT FROM AUTHOR]

Objective: To examine the Manukau Salivary Symptom Score (MSSS) questionnaire as a validated tool to assess obstructive sialadenitis-specific symptoms to both indicate disease severity and assess the outcome after sialendoscopic procedures. Study Design: A prospective observational study was performed from 2010 to 2019 comprising 164 patients undergoing sialendoscopy for nonneoplastic chronic obstructive salivary gland disease (COSGD). Setting: Department of Otolaryngology–Head and Neck Surgery at the Manukau Surgical Centre, Auckland, New Zealand, between June 2010 and September 2019. Methods: A prospective observational study was performed from 2010 to 2019 comprising 164 patients undergoing sialendoscopy for nonneoplastic COSGD. Patients completed the MSSS preoperatively and at postoperative follow-up. Statistical tests were used to compare pre- and postoperative answers. Cronbach's α was used to measure internal consistency. Finally, construct validity was determined by comparing the 5-question MSSS questionnaire to the preexisting 20-question Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire. Results: Postoperatively, patients had significant improvements in pain, eating, talking, swelling, and quality of life (P <.001). The MSSS questionnaire was found to have high internal consistency (α = 0.938). Questions in the MSSS had a very strong positive correlation with 3 COSS questions, a strong positive correlation with 8, a moderate positive correlation with 4, and a weak positive correlation with 1. Four COSS questions were not considered relevant and were not included in the MSSS questionnaire. Conclusion: The MSSS questionnaire is a simple, validated questionnaire that is useful for assessing the impact of sialendoscopy in patients with COSGD. [ABSTRACT FROM AUTHOR]

Abstracts: Lacertus fibrosus Syndrome (LFS) is a rare cause of persistent medial elbow pain in baseball players, often not considered in the initial diagnostic considerations. This case report details a 19-year-old collegiate baseball player who presented with insidious left anterior medial elbow pain, initially diagnosed as biceps tendonitis. The patient did not experience pain relief after six months of conservative management. Sonopalpation during diagnostic ultrasound localized the source of pain to the median nerve at the level of the lacertus fibrosus, and the decision was made to perform ultrasound-guided hydrodissection of the median nerve at this level. The procedure resulted in rapid and sustained symptom relief without the scarring that has been associated with traditional surgical techniques. To date, there has been no study investigating the use of ultrasound-guided hydrodissection targeting lacertus fibrosus. This report highlights the importance of considering LFS in throwing athletes with persistent elbow pain, and advocates for considering ultrasound-guided hydrodissection as a management option for patients with clinical suspicion of LFS., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)