SUMMARY Beige adipocytes are present in white adipose tissue (WAT) and have thermogenic capacity to orchestrate substantial energy metabolism and counteract obesity. However, adipocyte-derived signals that act on progenitor cells to control beige adipogenesis remain poorly defined. Here, we show that adipose-specific depletion of Raptor, a key component of mTORC1, promoted beige adipogenesis through prostaglandins (PGs) synthesized by cyclooxygenase-2 (COX-2). Moreover, Raptor-deficient mice were resistant to diet-induced obesity and COX-2 downregulation. Mechanistically, mTORC1 suppressed COX-2 by phosphorylation of CREB-regulated transcription coactivator 2 (CRTC2) and subsequent dissociation of CREB to cox-2 promoter in adipocytes. PG treatment stimulated PKA and promoted differentiation of progenitor cells to beige adipocytes in culture. Ultimately, we show that pharmacological inhibition or suppression of COX-2 attenuated mTORC1 inhibition-induced thermogenic gene expression in inguinal WAT in vivo and in vitro. Our study identifies adipocyte-derived PGs as key regulators of white adipocyte browning, which occurs through mTORC1 and CRTC2.

Up to 14% of the population may have an EHC tendon suitable for grafting in reconstructive surgeries, particularly surgeries related to hallux dysfunction. MRI may have a role in the preoperative identification of the EHC.

Objectives: Cervical chylous fistula is an uncommon but potentially severe occurrence associated with neck surgery. Methods for treating this problem have inconsistent efficacy and may result in lengthy hospital stays. Negative pressure wound therapy (NPWT) is a highly effective tool in the management of complex wounds. We report 3 cases where NPWT was successfully used to treat chylous fistulas following neck dissection. Methods: This is a retrospective chart review of 3 patients who developed chylous fistulas after neck dissection and were successfully treated with NPWT. Results: Chylous ouput ceased within 2 to 8 days of proper wound VAC placement. Hospital stays ranged from 6 to 47 days. Patients received altered diets, including TPN for 1 patient with high-flow output and nil-per-os (NPO) or clear liquids for the others. Patients received octreotide throughout their hospitalization. Conclusion: NPWT shows potential as a treatment option for both high-volume and low-volume chylous fistulas following neck dissection.

To determine the role played by the urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) system in choroidal neovascularization (CNV) and whether inhibition of this system can suppress the extent of CNV in an animal model. Methods: Choroidal neovascularization was induced in mice by laser photocoagulation using the slitlamp delivery system. Reverse transcriptase-polymerase chain reaction and immunocytochemical analysis were performed on the retina choroids of these animals to examine the expression of uPAR. For 2 weeks following laser treatment, animals were injected intraperitoneally with a novel peptide inhibitor of the uPA-uPAR system (100 mg/kg twice a day every day, every other day, and once a week). Control laser-treated animals receive an intraperitoneal injection of phosphate-buffered saline every day. Following treatment, animals were perfused with fluoresceinlabeled dextran, eyes were removed, and the areas of new vessels were examined in the retina-choroid whole mounts by fluorescence microscopy and quantitated using image analysis software. Results: In this study, uPAR was found to be upregulated in the choroidal tissues of mice with laserinduced CNV. The uPAR was localized to the endothelial cells of the fibrovascular tissue within the CNV complex. Systemic administration of the peptide inhibitor of the uPA-uPAR system resulted in a significant reduction of CNV (up to 94%). The response was found to be frequency-of-dose dependent. No toxic effects or tissue destruction was noted following the peptide treatment. Conclusions: Our results strongly suggest that upregulation of the uPA-uPAR system is an important step during CNV, and significant inhibition of CNV was seen when cell surface-associated uPA-uPAR activity was prevented with the peptide inhibitor.

Tragal pumping improves the middle ear penetration of ototopical medications via a patent pressure equalization tube.