The classic concept that GPCRs function as monomers has been challenged by the emerging evidence of GPCR dimerization and oligomerization. Rhodopsin (Rh) is the only GPCR whose native oligomeric arrangement was revealed by atomic force microscopy demonstrating that Rh exists as a dimer. However, the role of Rh dimerization in retinal physiology is currently unknown. In this study, we identified econazole and sulconazole, two small molecules that disrupt Rh dimer contacts, by implementing a cell‐based high‐throughput screening assay. Racemic mixtures of identified lead compounds were separated and tested for their stereospecific binding to Rh using UV‐visible spectroscopy and intrinsic fluorescence of tryptophan (Trp) 265 after illumination. By following the changes in UV‐visible spectra and Trp265 fluorescence in vitro, we found that binding of R‐econazole modulates the formation of Meta III and quenches the intrinsic fluorescence of Trp265. In addition, electrophysiological ex vivo recording revealed that R‐econazole slows photoresponse kinetics, whereas S‐econazole decreased the sensitivity of rods without effecting the kinetics. Thus, this study contributes new methodology to identify compounds that disrupt the dimerization of GPCRs in general and validates the first active compounds that disrupt the Rh dimer specifically.—Getter, T., Gulati, S., Zimmerman, R., Chen, Y., Vinberg, F., Palczewski, K. Stereospecific modulation of dimeric rhodopsin. FASEB J. 33, 9526–9539 (2019). http://www.fasebj.org

Cancellations or delays in surgical care for pediatric patients that present to the operating room create a great obstacle for both the physician and the patient. Perioperative outpatient management begins prior to the patient entering the hospital for the day of surgery, and many organizations practice using the perioperative surgical home (PSH), incorporating enhanced recovery concepts. This paper describes changes in standard operating procedures caused by the COVID-19 pandemic, and proposes the expansion of PSH, as a means of improving perioperative quality of care in pediatric populations.

Background: Hip reconstruction in patients with cerebral palsy (CP) is associated with. significant postoperative pain. However, adequate analgesia can be difficult to achieve. in this population due to spasticity, communication barriers, and postoperative. spasticity. Recently, multimodal pain management techniques such as epidurals and. regional nerve blocks have been described for postoperative pain control, but it is unclear if 1 technique is more beneficial. The purpose of this study was to compare the outcomes of different perioperative pain management techniques. Methods: This study is a retrospective review of a consecutive series of children with CP over a 5-year period at a single pediatric tertiary-care hospital who underwent hip reconstruction (proximal femoral osteotomy with or without a pelvic osteotomy). Patients were subdivided based on their anesthetic protocol into the following groups: general anesthesia alone (G), general anesthesia with an epidural (E), and general anesthesia with lumbar plexus block (LPB). Our primary outcome was cumulative postoperative narcotic consumption (converted to morphine equivalents). Secondary outcomes included length of stay (LOS), average postoperative heart rate, and pain scores. analysis of variance testing was utilized to compare differences between the groups. Results: Fifty-four patients who underwent hip reconstruction were included: 19 in the G group, 18 in the E group, and 17 in the LPB group. LOS was significantly higher in the E group compared with the G and LPB groups: F(2,51)=3.58, P=0.04. The average pain score was significantly lower in the LPB group compared with the others: F(2,51)=4.26, P=0.02. The average postoperative heart rate was significantly lower in the LPB group: F(2,51)=7.08, P<0.01. Postoperative narcotic consumption was significantly lower in the LPB group: F(2,51)=11.57, P<0.01. Conclusion: The LPB patients required the least amount of narcotics compared with the other groups. This, combined with a lower perioperative heart rate and shorter LOS would suggest these patients experienced less pain over the time of their in-patient stay. In comparison to general anesthesia alone and epidural anesthesia, lumbar plexus nerve blocks are an effective pathway for postoperative pain control after hip reconstruction in a CP population. Level of Evidence: Level III—Case control or retrospective comparative study.