Cotranslational formation of disulfides guides folding of the SARS CoV-2 receptor binding domain

Many secreted proteins contain multiple disulfide bonds. How disulfide formation is coupled to protein folding in the cell remains poorly understood at the molecular level. Here, we combine experiment and simulation to address this question as it pertains to the SARS-CoV-2 receptor binding domain (RBD). We show that, whereas RBD can refold reversibly when its disulfides are intact, their disruption causes misfolding into a nonnative molten-globule state that is highly prone to aggregation and disulfide scrambling. Thus, non-equilibrium mechanisms are needed to ensure disulfides form prior to folding in vivo. Our simulations suggest that co-translational folding may accomplish this, as native disulfide pairs are predicted to form with high probability at intermediate lengths, ultimately committing the RBD to its metastable native state and circumventing nonnative intermediates. This detailed molecular picture of the RBD folding landscape may shed light on SARS-CoV-2 pathology and molecular constraints governing SARS-CoV-2 evolution.

Comparision of Hyperreflective Foci after Treatment of Diabetic Macular Edema Patients between Intravitreal Injections

PURPOSE: To compare the outcomes in patients with diabetic macular edema (DME) treated with intravitreal dexamethasone implants and intravitreal bevacizumab injections.METHODS: A retrospective cohort study was designed using 66 patients with DME treated with intravitreal dexamethasone (n = 35; 35 eyes) and intravitreal bevacizumab (n = 31; 31 eyes). Post-treatment changes in hyperreflective foci in the inner and outer retina were characterized using optical coherence tomography, central macular thickness, outer limiting membrane, and photoreceptor inner segment-outer segment junctions. Visual acuities were analyzed 4 weeks after bevacizumab injections and 8 weeks after dexamethasone injections.RESULTS: Both groups showed a decrease in the number of hyperreflective foci after treatment: from 10.6 ± 11.8 to 6.3 ± 5.9 (p = 0.005) in the intravitreal dexamethasone implant group and from 11.6 ± 8.5 to 7.7 ± 6.7 (p < 0.001) in the intravitreal bevacizumab injection group. The mean central macular thickness in the dexamethasone group changed significantly from 586.8 µm to 297.7 µm after treatment and the visual acuity improved significantly from 0.33 logMAR to 0.38 logMAR after treatment (p < 0.001 and p = 0.018, respectively). The mean central macular thickness in the bevacizumab group showed a significant decrease from 467.1 µm to 353.2 µm after treatment (p < 0.001), but there was no significant change in the visual acuities: 0.34 logMAR to 0.32 logMAR after treatment (p = 0.464).CONCLUSIONS: Both intravitreal dexamethasone implants and bevacizumab treatments in patients with DME showed improved outcomes including a decrease in hyperreflective foci shown by optical coherence tomography.

Multi-DOF (Degree of Freedom) Articulating Laparoscopic Instrument is an Effective Device in Performing Challenging Sutures

PURPOSE: Although laparoscopic surgery had been performed in clinical practice for over 30 years, there has not been much improvement on instruments. Several articulating laparoscopic instruments have been developed including the robotic system. A new multi-degree of freedom (DOF) articulating laparoscopic device has been developed. We compared the ability to perform challenging sutures between the new device and the robotic system.METHODS: Five experienced surgeons with over 100 laparoscopic surgery cases performed the suture task with both instruments. Everyone was new at articulating instruments including a robotic system. The suturing task consisted of two vertical sutures, downward and upward vertical direction. The duration of needle grabbing, first surgical tie, square tie, and the final reverse tie was measured.RESULTS: When doing the downward suture, the median time to complete the suture was 127 vs. 136 seconds for ArtiSential® and the robot, respectively (p=0.754). Other measurements such as needle grabbing, first tie, second tie and final knot did not show any significant difference between the two instruments. Upward suture also did not show a significant difference. The total completion time was 127 vs. 112 seconds for for ArtiSential® and the robot, respectively (p=0.675). Time taken in each interval did not show any significant difference.CONCLUSION: Both instruments performed the suturing tasks with no difference in duration. ArtiSential® can be mixed up with usual instruments. Surgeons can choose any device, but when articulation is needed, ArtiSential® could be an alternative choice to the robotic system.

Result of Central Vault Depending on Lens Diameters in Patients with Implantable Collamer Lens Implantation

PURPOSE@#To compare vaulting height and clinical results in patients who underwent anterior chamber phakic intraocular lens implantation with different lens diameters.@*METHODS@#Thirty-five eyes (19 patients) who underwent anterior chamber phakic intraocular lens (V4C or V5) implantation were divided into two groups according to lens diameters, which were based on the patient C or V5) implantation were dividdiameters. Group 1 was implanted with a 12.6 mm diameter lens (WTW, 11.3–11.7 mm; 22 eyes) and group 2 was implanted with a 13.2 mm diameter lens (WTW, 11.8–12.2 mm; 13 eyes). Changes in the central vault over time, refractive error, visual acuity, endothelial cell count, and complications were evaluated as clinical outcomes.@*RESULTS@#The post operative mean central vaulting heights at 1, 3, and 6 months Group 2 showed significantly higher vaulting at each visit (all, p 0.05).@*CONCLUSIONS@#The results of optimal vaulting shows the lens diameter should be adjusted according to the surgeon's experience or nomogram when the horizontal corneal WTW diameter was used to determine lens diameter. Especially in cases using a V4C or V5 model anterior chamber phakic intraocular lens, 13.2 mm in diameter (V5) shows higher central vaulting than 12.6 mm in diameter (V4C).