KLF5/MDM2 Axis Modulates Oxidative Stress and Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells: The Role in Diabetic Cataract.

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then, KLF5 was knocked down in human lens epithelial cells (HLECs) to explore its functional roles and underlying mechanisms. Dual-luciferase reporter assay and chromatin immunoprecipitation analysis were used to detect whether KLF5 could bind the promoter of E3 ubiquitin ligase mouse double minute 2 (MDM2), a key regulator of EMT. Lastly, the regulation of KLF5 in the biological behaviors of HLECs via MDM2 was analyzed. We found a significant increase of KLF5 in the DC lens anterior capsular, diabetic rat lens, and high glucose (HG)-stimulated HLECs. Knockdown of KLF5 inhibited oxidative stress, inflammation, migration, and EMT of HG-stimulated HLECs. KLF5 silencing impeded MDM2 expression and restricted the activation of MARK1/FAK and NF-κB signaling pathways in HLECs under HG condition. Additionally, KLF5 was found to bind the MDM2 promoter and enhance the transcriptional activity of MDM2. The protective effects by silencing KLF5 on HG-cultured HLECs could be offset by MDM2 overexpression. We demonstrated that knockdown of KLF5 alleviated oxidative stress, migration, and EMT of HG-cultured HLECs by regulating MDM2, suggesting a potential therapeutic strategy for DC.

Second Guessing in Perceptual Decision-Making.

Human subjects of both sexes were asked to make a perceptual decision between multiple directions of visual motion. In addition to reporting a primary choice, they also had to report a second guess, indicating which of the remaining options they would rather bet on, assuming that they got their primary choice wrong. The second guess was clearly informed by the amounts of sensory evidence that were provided for the different options. A single computational integration-to-threshold model, based on the assumption that the second guess is determined by the rank ordering of accumulated evidence at or shortly after the time of the decision, was able to explain the distribution of primary choices, associated response times, and the distribution of second guesses. This suggests that the decision-maker has access to how well supported unchosen options are by the sensory evidence.SIGNIFICANCE STATEMENT Perceptual decisions require conversion of sensory evidence into a discrete choice. Computational models based on the accumulation of evidence to a decision threshold can explain the distribution of choices and associated decision times. Subjects are also able to report the level of confidence in their decision. Here we show that, when making decisions between more than two alternatives, the decision-maker can even report a second guess that is clearly informed by the sensory evidence. These second guesses show a distribution that is consistent with subjects having access to how much sensory evidence was accumulated for the unchosen options. The decision-maker therefore has knowledge about the outcome of the decision process that goes beyond just the choice and an associated confidence.

Endoscopic ultrasound-guided pelvic abscess drainage: a report of 2 cases and literature review.

BACKGROUND: Drainage is essential for source control of the infection in a pelvic abscess. The purpose of this study was to report 2 cases of endoscopic ultrasound (EUS)-guided drainage of the pelvic abscess and review the literature of different modalities of EUS-guided drainage of pelvic abscess. CASE PRESENTATION: A 60-year-old male developed a pelvic abscess 1 month after laparoscopic complete tumor resection. An abdominal CT showed a mass shadow (about 7.1 cm × 5.1 cm) in the right pelvic region. Another case was an 85-year-old male who developed a pelvic abscess 3 days after recurrent tumor resection of multiple organs. The CT showed pelvic effusion and gas accumulation (approximately 6.5 cm × 4.2 cm), and the intestinal tube above the small intestinal anastomosis was dilated with effusion. A 19G-A puncture needle was used to puncture the abscess. An 8-mm cylindrical balloon was inserted, followed by a 10 Fr-3 cm double pigtail stent and an 8.5 Fr drainage tube. After EUS-guided drainage of pelvic abscess, the symptoms disappeared without recurrence. CONCLUSIONS: EUS-guided drainage is an effective and safe method for treating pelvic abscesses as long as the drainage modality is appropriately selected based on the etiology, size, and mucus viscosity of the abscess.

Comparison of different corneal residual bed thickness after small incision lenticule extraction (SMILE).

PURPOSE: To evaluate the corneal biological parameters stability between the different corneal residual bed thickness (RBT) after Small Incision Lenticule Extraction (SMILE). METHODS: In this prospective clinical trial, 127 eyes of 64 patients underwent SMILE. According to the corneal RBT, the patients were divided into the 250-270 µm, 270-290 µm and 290-310 µm groups. Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) and Scheimpflug camera (Pentacam; Oculus Optikgeräte GmbH, Wetzlar, Germany) measurements were performed preoperatively, 1 day, 1week, 1month and 3 months after surgery. RESULTS: The keratometer values among the three groups were no significant differences in postoperative periods (each P > 0.05), except the corneal thickness values (each P < 0.05). In the 250-270 µm and 270-290 µm groups, the keratometer and corneal thickness values were decreased at postoperative 1 week and increased at 1 and 3 months. The 290-310 µm group significantly higher posterior maximum elevation (PME) than the 250-270 µm group at 1 and 3 months (P = 0.022, 0.022, respectively), and higher preoperative thinnest point (PTE) at 1 week and 1 month (P = 0.013, 0.035, respectively). The PME of the 290-310 µm group was higher than the 270-290 µm group at 3 months (P = 0.045), and higher PTE at 1 week and 3 months (P = 0.022, 0.02, respectively). In all three groups, the maximal deformation amplitude (DA) was significantly higher at 1 and 3 months compared to postoperative 1 day and 1 week, and the IOP was decreased at 1 month then recovered at 3 months (each P < 0.05).The DA of the 250-270 µm group was significantly higher than the 290-310 µm group at postoperative 1 week, 1 and 3 months (P = 0.001, 0.01, 0.02, respectively). The change of the posterior corneal elevation and biomechanical parameters values were no significant differences among the three groups in postoperative periods (each P > 0.05). CONCLUSIONS: The range of 250-310 µm RBT was safe and stable at the early postoperative of SMILE. The RBT may be positively correlated with the posterior corneal elevation.

Snowboard Landings from Different Heights: Electroencephalography Activity in Motor Preparation and Lower Limb Electromyography Changes.

The neural strategies for movements of the lower extremities for landings from different landing heights in trained half-pipe snowboarders are not well known. We observed changes in brain activity as measured by electroencephalography (EEG) and lower limb muscle activity as measured by electromyography (EMG) in trained and untrained half-pipe snowboarders landing from different heights (30 and 60 cm). There were 12 trained male half-pipe snowboarders (HS) and 12 untrained participants (UP). We recorded EEG signals during motor preparation prior to dropping and EMG signals from right lateral rectus femoris (RF), tibialis anterior (TA), and gastrocnemius lateralis (GL) muscles during landings. Generally, theta power in the frontal cortex significantly increased in the preparation period compared to the resting state, while the alpha 1 and alpha 2 power values in central and parietal cortical areas decreased as dropping heights increased. Additionally, the HS group displayed greater magnitudes of change in power values in three frequency bands compared to the UP group. The HS group (relative to UP group) also showed higher normalized EMG amplitudes for RF and GL during contact, especially at 60 cm. The HS group (relative to the UP group) presented lower antagonist EMG activity and a higher GL/TA ratio at the 60 cm dropping height. Long-term specialized training might lead to greater neural modulation of predictive sensorimotor control and specific neuromuscular activation patterns during landing.

Comparison of corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus.

AIM: To evaluate the differences in corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus. METHODS: In our prospective clinical trial, 40 patients (60 eyes) with progressive keratoconus were randomized to undergo corneal cross-linking with transepithelial (TE group, n=30) or epithelium-off (EO group, n=30) keratoconus. Examinations comprised topography, corneal biomechanical analysis and specular microscopy at 6mo postoperatively. RESULTS: The keratometer values were not significantly different between the TE and EO corneal cross-linked groups in different periods (each P>0.05). The corneal thickness of the EO group was greater than that of the TE group at 1wk after the operation (each P<0.05). Regarding corneal biomechanical responses, the EO group showed a longer second applanation length than TE group (P=0.003). Regarding the corneal endothelial function, standard deviation of the endothelial cell size, and coefficient of variation in the cell area, the values of EO group were larger than those of TE group at 1wk (P=0.011, 0.026), and the percentage of hexagonal cells in EO group was lower than that in TE group at 1 and 6mo (P=0.018, 0.019). CONCLUSION: Epithelium-off corneal cross-linking may strengthen corneal biomechanics better than TE procedure can. However, the TE procedure with a lower ultraviolet-A irradiation intensity would be safer for corneal endothelial function.

Evaluation of the Safety and Long-term Scleral Biomechanical Stability of UVA Cross-linking on Scleral Collagen in Rhesus Monkeys.

PURPOSE: To investigate the changes of retinal and choroidal parameters, scleral biomechanical strength, and ocular histopathology after scleral ultraviolet-A (UVA) cross-linking (CXL) in rhesus monkeys eyes, and to evaluate the safety and long-term biomechanical stability of scleral CXL for preventing myopia from progressing further in clinic. METHODS: Six 3-year-old male rhesus monkeys (12 eyes) were randomized to receive UVA-CXL procedures applied on the superotemporal equatorial sclera. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were used for examination before and 1 week and 1, 3, 6, and 12 months after CXL. The stress-strain behaviors of equatorial scleral strips were analyzed 12 months postoperatively by a biomaterial tester. Hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were performed 12 months postoperatively. RESULTS: For central retinal thickness, choroidal thickness, and flow density of central retinal superficial vascular networks, no statistical difference was noted between CXL eyes and control eyes at 12 months postoperatively (P > .05). The biomechanical stability of sclera was increased. The scleral stress and Young modulus at 8% strain corresponded to 184% and 183%, respectively, of the control values at 12 months (each P < .001). No retinal damage was detected on histology in scleral CXL eyes. There was no obvious difference between scleral CXL eyes and control eyes by hematoxylin-eosin and TUNEL staining (P > .05). CONCLUSIONS: Scleral CXL with riboflavin/UVA in rhesus monkey eyes could strengthen the biomechanical properties of scleral tissues and maintain the stability for 12 months postoperatively. The UVA-CXL on the sclera of rhesus monkey eyes seems to be effective and safe. [J Refract Surg. 2020;36(10):696-702.].

Effect of corneal stromal pocket irrigation in small-incision lenticule extraction.

OBJECTIVES: To investigate the effect of corneal stromal pocket irrigation after small-incision lenticule extraction (SMILE) on visual acuity, intraocular pressure (IOP), corneal parameters and complications after surgery. METHODS: A total of 242 eyes of 121 patients undergoing SMILE were enrolled in this prospective controlled study, and it was designed for one eye to randomly undergo SMILE with balanced salt solution irrigation of the corneal stromal pocket, while the other eye was not. The uncorrected distance visual acuity (UDVA) and slit lamp examination were recorded at 1 hour, 1 day, 1 week, and 1 month. Postoperative corneal density, corneal biomechanical, corneal endothelial cell number, and anterior OCT images were compared at 1 day, 1 week, and 1 month. RESULTS: Compared with the nonirrigation group, the irrigation group showed significantly higher UDVA at 1 day postoperatively (P < 0.05), but there was no significant difference during the rest of the postoperative period (1 hour, 1 week, and 1 month). In addition, no significant differences were found in IOP, corneal density, corneal biomechanics, corneal endothelial cells, and corneal morphology. No visual decline or severe postoperative complications were found in the patients in this study. CONCLUSIONS: Interlamellar irrigation did not affect IOP, corneal parameters, morphology, complications, or UDVA at 1 hour, 1 week, and 1 month after the operation, but it may promote UDVA 1 day after the operation.

Study of retina and choroid biological parameters of rhesus monkeys eyes on scleral collagen cross-linking by riboflavin and ultraviolet A.

To evaluate ocular fundus biological changes after scleral collagen cross-linking (CXL) with riboflavin/ ultraviolet A (UVA) on rhesus monkeys in vivo by analyzing retina and choroid biological parameters. Six 3-year-old male rhesus monkeys (12 eyes) were observed in this study, with scleral CXL procedures applied on superior temporal equatorial sclera on random eyes of all rhesus. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) examination were performed before and 1 week, 1 month, 3 months and 6 months after CXL. The thickness of retina and choroid and the flow density of retinal superficial vascular networks were analyzed respectively in different regions after CXL. As for retina thickness and flow density of retinal superficial vascular networks, no statistical difference was noted between CXL eyes and control eyes at 1 day, 1week, 1 month, 3 months and 6 months (P>0.05). Among choroid parameters, the choroidal thickness in 1500µm temporal to the fovea center of CXL eyes revealed a significant reduction in 1 week postoperatively (P<0.05), but it subsequently increased from 1 month postoperatively, and no statistical difference was found between two groups in the following periods (P>0.05). The choroidal thickness nearby crosslinked region may change temporarily following scleral CXL, and it might recover gradually after 1 month postoperatively. The vascular flow density and thickness of retina were not affected by scleral CXL. Further study should be performed to evaluate the potential adverse effects at the direct vicinity of the application site and the long-term effect of scleral CXL in clinical application.

Perceptual Decisions in the Presence of Relevant and Irrelevant Sensory Evidence.

Perceptual decisions in the presence of decision-irrelevant sensory information require a selection of decision-relevant sensory evidence. To characterize the mechanism that is responsible for separating decision-relevant from irrelevant sensory information we asked human subjects to make judgments about one of two simultaneously present motion components in a random dot stimulus. Subjects were able to ignore the decision-irrelevant component to a large degree, but their decisions were still influenced by the irrelevant sensory information. Computational modeling revealed that this influence was not simply the consequence of subjects forgetting at times which stimulus component they had been instructed to base their decision on. Instead, residual irrelevant information always seems to be leaking through, and the decision process is captured by a net sensory evidence signal being accumulated to a decision threshold. This net sensory evidence is a linear combination of decision-relevant and irrelevant sensory information. The selection process is therefore well-described by a strong linear gain modulation, which, in our experiment, resulted in the relevant sensory evidence having at least 10 times more impact on the decision than the irrelevant evidence.