Predicting post-operative vault and optimal implantable collamer lens size using machine learning based on various ophthalmic device combinations.

BACKGROUND: Implantable Collamer Lens (ICL) surgery has been proven to be a safe, effective, and predictable method for correcting myopia and myopic astigmatism. However, predicting the vault and ideal ICL size remains technically challenging. Despite the growing use of artificial intelligence (AI) in ophthalmology, no AI studies have provided available choices of different instruments and combinations for further vault and size predictions. This study aimed to fill this gap and predict post-operative vault and appropriate ICL size utilizing the comparison of numerous AI algorithms, stacking ensemble learning, and data from various ophthalmic devices and combinations. RESULTS: This retrospective and cross-sectional study included 1941 eyes of 1941 patients from Zhongshan Ophthalmic Center. For both vault prediction and ICL size selection, the combination containing Pentacam, Sirius, and UBM demonstrated the best results in test sets [R2 = 0.499 (95% CI 0.470-0.528), mean absolute error = 130.655 (95% CI 128.949-132.111), accuracy = 0.895 (95% CI 0.883-0.907), AUC = 0.928 (95% CI 0.916-0.941)]. Sulcus-to-sulcus (STS), a parameter from UBM, ranked among the top five significant contributors to both post-operative vault and optimal ICL size prediction, consistently outperforming white-to-white (WTW). Moreover, dual-device combinations or single-device parameters could also effectively predict vault and ideal ICL size, and excellent ICL selection prediction was achievable using only UBM parameters. CONCLUSIONS: Strategies based on multiple machine learning algorithms for different ophthalmic devices and combinations are applicable for vault predicting and ICL sizing, potentially improving the safety of the ICL implantation. Moreover, our findings emphasize the crucial role of UBM in the perioperative period of ICL surgery, as it provides key STS measurements that outperformed WTW measurements in predicting post-operative vault and optimal ICL size, highlighting its potential to enhance ICL implantation safety and accuracy.

Modulation of IrO6 Chemical Environment for Highly Efficient Oxygen Evolution in Acid.

The sluggish kinetics of the oxygen evolution reaction (OER) limits the commercialization of oxygen electrochemistry, which plays a key role in renewable energy technologies such as fuel cells and electrolyzers. Herein, a facile and practical strategy is developed to successfully incorporate Ir single atoms into the lattice of transition metal oxides (TMOs). The chemical environment of Ir and its neighboring lattice oxygen is modulated, and the lattice oxygen provides lone-pair electrons and charge balance to stabilize Ir single atoms, resulting in the enhancement of both OER activity and durability. In particular, Ir0.08 Co2.92 O4 NWs exhibit an excellent mass activity of 1343.1 A g-1 and turnover frequency (TOF) of 0.04 s-1 at overpotentials of 300 mV. And this catalyst also displays significant stability in acid at 10 mA cm-2 over 100 h. Overall water splitting using Pt/C as the hydrogen evolution reaction catalyst and Ir0.08 Co2.92 O4 NWs as the OER catalyst takes only a cell voltage of 1.494 V to achieve 10 mA cm-2 with a perfect stability. This work demonstrates a simple approach to produce highly active and acid-stable transition metal oxides electrocatalysts with trace Ir.

AQP1 suppression by ATF4 triggers trabecular meshwork tissue remodelling in ET-1-induced POAG.

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increased endothelin-1 (ET-1) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out-flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down-regulated in trabecular meshwork (TM) cells upon ET-1 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET-1-induced TM tissue remodelling, which requires the presence of ß-catenin. More importantly, we found that ET-1-induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of AQP1 and negatively regulates AQP1 transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET-1-induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG.

Corneal Epithelial Remodeling Induced by Photorefractive Keratectomy Enhancement After Small-Incision Lenticule Extraction.

Purpose: To assess changes in corneal epithelial thickness (ET) within 9-mm diameter cornea after photorefractive keratectomy (PRK) retreatment after small-incision lenticule extraction (SMILE). Methods: A total of 28 eyes of 19 patients with mean spherical equivalent of -1.30 ± 0.60 D who underwent retreatment after SMILE were included in this retrospective study. ET mapped across a 9-mm diameter area was obtained using wide-field optical coherence tomography (OCT) before and at one, three, and six months after surgery. The ET changes were compared between the different time points and analyzed zones. Results: Before enhancement, the ET were 63.64 ± 6.01 µm and 61.25 ± 4.32 µm in central and paracentral zones, respectively. The ET of central and paracentral zones significantly decreased at one month and subsequently increased until six months. Six months after surgery, significant epithelial thickening occurred in 2- to 9-mm diameter cornea (all P < 0.05), whereas no significant change was observed in central 2-mm diameter cornea (P = 0.460). There was no significant difference in the ET between the central and paracentral zones (P = 1.00). The degree of myopic correction significantly correlated with the average ET in the central (P = 0.046) and paracentral (P = 0.033) zones at six months after PRK enhancement. No significant correlation was detected between the average ET of all zones and the postoperative spherical equivalent at six months after surgery (all P > 0.05). Conclusions: PRK enhancement did not alter the overall trend of corneal epithelial remodeling induced by SMILE. An asymmetric and flatter lenticule-like pattern of epithelial remodeling was observed six months after surgery, which did not affect the refractive outcomes. Translational Relevance: An asymmetric and centrally flattened lenticule-like pattern of epithelial remodeling was observed after PRK enhancement. Surgeons should consider expanding the intended optical zones for enhancement surgery after SMILE.

Liraglutide, a glucagon-like peptide-1 receptor agonist, inhibits bone loss in an animal model of osteoporosis with or without diabetes.

Introduction: Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes. Methods: Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. Results: Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies. Discussion: Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.

Improved detection of botulinum neurotoxin serotype A by Endopep-MS through peptide substrate modification.

Botulinum neurotoxins (BoNTs) are a family of seven toxin serotypes that are the most toxic substances known to humans. Intoxication with BoNT causes flaccid paralysis and can lead to death if untreated with serotype-specific antibodies. Supportive care, including ventilation, may be necessary. Rapid and sensitive detection of BoNT is necessary for timely clinical confirmation of clinical botulism. Previously, our laboratory developed a fast and sensitive mass spectrometry (MS) method termed the Endopep-MS assay. The BoNT serotypes are rapidly detected and differentiated by extracting the toxin with serotype-specific antibodies and detecting the unique and serotype-specific cleavage products of peptide substrates that mimic the sequence of the BoNT native targets. To further improve the sensitivity of the Endopep-MS assay, we report here the optimization of the substrate peptide for the detection of BoNT/A. Modifications on the terminal groups of the original peptide substrate with acetylation and amidation significantly improved the detection of BoNT/A cleavage products. The replacement of some internal amino acid residues with single or multiple substitutions led to further improvement. An optimized peptide increased assay sensitivity 5-fold with toxin spiked into buffer solution or different biological matrices.

Vault Height Is a Key Predictive Factor for Anterior Segment Measurement Error by IOLMaster 700 in Eyes With Phakic Intraocular Lens.

Purpose: To identify risk factors of ocular anterior segment measurement error by the IOLMaster 700 in eyes implanted with an implantable Collamer lens (ICL). Methods: In total, 152 patients with clear lens (152 eyes, group 1) and another 32 cataract patients (57 eyes, group 2) who underwent ICL implantation were included, and the presence of measurement error by the IOLMaster 700 was determined based on B-scan images. The risk factors for measurement error were evaluated by logistic regression, and the optimal threshold was determined using receiver operating characteristic analysis. Results: The ICL was misidentified as the anterior surface of the crystalline lens in 51.97% of eyes (79/152) in group 1 and 80.70% of eyes (46/57) in group 2. For every 100-µm decrease in the vault height, a 3.57- and 5.78-fold increase in the risk of measurement error was observed in group 1 and group 2, respectively. We identified an optimal threshold of the vault height at 389.47 µm for predicting biometric measurement error in eyes implanted with ICL, which showed an area under the curve of 0.93 (95% confidence interval, 0.90-0.97), a sensitivity of 0.87, and a specificity of 0.86. Conclusions: Patients with ICL implantation, particularly those with a vault height less than 389.47 µm, are at a greater risk of anterior segment biometric measurement error by the IOLMaster 700. Translational Relevance: The threshold of vault height can help to identify high-risk patients and further optimize biometric measurement.

Ocular features in myopic eyes with longer horizontal ciliary sulcus diameters for intended implantable collamer lens surgery.

PURPOSE: To assess the ocular anterior segment characteristics in myopic eyes intended for ICL surgery with horizontal ciliary sulcus-to-sulcus (STS) diameters being greater than vertical STS diameters. METHODS: This retrospective, comparative case study included 1230 eyes of patients who underwent ICL implantation for the treatment of myopia or myopic astigmatism at the Zhongshan Ophthalmic Center from September 2020 to November 2021. The myopic eyes were divided into two groups according to the relatively long diameter of the ciliary sulcus. General parameters and anterior chamber parameters were compared between the two groups. RESULTS: 1230 eyes of 694 patients were included. The proportion of myopic eyes with longer horizontal STS diameters was 4.63%. Horizontal STS distances exceeding vertical meridians in these eyes were mainly attributed to the shortening of vertical STS distances (horizontal STS: P = 0.112; vertical STS: P < 0.001). Eyes with longer horizontal meridians of the ciliary sulcus displayed larger steep keratometry value (P = 0.001), larger corneal volume (P = 0.002), larger corneal astigmatism (P < 0.001), larger ocular residual astigmatism (P = 0.017), worse visual acuity (logMAR UDVA: P = 0.021; logMAR CDVA: P = 0.001), and more iridociliary cysts (P = 0.017) compared to eyes with vertically oval shapes. CONCLUSION: Myopic eyes with longer horizontal STS diameters are commonly accompanied by a change in corneal morphology and more iridociliary cysts. The anatomical features of the ciliary sulcus should be given sufficient consideration to ICL size and placement selection, contributing to more personalized and precise surgery.

Comparing Mycobacterium tuberculosis RNA Accuracy in Various Respiratory Specimens for the Rapid Diagnosis of Pulmonary Tuberculosis.

Objective: To evaluate the rapid diagnostic accuracy of Mycobacterium tuberculosis RNA (TB-RNA) for pulmonary tuberculosis (PTB) in a large patient sample and to evaluate the difference in TB-RNA diagnostic accuracy in various respiratory specimens. Methods: Patient medical records were retrospectively reviewed to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of the acid-fast bacillus (AFB) smear and TB-RNA to evaluate their diagnostic accuracy against final clinical diagnosis. Results: Of the 2336 patients ultimately included, 1123 provided 1 sputum specimen each and 1213 provided 1 bronchoalveolar lavage fluid (BALF) specimen each. The overall sensitivity, specificity, PPV, NPV, and AUC of the AFB smear were 36.2%, 86.4%, 90.6%, 27.3%, and 0.61, respectively. The overall sensitivity, specificity, PPV, NPV, and AUC of TB-RNA for the rapid detection of PTB were 57.4%, 99.4%, 99.7%, 39.3%, and 0.78, respectively. When sputum and BALF specimens were used for AFB smear testing, the sensitivity, specificity, PPV, NPV, and AUC of the AFB smear were 44.5%, 81.5%, 87.5%, 33.5%, and 0.63; and 29.2%, 92.7%, 94.8%, 22.5%, and 0.61, respectively. The sensitivity, specificity, PPV, NPV, and AUC of TB-RNA for the rapid detection of PTB using sputum were 49.6%, 99.3%, 99.5%, 40.4%, and 0.74, respectively; whereas those of TB-RNA determined using BALF were 63.9%, 99.5%, 99.8%, 38.0%, and 0.82, respectively. Conclusion: The diagnostic accuracy of TB-RNA for PTB was moderate and considerably better than that of the AFB smear. The diagnostic accuracy of TB-RNA for various respiratory specimens differed; the diagnostic accuracy of TB-RNA for BALF specimens was substantially better than that for sputum samples, and BALF specimens were more suitable for TB-RNA.

Prospective, Randomized, Contralateral Eye Comparison of Functional Optical Zone, and Visual Quality After SMILE and FS-LASIK for High Myopia.

PURPOSE: To compare the functional optical zone (FOZ) and visual quality after small-incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) in correcting high myopia. METHODS: Ninety-two eyes of 46 high myopic patients with the same programmed optical zone (POZ) received SMILE in one eye and FS-LASIK in the contralateral eye. FOZ was calculated using a refractive power method. The decentration, visual outcomes, wavefront aberrations, contrast sensitivity, and quality of vision (QoV) questionnaire were analyzed at 6 months postoperatively. RESULTS: The postoperative visual and refractive outcomes were comparable between SMILE and FS-LASIK. The FOZ for SMILE (5.62 ± 0.31 mm) was larger than for FS-LASIK (5.35 ± 0.28 mm; P < 0.001). Moreover, the total decentration for SMILE (0.29 ± 0.14 mm) was greater than in FS-LASIK (0.22 ± 0.11 mm; P < 0.001). The induced change in spherical aberration was less for SMILE than for FS-LASIK (P < 0.001). There was better contrast sensitivity under the mesopic condition with glare for SMILE than for FS-LASIK (P = 0.024). However, no significant difference was found in QoV scores between the two groups. CONCLUSIONS: SMILE created a larger FOZ and greater decentration than FS-LASIK when the same POZ was designed in high myopia. Objective and subjective visual symptoms were comparable between SMILE and FS-LASIK. TRANSLATIONAL RELEVANCE: The differences in FOZ and decentration between SMILE and FS-LASIK have little effect on vision outcomes. Surgeons should consider the FOZ and decentration in surgical options in high myopia.

Wide Corneal Epithelial Thickness Mapping in Eyes With Topical Antiglaucoma Therapy Using Optical Coherence Tomography.

Purpose: The purpose of this study was to assess the corneal epithelial thickness (CET) of the 9-mm diameter zone in patients treated using topical antiglaucoma medications and to evaluate the factors associated with CET changes. Methods: Seventy-five patients treated using topical antiglaucoma medications and 65 healthy subjects were included in this cross-sectional study. Each patient completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent examinations including the Schirmer I test, tear breakup time (TBUT), and fluorescein staining. CET mapping of the 9-mm diameter zone was performed using RTVue XR. The CET of the different analyzed zones was compared between groups. The relationship between CET and confounding factors was investigated. Results: The patient group had a significantly shorter TBUT, shorter Schirmer I test, and greater fluorescein staining than those of the control group (all P < 0.05). The mean CET of patients with glaucoma was significantly lower than that of controls in the central, paracentral, mid-peripheral, and peripheral zones (all P < 0.001). Age affected the CET in the paracentral, mid-peripheral, and peripheral zones (all P < 0.01). The number of medications affected the CET in the central, paracentral, and mid-peripheral zones (all P < 0.05). The duration of treatment affected the CET in the central and peripheral zones (all P < 0.05). Conclusions: Use of topical IOP-lowering medications leads to epithelial thinning in the 9-mm diameter zone in glaucomatous eyes. Epithelial protection should be considered in older patients and patients treated with multiple medications from the early stages of long-term topical antiglaucoma therapy. Translational Relevance: The 9-mm diameter CET mapping by using widefield optical coherence tomography (OCT) can be a valuable and convenient method to assess the ocular surface damage in patients with topical antiglaucoma therapy.

Evaluation of Wide Corneal Epithelial Remodeling after Small Incision Lenticule Extraction (SMILE) with Wide-Field Optical Coherence Tomography.

Purpose: This study aims to assess the corneal epithelial remodeling within a 9 mm diameter zone induced by small incision lenticule extraction (SMILE) and evaluate its relationship with the refractive outcomes. Methods: A total of 64 eyes of 64 patients were included. Wide-field optical coherence tomography (OCT) was used to measure the epithelial thickness (ET) across a 9 mm diameter area, preoperatively, and after one day, one week, one month, three months, and six months postoperatively. The ET changes were compared among the different time points and analyzed zones. Results: The ET increases from one week to three months and stabilized from three months to six months. Compared to the preoperative values, the mean ET changes at six months in central (2 mm), paracentral (2-5 mm), mid-peripheral (5-7 mm), and peripheral (7-9 mm) zones were 4.37, 4.36, 1.61, and -1.59 µm, respectively. The correlation between the epithelial thickening and the amount of myopia correction was positive in central (P = 0.001) and paracentral zones (P < 0.001) and negative in peripheral zone (P = 0.006). The intended diameter of the optical zone was negatively related to epithelial hyperplasia in the central (P = 0.020) and paracentral zone (P = 0.006), and the correlation was positive in the mid-peripheral zone (P = 0.001). The epithelial thickening of central zone (P = 0.012) and the difference of mean ET between central and paracentral zone (P = 0.020) were negatively related to the spherical equivalent at six months. Conclusion: An asymmetric lenticule-like pattern of epithelial remodeling occurred in 9 mm diameter cornea at six months after myopic SMILE. The epithelial remodeling may affect the refractive outcomes of SMILE.

A comparative and prospective study of corneal biomechanics after SMILE and FS-LASIK performed on the contralateral eyes of high myopia patients.

Background: To compare the corneal biomechanical changes after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) with the same programmed optical zone (POZ) and similar refractive correction in patients with high myopia. Methods: In this prospective comparative study of the contralateral eye, 50 patients with high myopia with the same POZ and similar refractive correction who underwent SMILE in one eye and FS-LASIK in the other eye. Corneal biomechanical parameters and central corneal thickness (CCT) were measured using a Corvis ST II. All the patients were evaluated during follow-up visits beyond one year. Additionally, the corneal volume (CV) of the 10-mm diameter region was measured using a Pentacam. Results: Ambrosio relational thickness to the horizontal profile (ARTh) and stiffness parameter A1 (SP-A1) decreased significantly after SMILE and FS-LASIK, whereas deformation amplitude ratio 2.0 mm (DA ratio 2.0 mm) and integrated radius (IR) increased significantly in both groups. The ARTh and SP-A1 were greater after SMILE than those after FS-LASIK at all the follow-up visits. In addition, there were greater amounts of CCT and CV after SMILE compared with that after FS-LASIK. Moreover, a positive correlation was found between ARTh and SP-A1 and postoperative CCT, while a negative correlation was found between IR and DA ratio 2.0 mm and postoperative CCT. A moderate correlation was observed between SP-A1 and CV after both SMILE and FS-LASIK, whereas there were no relationships between CV and ARTh, IR, or DA ratio 2.0 mm. Conclusions: SMILE had greater CCT, CV, ARTh, and SP-A1 than FS-LASIK in high myopia with the same POZ and similar refractive correction. Our results demonstrated that SMILE had lesser effect on corneal biomechanics than FS-LASIK in high myopia. Keywords: Corneal biomechanics; Corvis ST II; small incision lenticule extraction (SMILE); femtosecond laser-assisted in situ keratomileusis (FS-LASIK); high myopia.

Corneal Stiffness and Modulus of Normal-Tension Glaucoma in Chinese.

PURPOSE: To assess and compare the corneal biomechanics of normal-tension glaucoma (NTG), high-tension glaucoma (HTG), and normal controls based on stiffness and modulus. The correlations among central corneal thickness (CCT), visual field, retinal nerve fiber layer (RNFL) thickness, and corneal biomechanics in glaucoma eyes were also evaluated. DESIGN: A prospective, cross-sectional, comparative study. METHODS: This study included 334 eyes of 108 NTG patients, 113 HTG patients, and 113 control subjects at Zhongshan Ophthalmic Center, Sun Yat-Sen University. Corneal biomechanics were evaluated using a corneal indentation device (CID) and corneal visualization Scheimpflug technology (Corvis ST). Visual field and RNFL thickness were obtained using standard automated perimetry and spectral-domain optical coherence tomography. One-way analyses of variance with Bonferroni post hoc tests and a multivariable linear regression analysis with adjustment were conducted. Correlations among corneal biomechanical parameters, CCT, visual field, and RNFL thickness were analyzed. RESULTS: The corneal stiffness of the NTG patients (71.0 ± 10.9 N/m) was significantly lower than that of the HTG patients (77.3 ± 15.6 N/m; P = .001) and the CCT- and IOP-matched normal controls (75.6 ± 11.0 N/m; P = .023). The patients in the NTG group had lower corneal stiffness than those in the control group (ß = -4.88, 95% CI -9.002, -0.758; P = .020) after adjusting for confounders. Stiffness was positively correlated with CCT in the NTG group (P = .028) but not in the HTG group (P = .509). There was no significant correlation (P > .05) between corneal biomechanics, visual field, or RNFL thickness. CONCLUSIONS: The corneas of NTG patients were softer than those of HTG patients and controls, as assessed by CID, which were associated with thinner CCT. These might suggest different ocular biomechanical properties in NTG and HTG.

Calcium-dependent association of calmodulin with the rubella virus nonstructural protease domain.

The rubella virus (RUBV) nonstructural (NS) protease domain, a Ca(2+)- and Zn(2+)-binding papain-like cysteine protease domain within the nonstructural replicase polyprotein precursor, is responsible for the self-cleavage of the precursor into two mature products, P150 and P90, that compose the replication complex that mediates viral RNA replication; the NS protease resides at the C terminus of P150. Here we report the Ca(2+)-dependent, stoichiometric association of calmodulin (CaM) with the RUBV NS protease. Co-immunoprecipitation and pulldown assays coupled with site-directed mutagenesis demonstrated that both the P150 protein and a 110-residue minidomain within NS protease interacted directly with Ca(2+)/CaM. The specific interaction was mapped to a putative CaM-binding domain. A 32-mer peptide (residues 1152-1183, denoted as RUBpep) containing the putative CaM-binding domain was used to investigate the association of RUBV NS protease with CaM or its N- and C-terminal subdomains. We found that RUBpep bound to Ca(2+)/CaM with a dissociation constant of 100-300 nm. The C-terminal subdomain of CaM preferentially bound to RUBpep with an affinity 12.5-fold stronger than the N-terminal subdomain. Fluorescence, circular dichroism and NMR spectroscopic studies revealed a "wrapping around" mode of interaction between RUBpep and Ca(2+)/CaM with substantially more helical structure in RUBpep and a global structural change in CaM upon complex formation. Using a site-directed mutagenesis approach, we further demonstrated that association of CaM with the CaM-binding domain in the RUBV NS protease was necessary for NS protease activity and infectivity.

Corneal Epithelial Thickness Changes Following SMILE for Myopia With High Astigmatism.

PURPOSE: To evaluate the corneal epithelial thickness (CET) profile changes after small incision lenticule extraction (SMILE) surgery for myopic astigmatism correction of greater than 2.00 diopters (D). METHODS: This prospective observational study included 40 eyes (23 patients) treated with SMILE for myopia with cylinders of -2.25 to -4.50 D. Along with standard ophthalmic examinations, CET maps with a diameter of 9 mm were measured by high-resolution spectral-domain optical coherence tomography preoperatively and postoperatively. Correlations between the degree of residual astigmatism and the difference in CET values between preoperative flat and steep meridians were analyzed. RESULTS: The CET showed significant changes in the central (2 mm), paracentral (2 to 5 mm), midperipheral (5 to 7 mm), and peripheral (7 to 9 mm) zones 6 months after SMILE (P < .001). Among the regions, the CET in the paracentral zones displayed the largest increase (9.75%) with the highest average thickness (57.29 µm). Moreover, symmetrical regional epithelial thickening at the preoperative astigmatism axis was observed in the midperipheral zones. The difference in CET between preoperative flat and steep meridians in the mid-peripheral zones continuously increased from postoperative 1 day to 6 months. This difference was positively correlated with the residual cylinder errors at 6 months postoperatively (r = -0.334, P = .035). CONCLUSIONS: The 9-mm diameter CET in eyes with high astigmatism significantly increased 6 months after SMILE. Additionally, the difference in CET between preoperative flat and steep meridians in midperipheral zones may be related to astigmatic undercorrection in SMILE. [J Refract Surg. 2021;37(4):224-230.].

A Novel Indentation Assessment to Measure Corneal Biomechanical Properties in Glaucoma and Ocular Hypertension.

Purpose: To evaluate the ability of the new in vivo corneal indentation device (CID) to measure corneal biomechanical properties. Methods and Results: In total, 186 eyes from 46 healthy subjects, 107 patients with primary open-angle glaucoma, and 33 patients with ocular hypertension were enrolled in a cross-sectional study. Measurements were performed using corneal visualization Scheimpflug technology (Corvis ST) and the CID. The deformation amplitude (DA), inward applanation time, inward applanation velocity (A1V), outward applanation time (A2T), outward applanation velocity (A2V), highest concavity time, DA ratio, max inverse radius (MIR), integrated radius, and stiffness parameter A1 were included as Corvis ST parameters, and stiffness and modulus were included as CID parameters. Associations between the Corvis ST and CID parameters and correlations between central corneal thickness and corneal biomechanical parameters were analyzed. The stiffness was significantly correlated with all the Corvis ST parameters (P < 0.05). The modulus was significantly correlated with the DA, A1V, A2T, A2V, highest concavity time, and MIR (P < 0.05). The DA, inward applanation time, A1V, A2T, A2V, DA ratio, MIR, integrated radius, and stiffness parameter A1 values and both CID-derived values were significantly correlated with central corneal thickness (P < 0.05). Conclusions: Parameters derived from the CID and Corvis ST demonstrated agreement in the measurement of corneal biomechanical properties. The stiffness and modulus can characterize in vivo corneal biomechanical properties. Translational Relevance: Agreeing with the Corvis ST regarding the assessment of corneal biomechanical properties, the CID can be a novel clinical tool for biomechanical evaluation of the cornea.

Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG.

Primary open angle glaucoma (POAG) is the leading cause of irreversible blindness. Dysfunction of the trabecular meshwork (TM), resulting in decreased outflow of aqueous humor and increased intraocular pressure (IOP), plays an important role in the pathogenesis of POAG. However, the underlying mechanisms still remain unclear. In this study, we demonstrated that the eIF2-α/ATF4/CHOP branch of unfolded protein response (UPR) was activated in human trabecular meshwork cells (HTMCs) upon tert-butyl hydroperoxide (TBHP) exposure. Inhibition of ATF4 ameliorated TBHP-induced apoptosis and inflammatory cytokine production, while ectopic expression of ATF4 increased the expression of endothelial leukocyte adhesion molecule (ELAM)-1 and IL-8 in HTMCs. Furthermore, we found that ATF4 inhibition reduced tunicamycin-induced caspase-3 activation, ROS production, ELAM-1 expression, and HTMCs phagocytosis impairment. By an in vivo study in mice, we showed that overexpression of ATF4 in the TM induced C/EBP homologous protein (CHOP) expression and TM cells apoptosis, contributing to inflammatory cytokine production, and probably IOP elevation. More importantly, upregulation of ATF4 and CHOP, and colocalization of ATF4 with ELAM-1 were found in the TM of POAG patients. These results suggest that ATF4 is a critical mediator of oxidative stress and ER stress-induced TM cell dysfunction and apoptosis in POAG.

Characterization of the Human Cervical Mucous Proteome.

INTRODUCTION: Cervical cancer is among the most common cancers in women worldwide. Discovery of biomarkers for the early detection of cervical cancer would improve current screening practices and reduce the burden of disease. OBJECTIVE: In this study, we report characterization of the human cervical mucous proteome as the first step towards protein biomarker discovery. METHODS: The protein composition was characterized using one- and two-dimensional gel electrophoresis, and liquid chromatography coupled with mass spectrometry. We chose to use this combination of traditional biochemical techniques and proteomics to allow a more comprehensive analysis. RESULTS AND CONCLUSION: A total of 107 unique proteins were identified, with plasma proteins being most abundant. These proteins represented the major functional categories of metabolism, immune response, and cellular transport. Removal of high molecular weight abundant proteins by immunoaffinity purification did not significantly increase the number of protein spots resolved. We also analyzed phosphorylated and glycosylated proteins by fluorescent post-staining procedures. The profiling of cervical mucous proteins and their post-translational modifications can be used to further our understanding of the cervical mucous proteome.

A cysteine-rich metal-binding domain from rubella virus non-structural protein is essential for viral protease activity and virus replication.

The protease domain within the RUBV (rubella virus) NS (non-structural) replicase proteins functions in the self-cleavage of the polyprotein precursor into the two mature proteins which form the replication complex. This domain has previously been shown to require both zinc and calcium ions for optimal activity. In the present study we carried out metal-binding and conformational experiments on a purified cysteine-rich minidomain of the RUBV NS protease containing the putative Zn(2+)-binding ligands. This minidomain bound to Zn(2+) with a stoichiometry of approximately 0.7 and an apparent dissociation constant of <500 nM. Fluorescence quenching and 8-anilinonaphthalene-1-sulfonic acid fluorescence methods revealed that Zn(2+) binding resulted in conformational changes characterized by shielding of hydrophobic regions from the solvent. Mutational analyses using the minidomain identified residues Cys(1175), Cys(1178), Cys(1225) and Cys(1227) were required for the binding of Zn(2+). Corresponding mutational analyses using a RUBV replicon confirmed that these residues were necessary for both proteolytic activity of the NS protease and viability. The present study demonstrates that the CXXC(X)(48)CXC Zn(2+)-binding motif in the RUBV NS protease is critical for maintaining the structural integrity of the protease domain and essential for proteolysis and virus replication.