Efficacy and Safety Analysis of the New Aspheric Hydrophobic Acrylic Monofocal IOL Implantation at Short-Term Follow-Up

Aim. To evaluate the results of implantation of a new hydrophobic acrylic monofocal IOL in an automated preloaded delivery system in the short-term follow-up period.Patients and methods. The prospective study included 89 patients (114 eyes) after bilateral or monolateral Clareon IOL implantation with a mean follow-up of 2.1 ± 0.4 (1–4) months. The age range was 53 to 87 (71.1 ± 5.2) years. A corneal incision of 1.8 mm was used in all cases. For implantation using the AutonoMe® system , the incision was enlarged by 0.2 mm for implantation IOL 26 D and higher. IOL optical power was calculated using the SRK/T formula; retrospective analysis was performed using the Hoffer Q, Haigis, Holladay II, Olsen, Barrett Universal II, and Kane formulas.Results. In all studied periods (1 day, 1 week and 1 month) there was statistically significant (p < 0.05) increase both of NCDVA (from 0.13 ± 0.02 in the preoperative period to 0.81 ± 0.07 in 1 month after surgical intervention), and BCDVA (from 0.32 ± 0.15 before surgery to 0.94 ± 0.11 after surgery). When assessing the percentage of eyes with an BCDVA of 0.9 or higher, a statistically significant (p < 0.05) difference was shown in all studied periods. The lowest MAE was shown for the Barrett Universal II (0.292), SRK/T (0.312) Kane (0.301), and Olsen (0.325) formulas. For the Hoffer Q and Holladay 2 formulas, MAE values were significantly higher (p < 0.05). The highest frequency of achieving the target refraction of ± 0.25 D was shown for the Barrett Universal II and Kane formulas (68 and 69 %, respectively), and the lowest for the Hoffer Q and Holladay 2 formulas (28 and 35 %, respectively). The primary endpoint of the study (BCDVA = 1.0) was achieved in 95.6 % (n = 109), with a deviation in BCVA of ± 0.1 noted in 4 eyes (3.5 %). No glistening was detected in the follow-up period up to 4 months.Conclusion. The paper presents an analysis of the first experience with the implantation of new Clareon monofocal IOLs in Russian Federation. The results of implantation of a new hydrophobic acrylic monofocal IOL in an automated preloaded delivery system showed a good clinical and functional effect, a high frequency of achieving the target result and the absence of significant side effects. The Kane, Barrett Universal II, and SRK/T formulas, using the Verion diagnostic navigation system, are recommended for calculating the optical power of the new IOL.

A deletion containing a CTCF-element in intron 8 of the Bbs7 gene is partially responsible for juvenile obesity in the Berlin Fat Mouse

The Berlin Fat Mouse Inbred (BFMI) line is a model for juvenile obesity. Previous studies on crosses between BFMI and C57Bl/6N (B6N) have identified a recessive defect causing juvenile obesity on chromosome 3 (jObes1). Bbs7 was identified as the most likely candidate gene for the observed effect. Comparative sequence analysis showed a 1578 bp deletion in intron 8 of Bbs7 in BFMI mice. A CTCF-element is located inside this deletion. To investigate the functional effect of this deletion, it was introduced into B6N mice using CRISPR/Cas9. Two mice containing the target deletion were obtained (B6N Bbs7emI8∆1 and Bbs7emI8∆2) and were subsequently mated to BFMI and B6N to generate two families suitable for complementation. Inherited alleles were determined and body composition was measured by quantitative magnetic resonance. Evidence for a partial complementation (13.1–15.1%) of the jObes1 allele by the CRISPR/Cas9 modified B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles was found. Mice carrying the complementation alleles had a 23–27% higher fat-to-lean ratio compared to animals which have a B6N allele (P(Bbs7emI8∆1) = 4.25 × 10–7; P(Bbs7emI8∆2) = 3.17 × 10–5). Consistent with previous findings, the recessive effect of the BFMI allele was also seen for the B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles. However, the effect size of the B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles was smaller than the BFMI allele, and thus showed only a partial complementation. Findings suggest additional variants near Bbs7 in addition to or interacting with the deletion in intron 8.

Neurosteroid modulation of GABAA receptor function by independent action at multiple specific binding sites

: Neurosteroids are endogenous modulators of GABAA receptors that mediate anxiety, pain, mood and arousal. The 3-hydroxyl epimers, allopregnanolone (3α-OH) and epi-allopregnanolone (3β-OH) are both prevalent in mammalian brain and produce opposite effects on GABAA receptor function, acting as positive and negative allosteric modulators respectively. This Perspective provides a model to explain the actions of 3α-OH and 3β-OH neurosteroids. The model is based on evidence that the neurosteroid epimers bind to an overlapping subset of specific sites on GABAA receptors, with their net functional effect on channel gating being the sum of their independent effects at each site.

AgAnt: A computational tool to assess Agonist/Antagonist mode of interaction

Activity modulation of proteins is an essential biochemical process in cell. The interplay of the protein, as receptor, and it's corresponding ligand dictates the functional effect. It is imperative to decipher the receptor-ligand functional effect for understanding native biochemical processes as well as for drug discovery. Experimental activity determination is a time extensive process and computational solution towards prediction of activity specific to the receptor-ligand interaction would be of wide interest. We train machine learning models to differentiate between agonist and antagonist protein-ligand pairs and deploy a pairwise approach to utilize the properties of both the receptor and the ligand.

Single-molecule imaging of IQGAP1 regulating actin filament dynamics

IQGAP is a conserved family of actin-binding proteins with essential roles in cell motility, cytokinesis, and cell adhesion, yet there remains a limited understanding of how IQGAP proteins directly influence actin filament dynamics. To close this gap, we used single-molecule and single-filament TIRF microscopy to observe IQGAP regulating actin dynamics in real time. To our knowledge, this is the first study to do so. Our results demonstrate that full-length human IQGAP1 forms dimers that stably bind to actin filament sides and transiently cap barbed ends. These interactions organize filaments into thin bundles, suppress barbed end growth, and inhibit filament disassembly. Surprisingly, each activity depends on distinct combinations of IQGAP1 domains and/or dimerization, suggesting that different mechanisms underlie each functional effect on actin. These observations have important implications for how IQGAP functions as an actin regulator in vivo, and how it may be regulated in different biological settings. [Media: see text] [Media: see text] [Media: see text]

A case of spontaneous non-penetrating keratoprosthesis during multi-stage implantation of a Fedorov — Zuyev prosthesis in a patient with a severe chemical eye burn

Purpose: to evaluate the results of spontaneous non-penetrating keratoprosthesis with a Fedorov — Zuev prosthesis in a patient with severe chemical burns in both eyes. Material and methods.Patient K., 38, who had sustained a severe burn injury in the past and numerous reconstructive plastic operations on both eyes (amniotic tissue implantation, allolymbal transplantation, layer-by-layer and penetrative keratoplasty, cataract extraction with IOL implantation, total auto-conjunctival corneal plastic surgery) with no functional effect, was subjected to a multi-stage keratoprosthesis of the left eye according to the method practiced by the Helmholtz National Medical Research Center of Eye Diseases. Results.After one of the stages (implantation of the haptic part of the keratoprosthesis with a temporary cylindrical plug), an aseptic necrosis of the tissue above the cylinder occurred. As a result, an unexpected functional effect was revealed: visual acuity of the operated eye 0.02 sph -20.0 D = 0.2. During a dynamic follow-up that lasts 2.5 years, visual acuity remains stable, and the corneallayers behind the cylinder retain transparency. During this time, all stages of keratoprosthesis were performed on the fellow eye with a functional result of 1.0. Conclusion. The long-term result of spontaneous non-penetrating keratoprosthesis indicates the need to study the prospects and develop a method of non-penetrating keratoprosthesis with a Fedorov — Zuyev prosthesis.

Hemolytic, Biocompatible, and Functional Effect of Cellularized Polycaprolactone-Hydrolyzed Collagen Electrospun Membranes for Possible Application as Vascular Implants

In search of bioactive vascular prostheses that exhibit greater biocompatibility through the combination of natural and synthetic polymers, tissue engineering from a biomimetic perspective has proposed the development of three-dimensional structures as therapeutic strategies in the field of cardiovascular medicine. Techniques such as electrospinning allow obtaining of scaffolds that emulate the microarchitecture of the extracellular matrix of native vessels; thus, this study aimed to evaluate the biological influence of microarchitecture on polycaprolactone (PCL) and hydrolyzed collagen (H-Col) electrospun scaffolds, which have a homogeneous (microscale) or heterogeneous (micro-nanoscale) fibrillar structure. The hemolytic, biocompatible, and functional effect of the scaffolds in interaction with an in vitro fibroblast model was determined, in view of its potential use for vascular implants. Scaffolds were characterized by scanning electron microscopy and atomic force microscopy, Fourier transform infrared spectroscopy, wettability, static permeability, tensile test, and degradation. In addition, direct and indirect 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were used to identify the cell viability of fibroblasts, fluorescence assays were performed to establish morphological changes of the cell nuclei, and the hemolytic effect of the scaffolds was calculated. Results showed that ethanol-treated biocompositescaffolds exhibited mass losses lower than 6.65% and slow wettability and absorption, resulting from an increase in secondary structures that contribute to the crystalline phase of H-Col. The scaffolds demonstrated stable degradation in saline during the incubation period because of the availability of soluble structures in aqueous media, and the inclusion of H-Col increased the elastic properties of the scaffold. As regards hemocompatibility, the scaffolds had hemolysis levels lower than 1%; moreover, in terms of biocompatible characteristics, scaffolds exhibited good adhesion, proliferation, and cell viability and insignificant changes in the circularity of the cell nuclei. However, scaffolds with homogeneous fibers showed cell agglomerates after 48 h of interaction. By contrast, permeability decreased as the incubation period progressed, because of the cellularization of the three-dimensional structure. In conclusion, multiscale scaffolds could exhibit a suitable behavior as a bioactive small-diameter vascular implant.