Lysozyme binding with amikacin and levofloxacin studied by tritium probe, fluorescence spectroscopy and molecular docking.

Lysozyme complexes with amikacin and levofloxacin were studied by spectroscopy approaches as well as using a tritium probe. Tritium was used as a labeling agent to trace labeled compound concentration in a system of two immiscible liquids and in the atomic form to determine the possible position of the binding site. Co-adsorption of protein and drug at the liquid-liquid interface was analyzed by scintillation phase method that allowed us to directly determine the amount of protein and drug in the mixed adsorption layer. Also, tensiometric measuring of the interfacial tension was used for calculation of binding parameters accordingly to Fainerman model. The treatment of complexes with atomic tritium followed by trypsinolysis and analysis of tritium distribution in the lysozyme peptides reveals the binding sites, binding energies in which were analyzed using molecular docking. Formation of complexes with amikacin and levofloxacin preserves secondar structure of protein. However, the formation of complex with amikacin leads to the almost total loss of the enzymatic activity of lysozyme and the redshift of the maximum on the lysozyme fluorescence band. A slight decrease in the distribution coefficient of lysozyme in the presence of amikacin assumes that the complex has higher hydrophilicity in comparison to lysozyme without additives. The most favorable for binding were the positions of the active centers that included amino acids Asp52 and Glu35, as well as in the vicinity of peptide His15-Arg21, with the participation of amino acids Tyr20, Arg14. In the case of levofloxacin, the formation of lysozyme-ligand complex in aqueous solution is possible without changing the microenvironment of the active center of the protein. Binding of levofloxacin to the active center of the enzyme was the most favorable, but Asp52 and Glu35 that are responsible for the enzymatic activity of lysozyme, were not affected.

LAMPrimers iQ: New primer design software for loop-mediated isothermal amplification (LAMP).

Nucleic acids amplification is a widely used technique utilized for different manipulations with DNA and RNA. Although, polymerase chain reaction (PCR) remains the most popular amplification method, isothermal approaches are gained more attention last decades. Among these, loop-mediated isothermal amplification (LAMP) became an excellent alternative to PCR. LAMP requires an increased number of primers and, therefore, is considered a highly specific amplification reaction compared to PCR. LAMP primers design is still a non-trivial task, and all niceties should be taken into account during their selection. Here, we report on a new program called LAMPrimers iQ destined for high-quality LAMP primers design. LAMPrimers iQ is based on an original algorithm considering rigorous criteria for primers selection. Unlike alternative programs, LAMPrimers iQ can process long DNA or RNA sequences, and completely avoid primers that can form homo- and heterodimers. The quality of the primers designed was checked using SARS-CoV-2 coronavirus RNA as a model target. It was shown that primers selected with LAMPrimers iQ provide higher specificity and reliable detection of viral RNA compared to those obtained by alternative programs. The program is available at https://github.com/Restily/LAMPrimers-iQ.

Cataract Classification Systems: A Review.

Cataract is among the leading causes of visual impairment worldwide. Innovations in treatment have drastically improved patient outcomes, but to be properly implemented, it is necessary to have the right diagnostic tools. This review explores the cataract grading systems developed by researchers in recent decades and provides insight into both merits and limitations. To this day, the gold standard for cataract classification is the Lens Opacity Classification System III. Different cataract features are graded according to standard photographs during slit lamp examination. Although widely used in research, its clinical application is rare, and it is limited by its subjective nature. Meanwhile, recent advancements in imaging technology, notably Scheimpflug imaging and optical coherence tomography, have opened the possibility of objective assessment of lens structure. With the use of automatic lens anatomy detection software, researchers demonstrated a good correlation to functional and surgical metrics such as visual acuity, phacoemulsification energy, and surgical time. The development of deep learning networks has further increased the capability of these grading systems by improving interpretability and increasing robustness when applied to norm-deviating cases. These classification systems, which can be used for both screening and preoperative diagnostics, are of value for targeted prospective studies, but still require implementation and validation in everyday clinical practice.

Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting.

Currently, no ideal treatment exists to combat skeletal muscle disuse-induced atrophy and loss of strength. Because the activity of AMP-activated protein kinase (AMPK) in rat soleus muscle is suppressed at the early stages of disuse, we hypothesized that pre-treatment of rats with metformin (an AMPK activator) would exert beneficial effects on skeletal muscle during disuse. Muscle disuse was performed via hindlimb suspension (HS). Wistar rats were divided into four groups: (1) control (C), (2) control + metformin for 10 days (C+Met), (3) HS for 7 days (HS), (4) metformin treatment for 7 days before HS and during the first 3 days of 1-week HS (HS+Met). Anabolic and catabolic markers were assessed using WB and RT-PCR. Treatment with metformin partly prevented an HS-induced decrease in rat soleus weight and size of slow-twitch fibers. Metformin prevented HS-related slow-to-fast fiber transformation. Absolute soleus muscle force in the HS+Met group was increased vs. the HS group. GSK-3ß (Ser9) phosphorylation was significantly increased in the HS+Met group vs. the HS group. Metformin pre-treatment partly prevented HS-induced decrease in 18S+28S rRNA content and attenuated upregulation of calpain-1 and ubiquitin. Thus, pre-treatment of rats with metformin can ameliorate disuse-induced reductions in soleus muscle weight, the diameter of slow-type fibers, and absolute muscle strength.

A Prochlorperazine-Induced Decrease in Autonomous Muscle Activity during Hindlimb Unloading Is Accompanied by Preserved Slow Myosin mRNA Expression.

Skeletal muscle disuse leads to pathological muscle activity as well as to slow-to-fast fiber-type transformation. Fast-type fibers are more fatigable than slow-type, so this transformation leads to a decline in muscle function. Prochlorperazine injections previously were shown to attenuate autonomous rat soleus muscle electrical activity under unloading conditions. In this study, we found that prochlorperazine blocks slow-to-fast fiber-type transformation in disused skeletal muscles of rats, possibly through affecting calcium and ROS-related signaling.

Capsule Dynamics, Implantation, and Explantation of the Smaller Incision, New-Generation Implantable Miniature Telescope: a Miyake-Apple Study.

PURPOSE: The smaller incision, new-generation implantable miniature telescope is a novel implant to optimize vision in retinal patients with central vision loss. Using Miyake-Apple techniques we visualized the device implantation, repositioning, and explantation, while noting capsular bag dynamics. METHODS: Using the Miyake-Apple technique, we assessed capsular bag deformation after successful implantation of the device in human autopsy eyes. We assessed rescue strategies for converting a sulcus implantation to a capsular implantation and explantation strategies. We noted the occurrence of posterior capsule striae, zonular stress, and the haptics' arc of contact with the capsular bag after implantation. RESULTS: Acceptable zonular stress was observed during the successful implantation of the SING IMT. When it was implanted in the sulcus, one could reposition the haptics into the bag with two spatulas using counter-pressure in an effective strategy despite inducing tolerable, medium zonular stress. A similar technique, in reverse, allows safe explantation without damaging the rhexis or the bag, while inducing similar medium, tolerable zonular stress. In all eyes we examined, the implant considerably stretches the bag, inducing a capsular bag deformation and posterior capsule striae. CONCLUSION: The SING IMT can be safely implanted without significant zonular stress. In sulcus implantation and explantation, repositioning of the haptic is achievable without perturbing zonular stress using the presented approaches. It stretches average-sized capsular bags to support its weight. This is achieved by an increased arc of contact of the haptics with the capsular equator.

Electrochemical Behavior of Reduced Graphene Oxide Supported Germanium Oxide, Germanium Nitride, and Germanium Phosphide as Lithium-Ion Battery Anodes Obtained from Highly Soluble Germanium Oxide.

Germanium and germanium-based compounds are widely used in microelectronics, optics, solar cells, and sensors. Recently, germanium and its oxides, nitrides, and phosphides have been studied as active electrode materials in lithium- and sodium-ion battery anodes. Herein, the newly introduced highly soluble germanium oxide (HSGO) was used as a versatile precursor for germanium-based functional materials. In the first stage, a germanium-dioxide-reduced graphene oxide (rGO) composite was obtained by complete precipitation of GeO2 nanoparticles on the GO from an aqueous solution of HSGO and subsequent thermal treatment in argon at low temperature. The composition of the composite, GeO2-rGO (20 to 80 wt.% of crystalline phase), was able to be accurately determined by the HSGO to GO ratio in the initial solution since complete deposition and precipitation were achieved. The chemical activity of germanium dioxide nanoparticles deposited on reduced graphene oxide was shown by conversion to rGO-supported germanium nitride and phosphide phases. The GeP-rGO and Ge3N4-rGO composites with different morphologies were prepared in this study for the first time. As a test case, composite materials with different loadings of GeO2, GeP, and Ge3N4 were evaluated as lithium-ion battery anodes. Reversible conversion-alloying was demonstrated in all cases, and for the low-germanium loading range (20 wt.%), almost theoretical charge capacity based on the germanium content was attained at 100 mA g-1 (i.e., 2595 vs. 2465 mAh g-1 for Ge3N4 and 1790 vs. 1850 mAh g-1 for GeP). The germanium oxide was less efficiently exploited due to its lower conversion reversibility.

Differential Diagnosis of Changes in Intraocular Lenses. / Differenzialdiagnostik von Veränderungen in Intraokularlinsen.

Differentiating between various intraocular lens (IOL) changes can be a challenge. In particular, certain IOL models carry the risk of late postoperative calcification. A major cause of IOL exchange surgery could be avoided if appropriate modifications were made during the IOL manufacturing process. The use of a hydrophilic acrylate carries the risk of IOL calcification, especially when a secondary procedure, such as a pars plana vitrectomy or other procedures using gas or air, is performed. In secondary IOL calcification, there is a wide range of opacification patterns, which are usually located in the centre on the anterior surface of the IOL or sometimes elsewhere. Often, granular deposits accumulate just below or on the surface of the IOL, leading to significant deterioration in visual quality and eventually requiring IOL exchange surgery. Therefore, in the case of eyes requiring secondary surgical intraocular intervention in the future, the use of hydrophilic IOLs should be critically evaluated. With regard to hydrophobic IOL materials, there are clear differences in the susceptibility to the formation of glistenings. Over time, there has been a significant decrease in glistening formation over the past 30 years due to optimisation of the material. With hydrophobic IOLs, special care should also be taken to avoid mechanical damage. In general, the only treatment option for functionally-impairing IOL opacification is surgical lens exchange, which carries potential risks of complications. In cases with a low degree of functional impairment, and especially in eyes with additional ocular diseases, it may be difficult to weigh the risk of additional surgery against the potential benefit. In some cases, it may be more appropriate not to perform an IOL exchange despite the IOL opacification. Recent visualisation methods that allow high-resolution analysis of the opacities in vivo and in vitro may be used in the future to estimate the functional effects of various IOL material changes on the optical quality.

New type of RNA virus replication inhibitor based on decahydro-closo-decaborate anion containing amino acid ester pendant group.

In this work, a synthetic approach to prepare an example of new class of the derivatives of the closo-decaborate anion with amino acids detached from the boron cluster by pendant group has been proposed and implemented. Compound Na2[B10H9-O(CH2)4C(O)-His-OMe] was isolated and characterized. This compound has an inorganic hydrophobic core which is the 10-vertex boron cage and the -O(CH2)4C(O)-His-OMe organic substituent. It has been shown to possess strong antiviral activity in vitro against modern strains of A/H1N1 virus at 10 and 5 µg/mL. The compound has been found to be non-cytotoxic up to 160 µg/mL. At the same time, the compound has been found to be inactive against SARS-CoV-2, indicating specific activity against RNA virus replication. Molecular docking of the target derivative of the closo-decaborate anion with a model of the transmembrane region of the M2 protein has been performed and the mechanism of its antiviral action is discussed.

Inhibition of mTORC1 differentially affects ribosome biogenesis in rat soleus muscle at the early and later stages of hindlimb unloading.

Prolonged inactivity of skeletal muscles due to limb immobilization, bedrest, and exposure to microgravity results in a significant muscle atrophy. Inactivity-induced muscle atrophy is caused by a downregulation of protein synthesis (PS) and increased proteolysis. Mechanistic target of rapamycin complex 1 (mTORC1) is considered to be one of the main regulators of translational capacity (quantity of ribosomes), a key determinant of PS. Using a specific mTORC1 inhibitor (rapamycin) we aimed to determine if mTORC1 activity would influence ribosome biogenesis in rat soleus muscle at both early and later stages of mechanical unloading. Wistar rats were subjected to 1- and 7-day hindlimb suspension (HS) with and without rapamycin injections (1.5 mg/kg) and compared to weight-bearing control animals. The key markers of ribosome biogenesis were assessed by RT-PCR or agarose gel electrophoresis. The rate of PS was measured by SUnSET method. Both 1-day and 7-day HS resulted in a significant downregulation of ribosome biogenesis markers (c-Myc, 47S pre-rRNA, 18S + 28S rRNAs) and the rate of PS. Rapamycin administration during 1-day HS fully prevented a decrease in 47S pre-rRNA expression and amount of 18S + 28S rRNAs (without affecting c-Myc mRNA expression) and partially attenuated a decline in PS. Rapamycin treatment during 7-day HS significantly decreased p70S6K phosphorylation but failed to rescue a reduction in both the markers of ribosome biogenesis and the rate of PS. All together, our results suggest that mTORC1 inhibition at the initial (1 day), but not later (7 days) stage of HS can be beneficial for the maintenance of translational capacity (ribosome biogenesis) and the rate of PS in rat soleus muscle.

NOS-dependent effects of plantar mechanical stimulation on mechanical characteristics and cytoskeletal proteins in rat soleus muscle during hindlimb suspension.

The study was aimed at investigating the mechanisms and structures which determine mechanical properties of skeletal muscles under gravitational unloading and plantar mechanical stimulation (PMS). We hypothesized that PMS would increase NO production and prevent an unloading-induced reduction in skeletal muscle passive stiffness. Wistar rats were hindlimb suspended and subjected to a daily PMS and one group of stimulated animals was also treated with nitric oxide synthase (NOS) inhibitor (L-NAME). Animals received mechanical stimulation of the feet for 4 h a day throughout 7-day hindlimb suspension (HS) according to a scheme that mimics the normal walking of the animal. Seven-day HS led to a significant reduction in soleus muscle weight by 25%. However, PMS did not prevent the atrophic effect induced by HS. Gravitational unloading led to a significant decrease in maximum isometric force and passive stiffness by 38% and 31%, respectively. The use of PMS prevented a decrease in the maximum isometric strength of the soleus muscle. At the same time, the passive stiffness of the soleus in the PMS group significantly exceeded the control values by 40%. L-NAME (NOS inhibitor) administration attenuated the effect of PMS on passive stiffness and maximum force of the soleus muscle. The content of the studied cytoskeletal proteins (α-actinin-2, α-actinin-3, desmin, titin, nebulin) decreased after 7-day HS, but this decrease was successfully prevented by PMS in a NOS-dependent manner. We also observed significant decreases in mRNA expression levels of α-actinin-2, desmin, and titin after HS, which was prevented by PMS. The study also revealed a significant NOS-dependent effect of PMS on the content of collagen-1a, but not collagen-3a. Thus, PMS during mechanical unloading is able to maintain soleus muscle passive tension and force as well as mRNA transcription and protein contents of cytoskeletal proteins in a NOS-dependent manner.

The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions.

It is well-established that prolonged exposure to real or simulated microgravity/disuse conditions results in a significant reduction in the rate of muscle protein synthesis (PS) and loss of muscle mass. Muscle protein synthesis is largely dependent upon translational capacity (ribosome content), the regulation of which is poorly explored under conditions of mechanical unloading. Glycogen synthase kinase-3 (GSK-3) (a negative regulator of PS) is known to be activated in rat soleus muscle under unloading conditions. We hypothesized that inhibition of GSK-3 activity under disuse conditions (hindlimb suspension, HS) would reduce disuse-induced downregulation of ribosome biogenesis in rat soleus muscle. Wistar rats were randomly divided into four groups: (1) vivarium control (C), (2) vivarium control + daily injections (4 mg/kg) of AR-A014418 (GSK-3 inhibitor) for 7 days, (3) 7-day HS, (4) 7-day HS + daily injections (4 mg/kg) of AR-A014418. GSK-3beta and glycogen synthase 1 (GS-1) phosphorylation levels were measured by Western-blotting. The key markers of ribosome biogenesis were assessed via agarose gel-electrophoresis and RT-PCR. The rate of muscle PS was assessed by puromycin-based SUnSET method. As expected, 7-day HS resulted in a significant decrease in the inhibitory Ser9 GSK-3beta phosphorylation and an increase in GS-1 (Ser641) phosphorylation compared to the C group. Treatment of rats with GSK-3 inhibitor prevented HS-induced increase in GS1 (Ser641) phosphorylation, which was indicative of GSK-3 inhibition. Administration of GSK-3 inhibitor partly attenuated disuse-induced downregulation of c-Myc expression as well as decreases in the levels of 45S pre-rRNA and 18S + 28S rRNAs. These AR-A014418-induced alterations in the markers of ribosome biogenesis were paralleled with partial prevention of a decrease in the rate of muscle PS. Thus, inhibition of GSK-3 during 7-day HS is able to partially attenuate the reductions in translational capacity and the rate of PS in rat soleus muscle.

Cultured Myoblasts Derived from Rat Soleus Muscle Show Altered Regulation of Proliferation and Myogenesis during the Course of Mechanical Unloading.

The structure and function of soleus muscle fibers undergo substantial remodeling under real or simulated microgravity conditions. However, unloading-induced changes in the functional activity of skeletal muscle primary myoblasts remain poorly studied. The purpose of our study was to investigate how short-term and long-term mechanical unloading would affect cultured myoblasts derived from rat soleus muscle. Mechanical unloading was simulated by rat hindlimb suspension model (HS). Myoblasts were purified from rat soleus at basal conditions and after 1, 3, 7, and 14 days of HS. Myoblasts were expanded in vitro, and the myogenic nature was confirmed by their ability to differentiate as well as by immunostaining/mRNA expression of myogenic markers. The proliferation activity at different time points after HS was analyzed, and transcriptome analysis was performed. We have shown that soleus-derived myoblasts differently respond to an early and later stage of HS. At the early stage of HS, the proliferative activity of myoblasts was slightly decreased, and processes related to myogenesis activation were downregulated. At the later stage of HS, we observed a decrease in myoblast proliferative potential and spontaneous upregulation of the pro-myogenic program.

Synthesis, antitumor activity and structure-activity studies of novel pyridoxine-based bioisosteric analogs of estradiol.

A new efficient approach to the synthesis of 6-alkenyl substituted pyridoxine derivatives has been developed. A series of 31 novel alkenyl pyridoxine derivatives, stilbene-based bioisosteric analogs of estradiol, were synthesized. In vitro cytotoxicity of the obtained compounds against MCF-7 (ER+) breast cancer tumor cells was studied using the MTT assay. The most active compounds with IC50,MCF-7 < 10 µM were also tested for cytotoxicity in vitro against MDA-MB-231 (ER-) breast adenocarcinoma cells and conditionally normal human skin fibroblasts (HSF). The patterns of structure-antitumor activity relationships of the obtained compounds were analyzed. The most active compounds were found to contain a six-membered ketal ring, a methyl group in position 5, a 3,4-dimethoxystyryl fragment in positions 2 or 6 of the pyridoxine ring, and a trans-configuration of the double bond. Using the most active compound 5a as a representative cytotoxic agent, we have demonstrated that it has high specificity and antiproliferative activity against MCF-7 (ER+) tumor cells (IC50 < 5 µM), and a higher therapeutic index compared to the reference compound raloxifene (48 versus 5.8). Compound 5a decreased the mitochondrial membrane potential and increased the level of reactive oxygen species in MCF-7 cells, but not MDA-MB-231 cells. Compound 5a did not affect the distribution of cell cycle phases and induced apoptosis in MCF-7 cells, but not MDA-MB-231. Unlike compound 5a, raloxifene decreased mitochondrial potential, increased the ROS level, and induced apoptosis in both MCF-7 and MDA-MB-231 cells, which indicated a lack of selectivity for cells with estrogen receptor expression. It was also shown that compound 5a reduced the level of ERα expression in cells to a lesser extent than raloxifene and, unlike the latter, did not activate the PI3K/Akt signaling pathway.

A review of late intraocular lens opacifications.

PURPOSE OF REVIEW: Phacoemulsification cataract surgery is one of the most commonly performed surgical procedure worldwide. In the majority of cases, intraocular lenses (IOLs) are implanted. Due to the increasing life expectancy and the fact that cataract surgery is performed in earlier stages, the anticipated IOL duration in the eye has increased over the last decades. The aim of this study was to review the types and describe the characteristics of late intraocular lens opacifications. RECENT FINDINGS: Calcification was the most commonly reported type of opacification in hydrophilic IOLs; it usually negatively impacted the visual function and required IOL explantation. Glistening manifested in hydrophobic acrylic lenses and was frequent in some IOL models. In most cases glistening and subsurface nanoglistenigs do not lead to a decline in visual acuity or require IOL exchange. Current studies indicate that fluid-related phenomena may induce straylight, leading to a decrease of comfort and quality of vision. SUMMARY: Several reports on late IOL opacifications have been published in recent years. In some cases, particularly in glistening, the development of the opacifications might be related to IOL aging. The influence of the fluid-related microvacuoles on the quality of vision requires further research.

Laboratory analysis and ray visualization of diffractive optics with enhanced intermediate vision.

BACKGROUND: To assess the optical behavior of a new diffractive intraocular lens (IOL) and compare its performance to that of an established extended-depth-of-focus (EDOF) IOL. METHODS: This study assessed the Proming EDOF Multifocal AM2UX [Eyebright Medical Technology (Beijing) Co., Ltd., China] and the AT LARA 829MP [Carl Zeiss Meditec, Germany]. An experimental set-up with 0.01% fluorescein solution and monochromatic light (532 nm) was used to visualize the IOLs' ray propagation. In addition, the optical quality of the IOLs was assessed by measuring the modulation transfer function (MTF) values at 50lp/mm and 3.0 and 4.5 mm apertures on the optical bench OptiSpheric® IOL PRO II [Trioptics GmbH, Germany]. RESULTS: The ray propagation of the two IOLs showed two distinct foci. Light intensity assessment revealed that both IOLs allocate more energy to primary than secondary focus. At 3.0 mm pupil, the MTF values at 50lp/mm for the primary focus were 0.39 and 0.37, and for the secondary focus, 0.29 and 0.26 for the AT LARA and Proming IOLs, respectively. At 4.5 mm pupil, the single-frequency MTF for the primary focus was 0.51 and 0.24 and for the secondary focus 0.21 and 0.15 for the AT LARA and Proming IOLs, respectively. CONCLUSIONS: When tested with an aberration-free model cornea under monochromatic conditions, the Proming behaved as a low-add bifocal lens; however, its properties did not differ much from the well-established AT LARA EDOF IOL. The AT LARA outperformed the Proming at low defocus (up to 2D), while the latter demonstrated better image quality in the 2-3D range.

Reasons for explantation of phakic intraocular lenses and associated perioperative complications: cross-sectional explant registry analysis.

BACKGROUND: We discuss the safety, since their introduction, of phakic intraocular lenses (pIOLs) to correct refractive errors in healthy eyes. We investigated the reasons for pIOL explantation and the associated perioperative complications. METHODS: This retrospective, cross-sectional study included 69 pIOLs, explanted at a single tertiary center between July 2005 and March 2020: 34 angle-supported (G1), 28 iris-fixated (G2) and seven posterior chamber (G3) pIOLs. Case data including the reason for explantation was taken from the patient records. Intra- and postoperative complications were evaluated for an association with the pIOL. RESULTS: The mean duration in the eye was 10.4 (0.2-28) years. Cataractogenesis and subsequent surgery that required pIOL explantation was the reason in 42% of all cases. In 22%, cataract in combination with endothelial damage prompted explantation, with 26, 18 and 14% for G1, G2 and G3 respectively. The second most common reasons were corneal damage alone in the angle-supported group (26%), IOL subluxation in the iris-fixated group (18%), and photopic disturbance in the posterior chamber group (29%). In 68% of all explantations, the surgical course was unremarkable, while in the remaining cases perioperative complications were associated with the lens in 45.7%. CONCLUSION: Overall, the need for cataract surgery was the most common reason for pIOL explantation. Corneal complications were more frequent in the angle-supported pIOLs and their removal was associated with higher rates of complication compared to the other groups.

Augmented reality head-mounted display-based incision planning in cranial neurosurgery: a prospective pilot study.

OBJECTIVE: Monitor and wand-based neuronavigation stations (MWBNSs) for frameless intraoperative neuronavigation are routinely used in cranial neurosurgery. However, they are temporally and spatially cumbersome; the OR must be arranged around the MWBNS, at least one hand must be used to manipulate the MWBNS wand (interrupting a bimanual surgical technique), and the surgical workflow is interrupted as the surgeon stops to "check the navigation" on a remote monitor. Thus, there is need for continuous, real-time, hands-free, neuronavigation solutions. Augmented reality (AR) is poised to streamline these issues. The authors present the first reported prospective pilot study investigating the feasibility of using the OpenSight application with an AR head-mounted display to map out the borders of tumors in patients undergoing elective craniotomy for tumor resection, and to compare the degree of correspondence with MWBNS tracing. METHODS: Eleven consecutive patients undergoing elective craniotomy for brain tumor resection were prospectively identified and underwent circumferential tumor border tracing at the time of incision planning by a surgeon wearing HoloLens AR glasses running the commercially available OpenSight application registered to the patient and preoperative MRI. Then, the same patient underwent circumferential tumor border tracing using the StealthStation S8 MWBNS. Postoperatively, both tumor border tracings were compared by two blinded board-certified neurosurgeons and rated as having an excellent, adequate, or poor correspondence degree based on a subjective sense of the overlap. Objective overlap area measurements were also determined. RESULTS: Eleven patients undergoing craniotomy were included in the study. Five patient procedures were rated as having an excellent correspondence degree, 5 had an adequate correspondence degree, and 1 had poor correspondence. Both raters agreed on the rating in all cases. AR tracing was possible in all cases. CONCLUSIONS: In this small pilot study, the authors found that AR was implementable in the workflow of a neurosurgery OR, and was a feasible method of preoperative tumor border identification for incision planning. Future studies are needed to identify strategies to improve and optimize AR accuracy.

The Role of GSK-3ß in the Regulation of Protein Turnover, Myosin Phenotype, and Oxidative Capacity in Skeletal Muscle under Disuse Conditions.

Skeletal muscles, being one of the most abundant tissues in the body, are involved in many vital processes, such as locomotion, posture maintenance, respiration, glucose homeostasis, etc. Hence, the maintenance of skeletal muscle mass is crucial for overall health, prevention of various diseases, and contributes to an individual's quality of life. Prolonged muscle inactivity/disuse (due to limb immobilization, mechanical ventilation, bedrest, spaceflight) represents one of the typical causes, leading to the loss of muscle mass and function. This disuse-induced muscle loss primarily results from repressed protein synthesis and increased proteolysis. Further, prolonged disuse results in slow-to-fast fiber-type transition, mitochondrial dysfunction and reduced oxidative capacity. Glycogen synthase kinase 3ß (GSK-3ß) is a key enzyme standing at the crossroads of various signaling pathways regulating a wide range of cellular processes. This review discusses various important roles of GSK-3ß in the regulation of protein turnover, myosin phenotype, and oxidative capacity in skeletal muscles under disuse/unloading conditions and subsequent recovery. According to its vital functions, GSK-3ß may represent a perspective therapeutic target in the treatment of muscle wasting induced by chronic disuse, aging, and a number of diseases.

Glistening formation in a new hydrophobic acrylic intraocular lens.

BACKGROUND: The formation of fluid-filled microvacuoles, termed glistenings, is a common complication of intraocular lenses (IOLs) made from hydrophobic acrylate. Using our well-established in-vitro laboratory method, we evaluated a new IOL material's resistance to glistening formation. METHODS: An in-vitro stress test for glistening induction was performed on 20 samples of hydrophobic acrylic IOLs: ten of the new Eyecryl ASHFY600 (Biotech Vision Care, Ahmedabad, India) compared with ten samples of AcrySof IQ SN60WF (Alcon, Fort Worth, USA). The number of microvacuoles per square millimetre (MV/mm2) was evaluated in five sections of each IOL. The results for each model were compared and rated on a modified Miyata Scale for grading glistening severity. RESULTS: In all cases, glistening number was higher in the central section of the IOL optic than in the periphery. Mean number of MV/mm2 was highest in the central part of the AcrySof IQ SN60WF, with 41.84 (±27.67) MVs/mm2. The lowest number of glistenings was found in the five sections of the Eyecryl ASHFY600 with 0.52 (±0.24) MVs/mm2. Mean value of the Eyecryl ASHFY600 IOL, using the Miyata Scale, was Zero. CONCLUSION: In this in-vitro laboratory study, the new hydrophobic acrylic IOL showed a high resistance to microvacuole formation. Results from this in-vitro study suggest that glistening numbers will be low in clinical use in the Eyecryl ASHFY600.