Deep Anterior Lamellar Keratoplasty-Treated Keratoconic Eyes With Descemet Membrane Rupture.

PURPOSE: The aim of this study was to evaluate the outcomes of deep anterior lamellar keratoplasty (DALK) and compare it with penetrating keratoplasty (PKP) in keratoconic eyes with Descemet membrane (DM) rupture. METHODS: In this comparative retrospective case series, 33 keratoconic eyes with a history of hydrops underwent DALK and 27 received PKP. Baseline and postoperative visual acuity, corneal astigmatism, mean keratometry, endothelial cell density, and complication rates were measured. RESULTS: The median follow-up of patients who underwent DALK was 45 months (range, 4-76 months) and that of patients who underwent PKP was 84 months (range, 4-136 months). Both procedures had comparable postoperative visual acuity, astigmatism, and mean keratometry. Significantly higher endothelial cell densities were observed in DALK than in PKP at 2, 3, and 5 years postsurgery (2043 ± 767 vs. 1165 ± 683 cell/mm2, P = 0.007, n = 12 in both groups at 2 years). Intra-DALK, 15 perforations occurred (44.12%) and 1 (2.94%) was converted to PKP. Graft rejection was diagnosed in 1 (3.03%) DALK procedure versus 8 (29.63%) PKP (P = 0.008), and other long-term complication rates were equivalent. Kaplan-Meier survival analysis also revealed a higher rejection-free survival rate for the DALK group (P = 0.012). Subgroup analysis within both groups based on the severity of preoperative DM rupture revealed no significant difference in any major 2-year outcomes. CONCLUSIONS: DALK showed similar beneficial visual outcome and safety but significantly better endothelial protection over PKP in eyes with keratoconus and previous hydrops. Therefore, DALK is recommended in posthydrops cases irrespective of the DM rupture severity.

The Innovative Biomaterials and Technologies for Developing Corneal Endothelium Tissue Engineering Scaffolds: A Review and Prospect.

Corneal transplantation is the only treatment for corneal endothelial blindness. However, there is an urgent need to find substitutes for corneal endothelium grafts due to the global shortage of donor corneas. An emerging research field focuses on the construction of scaffold-based corneal endothelium tissue engineering (CETE). Long-term success in CETE transplantation may be achieved by selecting the appropriate biomaterials as scaffolds of corneal endothelial cells and adding bioactive materials to promote cell activity. This article reviews the research progress of CETE biomaterials in the past 20 years, describes the key characteristics required for corneal endothelial scaffolds, and summarizes the types of materials that have been reported. Based on these, we list feasible improvement strategies for biomaterials innovation. In addition, we describe the improved techniques for the scaffolds' surface topography and drug delivery system. Some promising technologies for constructing CETE are proposed. However, some questions have not been answered yet, and clinical trials and industrialization should be carried out with caution.

Methane Activation by [AlFeO3 ]+ : the Hidden Spin Selectivity.

The performance of heteronuclear cluster [AlFeO3 ]+ in activating methane has been explored by a combination of high-level quantum chemical calculations with gas-phase experiments. At room temperature, [AlFeO3 ]+ is a mixture of 7 [AlFeO3 ]+ and 5 [AlFeO3 ]+ , in which two states lead to different reactivity and chemoselectivity for methane activation. While hydrogen extracted from methane is the only product channel for the 7 [AlFeO3 ]+ /CH4 couple, 5 [AlFeO3 ]+ is able to convert this substrate to formaldehyde. In addition, the introduction of an external electric field may regulate the reactivity and product selectivity. The interesting doping effect of Fe and the associated electronic origins are discussed, which may guide one on the design of Fe-involved catalyst for methane conversion.

Comparison of Femtosecond Laser Assistance and Manual Trephination in Deep Anterior Lamellar Keratoplasty in the Treatment of Keratoconus: A Meta-Analysis.

PURPOSE: To compare the efficacy and safety of femtosecond laser-assisted deep anterior lamellar keratoplasty (F-DALK) with those of manual-trephination DALK (M-DALK) in treating keratoconus. DESIGN: Systematic review and meta-analysis. METHODS: Through November 2022, we comprehensively searched PubMed, EMBASE, the Cochrane Library, and 4 Chinese databases. Studies that involved comparisons between F-DALK and M-DALK groups and that reported on relevant efficacy and/or safety parameters were included. Primary outcomes were uncorrected- and corrected-distance visual acuity and intraoperative complication rates. Secondary outcomes were spherical equivalent, topographic astigmatism, refractive cylinder, mean keratometry, endothelial cell density, suture removal time, and postoperative complication rates. These data were analyzed using Cochrane Review Manager software version 5.3. RESULTS: This meta-analysis included 9 nonrandomized controlled studies involving 1713 eyes. In eyes treated with F-DALK, corrected-distance visual acuity at 1 to 6 months (weighted mean difference = -0.07 [95% confidence interval {CI} -0.10 to -0.03]; I2 = 0%; P < .001) after surgery was better and intraoperative Descemet membrane perforation occurred less often (odds ratio = 0.53 [95% CI 0.31-0.92]; I2 = 6%; P = .02) than in eyes treated with M-DALK. No clinically significant differences in other outcomes were found among the groups. CONCLUSIONS: Both F-DALK and M-DALK are safe and efficacious for patients with keratoconus. Compared with M-DALK, F-DALK can provide better early visual acuity and reduce the intraoperative perforation rate, and its likely improvements to long-term visual quality and endothelial cell preservation warrant further investigation. In addition, the 2 techniques seem to be comparable regarding refractive outcomes and other complications.

Role of epigenetics in mycotoxin toxicity: A review.

Mycotoxins can induce cell cycle disorders, cell proliferation, oxidative stress, and apoptosis through pathways such as those associated with MAPK, JAK2/STAT3, and Bcl-w/caspase-3, and cause reproductive toxicity, immunotoxicity, and genotoxicity. Previous studies have explored the toxicity mechanism of mycotoxins from the levels of DNA, RNA, and proteins, and proved that mycotoxins have epigenetic toxicity. To explore the toxic effects and mechanisms of these changes in mycotoxins, this paper summarizes the changes in DNA methylation, non-coding RNA, RNA and histone modification induced by several common mycotoxins (zearalenone, aflatoxin B1, ochratoxin A, deoxynivalenol, T-2 toxin, etc.) based on epigenetic studies. In addition, the roles of mycotoxin-induced epigenetic toxicity in germ cell maturation, embryonic development, and carcinogenesis are highlighted. In summary, this review provides theoretical support for a better understanding of the regulatory mechanism of mycotoxin epigenotoxicity and the diagnosis and treatment of diseases.

Correlation Between the Computed Tomography and 3D Scanning System-Based Periorbital Morphology of Children with Congenital Microphthalmia.

PURPOSE: This article aimed to explore the correlation between the periorbital morphology determined using a 3D scanning system and CT in congenital microphthalmia. METHODS: Fifty-two children with microphthalmia aged 0-6 were enrolled in this study. All the participants were subjected to orbital CT scans and 3D scanning. The CT and 3D scanning images were separately processed to obtain the orbital and facial parameters. Multivariate regression was used to analyze the correlation between 3D parameters and orbital volume. RESULTS: The orbital volume of the affected side (15.25 ± 3.35 cm3) was generally smaller than the unaffected side (18.58 ± 2.65 cm3, p < .001). Based on CT, at all ages, the parameters of the unaffected orbit were greater than the affected side. In the 3D scanning and 3D reconstruction based on CT, both unaffected and affected sides were highly correlated. A multiple linear regression equation including three 3D scanning factors was obtained for the orbital volume (R2 = 0.808, p < .001). CONCLUSIONS: The retarded orbital volume could be estimated by the parameters based on 3D scanning, along with axial length. In the follow-up stage, 3D scanning can be a novel alternative method to assess the degree of orbital growth retardation in congenital microphthalmia.

Size Effects in Gas-phase C-H Activation.

The gas-phase clusters reaction permits addressing fundamental aspects of the challenges related to C-H activation. The size effect plays a key role in the activation processes as it may substantially affect both the reactivity and selectivity. In this paper, we reviewed the size effect related to the hydrocarbon oxidation by early transition metal oxides and main group metal oxides, methane activation mediated by late transition metals. Based on mass-spectrometry experiments in conjunction with quantum chemical calculations, mechanistic discussions were reviewed to present how and why the size greatly regulates the reactivity and product distribution.

Application of the CRISPR/Cas System in Pathogen Detection: A Review.

Early and rapid diagnosis of pathogens is important for the prevention and control of epidemic disease. The polymerase chain reaction (PCR) technique requires expensive instrument control, a special test site, complex solution treatment steps and professional operation, which can limit its application in practice. The pathogen detection method based on the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated protein (CRISPR/Cas) system is characterized by strong specificity, high sensitivity and convenience for detection, which is more suitable for practical applications. This article first reviews the CRISPR/Cas system, and then introduces the application of the two types of systems represented by Type II (cas9), Type V (cas12a, cas12b, cas14a) and Type VI (cas13a) in pathogen detection. Finally, challenges and prospects are proposed.

Striking Size and Doping Effects of Ti-Si-O Clusters on Methane Conversion Reactions.

The size and doping effects in methane activation by Ti-Si-O clusters have been explored by using a combination of gas-phase experiments and quantum chemical calculations. All [Tim Sin O2(m+n) ].+ (m+n=2, 3, 8, 10, 12, 14) clusters can extract a hydrogen from methane. The associated energies and structures have been revealed in detail. Moreover, the doping and size effects have been discussed involving generalized Kohn-Sham energy decomposition analysis, natural population analysis, Wiberg bond indexes (WBI), molecular polarity index (MPI) and ionization potential (IP). It suggested that Ti-Si-O clusters with a low Ti : Si ratio is beneficial to adsorbing methane and inclination to the hydrogen atom transfer (HAT) process, while the clusters with a high Ti : Si ratio favors the generation of a terminal oxygen radical and results in high reactivity and turnover frequency. On the other hand, a cluster size of m+n=12 is recommended considering both the ionization potential and the turnover frequency of the reaction. Hopefully, these finding will be instructive for the design of high-performance Ti-Si-O catalyst toward methane conversion.

An electro-spun tri-component polymer biomaterial with optoelectronic properties for neuronal differentiation.

Optoelectronic biomaterials have recently emerged as a potential treatment option for neurodegenerative diseases, such as optic macular degeneration. Though initial works in the field have involved bulk heterojunctions mimicking solar panels with photovoltaics (PVs) and conductive polymers (CPs), recent developments have considered abandoning CPs in such systems. Here, we developed a simple antioxidant, biocompatible, and fibrous membrane heterojunction composed of photoactive polymer poly(3-hexylthiophene) (P3HT), polycaprolactone (PCL) and polypyrrole (PPY), to facilitate neurogenesis of PC-12 cells when photo-stimulated in vitro. The photoactive prototype, referred to as PCL-P3HT/PPY, was fabricated via polymerization of pyrrole on electro-spun PCL-P3HT nanofibers to form a membrane. Four experimental groups, namely PCL alone, PCL/PPY, PCL-P3HT and PCL-P3HT/PPY, were tested. In the absence of the CP, PCL-P3HT demonstrated lower cell survival due to increased intracellular reactive oxygen/nitrogen species production. PCL-P3HT/PPY rescued these cells by virtue of scavenging radicals, where the CP, PPY, acted as an antioxidant. Apart from having lower impedance, the material also enhanced neurogenesis of PC-12 cells when photo-stimulated, compared to the traditional PCL-P3HT. Lastly, the in vitro system with PC-12 was used to demonstrate the practicality of the material for potential use as a cellular patch in optic and nerve regeneration. This work demonstrated the importance of maintaining PV-CP heterojunctions while simultaneously providing an optoelectrical platform for neural and optical tissue engineering. STATEMENT OF SIGNIFICANCE: Regeneration and repair of injured nervous systems have always been a major clinical challenge. Stem cell therapy is a promising approach for nerve regeneration, and opto-electrical stimulation, which converts light into an electrical signal, has been shown to efficiently regulate stem cell behaviors with enhanced neurogenesis. We developed a micro-fibrous membrane, composed of photoactive polymer, P3HT, scaffold material PCL and conductive polymer PPY. Our heterojunction system improved cell survival via PPY quenching PCL-P3HT-generated cell-damaging reactive oxygen species. PPY also conducted electrons produced from light-stimulated P3HT to promote neurogenesis. This photoactive microfiber biomaterial has great potential as a highly biocompatible and efficient platform to wirelessly promote neurogenesis and survival. Our approach thus showed possibilities with respect to optical tissue engineering.

A Finite Element Analysis Model is Suitable for Biomechanical Analysis of Orbital Development.

ABSTRACT: The authors investigated orbital bone development in congenital microphthalmia (CM) using a three-dimensional finite element analysis model, after the orbital dimension deficiency was improved with a self-inflating hydrogel expander implant.Data of a 2-year-old male CM patient were examined. The orbital structure, eyeball, eye muscles, and self-inflating hydrogel expander were constructed according to computed tomography examination data. The effects of self-expanding spherical hydrogel at various locations in the muscle cone on orbital bone development were examined using 3-mL self-expanding expanders placed at shallow (model 1: 2 mm depth) and deep (model 2: 8 mm depth) muscle cone positions. This model simulated the hydrogel expansion process; the orbital bone biomechanics and radial displacement nephograms were obtained when the hydrogel volume increased 3, 5, 7, and 9 times and analyzed.The orbital bone biomechanics were concentrated at the medial orbital wall center, gradually spreading to the whole orbital wall. Biomechanics and radial displacement of the inferior temporal and lateral distal orbital wall region were the most significant, and were more significant in model 1 than in model 2.Finite element analysis is suitable for the biomechanical analysis of orbital development in CM. The shallow position inside CM patients' muscle cone is the optimal site for hydrogel implantation.

Management of blepharospasm and blepharophimosis associated with Schwartz-Jampel syndrome.

We report the case of a 5-year-old boy with progressive bilateral blepharospasm and blepharophimosis secondary to Schwartz-Jampel syndrome type 1A. Molecular findings confirmed two novel heterozygous mutations in the HSPG2 gene. After the patient did not respond to a single injection of botulinum toxin, he underwent levator resection combined with orbicularis myectomy of bilateral upper and lower eyelids, with satisfactory aesthetic and functional outcomes.

Three-dimensional periorbital asymmetry assessment of congenital microphthalmia children with a structured light 3D scanning system.

Congenital microphthalmia is a rare phenotype characterized by eye growth retardation. Due to the lack of eyeball stimulation, children suffering from congenital microphthalmia always have bony orbital maldevelopment, which leads to facial asymmetry. In the present study, a structured light 3D scanning system was used as a novel method to measure the three-dimensional periorbital asymmetry in children with congenital microphthalmia. Children with unilateral congenital microphthalmia of 0-6 years old were enrolled in the present study. All participants underwent an ultrasound scan to measure the axial length, and accepted the structured light 3D scanning system for their periorbital appearance. The degree of periorbital asymmetry was evaluated using 17 facial landmarks within a three-dimensional cartesian coordinate system (the X-axis represented the horizontal direction, the Y-axis represented the vertical direction, and the Z-axis represented the sagittal direction). Paired student t-test and ANOVA were used in the present study. A three-dimensional periorbital topography was also established to further illustrate the periorbital asymmetry. A total of 67 children were recruited, which included 31 boys and 34 girls. The axial length on the affected side (12.28 ± 3.35 mm) was generally smaller than that on the unaffected side (20.54 ± 1.65 mm, P < 0.001). When grouped by age, the periorbital asymmetry mainly manifested in the Y-axis and Z-axis directions. The unaffected side had a higher orbitale superior (5.09 ± 0.35 vs. 3.02 ± 0.30, P < 0.001) and a lower orbitale inferior (-19.52 ± 0.51 vs. -16.90 ± 0.53, P < 0.001) in 0-1 year old group. Same performances were also found in the 1-3 and 3-6 age groups. When grouped according to the proportion of axial length on the bilateral sides, seven of the 12 Y-values and all 12 Z-values had statistical differences. The structured Light 3D scanning system may serve as a beneficial complementary tool for computed tomography, in order to better understand the periorbital deformities caused by congenital microphthalmia.

HUME: large-scale detection of causal genetic factors of adverse drug reactions.

Motivation: Adverse drug reactions are one of the major factors that affect the wellbeing of patients and financial costs of healthcare systems. Genetic variations of patients have been shown to be a key factor in the occurrence and severity of many ADRs. However, the large number of confounding drugs and genetic biomarkers for each adverse reaction case demands a method that evaluates all potential genetic causes of ADRs simultaneously. Results: To address this challenge, we propose HUME, a multi-phase algorithm that recommends genetic factors for ADRs that are causally supported by the patient record data. HUME consists of the construction of a network from co-prevalence between significant genetic biomarkers and ADRs, a link score phase for predicting candidate relations based on the Adamic-Adar measure, and a causal refinement phase based on multiple hypothesis testing of quasi experimental designs for evaluating evidence and counter evidence of candidate relations in the patient records. Supplementary information: Supplementary data are available at Bioinformatics online.

Gene polymorphisms and chronic obstructive pulmonary disease.

The genetic component was suggested to contribute to the development of chronic obstructive pulmonary disease (COPD), a major and growing public health burden. The present review aims to characterize the evidence that gene polymorphisms contribute to the aetiology of COPD and related traits, and explore the potential relationship between certain gene polymorphisms and COPD susceptibility, severity, lung function, phenotypes, or drug effects, even though limited results from related studies lacked consistency. Most of these studies were association studies, rather than confirmatory studies. More large-sized and strictly controlled studies are needed to prove the relationship between gene polymorphisms and the reviewed traits. More importantly, prospective confirmatory studies beyond initial association studies will be necessary to evaluate true relationships between gene polymorphisms and COPD and help individualized treatment for patients with COPD.