Search Results (53)

Background/Objectives: Vogt–Koyanagi–Harada (VKH) disease is a bilateral granulomatous panuveitis that can progress to a chronic, relapsing phase. Patients refractory or intolerant to systemic corticosteroids and conventional immunomodulatory therapy pose a major therapeutic challenge, as persistent inflammation can lead to cumulative ocular damage and permanent vision loss. This study assessed the efficacy of tumor necrosis factor-α (TNF-α) inhibitor adalimumab in chronic recurrent VKH disease. Methods: We retrospectively reviewed 16 eyes from 8 patients with chronic recurrent VKH disease who had persistent inflammation despite treatment with corticosteroids and conventional immunomodulatory therapy, and subsequently received adalimumab. Primary outcomes were changes in subfoveal choroidal thickness (SFCT) and systemic corticosteroid dose reduction. Secondary outcomes included visual acuity, inflammatory parameters (anterior chamber cell, flare, and vitreous haze), and central macular thickness (CMT). All outcomes were compared between baseline and 6 months after adalimumab initiation using the Wilcoxon signed-rank test. Results: Mean patient age was 47.6 years and mean follow-up was 31.8 months. SFCT decreased from 326.7 ± 129.1 µm to 231.6 ± 72.9 µm at 6 months (p < 0.001). Systemic steroid dose decreased from 14.7 ± 14.0 mg to 4.1 ± 3.8 mg (p = 0.027). Mean annualized relapse rate decreased from 3.61 to 0.08 episodes/year (p = 0.012). Anterior chamber cell grade decreased from 0.81 ± 0.66 to 0.09 ± 0.20 (p < 0.001). Visual acuity, flare, vitreous haze, and CMT showed no significant change. No serious adverse events occurred. Conclusions: TNF-α inhibition with adalimumab appears effective as steroid-sparing therapy for controlling recurrent inflammation and reducing steroid dependence in patients with chronic recurrent VKH disease refractory to conventional treatment. Full article

Purpose: To investigate the therapeutic potential of inducible pluripotent stem cell (hiPSC)-based vascular repair, we evaluated two vascular reparative cell populations, CD34⁺ cells derived from hiPSC (hiPSC-CD34⁺) and endothelial colony forming cells (ECFCs) derived from hiPSC (iPS-ECFCs), alone and in combination, in a type 2 diabetic (db/db) mouse model of DR. Methods: hiPSC-CD34⁺ cells (1 × 10⁴) or iPSC- ECFCs (1 × 10⁵) alone or in combination (1.1 × 10⁵) were injected into the vitreous of immunosuppressed db/db mice with six months of established diabetes. One month post-injection, mice underwent electroretinography (ERG) and optical coherence tomography (OCT) to evaluate functional and structural retinal recovery with iPSC administration. Immunohistochemistry (IHC) was used to assess recruitment and incorporation of cells into the retinal vasculature. Retinas from the experimental groups were analyzed using Functional Proteomics via Reverse Phase Protein Array (RPPA). Results: Functional assessment via ERG demonstrated significant improvements in retinal response in the diabetic cohorts treated with either hiPSC-derived CD34⁺ cells or hiPSC-ECFCs. Retinal thickness, assessed by OCT, was restored to near-nondiabetic levels in mice treated with hiPSC-CD34⁺ cells alone and the combination group, whereas hiPSC-ECFCs alone did not significantly affect retinal thickness. One month following intravitreal injection, hiPSC-CD34⁺ cells were localized to perivascular regions, whereas hiPSC-ECFCs were observed to integrate directly into the retinal vasculature. RPPA analysis revealed interaction-significant changes, and this was interpreted as a combination-specific, non-additive host responses (m⁶A, PI3K–AKT–mTOR, glycolysis, endothelial junction pathways). Conclusions: The studies support that injection of hiPSC-CD34⁺ cells and hiPSC-ECFCs, both individually and in combination, showed benefit; however, iPSC combination-specific effects were identified by measurement of retinal thickness and by RPPA. Full article

Parametric changes in the first coordination shell (FCS) of a vitreous metallic Pd_42.5Cu₃₀Ni_7.5P₂₀ alloy are analysed, aiming to confirm the identification of the glass transition temperature (T_g) via processing of XRD patterns utilising radial and pair distribution functions (RDFs and PDFs) and their evolution with temperature. The Wendt–Abraham empirical criterion of glass transition and its modifications are confirmed in line with previous works, which utilised the kink of the temperature dependences of the minima and maxima of both the PDF and the maxima of the structure factor S(q). Massive fluctuations are, however, identified near the T_g of the derivatives of the minima and maxima of the PDF and maxima of S(q), which adds value to understanding the glass transition in the system as a true second-order-like phase transformation in the non-equilibrium system of atoms. Full article

Diverging from conventional dephosphorization approaches, this study employs a novel pre-reduction and smelting separation (PR-SS) to efficiently co-recover iron and phosphorus from high-phosphorus oolitic iron ore, directly yielding Fe–P alloy, and the Fe–P alloy shows potential as feedstock for high-phosphorus weathering steel or wear-resistant cast iron, indicating promising application prospects. Using oolitic magnetite concentrate (52.06% Fe, 0.37% P) as feedstock, optimized conditions including pre-reduction at 1050 °C for 2 h with C/Fe mass ratio of 2, followed by smelting separation at 1550 °C for 20 min with 5% coke, produced a metallic phase containing 99.24% Fe and 0.73% P. Iron and phosphorus recoveries reached 99.73% and 99.15%, respectively. EPMA microanalysis confirmed spatial correlation between iron and phosphorus in the metallic phase, with undetectable phosphorus signals in vitreous slag. This evidence suggests preferential phosphorus enrichment through interfacial mass transfer along the pathway of the slag phase to the metal interface and finally the iron matrix, forming homogeneous Fe–P solid solutions. The phosphorus migration mechanism involves sequential stages: apatite lattice decomposition liberates reactive P₂O₅ under SiO₂/Al₂O₃ influence; slag–iron interfacial co-reduction generates Fe₃P intermediates; Fe₃P incorporation into the iron matrix establishes stable solid solutions. Full article

Recent archaeological sites dating to the late 19th and early 20th centuries have rarely been studied to date. Among the 500 “glassy” beads excavated from Dohouan (Côte d’Ivoire), elemental analyses reveal that fewer than half contain abnormally high alumina contents, associated with a soda–potash–lime flux (three compositional groups). The remaining beads are typical lead-based glass. The Raman spectra of the alumina-rich beads are quite complex due to their glass–ceramic nature, combining features similar to the vitreous phase of porcelain glaze with the presence of various crystalline phases (quartz, wollastonite, calcium phosphate, calcite). Organic residues are also observed. Colors are primarily produced by transition metal ions, although some specific pigments have also been identified. These characteristics suggest that the alumina-rich beads were manufactured by pressing followed by sintering, as described in patents by Richard Prosser (1840, UK) and Jean Félix Bapterosse (1844, France). A comparison is made with beads from scrap piles at the site of the former Bapterosse factory in Briare, France. This process represents one of the earliest examples of replacing traditional glassmaking with a ceramic process to enhance productivity and reduce costs. Full article

Vitreous carriers of essential nutrients should release elements in response to plant demand, minimizing over-fertilization risks. This study focused on designing and characterizing sulfate-bearing slow-release fertilizers based on four glass series (41SiO₂∙6(10)P₂O₅∙20K₂O–33(29)MgO/CaO/MgO + CaO) with increasing sulfate content. Structural analysis identified a network dominated by ${\mathrm{Q}}_{\mathrm{Si}}^2$ units, with some ${\mathrm{Q}}_{\mathrm{Si}}^3$ species and isolated ${\mathrm{Q}}_{\mathrm{P}}^0$ units. This fragmented structure resulted in high solubility in acidic environments while maintaining water resistance. Such dual behavior is a direct consequence of the delicate balance between depolymerized silicate chains and isolated orthophosphate units, which ensure rapid ion exchange under acidic conditions while preventing uncontrolled leaching in neutral media. Nutrient leaching depended on SO₃ content, affecting matrix rigidity, and on the type of alkaline earth modifier and P₂O₅ content. Dissolution kinetics showed an initial rapid release phase, followed by stabilization governed by silicate hydrolysis. Thermal analysis linked network flexibility to dissolution behavior—CaO promoted an open structure with high SiO₂ release, MgO increased rigidity, while their co-addition reduced ion diffusion and silica dissolution. The thermal behavior of the glasses provided indirect insight into their structural rigidity, revealing how compositional variations influence the mechanical stability of the network. This structural rigidity, inferred from glass transition and crystallization phenomena, was found to correlate with the selective dissolution profiles observed in acidic versus neutral environments. These results reveal complex interactions between composition, structure, and nutrient release, shaping the agricultural potential of these glasses. Full article

The recycling of spent automotive batteries is essential for minimizing their environmental impact. This requires eco-innovative methods with low cost and energy use. The present study explores the recycling of battery electrodes through the melt quenching method, a process that incorporates spent anode and cathode plates into a vitreous host matrix. Samples with the xCuO·10Sb₂O₃·(90 − x)[4PbO₂·Pb] composition, where x = 0 to 30 mol% CuO, were prepared by the melt quenching method. The XRD analysis indicates the vitroceramic structures of the obtained samples. Thus, the presence of varied crystalline phases such as Pb₂(SO₄)O, PbSO₄, and metallic Pb was detected. The SEM micrographs highlighted heterogeneous regions within the samples and showed a decreases of the size of crystallites with increased dopant concentrations. IR and UV-Vis spectra suggest that the copper ions act as network modifiers, creating bond defects and free oxygen ions, and yielding a reduction of the optical bandgap energy at higher dopant contents. EPR data show that the shape of the resonance lines and the coordination geometry of the Cu²⁺ ions are influenced by the dopant concentrations. The analysis of the voltammetric data indicates that doping the recycled material with 20 mol% CuO and 10 mol% Sb₂O₃ eliminates the process of hydrogen evolution and reduces the anodic electrode passivation. Full article

Rhegmatogenous retinal detachment (RRD) is a sight-threatening condition involving retinal detachment and the accumulation of fluid in the subretinal space. Proliferative vitreoretinopathy (PVR) is a pathologic complication that develops after RRD surgery, and approximately 5–10% of RRD cases develop post-operative PVR. Prolonged inflammation in the wound healing process, epithelial–mesenchymal transition (EMT), retinal pigment epithelial (RPE) cell migration and proliferation, and epiretinal, intraretinal, and subretinal fibrosis are typical in the formation of PVR. RPE cells undergo EMT and become fibroblast-like cells that migrate to the retina and vitreous, promoting PVR formation. Fibroblasts transform into myofibroblasts, which promote fibrosis by overproducing the extracellular matrix (ECM). RPE cells, fibroblasts, glial cells, macrophages, T lymphocytes, and increased ECM production form contractile epiretinal membranes. Cytokine release, complement activation, RPE cells, glial cells, and endothelial cells are all involved in retinal immune responses. Normally, wounds heal within 4 to 6 weeks, including hemostasis, inflammation, proliferation, and remodeling phases. Properly initiated inflammation, complement activation, and the function of neutrophils and glial cells heal the wound in the first stage. In a retinal wound, glial cells proliferate and fill the injured area. Gliosis tries to protect the neurons and prevent damage, but it becomes harmful when it causes scarring. If healing is complicated, prolonged inflammation leads to pathological fibrosis. Currently, there is no preventive treatment for the formation of PVR, and it is worth studying in the future. Full article

In the search for alternative cementitious materials, the alkali activation of aluminosilicates has been found to be a mechanically effective binder. Among precursors, metakaolin is most frequently used, with a primary source, kaolin, distributed globally in varying compositions. This variability may indicate potential compositional limitations for the large-scale production of such binders. Thus, four types of commercial calcined clays, activated under identical conditions, were evaluated, and their physicochemical characteristics were correlated with the mechanical properties of the resulting binder. Different characterization methods were used for the raw material and for each alkali-activated system. Anhydrous metakaolin was assessed through particle size distribution, specific surface area, zeta potential, vitreous phases, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), amorphism, and pozzolanic activity. The pastes were evaluated in the fresh state through apparent activation energy progression and isothermal conduction calorimetry, and in the hardened state through compressive strength and dilatometry. Compressive strength values ranged from 7 to 42 MPa. From these results, a mathematical model was developed to estimate mechanical performance based on key variables, specifically amorphism, the pozzolanic index, and the silica-to-alumina ratio. This model allows for performance predictions without the need to prepare additional pastes. Interestingly, it was found that while some systems displayed low initial reactivity, their relative reactivity over time increased more significantly than those with higher early-stage reactivity, suggesting their potential for reconsideration in long-term applications. Full article

Thermal plasma is a versatile technology that can be used to treat various types of wastes, including vegetal and mineral oils, solvents, plastics, paper and cardboard, glasses, bricks and rocks, metals, clothes, and mixtures of these materials. In this study, we utilized a commercial plasma cutter as a thermal plasma source to decrease the volume of a simulated low-level radioactive mixed solid waste. The simulated waste included papers, plastics, clothes, gloves, metals, and stable Co, Cs, Sr, and Ce additives as surrogates of ⁶⁰Co, ¹³⁷Cs, ⁹⁰Sr, and ¹⁴⁴Ce, respectively, the latter being typical contaminants in nuclear LLW. As a result of the process, two products were obtained: a solid phase, on which we focused this work, and a gaseous phase. To retain as many as surrogates as possible in the solid final phase, crushed glass from broken bottles was included as a vitrification additive to the original waste. After undergoing heat treatment, a dense vitreous slag was produced along with ashes. The process resulted in a volume reduction of 70%, indicating the successful gasification of organic excess materials. The surrogate elements were retained in the process and were found in the ashes composition: Co (3.4% w/w), Cs (37.7% w/w), and Ce (0.6% w/w) and in the glass matrix composition of Co, Cs, Sr and Ce: 72.4 ± 14.7, 32 ± 18.2, 125.3 ± 31.6, 80 ± 13.1% w/w, respectively. For the actual experimental conditions, retention efficiencies were estimated for cobalt (Co) at 72.4 ± 14.7%, cerium (Ce) at 80 ± 13.1%, strontium (Sr) at 125.3 ± 31.6%, and notably cesium (Cs) at 32 ± 18.2%. Full article

Anti-VEGF agents, e.g., bevacizumab, are used in retinal surgery, while their interaction with silicone oils and novel hydrogels remains unclear. This study examines the in vitro pharmacokinetics of bevacizumab in silicone oil-filled eyes compared to various hydrogel replacements and the porcine vitreous body as well as its impact on the interface tension of silicone oils. An in vitro model filled with light or heavy silicone oil, porcine vitreous bodies, or hydrogels (alginate and polyethylene glycol (PEG)-based) was equilibrated with a balanced salt solution. Monitoring of bevacizumab in the aqueous phase was conducted for up to 24 h, and its effect on interfacial tension was studied. Significant differences in bevacizumab partitioning were observed across endotamponades after 24 h. In silicone oils, bevacizumab was found exclusively in the aqueous phase, while in the other endotamponades, it accumulated in the gel phase (96.1% in porcine vitreous body, 83.5% in alginate, and 27.6% in PEG-based hydrogel). Bevacizumab significantly reduced interfacial tension (40 to 8 mN/m), possibly enhancing silicone oil emulsification. The type of endotamponade heavily influenced the bevacizumab concentration in the aqueous. The vitreous body and replacement hydrogels likely serve as a drug reservoir, highlighting the need for in vivo studies to explore these interactions prior to clinical application. Full article

Previous studies reported the expression of toll-like receptors (TLRs), merely TLR2 and TLR4, and complement fragments (C3a, C5b9) in vitreoretinal disorders. Other than pathogens, TLRs can recognize endogenous products of tissue remodeling as damage-associated molecular pattern (DAMPs). The aim of this study was to confirm the expression of TLR2 and TLR4 in the fibrocellular membranes and vitreal fluids (soluble TLRs) of patients suffering of epiretinal membranes (ERMs) and assess their association with disease severity, complement fragments and inflammatory profiles. Twenty (n = 20) ERMs and twelve (n = 12) vitreous samples were collected at the time of the vitrectomy. Different severity-staged ERMs were processed for: immunolocalization (IF), transcriptomic (RT-PCR) and proteomics (ELISA, IP/WB, Protein Chip Array) analysis. The investigation of targets included TLR2, TLR4, C3a, C5b9, a few selected inflammatory biomarkers (Eotaxin-2, Rantes, Vascular Endothelial Growth Factor (VEGFA), Vascular Endothelial Growth Factor receptor (VEGFR2), Interferon-γ (IFNγ), Interleukin (IL1β, IL12p40/p70)) and a restricted panel of matrix enzymes (Matrix metalloproteinases (MMPs)/Tissue Inhibitor of Metallo-Proteinases (TIMPs)). A reduced cellularity was observed as function of ERM severity. TLR2, TLR4 and myD88 transcripts/proteins were detected in membranes and decreased upon disease severity. The levels of soluble TLR2 and TLR4, as well as C3a, C5b9, Eotaxin-2, Rantes, VEGFA, VEGFR2, IFNγ, IL1β, IL12p40/p70, MMP7 and TIMP2 levels were changed in vitreal samples. Significant correlations were observed between TLRs and complement fragments and between TLRs and some inflammatory mediators. Our findings pointed at TLR2 and TLR4 over-expression at early stages of ERM formation, suggesting the participation of the local immune response in the severity of disease. These activations at the early-stage of ERM formation suggest a potential persistence of innate immune response in the early phases of fibrocellular membrane formation. Full article

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin–Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies. Full article

The ranibizumab (RBZ) port delivery system (PDS) is a device designed to continuously deliver RBZ in the vitreous chamber for the treatment of neovascular age-related macular degeneration (nAMD). It is implanted during a surgical procedure and can provide sustained release of the medication for several months. This review, updated to January 2024, focuses on past clinical studies as well as current and forthcoming trials looking into a PDS with RBZ. In the phase 2 LADDER trial, the mean time to first refill of a PDS with RBZ 100 mg/mL was 15.8 months, with the pharmacokinetic (PK) profile showing a sustained concentration of RBZ in the blood and aqueous humor. More recently, a PDS with RBZ (100 mg/mL) refilled every 24 weeks was shown to be non-inferior to a monthly intravitreal injection (IVI) with RBZ (0.5 mg) over 40 and 92 weeks in the phase 3 ARCHWAY trial. The refill every 24 weeks allowed for a RBZ vitreous exposure within the concentration range of monthly intravitreal injections (IVIs), and the expected half-life (106 days) was comparable with the in vitro results. Nonetheless, vitreous hemorrhage and endophthalmitis were more common side effects in PDS patients. In conclusion, a PDS continuously delivering RBZ has a clinical effectiveness level comparable with IVI treatment. However, a greater frequency of unfavorable occurrences highlights the need for procedure optimization for a wider adoption. Ongoing trials and possible future approaches need to be addressed. Full article