Towards synergistic oscillations in enzymatically active hydrogel spheres.

Stimuli-responsive polymers are capable of reacting to an external trigger. We report self-regulated, enzymatically active, and pH-responsive hydrogels that show dynamic behavior without an external trigger. This is enabled by a feedback loop between the enzymatic conversion of glucose into gluconic acid and the pH-induced volume phase transition that leads to a modulation in glucose permeability. The synthesized hydrogel spheres combine all required properties for sustained oscillation including enzymatic activity, switchable reactivity, hysteresis in volume phase transition and feedback between the reaction and permeation. A simple model of the system identified possible operating points where sustained oscillations are possible. Experiments at these operating points revealed that the system is able to perform a self-regulated oscillation cycle under a constant nutrient supply. A sensitivity analysis showed that the system is especially sensitive around the point of oscillation, so that precise control of the process parameters is essential to achieve sustained oscillations.

Gonioscopy-assisted transluminal trabeculotomy in primary angle-closure glaucoma.

PURPOSE: This study aims to report on outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in eyes with primary angle-closure glaucoma (PACG). METHODS: This study is a prospective, interventional, non-comparative case series. A total of 103 eyes from 88 patients with PACG underwent an ab interno trabeculotomy, using either a 5.0 polypropylene suture or an illuminated microcatheter, with up to 24 months of follow-up. The main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, success rate (IOP reduction ≥ 20% from baseline or IOP between 6 and 21 mmHg, without further glaucoma surgery) and complication rate. RESULTS: The mean preoperative IOP was 21.4 (SD 7.4) mmHg using 2.5 (SD 1.1) glaucoma medications. These decreased postoperatively to 12.1 (SD 2.4) mmHg and 0.8 (SD 1.2) medications, at 24 months (P < 0.05). Success rate was 78% at 24 months of follow-up, and complication rate was 4.8%. CONCLUSION: At 24 months of follow-up, our results for GATT in PACG demonstrate that this procedure effectively lowers IOP in this subtype of glaucoma, with a low complication rate.

Catalytically Active Hollow Fiber Membranes with Enzyme-Embedded Metal-Organic Framework Coating.

Metal-organic frameworks (MOFs) are suitable enzyme immobilization matrices. Reported here is the in situ biomineralization of glucose oxidase (GOD) into MOF crystals (ZIF-8) by interfacial crystallization. This method is effective for the selective coating of porous polyethersulfone microfiltration hollow fibers on the shell side in a straightforward one-step process. MOF layers with a thickness of 8 µm were synthesized, and fluorescence microscopy and a colorimetric protein assay revealed the successful inclusion of GOD into the ZIF-8 layer with an enzyme concentration of 29±3 µg cm-2 . Enzymatic activity tests revealed that 50 % of the enzyme activity is preserved. Continuous enzymatic reactions, by the permeation of ß-d-glucose through the GOD@ZIF-8 membranes, showed a 50 % increased activity compared to batch experiments, emphasizing the importance of the convective transport of educts and products to and from the enzymatic active centers.

Advanced Therapies for Human Immunodeficiency Virus.

Human Immunodeficiency Virus (HIV) remains a significant global health challenge with approximately 38 million people currently having the virus worldwide. Despite advances in treatment development, the virus persists in the human population and still leads to new infections. The virus has a powerful ability to mutate and hide from the human immune system in reservoirs of the body. Current standard treatment with antiretroviral therapy effectively controls viral replication but requires lifelong adherence and does not eradicate the virus. This review explores the potential of Advanced Therapy Medicinal Products as novel therapeutic approaches to HIV, including cell therapy, immunisation strategies and gene therapy. Cell therapy, particularly chimeric antigen receptor T cell therapy, shows promise in preclinical studies for targeting and eliminating HIV-infected cells. Immunisation therapies, such as broadly neutralising antibodies are being investigated to control viral replication and reduce reservoirs. Despite setbacks in recent trials, vaccines remain a promising avenue for HIV therapy development. Gene therapy using technologies like CRISPR/Cas9 aims to modify cells to resist HIV infection or eliminate infected cells. Challenges such as off-target effects, delivery efficiency and ethical considerations persist in gene therapy for HIV. Future directions require further research to assess the safety and efficacy of emerging therapies in clinical trials. Combined approaches may be necessary to achieve complete elimination of the HIV reservoir. Overall, advanced therapies offer new hope for advancing HIV treatment and moving closer to a cure.

Evolution and Applications of Artificial Intelligence to Cataract Surgery.

Topic: Despite significant recent advances in artificial intelligence (AI) technology within several ophthalmic subspecialties, AI seems to be underutilized in the diagnosis and management of cataracts. In this article, we review AI technology that may soon become central to the cataract surgical pathway, from diagnosis to completion of surgery. Clinical Relevance: This review describes recent advances in AI in the preoperative, intraoperative, and postoperative phase of cataract surgery, demonstrating its impact on the pathway and the surgical team. Methods: A systematic search of PubMed was conducted to identify relevant publications on the topic of AI for cataract surgery. Articles of high quality and relevance to the topic were selected. Results: Before surgery, diagnosis and grading of cataracts through AI-based image analysis has been demonstrated in several research settings. Optimal intraocular lens (IOL) power to achieve the desired postoperative refraction can be calculated with a higher degree of accuracy using AI-based modeling compared with traditional IOL formulae. During surgery, innovative AI-based video analysis tools are in development, promoting a paradigm shift for documentation, storage, and cataloging libraries of surgical videos with applications for teaching and training, complication review, and surgical research. Situation-aware computer-assisted devices can be connected to surgical microscopes for automated video capture and cloud storage upload. Artificial intelligence-based software can provide workflow analysis, tool detection, and video segmentation for skill evaluation by the surgeon and the trainee. Mixed reality features, such as real-time intraoperative warnings, may have a role in improving surgical decision-making with the key aim of reducing complications by recognizing surgical risks in advance and alerting the operator to them. For the management of patient flow through the pathway, AI-based mathematical models generating patient referral patterns are in development, as are simulations to optimize operating room use. In the postoperative phase, AI has been shown to predict the posterior capsule status with reasonable accuracy, and can therefore improve the triage pathway in the treatment of posterior capsular opacification. Discussion: Artificial intelligence for cataract surgery will be as relevant as in other subspecialties of ophthalmology and will eventually constitute a future cornerstone for an enhanced cataract surgery pathway.

Wet-Spun PEDOT/CNT Composite Hollow Fibers as Flexible Electrodes for H2O2 Production.

The electrochemical synthesis of hydrogen peroxide (H2O2) using the oxygen reduction reaction (ORR) requires highly catalytic active, selective, and stable electrode materials to realize a green and efficient process. The present publication shows for the first time the application of a facile one-step bottom-up wet-spinning approach for the continuous fabrication of stable and flexible tubular poly(3,4-ethylene dioxythiophene) (PEDOT : PSS) and PEDOT : PSS/carbon nanotube (CNT) hollow fibers. Additionally, electrochemical experiments reveal the catalytic activity of acid-treated PEDOT : PSS and its composites in the ORR forming hydrogen peroxide for the first time. Under optimized conditions, the composite electrodes with 40 wt % CNT loading could achieve a high production rate of 0.01 mg/min/cm2 and a current efficiency of up to 54 %. In addition to the high production rate, the composite hollow fiber has proven its long-term stability with 95 % current retention after 20 h of hydrogen peroxide production.

Outcomes of gonioscopy-assisted transluminal trabeculotomy in pseudoexfoliative glaucoma: 24-month follow-up.

AIM: To report on outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in eyes with pseudoexfoliative glaucoma (PXG). METHODS: Prospective, interventional, non-comparative case series. A total of 103 eyes from 84 patients with PXG were enrolled to undergo a 360-degree ab interno trabeculotomy with gonioscopic assistance using either a 5.0 polypropylene suture or an illuminated microcatheter with up to 24 months of follow-up. Main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, success rate (IOP reduction ≥20% from baseline or IOP between 6 and 21 mm Hg, without further glaucoma surgery) and complication rate. RESULTS: Mean preoperative IOP was 27.1 mm Hg (95% CI 25.5 to 28.7) using 2.9 (SD 1.1) glaucoma medications which decreased postoperatively to 13.0 mm Hg (95% CI 11.5 to 14.4) and 1.0 (SD 1.1) medications at 24 months (p<0.001). Success rate was 89.2% at 24 months of follow-up, and complication rate was 2.9%. CONCLUSION: At 24 months of follow-up, our results for GATT in PXG demonstrate that this conjunctival sparing procedure effectively lowers IOP and reduces the medications with a low complication rate, in this relatively aggressive glaucoma subtype.

Impact Wear of the Protective Cr3C2-Based HVOF-Sprayed Coatings.

High velocity oxygen-fuel (HVOF) prepared CrC-based hardmetal coatings are generally known for their superior wear, corrosion, and oxidation resistance. These properties make this coating attractive for application in industry. However, under some loading conditions and in aggressive environments, the most commonly used NiCr matrix is not sufficient. The study is focused on the evaluation of dynamic impact wear of the HVOF-sprayed Cr3C2-25%NiCr and Cr3C2-50%NiCrMoNb coatings. Both coatings were tested by an impact tester with a wide range of impact loads. The Wohler-like dependence was determined for both coatings' materials. It was shown that, due to the different microstructure and higher amount of tough matrix, the impact lifetime of the Cr3C2-50%NiCrMoNb coating was higher than the lifetime of the Cr3C2-25%NiCr coating. Differences in the behavior of the coatings were the most pronounced at high impact loads.

Comparison of Lifetime of the PVD Coatings in Laboratory Dynamic Impact Test and Industrial Fine Blanking Process.

Protective hard PVD coatings are used to improve the endurance of the tools exposed to repeated impact load, e.g., fine blanking punches. During the fine blanking process, a coated punch repeatedly impacts sheet metal. Thus, the coating which protects the punch surface is exposed to the dynamic impact load. On the other hand, the laboratory method of dynamic impact testing is well known and used for the development and optimization of protective coatings. This paper is focused on the comparison of tool life and lifetime of the industrial prepared PVD coatings exposed to repeated dynamic impact load in the industrial fine blanking process and the laboratory dynamic impact testing. Three different types of protective coatings were tested and the results were discussed. It was shown that the lifetime of coated specimens in both the fine blanking and the dynamic impact processes was influenced by similar mechanical properties of the protective coatings. The qualitative comparison shows that the lifetime obtained by the dynamic impact test was the same as the lifetime obtained by the industrial fine blanking process. The laboratory impact test appears to be a suitable alternative for the optimisation and development of protective PVD coatings for punches used in the industrial fine blanking process.

Concurrent varicella and herpes simplex virus reactivation in the same trigeminal dermatome in a person living with HIV.

We report a case of a concurrent reactivation of varicella zoster virus and herpes simplex virus in an immunocompromised patient unaware of her longstanding human immunodeficiency virus (HIV) infection. Despite being a rare event, concurrent reactivation of the two alphaherpesvirinae has been reported in various conditions, either in immunocompetent or immunocompromised patients. However, a reactivation in the same anatomical location in a person living with HIV seems to be an extremely rare event.