Search Results (316)

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Background: Toxoplasma gondii is a globally widespread parasite responsible for toxoplasmosis, a zoonotic disease with significant impact on both human and animal health. The current lack of safe and effective treatments underscores the need for new drugs. Earlier, thiosemicarbazones (TSCs) and their metal complexes have shown promising activities against T. gondii. This study evaluated a gold (III) complex C3 and its TSC ligand C4 for safety in host immune cells and zebrafish embryos, followed by efficacy assessment in a murine model for chronic toxoplasmosis. Methods: The effects on viability and proliferation of murine splenocytes were determined using Alamar Blue assay and BrdU ELISA, and potential effects of the drugs on zebrafish (Danio rerio) embryos were detected through daily light microscopical inspection within the first 96 h of embryo development. The parasite burden in treated versus non-treated mice was measured by quantitative real-time PCR in the brain, eyes and the heart. Results: Neither compound showed immunosuppressive effects on the host immune cells but displayed dose-dependent toxicity on early zebrafish embryo development, suggesting that these compounds should not be applied in pregnant animals. In the murine model of chronic toxoplasmosis, C4 treatment significantly reduced the parasite load in the heart but not in the brain or eyes, while C3 did not have any impact on the parasite load. Conclusions: These results highlight the potential of C4 for further exploration but also the limitations of current approaches in effectively reducing parasite burden in vivo. Full article

Background/Objectives: Infectious endophthalmitis is a vision-threatening complication of intraocular surgery and intravitreal injections. Standard treatment involves intravitreal antibiotics; however, concerns regarding multidrug resistance and vancomycin-associated hemorrhagic occlusive retinal vasculitis (HORV) highlight the need for alternative antimicrobial strategies. This study aimed to evaluate the clinical efficacy and safety of a protocol combining intravitreal injection of 1.25% povidone-iodine (PI) with intraoperative irrigation using low concentrations of vancomycin and ceftazidime. Methods: We retrospectively analyzed 11 eyes from patients diagnosed with postoperative or injection-related endophthalmitis. Six of the eleven cases received an initial intravitreal injection of 1.25% PI, followed by pars plana vitrectomy with irrigation using balanced salt solution PLUS containing vancomycin (20 μg/mL) and ceftazidime (40 μg/mL). A second intravitreal PI injection was administered at the end of surgery in all cases. Additional PI injections were administered postoperatively based on clinical response. Clinical outcomes included best-corrected visual acuity (BCVA), microbial culture results, corneal endothelial cell density, and visual field testing. Results: All eyes achieved complete infection resolution without recurrence. The mean BCVA improved significantly from 2.18 logMAR at baseline to 0.296 logMAR at final follow-up (p < 0.001). No adverse events were observed on specular microscopy or visual field assessment. The protocol was well tolerated, and repeated PI injections showed no signs of ocular toxicity. Conclusions: This combination protocol provides a safe and effective treatment strategy for infectious endophthalmitis. It enables rapid and complete infection resolution while minimizing the risks associated with intravitreal antibiotics. These findings support further investigation of this protocol as a practical and globally accessible alternative to standard intravitreal antimicrobial therapy. Full article

The present study investigated the neuroprotective potential of the Murraya carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T) of the carbazole derivatives were assessed to evaluate their prospects as up-and-coming drug candidates. Molecular docking was used to investigate the interactions of the compounds with Aβ (PDB: 1IYT, 2BEG, and 8EZE) and AChE receptors (PDB: 4EY7 and 1C2B). The results from the in vitro assays were used to validate and support the findings from the in silico assays. The compounds demonstrated significant inhibition of acetylcholinesterase (AChE), a key target in neurodegenerative disorders. Murrayanol and mahanimbine presented superior inhibitory activity (IC₅₀ ~0.2 μg/mL), outperforming the reference drug, galantamine. The inhibition mechanisms were competitive (murrayanol, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde) and non-competitive (mahanimbine), supported by low Ki values and strong docking affinities. The compounds also proved effective in reducing Aβ fibrillization (murrayanol: 40.83 ± 0.30%; murrayafoline A: 33.60 ± 0.55%, mahanimbine: 27.68 ± 2.71%). These findings highlight Murraya carbazoles as promising scaffolds for multifunctional agents in AD therapy. Further optimization and mechanistic studies are warranted to advance their development into clinically relevant neuroprotective agents. Full article

Background/Objectives: In rhegmatogenous retinal detachment (RRD), vitreous cortex remnants (VCRs) may contribute to the development and progression of proliferative vitreoretinopathy (PVR). This study aimed to evaluate potential toxicity and trauma secondary to VCRs visualization and removal during pars plana vitrectomy (PPV) for RRD. Methods: Prospective study on patients with primary RRD who underwent PPV. Imaging assessment included widefield OCT (WF-OCT), ultra-WF retinography and fundus autofluorescence (FAF). During PPV, a filtered and diluted triamcinolone acetonide (TA) solution (20 mg/mL) was used to evaluate the presence and extension of VCRs, removed using an extendible diamond-dusted sweeper (EDDS). After six months, retinal and retinal pigment epithelium toxicity and retinal trauma due to VCRs removal were investigated. Results: Retinal reattachment was achieved in 21/21 cases included in the study. No signs of retinal or RPE toxicity were detected and WF-OCT performed in the areas of VCRs removal revealed an intact inner retinal architecture in the majority of eyes, with minor and localized inner retinal indentations in 4 cases. Conclusions: VCRs visualization and removal using TA and EDDS appears to be safe, with no retinal toxicity and very limited and circumscribed mechanical trauma. This approach may contribute to reducing the risk of postoperative PVR. Full article

Background/Objectives: Haloperidol is a typical antipsychotic drug widely used for acute confusional state, psychotic disorders, agitation, delirium, and aggressive behavior. Methods: The toxicity of haloperidol was studied using zebrafish (ZF) embryos as a model organism. Dechorionated embryos were exposed to various concentrations of haloperidol (0.5–6.0 mg/L). The lethal dose concentration was estimated and was found to be 1.941 mg/L. Results: The impact of haloperidol was dose-dependent and significant from 0.25 mg/L. Haloperidol induced several deformities at sublethal doses, including abnormal somites, yolk sac edema, and skeletal deformities. Haloperidol significantly affected heart rate and blood flow and induced pericardial edema and hyperemia in a dose-dependent manner, suggesting its influence on heart development and function. Embryos exposed to haloperidol during their ontogenetic development had smaller body length and eye surface area than non-exposed ones in a dose-dependent manner. Conclusions: It was found that haloperidol significantly affects the behavior of the experimental organisms in terms of mobility, reflexes to stimuli, and adaptation to dark/light conditions. Full article

Background/Objectives: Simplexvirus humanalpha1 (HSV-1) can cause herpetic keratitis, which is the most common cause of infectious blindness in developed countries. Some patients can develop toxicity or resistance to available treatments and may require keratoplasty. Methods: As an alternative therapy, the CRISPR/Cas9 anti-HSV-1 activity was assessed in an experimental model of BALB/c mice. Results: The results showed that the viral load in the eyes of mice inoculated with HSV-1 at 10⁷ PFU/mL was 4.5 ± 0.2 log₁₀ copies/mL. In contrast, mice inoculated with 10⁹ PFU/mL exhibited a high viral load of 8.1 ± 0.4 log₁₀ copies/mL. The detection of HSV-1 DNA and lesions in the eye was consistent with the viral inoculum of the infection. Next, antiviral activity showed that 200 ng/µL of CRISPR/Cas9 reduced the viral load by 2 logs (p ≤ 0.0001), as well as the lesion scores, compared to the untreated group. Conclusions: Together, the data suggest that CRISPR/Cas9 could be investigated as an alternative therapy for ocular herpes. Full article

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

Nowadays, a significant portion of the population uses eye cosmetics, a trend that is not limited to women, as men increasingly adopt stylish makeup techniques. Eye cosmetics, often termed eye makeup, include a diverse array of products such as eyelash enhancers (mascara, false eyelashes, growth serums, and dyes), eyelid products (eyeliner, kohl, eye contour cream, and eyeshadow), and eye makeup removers. There is a persistent interest among dermatologists in the influence of eye cosmetics on the skin surrounding the eye. The formulation of these cosmetics typically consists of various ingredients, some of which may present potential health risks to users. The application of eye cosmetics is linked to a range of adverse effects on the ocular surface, which may manifest as mechanical injury, tear film instability, toxicity, inflammation, and infections. Therefore, the use of cosmetics in this sensitive area is of paramount importance, necessitating a cooperative approach among eyecare professionals, dermatologists, and beauty experts. Despite the widespread use of eye makeup, its possible ocular side effects have not been sufficiently addressed. This report aims to elucidate how the use of eye cosmetics represents a lifestyle challenge that may exacerbate or initiate ocular surface and adnexal disorders. Full article

Eugenol-based azo dyes illustrate how bio-sourced compounds like eugenol can be transformed through synthetic processes into functional and colorful compounds. The main purpose of the present work was to develop new responsive colorimetric sensors for metal cations based on eugenol-derived azo compounds. The incorporation of the azo group into the eugenol framework allows for strong electronic interactions with metal cations, leading to distinct color changes observable to the naked eye. These azo-eugenol dyes exhibit shifts in their UV-Vis absorption spectra upon complexation with metal cations such as copper (Cu²⁺) and lead (Pb²⁺), making them effective sensors for environmental and analytical applications. The eugenol-based azo dyes were subjected to photophysical studies to understand selectivity, response time, and stability in relation to metal cations, which will be a starting point for the monitoring of toxic metal contaminants in aqueous environments. Full article

Dry age-related macular degeneration (AMD) is a leading cause of vision loss in individuals over 50, yet no approved therapies exist for early or intermediate stages of the disease. Oxidative stress is a central driver of retinal degeneration in AMD, and sodium iodate (NaIO₃)-induced injury serves as a well-characterized model of oxidative damage to the retinal pigment epithelium (RPE) and photoreceptors. BMI1, a poly-comb group protein involved in DNA repair, mitochondrial function, and cellular renewal, has emerged as a promising therapeutic target for retinal neuroprotection. We evaluated the efficacy of AAV-mediated BMI1 gene delivery in murine models using two administration routes: subretinal (SR) and suprachoroidal (SC). AAV5.BMI1 (1 × 10⁹ vg/eye) was delivered SR in Balb/c mice and evaluated at 4 and 15 weeks post-injection. AAV8.BMI1 (5 × 10⁹ or 1 × 10¹⁰ vg/eye) was administered SC in C57BL/6 mice and assessed at 4 weeks. Control groups received BSS or AAV8.stuffer. Following NaIO₃ exposure, retinal structure and function were analyzed by optical coherence tomography (OCT), electroretinography (ERG), histology, and molecular assays. SC delivery of AAV8.BMI1 achieved the highest levels of retinal BMI1 expression with no evidence of local or systemic toxicity. Treated eyes showed dose-dependent preservation of outer nuclear layer (ONL) thickness and significantly improved ERG responses indicating structural and functional protection. These findings support SC AAV.BMI1 gene therapy as a promising, minimally invasive, and translatable approach for early intervention in intermediate AMD. Full article

Severe bushfires in South-Eastern Australia during the summer of 2019/2020 killed tens of thousands of livestock, while many more survived on fire-affected properties. At the time, the literature on bushfire and livestock in Australia primarily described animals with burns. The mid- to long-term health effects, if any, of fire exposure and the effectiveness of recovery activities for surviving animals and farm enterprises were rarely reported. This study aimed to describe the key impacts of bushfire exposure on the health, welfare, and management of surviving cattle and sheep to inform recommendations for future fire-affected farmers and to guide future research. As part of a broad research programme, data on bushfire experiences, consequences for the livestock and the farm enterprise, and lessons learnt were gathered through face-to-face interviews and an online survey, collating information from 58 fire-affected farmers. A variety of health conditions at low frequency were reported in livestock surviving bushfires, including respiratory disease, eye disease, ruminal acidosis, lameness, and plant toxicities. No single disease was observed widely across participating farms, with many conditions likely associated with management changes post-fire rather than direct fire exposure. A variety of management and farm biosecurity challenges were also described by farmers. Key strategies for the prevention and treatment of health conditions in livestock post-bushfire include supporting effective farm management through the challenges of post-fire recovery and early detection for treatment on a case-by-case basis. Full article

Background: Intra-arterial chemotherapy (IAC) is increasingly useful for treating intraocular retinoblastoma (Rb). It offers targeted delivery of chemotherapy with reduced systemic exposure. In this study, we evaluate management outcomes and identify predictive factors for globe salvage following IAC in children with Rb. Methods: This retrospective study included 20 eyes of 20 melphalan-based IAC-treated patients (67 sessions) between 2015 and 2023 in a tertiary cancer center (King Hussein Cancer Center) in Jordan. Data collection included patients’ demographics, tumor staging, eye salvage, complications, and survival, followed by statistical comparisons between eye salvage rates and clinical factors. Results: The median age of IAC initiation was 38 months (range: 6–78 months). IAC was used as a primary treatment in 35% (7/20) of eyes and as a secondary treatment following systemic chemotherapy in 65% (13/20) of eyes. Nineteen (95%) eyes showed initial tumor regression, 15 (75%) eyes showed short term tumor control, and long-term eye salvage was achieved in 11 (55%) eyes. Poor prognostic factors for eye salvage included advanced tumor stage (Group D/E: 43% salvage rate vs. Group C: 83%; p = 0.047), vitreous seeding at the time of IAC (38% with seeding vs. 75% without; p = 0.046), use of IAC as a secondary rather than a primary treatment (46% vs. 71%; p = 0.047), and the need for >3 IAC cycles (20% success with >3 cycles vs. 67% with ≤3 cycles; p = 0.034). Complications were notable: systemic adverse effects were seen in five (25%) patients, including neutropenia (20%) and bronchospasm (6%). Procedure-related complications were seen with 22% of injections, including failure of the procedure (7%), ophthalmic artery spasm (6%), and intra-procedural stroke (3%). Five (25%) eyes developed ocular complications, including vitreous hemorrhage (15%), retinal detachment (10%), optic atrophy (10%), and retinal or choroidal ischemia (10%). Notably, all infants under 12 months of age (4/4) developed complications, including the two events of stroke. At a median follow-up of 60 months, eye salvage was achieved in 11 (55%) eyes, and none of the 9 (45%) enucleated eyes showed high-risk pathological features. There was no orbital recurrence, and one (5%) child developed CNS metastasis and passed away. Conclusion: IAC achieves long-term globe salvage in 55% of Rb cases; however, outcomes are poorer with Group D/E tumors, vitreous seeds, prior IVC failure, or requiring >3 IAC cycles. While reducing systemic chemotherapy toxicity, IAC carries significant risks of vision- and life-threatening complications. Infants and single-eyed patients require particularly cautious consideration. Though IAC remains crucial for globe preservation, optimal implementation demands improved patient selection criteria, multicenter collaboration, and long-term outcome studies to maximize safety and efficacy. Full article

The rapid pace of modern life has contributed to a significant decline in sleep quality, which has become an urgent global public health issue. Melatonin, an endogenous hormone that regulates circadian rhythms, is vital in maintaining normal sleep cycles. While oral melatonin supplementation is widely used, transdermal delivery systems present advantages that include the avoidance of first-pass metabolism effects and enhanced bioavailability. In this study, a novel melatonin transdermal delivery system was successfully developed using a thermosensitive poly(N-vinylcaprolactam) [p(NVCL)]-based carrier. The p(NVCL) polymer was synthesized through free radical polymerization and characterized for its structural properties and phase transition temperature, in alignment with skin surface conditions. Orthogonal optimization experiments identified 3% azone, 3% menthol, and 4% borneol as the optimal enhancer combination for enhanced transdermal absorption. The formulation demonstrated exceptional melatonin loading characteristics with high encapsulation efficiency and stable physicochemical properties, including an appropriate pH and optimal moisture content. Comprehensive in vivo evaluation using normal mouse models revealed significant sleep quality improvements, specifically a shortened sleep latency and extended non-rapid eye movement sleep duration, with elevated serum melatonin and serotonin levels. Safety assessments including histopathological examination, biochemical analysis, and 28-day continuous administration studies confirmed excellent biocompatibility with no adverse reactions or systemic toxicity. Near-infrared fluorescence imaging provided direct evidence of enhanced transdermal absorption and superior biodistribution compared to oral administration. These findings indicate that the p(NVCL)-based melatonin transdermal gel system offers a safe, effective and convenient non-prescription option for sleep regulation, with promising potential for clinical translation as a consumer sleep aid. Full article

Selenium (Se) is an essential trace element required for various physiological functions in agriculture. Nanotechnology is applied to produce selenium nanoparticles (SeNPs) that offer new advantages, enhancing their bioavailability and reducing toxicity. To further improve the stability of Se nanoelements in the poultry industry, the grey form of Se was recently offered as a potential alternative. However, its impact on bioaccessibility, metabolism, and overall animal efficiency remains undetermined. This study investigates the impact of red and grey SeNPs on Se content in the liver, blood cellular fraction (BCF), kidney, testis, and eyes, as well as the feed intake (FI) and growth performance, of adult Japanese quails. Adult quails were randomly assigned to five groups: a control (C0) and four groups receiving either red or grey Se nanoparticles (SeNPs) at 0.05 or 0.5 mg/kg, in addition to the basal diet which already contained 0.042 mg/kg Se from the premix, resulting in total Se contents of approximately 0.092 and 0.542 mg/kg in the treatment groups (T1–T4), with four replicates per group. The growth performance of quails fed with nano-Se-supplemented diets showed significant variation across groups (p < 0.05), with body weight differing by up to 20% between the highest performing group (T2) and the lowest (T1). FI showed no significant differences across groups. The results indicated that Se accumulation differed significantly between treatments. The selenium levels in the liver increased in a dose-dependent manner, with the highest accumulation observed in T4 (0.5 mg/kg grey SeNPs), at 42% above control levels. This pattern suggests that the liver is a primary organ for selenium storage and metabolism. The greatest Se content in BCFs was recorded in the groups that received grey selenium (T3 and T4) and red selenium at high concentrations (T2), while the group given red selenium at low concentrations (T1) and the control (C0) had the lowest Se accumulation. In the kidney tissues and testis, the Se content exhibited no significant differences between the treated groups and the control. The observed variations in the eye and breast muscle Se content among treatment groups reflect the differences in selenium bioavailability, metabolism, and tissue-specific regulatory mechanisms. These findings demonstrate that grey SeNPs can significantly elevate Se bioavailability in quails, particularly in target organs, and enhance the growth performance without notable changes in feed intake. This highlights the potential of SeNPs in enhancing quail nutrition, although further research is needed to establish optimal dosing strategies for safe, effective use. Full article