Search Results (65)

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article

Background and Objectives: This study evaluates the safety, tolerability, and efficacy of preservative-free Dorzolamide 2%-Timolol 0.5% (PF-DT), with a focus on improving the ocular microenvironment in a real-world transition setting. Materials and Methods: A prospective, multicenter, open-label study involving thirty patients with dry eye disease previously treated with BAK-DT was conducted. Participants were transitioned to PF-DT, and evaluated at weeks 4, 12, and 24. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary outcomes included Break-Up Time (BUT), Schirmer test results, corneal staining, conjunctival hyperemia, intraocular pressure (IOP), and patient satisfaction. Results: Twenty-five patients completed the study. The OSDI improved from 21.5 to 12.5 (p < 0.001), with 60.0% of patients showing improvement and 52.0% achieving complete symptom resolution. Among eyes with corneal staining, 78.4% demonstrated a reduction of at least one grade, and 50.0% of those with conjunctival redness showed similar improvement. By week 24, 78.0% exhibited no corneal staining, and 50.0% had no conjunctival redness. BUT increased from 5.0 to 7.0 (p < 0.01), while IOP decreased by 1 mmHg (p < 0.01). Satisfaction regarding comfort (≥80%) and handling (≥50%) was high, with 88.0% preferring PF-DT. Conclusions: Transitioning to PF-DT improved ocular surface health while maintaining IOP control, supporting the benefits of preservative-free formulations in restoring microenvironment homeostasis and enhancing tolerability and patient satisfaction. Full article

The breakup process of molten metal is the most critical stage in atomization powder production. Conducting systematic research on the breakup process of molten metal during gas atomization is highly significant for understanding the formation mechanism of droplets. In this study, a mathematical model suitable for investigating the breakup mechanism of molten aluminum in high-speed gas atomization was developed by coupling large eddy simulation (LES) with the volume of fluid (VOF) model, incorporating adaptive mesh refinement technology and periodic boundary conditions. Furthermore, the breakup behavior of molten aluminum in two close-coupled atomizers with distinct delivery tube end geometric (non-expanded type and expanded type, abbreviated as ET atomizer and NET atomizer) were compared. The development of surface waves, as well as the formation mechanisms of liquid cores, liquid ligaments, and liquid droplets during gas atomization, were systematically analyzed. The results indicated that Kelvin–Helmholtz instability was the predominant factor contributing to the primary breakup of molten metals. For the NET atomizer, the recirculation zone predominantly governed the primary breakup of molten metal, whereas the nitrogen main jet primarily controlled the secondary breakup. In the case of ET atomizer, under the influence of atomizing gas, a “conical” liquid core gradually formed, and numerous primary liquid droplets separated from the liquid core before undergoing secondary breakup. Compared to the ET atomizer, the NET atomizer produced droplets with a smaller average size. Full article

Background: The present study assesses the effectiveness and tolerability of preservative-free travoprost in patients with primary open-angle glaucoma (POAG), focusing on intraocular pressure (IOP) reduction and ocular surface health over a six-month period. Methods: The study was prospectively designed and conducted at the University General Hospital of Alexandroupolis, Greece. A total of 45 patients diagnosed with either POAG or ocular hypertension (OHT) were included in the study; all were either newly diagnosed or had previously discontinued prostaglandin therapy due to intolerance. Of these, 39 participants completed the study. All subjects were administered preservative-free travoprost once daily. Clinical evaluations were conducted at baseline (T0), and at 1 month (T1), 3 months (T3), 6 months (T6) and 12 months (T12) following treatment initiation. The primary outcomes encompassed reductions in intraocular pressure (IOP), Schirmer test values, tear break-up time (TBUT), conjunctival hyperemia, as well as measurements of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness. Visual field parameters were also assessed. Results: A significant reduction in IOP was observed at T1, T3, T6 and T12 compared to baseline (p < 0.01). Schirmer test scores improved significantly from T0 to all subsequent time points (p < 0.01). Conjunctival hyperemia decreased significantly across follow-ups, while TBUT showed no significant change (p > 0.05). No significant changes were noted in mean deviation (MD), pattern standard deviation (PSD), RNFL, or GCC thickness over six months. Conclusion: Preservative-free travoprost effectively reduces IOP while improving ocular surface health, particularly in tear production and conjunctival hyperemia. Full article

The study of the dynamics during droplet breakup is fascinating to engineers. Some industrial applications include fire extinguishing by sprinkler systems, painting of various components, washing processes, and fuel spraying in internal combustion engines, which involve the interaction between liquid droplets, gaseous flow field, and walls. In this work, washing operations effectiveness of civil aviation aircraft engines is analyzed. Periodic washing operations are necessary to slow down the effects of particle deposition, e.g., gas turbine fouling, to reduce the specific fuel consumption and the environmental impact of the gas turbine operation. This analysis describes the dynamics in the primary breakup, related to the breakup of droplets due to aerodynamic forces, which occur when the droplets are set in motion in a fluid domain. The secondary breakup is also considered, which more generally refers to the impact of droplets on surfaces. The latter is studied with particular attention to dry surfaces, investigating the limits for different breakup regimes and how these limits change when the impact occurs with surfaces characterized by different wettability. Surfaces with different roughness are also compared. All the tested cases are referred to surfaces at ambient temperature. Dimensionless numbers generalize the analysis to describe the droplet behavior. The analysis is based on several data reported in the open literature, demonstrating how different washing operations involve different droplet breakup regimes, generating a non-trivial data interpretation. Impact dynamics, droplet characteristics, and erosion issues are analyzed, showing differences and similarities between the literature data proposed in the last twenty years. Washing operation and the effects of gas turbine fouling on the aero-engine performance are still under investigation, demonstrating how experiments and numerical simulations are needed to tackle this detrimental issue. Full article

Edible coatings are widely used to modulate oil uptake and moisture in fried foods. In this study, we evaluated a microfluid-assisted flow-blurring spray against conventional application by dipping/spraying, focusing on the coating efficiency and preliminary implications for sustainable process. This study combines benchtop experiments with a near-nozzle numerical analysis where the gas–liquid interface and primary breakup are modeled using the Volume of Fluid (VOF) approach implemented in OpenFOAM, configured for a flow-blurring geometry to generate whey protein isolate (WPI) coatings. Viscosity, density, solid content, and contact angle were validated experimentally and used in the simulation setup. An image-based droplet pipeline quantified spray characteristics, yielding a volumetric median diameter D₅₀ = 83.69 µm and confirming process uniformity. Contact angles showed marked substrate dependence: hydrophilic surfaces, 68°–85°; hydrophobic surfaces, 95°–110°. For turkey sausages, sessile-drop contact angles were not determinable (N.D.) due to wicking/roughness; wettability was therefore assessed on smooth surrogates and via performance metrics. Fit-for-purpose simulation procedures are outlined. Microfluidic application (WPI-McF) lowered oil uptake versus uncoated controls. Together, robust modeling, targeted image analytics, and high-precision microfluidics enable rational tuning of coating microstructure and barrier performance, offering a scalable pathway to reduce lipid content and enhance fried food quality. Full article

Purpose: The aim of this study was to evaluate the different approaches used in the treatment of meibomian gland dysfunction (MGD). Materials and Methods: This open-label, single-center, prospective pilot study with a parallel-group design was conducted in February 2025. Ninety-two patients presenting to our clinic with symptoms and signs of MGD were enrolled and diagnosed according to Japanese MGD diagnostic criteria. Patients were assigned to five treatment groups: conservative management alone, conservative management plus intense pulsed light (IPL) therapy, conservative management plus oral azithromycin, conservative management plus oral doxycycline, and conservative management plus topical cyclosporine. Conservative management consisted of preservative-free artificial tears containing polyvinyl alcohol and povidone, warm compresses, and eyelid hygiene. Primary outcome measures included ocular surface parameters such as the Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), Standard Patient Evaluation of Eye Dryness (SPEED) scores, and meibomian gland parameters evaluated using a slit-lamp examination. All parameters were assessed at baseline and during follow-up examinations after treatment initiation to observe changes in symptoms and signs. Results: A statistically significant increase was determined in meibum grade plugging (grades 0–3; higher = greater obstruction) and Marx line scores with IPL therapy (p < 0.05). The group receiving doxycycline treatment exhibited a significant improvement in OSDI and SPEED scores, plugging, TBUT, and meibum grades. The group receiving cyclosporine registered a significant improvement in OSDI and SPEED scores, plugging, TBUT, and meibum grades. A statistically significant increase was observed in the conservative treatment group in terms of lid margin irregularity, Marx line score, and OSDI and SPEED scores. In the group receiving azithromycin treatment, plugging, lid margin irregularity, TBUT, and OSDI and SPEED scores increased significantly. Compared with conservative care, the doxycycline group exhibited lengthened TBUT and lowered meibomian gland plugging and symptoms (p < 0.05), and the oral azithromycin group achieved a similar TBUT gain with slightly greater symptom relief. The topical cyclosporine group principally registered improved lid vascularity and meibum quality (p < 0.05), while the IPL group achieved the greatest overall improvements, reducing plugging and Marx line scores and adding ≈3 s to TBUT (p < 0.05 for all endpoints). Doxycycline exhibited notable short-term improvements, with 35.26% meibum grade improvement and a 40.48% foaming response, while IPL therapy demonstrated substantial OSDI improvements at 54.06%, with traditional parameters indicating limited treatment responsiveness. Conclusions: Various methods can be used in the treatment of MGD. All the conservative treatment methods used in this study were successful. Full article

The spray evaporation process in the boiler desuperheater involves complex droplet behaviors and fluid–thermal coupling, and its temperature distribution characteristics greatly affect the performance and safety of industrial processes. To better understand the process characteristics and develop the optimal desuperheater design, computational fluid dynamics (CFDs) was applied to numerically investigate the flow and thermal characteristics. The Eulerian–Lagrangian approach was used to describe the two-phase flow characteristics. Both primary and secondary droplet breakup, the coupling effect of gas–liquid and stochastic collision and coalescence of droplets were considered in the model. The plain-orifice atomizer model was applied to simulate the atomization process. The numerical model was validated with the plant data. The spray tube structure was found to greatly affect the flow pattern, resulting in the uneven velocity distribution, significant temperature difference, and local reverse flow downstream of the orifices. The velocity and temperature distributions tend to be more uniform due to the complete evaporation and turbulent mixing. Smaller orifices are beneficial for generating smaller-sized droplets, thereby promoting the mass and heat transfer between the steam and droplets. Under the same operating conditions, the desuperheating range of cases with 21, 15, and 9 orifices is 33.7 K, 32.0 K, and 29.8 K, respectively, indicating that the desuperheater with more orifices (i.e., with smaller orifices) shows better desuperheating ability. Additionally, a venturi-type desuperheater was numerically studied and compared with the straight liner case. By contrast, discernible differences in velocity and temperature distribution characteristics can be observed in the venturi case. The desuperheating range of the venturi and straight liner cases is 38.1 K and 35.4 K, respectively. The velocity acceleration through the venturi throat facilitates the droplet breakup and improves mixing, thereby achieving better desuperheating ability and temperature uniformity. Based on the investigation of the spray evaporation process, the complex droplet behaviors and fluid–thermal coupling characteristics in an industrial boiler desuperheater under high temperature and high pressure can be better understood, and effective guidance for the process and design optimizations can be provided. Full article

Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown benefits in promoting tear secretion and corneal healing. This study evaluated the safety and efficacy of insulin nanoemulsion eye drops (20 IU/mL, three times daily for 30 days) in patients with SjD. Thirty-two patients were randomized in a double-masked design to receive either insulin or placebo drops. Symptoms (assessed by OSDI questionnaire) and objective measures (tear film breakup time, corneal and conjunctival staining, and Schirmer Test) were recorded at baseline, after 4 weeks of treatment, and at a 4-week follow-up. Twenty-three participants completed the study. Both groups showed significant improvement in symptoms and objective signs after treatment (p < 0.05), but no significant differences were found between the insulin and placebo groups. No clinically relevant adverse effects were reported. Insulin nanoemulsion eye drops are safe for SjD patients, but their therapeutic advantage remains unclear. Further studies with larger samples, extended follow-up, and dose adjustments are needed to better understand their potential. Full article

The primary atomization of planar liquid sheets near nozzle exits plays a critical role in the study of pressure-swirl atomizers, yet its intrinsic destabilization and breakup mechanisms remain insufficiently characterized due to the multi-scale nature of gas–liquid interactions, significantly limiting the predictive capacity of current widely adopted atomization models. This study utilizes three-dimensional direct numerical simulations (DNSs) with adaptive mesh refinement and the Volume-of-Fluid (VOF) method to examine the instability and disintegration of a spatially developing planar liquid sheet under operating conditions representative of aero-engine combustors (thickness $h=100 \mathsf{\mu }\mathrm{m}$, $We=2544$, $Re=886$). Adaptive grid resolution (minimum cell size $2.5 \mathsf{\mu }\mathrm{m}$) enables precise resolution of multi-scale interface dynamics while maintaining mass conservation errors below 0.1‱. High-fidelity simulations reveal distinct atomization cascades originating from the jet tip, characterized by liquid sheet roll-up, interface expanding, interface tearing, and ligament/droplet formation. Through extraction and surface characterization of representative shed liquid ligaments, we quantify temporal and spatial variations between ligaments propagating toward and away from the jet core region. Key findings demonstrate that ligament impingement on the liquid core serves as the dominant mechanism for surface wave destabilization, surpassing the influence of initial gas–liquid shear at the nozzle exit. Spectral analysis of upstream surface waves reveals a pronounced correlation between high-wavenumber disturbances and the mean diameter of shed ligaments. These results challenge assumptions in classical atomization models (e.g., LISA) by highlighting self-destabilization mechanisms driven by droplet–ligament interactions. This work provides critical insights for refining engineering atomization models through physics-based ligament diameter prediction criteria. Full article

We propose a field mapping approach for the propagation of laser beams through atmospheric turbulence, leveraging a Generative Adversarial Network (GAN). The proposed GAN utilizes a U-Net architecture as its generator, with turbulence characteristic parameters introduced into the bottleneck layer of the U-Net network, enabling effective control over the generator. This design allows for the flexible simulation of Gaussian beam propagation across a range of turbulence intensities and transmission distances. A comparative analysis between the neural network predictions and numerical simulation results indicates that the neural network can achieve a field mapping speedup of four orders of magnitude while maintaining a relative error within 16% for the second-order statistical moments of the light spot. Additionally, the study investigates the effect of varying turbulence intensities on prediction accuracy. The results indicate that high-frequency speckle patterns caused by beam breakup are the primary factor limiting prediction accuracy under strong or saturated turbulence conditions. Full article

Background/Objectives: Epithelial basement membrane dystrophy (EBMD) is a common corneal dystrophy characterized by recurrent corneal erosions and visual impairments due to surface irregularities and opacities. This study aims to evaluate the effectiveness of alcohol-assisted delamination (ALD) of the corneal epithelium in patients with EBMD affecting the visual axis, who experience decreased vision quality due to higher-order aberrations (HOAs) and irregular astigmatism. Methods: Eleven eyes of nine patients (four males and five females) were treated with ALD, with a mean age of 51.3 ± 19.7 years. All patients underwent refraction, best-corrected visual acuity (BCVA) assessment, a comprehensive slit-lamp examination for EBMD pattern identification, anterior segment imaging with and without fluorescein, tear break-up time (BUT) testing, corneal topography, corneal aberrometry (Zernike coefficients ($Z_n^m$) were calculated for a 5.0 mm simulated pupil), and anterior segment optical coherence tomography preoperatively and at 1-day, 14-day, 1-month, 3-month, 6-month, and 12-month intervals. Results: All patients demonstrated improvements in BCVA and visual quality, ocular comfort, and BUT results. The mean root mean square (RMS) value of total corneal aberrations decreased from 1.72 ± 0.90 μm to 0.90 ± 0.62 μm, while the mean RMS value of HOAs reduced from 0.92 ± 0.48 μm to 0.53 ± 0.28 μm. Astigmatism and trefoil were the aberration components that exhibited the most significant reductions. Conclusions: Alcohol-assisted delamination of the corneal epithelium is a safe and effective treatment for central EBMD patients experiencing visual quality deterioration. Astigmatism and trefoil appear to be the primary aberrations contributing to visual disturbances in this patient population. Full article

The objectives of the study were to compare the efficacy and safety using ocular surface assessment between preserved and preservative-free brimonidine/timolol fixed-combination eye drops in glaucoma or ocular hypertension patients. Methods: This study was designed as a prospective, multicenter (three institutions), investigator-masked, parallel-grouped randomized clinical trial. The primary outcomes were corneal and conjunctival staining score, ocular surface disease index (OSDI) score, drug tolerance, and adherence rates at 12-week visits. The secondary outcomes were corneal and conjunctival staining score, OSDI score at 4-week visits and intraocular pressure (IOP), tear-film break-up time (TBUT), and bulbar/limbal hyperemia score at the 4- and 12-week visits. For safety assessment, best-corrected visual acuity (BCVA), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and physical examination at 4 and 12 weeks and adverse events during the whole study period were analyzed. Results: Overall, 59 patients were enrolled and randomized into each group (29 preserved and 30 preservative-free). At the endpoint, 5 patients in the preserved group and 2 patients in the preservative-free group dropped out, leaving 24 and 28 patients in the preserved and preservative-free groups, respectively. Baseline characteristics showed no significant difference between the groups including age and sex. At the 12-week visit, intra-group change of OSDI scores did not change significantly compared to the baseline scores in both preserved and preservative-free groups (p = 0.791, 0.478, respectively). On the contrary, the corneal staining score and the conjunctival staining score showed a significant increase compared to the baseline score in the preserved group (p = 0.015, 0.009, respectively). Regarding drug satisfaction, higher proportions of patients in the preservative-free group reported convenience of installation (p = 0.002). Also, stinging and burning sensations in drug tolerance showed better results in the preservative-free group with a significant difference (p = 0.011). Safety assessment regarding systemic side effects such as SBP, DBP, and HR showed similar results between the preserved and preservative-free groups (p = 0.711, 0.232, 0.666, respectively). Conclusions: Preservative-free brimonidine/timolol showed comparable efficacy and safety, better corneal and conjunctival staining score with convenience of installation, and lower stinging and burning sensation. It is expected to be a proper treatment option for patients with glaucoma or ocular hypertension. Full article

Ice jamming is the primary mechanism that can generate overland flooding and recharge the isolated basins of the Peace–Athabasca Delta (PAD), a valuable ecosystem of international importance and the ancient homeland of the Indigenous Peoples of the region. Focusing on the regulated Peace River and the Peace Sector of the delta, which has been experiencing a drying trend in between rare ice-jam floods over the last ~50 years, this study describes recent notable breakup events, associated observational data, and numerical applications to determine river discharge during the breakup events. Synthesis and interpretation of this material provide a new physical understanding that can inform the ongoing development of a protocol for strategic flow releases toward enhancing basin recharge in years when major ice jams are likely to form near the PAD. Additionally, several recommendations are made for future monitoring activities and improvements in proposed antecedent criteria for early identification of “promising” breakup events. Full article

The noise analysis of a large-scale aquaculture vessel reveals that during its navigation, the primary equipment noise, particularly from the propeller, exerts a notable influence on the aquaculture environment for large yellow croaker. The free surface greatly impacts the noise performance of propellers, which is a significant factor affecting the fish’s habitat. This study adopts the numerical simulation method to analyze the hydrodynamic and acoustic characteristics of the E1619 propeller operating near the free surface. The open-water performance and noise calculations of the propeller are verified through experiments, and the effects of different immersion depths and advance coefficients on the propeller are explored. The results demonstrate that the free surface significantly affects the thrust, torque, and noise of the propeller, especially at shallow immersion depths and low advance coefficients. Surface wave pattern causes the instability and breakup of tip vortices, causing increased thrust and torque fluctuations, reduced efficiency, and significant overall sound pressure levels in the entire flow field. As immersion depth and advance coefficients increase, the interaction between tip vortices and the free surface weakens, wake vortex instability decreases, and noise levels gradually reduce. These analyses and conclusions can guide the design of next-generation propellers for aquaculture vessels to optimize performance near the free surface. Full article