Cationic liposomes as promising vehicles for timolol/brimonidine combination ocular delivery in glaucoma: formulation development and in vitro/in vivo evaluation.

Glaucoma is a chronic eye disease in which the pressure inside the eye increases and leads to damage to the optic nerve, and eventually causes blindness. In this disease, it is often necessary to use a multi-drug treatment system. There is a fixed combination of timolol maleate and brimonidine tartrate among the combination drugs in glaucoma treatment. Liposomes are one of the most important targeted drug delivery systems to eye tissue, which leads to improved drug permeability and durability in ocular tissue. In this study, thin layer hydration was used to make liposomal formulations containing timolol maleate (TM) and brimonidine tartrate (BT). After the necessary evaluations, one of the eight initial formulations was selected as an optimization formulation. Then, characteristics such as drug loading percentage, particle size, pH, zeta potential, and drug release were performed on the optimized formulation. The study of reducing intraocular pressure was performed on the optimized formulation. This study in total was performed on 18 rabbits in three groups. Hydroxypropyl methylcellulose (HPMC) polymer was injected into the anterior chamber to experimental induce glaucoma. The selected formulation was within the acceptable range of ocular products in terms of physical properties. HPMC polymer injection successfully induced glaucoma in the animal model, resulting in a 79% increase in intraocular pressure. The results showed that the liposomal formulation significantly reduced the intraocular pressure compared to the simple formulation of the aqueous solution, and both formulations were able to significantly reduce the intraocular pressure compared to the control group (P < 0.001). The results also showed that liposomal formulation has a therapeutic effect in reducing intraocular pressure. It seems that the selected liposomal formulation made by thin layer hydration can act as a suitable drug carrier to increase the effectiveness of the fixed combination of timolol maleate and brimonidine tartrate and be proposed as a new drug formulation for targeted and controlled drug delivery in the treatment of glaucoma.

How is COVID-19 altering the manufacturing landscape? A literature review of imminent challenges and management interventions.

Disruption from the COVID-19 pandemic has caused major upheavals for manufacturing, and has severe implications for production networks, and the demand and supply chains underpinning manufacturing operations. This paper is the first of its kind to pull together research on both-the pandemic-related challenges and the management interventions in a manufacturing context. This systematic literature review reveals the frailty of supply chains and production networks in withstanding the pressures of lockdowns and other safety protocols, including product and workforce shortages. These, altogether, have led to closed facilities, reduced capacities, increased costs, and severe economic uncertainty for manufacturing businesses. In managing these challenges and stabilising their operations, manufacturers are urgently intervening by-investing in digital technologies, undertaking resource redistribution and repurposing, regionalizing and localizing, servitizing, and targeting policies that can help them survive in this altered economy. Based on holistic analysis of these challenges and interventions, this review proposes an extensive research agenda for future studies to pursue.

Comparing Sedative Effect of Dexmedetomidine versus Midazolam for Sedation of Children While Undergoing Computerized Tomography Imaging.

BACKGROUND: Pediatric anxiety and restlessness may create issues and difficulties in performing accurate diagnostic studies even noninvasive ones, such as radiological imaging. There are some agents that will help to get this goal. This study aimed to compare the intranasal effect of dexmedetomidine (DEX) and midazolam (MID) for sedation parameters of children undergoing computerized tomography (CT) imaging. MATERIALS AND METHODS: A double-blind clinical trial was conducted on 162 eligible children who underwent CT imaging. These patients were divided into two groups including MID (n = 81) with dose of 0.3 mg.kg and DEX (n = 81) with dose of 3 µg.kg, which was consumed intranasally. The mean blood pressure (MBP), respiratory rate (RR), heart rate (HR), and oxygen saturation (O2Sat) in children were recorded. Then, time of initiation, level of sedation, and duration effect of medication were measured at 0, 10, 20, and 30 min. Parents and clinician satisfaction score was asked. All data were analyzed using the Statistical Package for the Social Sciences (SPSS) software by t test and chi-square test. RESULTS: Decreasing in MBP and HR was higher in DEX group than MID group (P < 0.001), whereas decrease of O2Sat in MID group was higher than DEX group (0.009). Starting time of sedation (22.72 ± 11.64 vs. 33.38 ± 10.17, P = 0.001) was lower in DEX group. Parents (P < 0.001) and physician (P < 0.001) satisfaction score was higher in DEX group than the MID group. CONCLUSION: Using 3 µg/kg intranasal DEX for sedation of 1-6-year-old children was a suitable method to undergo noninvasive studies such as CT imaging. Intranasal DEX is superior to MID due to higher sedation satisfactory, faster starting effect of sedation, and lower side effects and complications. Nevertheless, in children with hemodynamic instability DEX is not an appropriate choice.

Operational Modal Analysis, Testing and Modelling of Prefabricated Steel Modules with Different LSF Composite Walls.

The modal properties of modular structures, such as their natural frequencies, damping ratios and mode shapes, are different than those of conventional structures, mainly due to different structural systems being used for assembling prefabricated modular units onsite. To study the dynamic characteristics of modular systems and define a dynamic model, both the modal properties of the individual units and their connections need to be considered. This study is focused on the former aspect. A full-scale prefabricated volumetric steel module was experimentally tested using operational modal analysis technique under pure ambient vibrations and randomly generated artificial hammer impacts. It was tested in different situations: [a] bare (frame only) condition, and [b] infilled condition with different configurations of gypsum and cement-boards light-steel framed composite walls. The coupled module-wall system was instrumented with sensitive accelerometers, and its pure and free vibration responses were synchronously recorded through a data acquisition system. The main dynamic characteristics of the module were extracted using output-only algorithms, and the effects of the presence of infill wall panels and their material are discussed. Then, the module's numerical micromodel for bare and infilled states is generated and calibrated against experimental results. Finally, an equivalent linear strut macro-model is proposed based on the calibrated data. The contribution of this study is assessing the effects of different infill wall materials on the dynamic characteristics of modular steel units, and proposing simple models for macro-analysis of infilled module assemblies.