Formulation and Development of Nanofiber-Based Ophthalmic Insert for the Treatment of Bacterial Conjunctivitis.

A novel ophthalmic delivery system utilizing levofloxacin-loaded, preservative-free, nanofiber-based inserts was investigated. Polyvinyl alcohol (PVA) and Poloxamer 407 (Polox)were employed as matrix materials, while hydroxypropyl-beta-cyclodextrin (HP-ß-CD) was a solubilizer. The formulations were prepared via electrospinning and characterized for fiber morphology, drug dissolution, cytotoxicity, and antimicrobial activity. Scanning electron microscopy confirmed uniform fibrous structures. Fourier Transform Infrared spectroscopy and X-ray diffraction analyses demonstrated the amorphous state of levofloxacin within the fibers. In vitro dissolution studies revealed a rapid (within 2 min) and complete drug release, with higher HP-ß-CD levels slightly delaying the release. Cytotoxicity tests showed increased HP-ß-CD concentrations induced irritation, that was mitigated by sodium hyaluronate. The antimicrobial efficacy of the nanofibers was comparable to conventional eye drops, with lower minimum inhibitory concentrations for most tested strains. The nanofibrous formulation prepared from a PVA-Polox-based viscous solution of the drug:CD 1:1 mol ratio, containing 0.4% (w/w) sodium hyaluronate) was identified as a particularly promising alternative formulation due to its rapid and complete dissolution, good biocompatibility, and effective antimicrobial properties. Its gelling properties indicate that the residence time on the eye surface can be increased, potentially reducing discomfort and enhancing therapeutic outcomes. The nanofibrous formulations enhanced antimicrobial efficacy, providing a preservative-free alternative that minimizes the potential eye irritation that might occur because of the preservative agent and reduces the administrated dose frequency by extending the drug's retention time on the eye's surface. Subsequently, it improves patients' adherence, which would reflect positively on the bioavailability. The levofloxacin-HP-ß-CD nanofibers demonstrate promise as an alternative to traditional eye drops, offering advantages in solubility, stability, and patient compliance for ocular infection treatment.

Dysregulation of the endothelial nitric oxide pathway is associated with airway inflammation in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is related to endothelial dysfunction and the impaired generation of nitric oxide (NO) from L-arginine by the endothelial NO synthase (eNOS). The relationship between eNOS dysfunctionality and airway inflammation is unknown. We assessed serum asymmetric and symmetric dimethylarginine (ADMA and SDMA) and nitrite/nitrate concentrations, indicators of eNOS function, in patients with COPD and correlated them with markers of inflammation. METHODS: We recruited 15 control smokers, 29 patients with stable and 32 patients with exacerbated COPD requiring hospitalization (20 of them were measured both at admission and discharge). Serum L-arginine, ADMA, SDMA, nitrite and nitrate were measured and correlated with airway inflammatory markers (fractional exhaled nitric oxide concentration - FENO, sputum nitrite and nitrate, sputum cellularity), serum C-reactive protein - CRP, white blood cell count, lung function and blood gases. ANOVA, t-tests and Pearson correlation were used (mean ± SD or geometric mean ± geometric SD for nitrite/nitrate). RESULTS: Serum L-arginine/ADMA, a marker of substrate availability for eNOS, was lower in stable (214 ± 58, p < 0.01) and exacerbated COPD (231 ± 68, p < 0.05) than in controls (287 ± 64). The serum concentration of SDMA, a competitor of L-arginine transport, was elevated during an exacerbation (0.78 ± 0.39 µM) compared to stable patients (0.53 ± 0.14 µM, p < 0.01) and controls (0.45 ± 0.14 µM, p < 0.001). ADMA correlated with blood neutrophil percentage (r = 0.36, p < 0.01), FENO (r = 0.42, p < 0.01) and a tendency for positive association was observed to sputum neutrophil count (r = 0.33, p = 0.07). SDMA correlated with total sputum inflammatory cell count (r = 0.61, p < 0.01) and sputum neutrophil count (r = 0.62, p < 0.01). Markers were not related to lung function, blood gases or CRP. L-arginine/ADMA was unchanged, but serum SDMA level decreased (0.57 ± 0.42 µM, p < 0.05) after systemic steroid treatment of the exacerbation. Serum nitrite level increased in stable and exacerbated disease (4.11 ± 2.12 and 4.03 ± 1.77 vs. control: 1.61 ± 1.84 µM, both p < 0.001). CONCLUSIONS: Our data suggest impaired eNOS function in stable COPD, which is transiently aggravated during an exacerbation and partly reversed by systemic steroid treatment. Serum ADMA and SDMA correlate with airway inflammatory markers implying a possible effect of anti-inflammatory therapy on endothelial dysfunction. Serum nitrite can serve as a compensatory pool for impaired endothelial NO generation.

Wartime scars or reservoirs of biodiversity? The value of bomb crater ponds in aquatic conservation.

Considering the ongoing loss of aquatic habitats, anthropogenic ponds are gaining importance as substitute habitats. It is therefore important to assess their functioning in comparison to their natural precursors. Here we assess the biodiversity value of sodic bomb crater ponds by comparing their gamma diversity to that of natural reference habitats, astatic soda pans, and assess their importance on the landscape level by studying alpha and beta diversity. We studied aquatic organisms ranging from algae to vertebrates in a dense cluster of 54 sodic bomb crater ponds in Central Europe. Despite the overall small area of the pond cluster, gamma diversity was comparable to that found in surveys of natural habitats that encompassed much wider spatial and temporal scales. We also found a considerable number of species shared with reference habitats, indicating that these anthropogenic habitats function as important refuge sites for several species that are associated with the endangered soda pans. Moreover, we found a number of regionally or worldwide rare species. Among the components of beta diversity, species replacement dominated community assembly. Individual ponds contributed similarly to beta diversity in terms of replacement, being equally important for maintaining high gamma diversity and emphasising the role of the pond network rather than individual ponds. This pattern was seen in all studied groups. Bomb crater ponds therefore acted as important contributors to aquatic biodiversity. Considering the tremendous losses of ponds throughout Europe, anthropogenic ponds should be taken into consideration in nature conservation, especially when occurring in pond networks.

Global Contract-level Public Procurement Dataset.

One-third of total government spending across the globe goes to public procurement, amounting to about 10 trillion dollars a year. Despite its vast size and crucial importance for economic and political developments, there is a lack of globally comparable data on contract awards and tenders run. To fill this gap, this article introduces the Global Public Procurement Dataset (GPPD). Using web scraping methods, we collected official public procurement data on over 72 million contracts from 42 countries between 2006 and 2021 (time period covered varies by country due to data availability constraints). To overcome the inconsistency of data publishing formats in each country, we standardized the published information to fit a common data standard. For each country, key information is collected on the buyer(s) and supplier(s), geolocation information, product classification, price information, and details of the contracting process such as contract award date or the procedure type followed. GPPD is a contract-level dataset where specific filters are calculated allowing to reduce the dataset to the successfully awarded contracts if needed. We also add several corruption risk indicators and a composite corruption risk index for each contract which allows for an objective assessment of risks and comparison across time, organizations, or countries. The data can be reused to answer research questions dealing with public procurement spending efficiency among others. Using unique organizational identification numbers or organization names allows connecting the data to company registries to study broader topics such as ownership networks.

Evaluation of floatability characteristics of gastroretentive tablets using VIS imaging with artificial neural networks.

Gastroretentive dosage forms are recommended for several active substances because it is often necessary for the drug to be released from the carrier system into the stomach over an extended period. Among gastroretentive dosage forms, floating tablets are a very popular pharmaceutical technology. In this study, it was investigated whether a rapid, nondestructive method can be used to characterize the floating properties of a tablet. To accomplish our objective, the same composition was compressed, and varied compression forces were applied to achieve the desired tablet. In addition to physical examinations, digital microscopic images of the tablets were captured and analyzed using image analysis techniques, allowing the investigation of the floatability of the dosage form. Image processing algorithms and artificial neural networks (ANNs) were utilized to classify the samples based on their strength and floatability. The input dataset consisted solely of the acquired images. It has been shown by our research that visible imaging coupled with pattern recognition neural networks is an efficient way to categorize these samples based on their floatability. Rapid and non-destructive digital imaging of tablet surfaces is facilitated by this method, offering insights into both crushing strength and floating properties.

Study on the dissolution improvement of albendazole using reconstitutable dry nanosuspension formulation.

The aim of the study was to improve the solubility and dissolution rate of the poorly water soluble drug albendazole via surfactant assisted media milling process. Preparation of a nanosuspension and then post-processing with a solidification technique applied to improve the applicability of nanosuspension in a solid dosage forms carrier. The dry nanosuspension was obtained using microcrystalline cellulose as solid carrier after tray drying at 40 °C. Both reconstitution from the solid carrier and dissolution profile studies were investigated in biorelevant Artificial Rumen Fluid (ARF) at pH = 6.50 and dissolution media at pH = 1.20 and pH = 6.80. Reconstitution studies have demonstrated that the mean hydrodynamic diameter values of albendazole crystals released from the dry suspension were nanosized (intensity weighted hydrodynamic diameter values: 200.40 ±â€¯2.318 nm in ARF at pH = 6.50, 197.17 ±â€¯0.208 nm in dissolution medium at pH = 6.80). Thermodynamic solubility studies have indicated a 2.98 times increase in water solubility (144.41 ±â€¯0.09 µg/ml milled, 48.38 ±â€¯0.01 µg/ml unmilled, 8.21 ±â€¯0.02 µg/ml albendazole powder) in ARF at pH = 6.50, and 2.33 times in dissolution medium at pH = 6.8: (146.27 ±â€¯0.28 µg/ml milled, 62.71 ±â€¯0.04 µg/ml unmilled, 9.00 ±â€¯0.01 µg/ml albendazole powder), and 13.65% increase at pH = 1.20 (1728.31 ±â€¯3.31 µg/ml milled, 1559.41 ±â€¯0.40 µg/ml unmilled, 1520.70 ±â€¯1.39 µg/ml albendazole powder), dissolution rates have also increased. Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM) imaging investigations detected no albendazole nanocrystals on the surface of the carrier, which demonstrated the incorporation of albendazole into the microcrystalline cellulose solid carrier structure.

Agent-based models for latent liquidity and concave price impact.

We revisit the "ɛ-intelligence" model of Tóth et al. [Phys. Rev. X 1, 021006 (2011)], which was proposed as a minimal framework to understand the square-root dependence of the impact of meta-orders on volume in financial markets. The basic idea is that most of the daily liquidity is "latent" and furthermore vanishes linearly around the current price, as a consequence of the diffusion of the price itself. However, the numerical implementation of Tóth et al. (2011) was criticized as being unrealistic, in particular because all the "intelligence" was conferred to market orders, while limit orders were passive and random. In this work, we study various alternative specifications of the model, for example, allowing limit orders to react to the order flow or changing the execution protocols. By and large, our study lends strong support to the idea that the square-root impact law is a very generic and robust property that requires very few ingredients to be valid. We also show that the transition from superdiffusion to subdiffusion reported in Tóth et al. (2011) is in fact a crossover but that the original model can be slightly altered in order to give rise to a genuine phase transition, which is of interest on its own. We finally propose a general theoretical framework to understand how a nonlinear impact may appear even in the limit where the bias in the order flow is vanishingly small.

Biogeography and phylogenetic position of a warm-stenotherm centric diatom, Skeletonema potamos (C.I. Weber) hasle and its long-term dynamics in the River Danube.

Skeletonema potamos is a poorly known freshwater species in the ancestrally and predominantly marine genus Skeletonema. With phylogenetic analysis of two nuclear {partial SSU (18S) and partial LSU (28S) rDNA)} and two chloroplast (rbcL and psbC) genes, we verified its placement within the genus Skeletonema and identified the mostly brackish species, Skeletonema subsalsum, as its closest known relative. Comparisons of SSU and LSU rRNA genes from S. potamos populations from Europe and North America revealed no intraspecific variation. Skeletonema potamos can be a dominant element of the phytoplankton community in various ecosystems, including the River Danube. We tracked phytoplankton composition in the River Danube weekly from 1979 to 2 012, and throughout this period, S. potamos exhibited a strong increase in proportion of total phytoplankton abundance and biomass - an increase that was correlated with increasing water temperature over the same time period. Current records indicate a temperate distribution of S. potamos, but ecological data predict possible expansion of its geographic range and increase in seasonal duration within existing habitats in response to the warming of surface waters.