Fexofenadine-loaded chitosan coated solid lipid nanoparticles (SLNs): A potential oral therapy for ulcerative colitis.

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.

What makes Ethereum blockchain transactions be processed fast or slow? An empirical study.

The Ethereum platform allows developers to implement and deploy applications called ÐApps onto the blockchain for public use through the use of smart contracts. To execute code within a smart contract, a paid transaction must be issued towards one of the functions that are exposed in the interface of a contract. However, such a transaction is only processed once one of the miners in the peer-to-peer network selects it, adds it to a block, and appends that block to the blockchain This creates a delay between transaction submission and code execution. It is crucial for ÐApp developers to be able to precisely estimate when transactions will be processed, since this allows them to define and provide a certain Quality of Service (QoS) level (e.g., 95% of the transactions processed within 1 minute). However, the impact that different factors have on these times have not yet been studied. Processing time estimation services are used by ÐApp developers to achieve predefined QoS. Yet, these services offer minimal insights into what factors impact processing times. Considering the vast amount of data that surrounds the Ethereum blockchain, changes in processing times are hard for ÐApp developers to predict, making it difficult to maintain said QoS. In our study, we build random forest models to understand the factors that are associated with transaction processing times. We engineer several features that capture blockchain internal factors, as well as gas pricing behaviors of transaction issuers. By interpreting our models, we conclude that features surrounding gas pricing behaviors are very strongly associated with transaction processing times. Based on our empirical results, we provide ÐApp developers with concrete insights that can help them provide and maintain high levels of QoS.

Construction of Porous Organic/Inorganic Hybrid Polymers Based on Polyhedral Oligomeric Silsesquioxane for Energy Storage and Hydrogen Production from Water.

In this study, we used effective and one-pot Heck coupling reactions under moderate reaction conditions to construct two new hybrid porous polymers (named OVS-P-TPA and OVS-P-F HPPs) with high yield, based on silsesquioxane cage nanoparticles through the reaction of octavinylsilsesquioxane (OVS) with different brominated pyrene (P-Br4), triphenylamine (TPA-Br3), and fluorene (F-Br2) as co-monomer units. The successful syntheses of both OVS-HPPs were tested using various instruments, such as X-ray photoelectron (XPS), solid-state 13C NMR, and Fourier transform infrared spectroscopy (FTIR) analyses. All spectroscopic data confirmed the successful incorporation and linkage of P, TPA, and F units into the POSS cage in order to form porous OVS-HPP materials. In addition, the thermogravimetric analysis (TGA) and N2 adsorption analyses revealed the thermal stabilities of OVS-P-F HPP (Td10 = 444 °C; char yield: 79 wt%), with a significant specific surface area of 375 m2 g-1 and a large pore volume of 0.69 cm3 g-1. According to electrochemical three-electrode performance, the OVS-P-F HPP precursor displayed superior capacitances of 292 F g-1 with a capacity retention of 99.8% compared to OVS-P-TPA HPP material. Interestingly, the OVS-P-TPA HPP showed a promising HER value of 701.9 µmol g-1 h-1, which is more than 12 times higher than that of OVS-P-F HPP (56.6 µmol g-1 h-1), based on photocatalytic experimental results.

Silent bleeding in children and adolescents with immune thrombocytopenia: relation to laboratory parameters and health related quality of life.

Occult hemorrhage can occur in any internal organ in ITP patients. Four sites of occult hemorrhage require attention including microscopic hematuria, fecal occult blood loss, retinal hemorrhage, and silent intracranial hemorrhage. The aim of this study was to investigate the frequency of subclinical bleeding in children with ITP and its relation to clinical and laboratory disease parameters including bleeding score and health related quality of life. This cross-sectional study included 40 ITP patients recruited from the Pediatric Hematology/Oncology unit, Children's Hospital, Ain Shams University, Cairo, Egypt. Inclusion criteria were patients with ITP (acute, persistent or chronic) having platelet count of 20,000/cmm or less at diagnosis/relapse, patients with overt bleeding and patients with secondary ITP were excluded. Occult blood in stools and urine analysis, fundus examination, and non-contrast brain MRI for microbleeds were done. Out of the forty included patients, 24 had chronic, 11 had acute and 5 had persistent ITP. Eleven patients had occult bleeds. Two patients had occult blood in stools, five had microscopic hematuria, one had retinal bleeds and three patients had brain microbleeds. Their mean age was 10.23 ± 4.18 years and their mean initial bleeding score was 2.55 ± 0.82. Nine patients with occult bleeding were chronic, one persistent and one acute ITP patients. There were no significant differences between patients with occult bleeding and those without as regards the initial bleeding score, platelet counts and hemoglobin level, as well as the mean platelet counts and mean hemoglobin level over the disease duration (p > 0.5). The scoring of the parent's life, Child and parents' quality of life was low in 3 out of 11 patients with occult bleeding. There was no significant difference between patients with occult bleeding and those without as regards the ITP child and parents' quality of life items (p = 0.850 and 0.511 respectively). Our results suggest that subclinical bleeding is a potential risk in children with ITP, more commonly chronic ITP patients. We could not demonstrate a significant relation of occult bleeding to the laboratory findings, bleeding score, and the ITP health quality of life; nevertheless, the significance of the routine assessment of occult bleeding in ITP and the identification of high-risk patients require additional studies.

Diagnostic accuracy of intermediate b-value diffusion-weighted imaging for detection of residual hepatocellular carcinoma following transarterial chemoembolization with drug-eluting beads.

PURPOSE: To evaluate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the detection of residual malignant tumor of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) with drug-eluting beads (DEBs). SUBJECTS AND METHODS: Pre-contrast T1, T2, dynamic contrast-enhanced, and respiratory-triggered DW-MRI (b factor 0, 400, and 800 s/mm2) were obtained in 60 patients with HCC who underwent tran-sarterial hepatic chemoembolization with DEBs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the DW imaging images. Apparent diffusion coefficients (ADCs) were calculated searching for the optimal cut-off value using the receiver operating characteristic (ROC) curve. RESULTS: DW-MRI had a sensitivity of 77.1%, a specificity of 60.7%, a PPV of 71.05%, and a NPV of 68%. The difference between the malignant and benign groups' ADC variables was statistically significant (P < 0.003). The ROC curve showed that the area under the curve is C = 0.718 with SE = 0.069 and 95% confidence interval from 0.548 to 0.852. CONCLUSION: In our study, we demonstrated that diffusion MRI has limited diagnostic value in the assessment of viable tumor tissue after TACE with DEBs in cases of HCC.

Contaminant transport in groundwater in the presence of colloids and bacteria: model development and verification.

Colloids and bacteria (microorganisms) naturally exist in groundwater aquifers and can significantly impact contaminant migration rates. A conceptual model is first developed to account for the different physiochemical and biological processes, reaction kinetics, and different transport mechanisms of the combined system (contaminant-colloids-bacteria). All three constituents are assumed to be reactive with the reactions taking place between each constituent and the porous medium and also among the different constituents. A general linear kinetic reaction model is assumed for all reactive processes considered. The mathematical model is represented by fourteen coupled partial differential equations describing mass balance and reaction processes. Two of these equations describe colloid movement and reactions with the porous medium, four equations describe bacterial movement and reactions with colloids and the porous medium, and the remaining eight equations describe contaminant movement and its reactions with bacteria, colloids, and the porous medium. The mass balance equations are numerically solved for two-dimensional groundwater systems using a third-order, total variance-diminishing scheme (TVD) for the advection terms. Due to the complex coupling of the equations, they are solved iteratively each time step until a convergence criterion is met. The model is tested against experimental data and the results are favorable.

Experimental and numerical iInvestigations of effects of silica colloids on transport of strontium in saturated sand columns.

Transport experiments with strontium were conducted using saturated sand columns in the presence and absence of silica colloids, and numerical modeling was performed with modeling results compared to experimental data. The experiments were aimed at testing the hypothesis that under certain chemical conditions colloids act as movement-retarding agents and yield a larger effective retardation factor for the migrating contaminant. Four individual experiments were conducted to identify conditions where the mobility of silica colloids is increased or decreased, and a similar set was conducted for strontium transport in the absence of colloids. Mobility of colloids was found to increase with decreasing ionic strength and increasing pH, with the ionic strength having the more significant impact. The reverse effect was obtained for strontium. Based on these results, two additional experiments were conducted where both colloids and strontium were injected at the column inlet. Results showed that under certain conditions of ionic strength and pH (I = 3.0 x 10(-2) M and pH = 4-5.4) colloids retarded the movement of strontium. The retardation effect was obtained in two experiments under slightly modified conditions, which confirms the role of colloids as retarding agents. Afinite difference numerical model was used to (a) simulate mobile breakthrough curves and compare to experimental data and (b) estimate the model parameters describing cotransport of strontium and colloids. The model accurately predicted arrival time and the overall shape of the breakthrough curves.

Developing a long-term monitoring network under uncertain flowpaths.

A long-term monitoring well network is developed using complementary and simple approaches in conjunction with a stochastic ground water flow and transport model. The development is illustrated for a case study of a U.S. nuclear testing site (Shoal) that is undergoing environmental restoration. The network design builds on three different, yet complementary, tools for locating the monitoring wells with a main objective of detection monitoring. The first tool is applied to select potential siting horizons where monitoring wells could be located. The second tool is used to place monitoring wells in locations with high success probability. The success here is defined as the detection of migrating stochastic plumes before a certain mass percentage reaches a compliance boundary. The third tool is used to analyze detection efficiency of multiple combinations of three wells. Seventy-six different three-well networks are selected from 20 candidate locations and are evaluated for detection efficiency. From the 76 networks analyzed, 28 attain detection efficiency close to or above 70%. The results of the different analyses provide multiple alternatives for the locations of the three wells, which will become part of the long-term monitoring network at Shoal. A number of combinations are equally good, and the final choice will depend on practical considerations and future agreements between model sponsor and regulators.

A methodology for validating numerical ground water models.

Ground water validation is one of the most challenging issues facing modelers and hydrogeologists. Increased complexity in ground water models has created a gap between model predictions and the ability to validate or build confidence in predictions. Specific procedures and tests that can be easily adapted and applied to determine the validity of site-specific ground water models do not exist. This is true for both deterministic and stochastic models, with stochastic models posing the more difficult validation problem. The objective of this paper is to propose a general validation approach that addresses important issues recognized in previous validation studies, conferences, and symposia. The proposed method links the processes for building, calibrating, evaluating, and validating models in an iterative loop. The approach focuses on using collected validation data to reduce uncertainty in the model and narrow the range of possible outcomes. This method is designed for stochastic numerical models utilizing Monte Carlo simulation approaches, but it can be easily adapted for deterministic models. The proposed methodology relies on the premise that absolute validity is not theoretically possible, nor is it a regulatory requirement. Rather, the proposed methodology highlights the importance of testing various aspects of the model and using diverse statistical tools for rigorous checking and confidence building in the model and its predictions. It is this confidence that will encourage regulators and the public to accept decisions based on the model predictions. This validation approach will be applied to a model, described in this paper, dealing with an underground nuclear test site in rural Nevada.

Validation of numerical ground water models used to guide decision making.

Many sites of ground water contamination rely heavily on complex numerical models of flow and transport to develop closure plans. This complexity has created a need for tools and approaches that can build confidence in model predictions and provide evidence that these predictions are sufficient for decision making. Confidence building is a long-term, iterative process and the author believes that this process should be termed model validation. Model validation is a process, not an end result. That is, the process of model validation cannot ensure acceptable prediction or quality of the model. Rather, it provides an important safeguard against faulty models or inadequately developed and tested models. If model results become the basis for decision making, then the validation process provides evidence that the model is valid for making decisions (not necessarily a true representation of reality). Validation, verification, and confirmation are concepts associated with ground water numerical models that not only do not represent established and generally accepted practices, but there is not even widespread agreement on the meaning of the terms as applied to models. This paper presents a review of model validation studies that pertain to ground water flow and transport modeling. Definitions, literature debates, previously proposed validation strategies, and conferences and symposia that focused on subsurface model validation are reviewed and discussed. The review is general and focuses on site-specific, predictive ground water models used for making decisions regarding remediation activities and site closure. The aim is to provide a reasonable starting point for hydrogeologists facing model validation for ground water systems, thus saving a significant amount of time, effort, and cost. This review is also aimed at reviving the issue of model validation in the hydrogeologic community and stimulating the thinking of researchers and practitioners to develop practical and efficient tools for evaluating and refining ground water predictive models.