Identification of Hydrodynamic Dispersion Tensor by Optimization Algorithm Based LBM/CMA-ES Combination

The hydrodynamic dispersion tensor (HDT) of a porous medium is a key parameter in engineering and environmental sciences. Its knowledge allows for example, to accurately predict the propagation of a pollution front induced by a surface (or subsurface) flow. This paper proposes a new mathematical model based on inverse problem-solving techniques to identify the HDT (noted D=) of the studied porous medium. We then showed that in practice, this new model can be written in the form of an integrated optimization algorithm (IOA). The IOA is based on the numerical solution of the direct problem (which solves the convection–diffusion type transport equation) and the optimization of the error function between the simulated concentration field and that observed at the application site. The partial differential equations of the direct model were solved by high resolution of (Δx=Δy=1 m) Lattice Boltzmann Method (LBM) whose computational code is named HYDRODISP-LBM (HYDRO-DISpersion by LBM). As for the optimization step, we opted for the CMA-ES (Covariance Matrix Adaptation-Evolution Strategy) algorithm. Our choice for these two methods was motivated by their excellent performance proven in the abundant literature. The paper describes in detail the operation of the coupling of the two computer codes forming the IOA that we have named HYDRODISP-LBM/CMA-ES. Finally, the IOA was applied at the Beauvais experimental site to identify the HDT D=. The geological analyzes of this site showed that the tensor identified by the IOA is in perfect agreement with the characteristics of the geological formation of the site which are connected with the mixing processes of the latter.

Does the Bleaching Gel Application Site Interfere With the Whitening Result? A Randomized Clinical Trial

SUMMARY This study aimed to evaluate the effect of the bleaching gel application site on chromatic changes and postoperative sensitivity in teeth. Thirty patients were selected and allocated to three groups (n=10 per group), according to the location of the gel: GI, cervical application; GII, incisal application; and GIII, total facial. The amount and time of application of the 35% hydrogen peroxide (H2O2) gel were standardized. Color changes were analyzed by ΔE and Wid (bleaching index), using the values obtained in the readings conducted on a digital spectrophotometer in the cervical (CRs) and incisal regions (IRs) of the teeth. Spontaneous sensitivity was assessed using the questionnaire, and the stimulated sensitivity caused by the thermosensory analysis (TSA). The analysis occurred in five stages: baseline, after the first, second, and third whitening sessions (S), and 14 days after the end of the whitening, using the linear regression statistical model with mixed effects and post-test by orthogonal contrasts (p<0.05). Although the IR was momentarily favored, at the end of the treatment, the restriction of the application site provided results similar to those obtained when the gel was applied over the entire facial surface. Regarding sensitivity, only the GI showed spontaneous sensitivity. In the TSA, GIII had less influence on the threshold of the thermal sensation. It was concluded that the chromatic alteration does not depend on the gel application site. Spontaneous sensitivity is greater when the gel is concentrated in the cervical region (CR), and the teeth remain sensitized by thermal stimuli even after 14 days.

Evapotranspiration measurements in the Brazilian Caatinga dry forest

<p>The Brazilian semiarid region (one million km²) is densely populated (25 million inhabitants), but its natural water availability is low. Despite the fact that evaporative processes are key to the regional water deficit, the actual evapotranspiration of natural environment has rarely been measured, especially in the native Caatinga dry forest. We hereby propose a simple method that demands the monitoring of five meteorological variables: relative humidity, global radiation, canopy and air temperature, as well as wind speed. These values are used to assess leaf energy balance, yielding net radiation (Rn) and actual evapotranspiration (LE). To estimate the actual Caatinga evapotranspiration under natural conditions and in different seasons, the proposed method was applied <em>in situ</em> during nine months. The application site was the Aiuaba Experimental Basin, situated in an environmental protection area in the North-eastern Brazil. The method provided consistent results when compared with independent measurements, such as atmospheric demand, leaf area, and soil water content variation. Results indicate that the daily average net radiation is 12 MJ m<sup>-</sup>². During the dry season, the actual evapotranspiration is very low, with negligible LE/Rn ratio. Contrastingly, in the rainy season, it raises to 6 mm per day, with average LE/Rn ratio equalling 0.89. The results show that the actual evapotranspiration in the Caatinga long-lasting dry season (up to nine months per year) is controlled by the water availability in the soil.</p>

Efficacy and Safety of Different Formulations of Calcipotriol/Betamethasone Dipropionate in Psoriasis: Gel, Foam, and Ointment

Preparations containing calcipotriol combined with betamethasone dipropionate (in the forms of ointment, gel, and foam) are available for the topical treatment of psoriasis. This review summarizes the differences in the efficacy and safety of these formulations, as well as the preferences of patients with various forms of psoriasis (plaque, scalp, and nail psoriasis). It has been documented that foams provide higher bioavailability, resulting in increased efficacy in plaque psoriasis compared to ointments and gels. Gels or foams are preferred by patients for their different practical qualities (e.g., gels for “easy application”, and foams for “immediate relief”). The available data indicate that ointments may be the most effective formulation in nail psoriasis, and gels are preferred by patients with scalp psoriasis because of their cosmetic features. Treatment with a foam formulation is associated with a lower number of medical appointments compared to treatment with an ointment and with a lower probability of developing indications for systemic treatment. The safety profiles of foams, ointments, and gels are comparable, with the most common adverse effect being pruritus at the application site (in 5.8% of the patients). A long-term proactive maintenance therapy markedly reduces the number of relapses and is likely to close the gap between topical and systemic treatment in psoriasis.

Immunogenicity and safety of inactivated Influenza Split-Virion vaccine administered via a transdermal micro needle system

The purpose of the study was to evaluate the immunogenicity and safety of an inactivated influenza split virion vaccine administered via a transdermal microneedle system. In this Phase 1, single-center, randomized, controlled study, 90 subjects aged 18 to 40 years received influenza vaccine (strains (A/H1N1, A/H3N2, and B) either via a transdermal microneedle system (“patch”; 10 µg) for 5 or 15 minutes or by Intramuscular (IM) injection (15g). Influenza antibody titers were measured by the hemagglutinin inhibition method and compared to EMEA guidelines for influenza vaccines (seroconversion rate, mean increase in hemagglutinin inhibition titer, and percentage of seroprotected subjects). Safety was assessed through local and systemic adverse events, and specific application site events in the transdermal groups. At Day 21, the EMEA criteria were met in all treatment groups for all three influenza strains. The immunogenicity response was similar between all three groups and increased antibody levels persisted to Month 6. The transdermal microneedle system was generally well tolerated, although pinpoint red spots, edema, and erythema were noted after patch removal in most subjects. Influenza vaccination administered via a novel transdermal microneedle system was generally well tolerated and provided similar antibody response using a lower dose than IM injection.

Improvement of the Antimicrobial Activity of Oregano Oil by Encapsulation in Chitosan–Alginate Nanoparticles

Oregano oil (OrO) possesses well-pronounced antimicrobial properties but its application is limited due to low water solubility and possible instability. The aim of this study was to evaluate the possibility to incorporate OrO in an aqueous dispersion of chitosan–alginate nanoparticles and how this will affect its antimicrobial activity. The encapsulation of OrO was performed by emulsification and consequent electrostatic gelation of both polysaccharides. OrO-loaded nanoparticles (OrO-NP) have small size (320 nm) and negative charge (−25 mV). The data from FTIR spectroscopy and XRD analyses reveal successful encapsulation of the oil into the nanoparticles. The results of thermogravimetry suggest improved thermal stability of the encapsulated oil. The minimal inhibitory concentrations of OrO-NP determined on a panel of Gram-positive and Gram-negative pathogens (ISO 20776-1:2006) are 4–32-fold lower than those of OrO. OrO-NP inhibit the respiratory activity of the bacteria (MTT assay) to a lower extent than OrO; however, the minimal bactericidal concentrations still remain significantly lower. OrO-NP exhibit significantly lower in vitro cytotoxicity than pure OrO on the HaCaT cell line as determined by ISO 10993-5:2009. The irritation test (ISO 10993-10) shows no signs of irritation or edema on the application site. In conclusion, the nanodelivery system of oregano oil possesses strong antimicrobial activity and is promising for development of food additives.

Development, Optimization, and Evaluation of Luliconazole Nanoemulgel for the Treatment of Fungal Infection

The present study aimed to optimize luliconazole nanoemulsion using Box–Behnken statistical design, which was further incorporated into the polymeric gel of Carbopol 934. The formulation was characterized for its size, entrapment efficiency, ex vivo permeation, and mechanism of release. The size of the dispersed globules of the optimized drug-loaded nanoemulsion was found to be 17 ± 3.67 nm with a polydispersity index (PDI) less than 0.5. Although the surface charge was recorded at –9.53 ± 0.251, the stability was maintained by the polymeric matrix that prevented aggregation and coalescence of the dispersed globules. The luliconazole-nanoemulgel (LUL-NEG) was characterized for drug content analysis, viscosity, pH, and refractive index, where the results were found to be 99.06 ± 0.59%, 9.26 ± 0.08 Pa.s, 5.65 ± 0.17, and 1.31 ± 0.08, respectively. The permeation across the rat skin was found to be significantly higher with LUL-NEG when compared with LUL gel. Furthermore, the skin irritation test performed in experimental animals revealed that the blank NEG, as well as the LUL-NEG, did not produce any signs of erythema following 48 h exposure. In addition, the histopathological findings of the experimental skins reported no abnormal signs at the formulation application site. Finally, the NEG formulation was found to create a statistically significant zone of inhibition ( P < 0.05) when compared to all other test groups. Overall, it could be summarized that the nanoemulgel approach of delivering luliconazole across the skin to treat skin fungal infections could be a promising strategy.

Formulation and Evaluation of Topical Microemulgel Containing Terbinafine Hydrochloride

The purpose of this study is to create and test a Terbinafine hydrochloride microemulgel. Terbinafine hydrochloride is an FDA-approved antifungal medication used to treat fungal infections on the skin. It's a BCS class II medication with little bioavailability. In the realm of pharmaceutical sciences, microemulgel has evolved into one of the most intriguing topical preparations. Microemulgel as a delivery technique has several advantages over simple traditional formulations, including simplicity of administration, increased residence duration at the application site, consistent drug release with improved bioavailability, superior thermodynamic stability, and excellent transdermal permeability. Terbinafine hydrochloride microemulgels were made with carbopol 940 and HPMC as gelling agents, oleic acid as an oil, parabens as a preservative, and tween 20 as an emulgent and penetration enhancer. The appearance, spreadability, homogeneity, viscosity, pH, percent drug content, and in vitro diffusion studies of the generated microemulgel formulation were all visually checked. The findings show that developing a terbinafine-containing microemulgel is more effective, but clinical efficacy must be determined through clinical trials.

A randomized, controlled, feasibility study of RD-X19 in patients with mild-to-moderate COVID-19 in the outpatient setting

These studies aimed to further understand the antiviral effects of safe, visible light and demonstrate a therapeutic effect of an investigational treatment device for outpatients with mild to moderate COVID-19. RD-X19 is a handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses that are well-tolerated in an in vitro human epithelial tissue model, the monochromatic visible light delivered by RD-X19 results in light-initiated expression of IL-1α and IL-1β cytokines with corresponding inhibition of SARS-CoV-2 replication. A randomized, double-blind, sham-controlled early feasibility study using the investigational device enrolled 31 subjects with a positive SARS-CoV-2 antigen test and possessing at least two moderate COVID-19 signs and symptoms. Subjects were randomized 2:1 (RD-X19 to sham), treated twice daily for four days, and evaluated over one week. Prespecified outcome measures included assessments of SARS-CoV-2 viral load and clinical assessments of COVID-19. There were no local application site reactions and no device-related adverse events. The time-weighted average change in log viral load throughout the study demonstrated a favorable reduction for RD-X19 compared to sham and at the end of study the mean change in log10 viral load was -3.29 for RD-X19 and -1.81 for sham at Day 8, demonstrating a treatment benefit of -1.48 [95% confidence internal (CI), -2.88 to -0.071]. Among the clinical outcome measures, differences between RD-X19 and sham were also observed, with a 57-hour reduction of median time to sustained resolution of COVID-19 signs and symptoms.

Optimized Rivastigmine Nanoparticles Coated with Eudragit for Intranasal Application to Brain Delivery: Evaluation and Nasal Ciliotoxicity Studies

Rivastigmine, a reversible cholinesterase inhibitor, is frequently indicated in the management of demented conditions associated with Alzheimer disease. The major hurdle of delivering this drug through the oral route is its poor bioavailability, which prompted the development of novel delivery approaches for improved efficacy. Due to numerous beneficial properties associated with nanocarriers in the drug delivery system, rivastigmine nanoparticles were fabricated to be administer through the intranasal route. During the development of the nanoparticles, preliminary optimization of processing and formulation parameters was done by the design of an experimental approach. The drug–polymer ratio, stirrer speed, and crosslinking time were fixed as independent variables, to analyze the effect on the entrapment efficiency (% EE) and in vitro drug release of the drug. The formulation (D8) obtained from 23 full factorial designs was further coated using Eudragit EPO to extend the release pattern of the entrapped drug. Furthermore, the 1:1 ratio of core to polymer depicted spherical particle size of ~175 nm, % EE of 64.83%, 97.59% cumulative drug release, and higher flux (40.39 ± 3.52 µg·h/cm2). Finally, the intranasal ciliotoxicity study on sheep nasal mucosa revealed that the exposure of developed nanoparticles was similar to the negative control group, while destruction of normal architecture was noticed in the positive control test group. Overall, from the in vitro results it could be summarized that the optimization of nanoparticles’ formulation of rivastigmine for intranasal application would be retained at the application site for a prolonged duration to release the entrapped drug without producing any local toxicity at the mucosal region.