The effect of inlet flow profile and nozzle diameter on drug delivery to the maxillary sinus

In this paper, the effect of the turbulence and swirling of the inlet flow and the diameter of the nozzle on the flow characteristics and the particles' transport/deposition patterns in a realistic combination of the nasal cavity (NC) and the maxillary sinus (MS) were examined. A computational fluid dynamics (CFD) model was developed in ANSYS® Fluent using a hybrid Reynolds averaged Navier–Stokes–large-eddy simulation algorithm. For the validation of the CFD model, the pressure distribution in the NC was compared with the experimental data available in the literature. An Eulerian–Lagrangian approach was employed for the prediction of the particle trajectories using a discrete phase model. Different inlet flow conditions were investigated, with turbulence intensities of 0.15 and 0.3, and swirl numbers of 0.6 and 0.9 applied to the inlet flow at a flow rate of 7 L/min. Monodispersed particles with a diameter of 5 µm were released into the nostril for various nozzle diameters. The results demonstrate that the nasal valve plays a key role in nasal resistance, which damps the turbulence and swirl intensities of the inlet flow. Moreover, it was found that the effect of turbulence at the inlet of the NC on drug delivery to the MS is negligible. It was also demonstrated that increasing the flow swirl at the inlet and decreasing the nozzle diameter improves the total particle deposition more than threefold due to the generation of the centrifugal force, which acts on the particles in the nostril and vestibule. The results also suggest that the drug delivery efficiency to the MS can be increased by using a swirling flow with a moderate swirl number of 0.6. It was found that decreasing the nozzle diameter can increase drug delivery to the proximity of the ostium in the middle meatus by more than 45%, which subsequently increases the drug delivery to the MS. The results can help engineers design a nebulizer to improve the efficiency of drug delivery to the maxillary sinuses.

     

Altered tubulin assembly dynamics with N-homocysteinylated human 4R/1N tau in vitro

Tau isoforms promote neuronal integrity through binding and stabilization of microtubule proteins (MTP). It has been shown that hyperphosphorylation of tau contributes to Alzheimer’s disease (AD) pathology and related tauopathies. However, other pathogenic modifications of tau have not been well characterized. It is well accepted that elevated level of homocysteine (Hcy) is associated with neurodegenerative diseases such as AD. As a result of N-homocysteinylation of lysine residues, Hcy becomes a component of proteins, as a protein–homocystamide adduct, which affects protein structure and function. Here we demonstrate that N-homocysteinylation of human tau (4R/1N isoform) inhibits its function via impaired tau–tubulin specific binding and MTP assembly dynamics in vitro.     

CFD simulation of aerosol delivery to a human lung via surface acoustic wave nebulization

Administration of drug in the form of particles through inhalation is generally preferable in the treatment of respiratory disorders. Conventional inhalation therapy devices such as inhalers and nebulizers, nevertheless, suffer from low delivery efficiencies, wherein only a small fraction of the inhaled drug reaches the lower respiratory tract. This is primarily because these devices are not able to produce a sufficiently fine drug mist that has aerodynamic diameters on the order of a few microns. This study employs computational fluid dynamics to investigate the transport and deposition of the drug particles produced by a new aerosolization technique driven by surface acoustic waves (SAWs) into an in silico lung model geometrically reconstructed using computed tomography scanning. The particles generated by the SAW are released in different locations in a spacer chamber attached to a lung model extending from the mouth to the 6th generation of the lung bronchial tree. An Eulerian approach is used to solve the Navier–Stokes equations that govern the airflow within the respiratory tract, and a Lagrangian approach is adopted to track the particles, which are assumed to be spherical and inert. Due to the complexity of the lung geometry, the airflow patterns vary as it penetrates deeper into the lung. High inertia particles tend to deposit at locations where the geometry experiences a significant reduction in cross section. Our findings, nevertheless, show that the injection location can influence the delivery efficiency: Injection points close to the spacer centerline result in deeper penetration into the lung. Additionally, we found that the ratio of drug particles entering the right lung is significantly higher than the left lung, independent of the injection location. This is in good agreement with this fact that the most of airflow enters to the right lobes.     

Effect of swirling flow and particle-release pattern on drug delivery to human tracheobronchial airways

Biomechanics and Modeling in Mechanobiology - The present study aims to investigate the effect of swirling flow on particle deposition in a realistic human airway. A computational fluid dynamic...     

Remediation of a Diesel-Contaminated Soil Using a Fenton-Like Advanced Oxidation Process: Optimization by Response Surface Methodology

Magnetite, a naturally occurring mineral of iron oxide, and zero-valent iron (ZVI) were used to catalyze hydrogen peroxide and initiate a dark Fenton-like reaction of diesel-contaminated loamy sand in a batch system at circumneutral pH. The effects of hydrogen peroxide concentration and catalyst content on the removal efficiency of total petroleum hydrocarbons (TPHs) were studied. A central composite rotatable design was applied and the derived equation for magnetite and ZVI were linear and quadratic, respectively. In both equations, the factor of hydrogen peroxide concentration was more significant than catalyst content. At optimum conditions (4.27 wt% of catalyst content and 2.17 mol/L of hydrogen peroxide), 57% and 67% of TPH removal were achieved by magnetite and ZVI, respectively. The obtained results suggest the potential of ZVI and magnetite to catalyze a heterogeneous Fenton-like reaction at circumneutral pH. It seems that using ZVI, rather than magnetite, as a catalyst may result in slightly more TPH mineralization; however, since magnetite is a naturally occurring mineral, it may be able to compete economically with ZVI.     

Teasing,Taunting, and the Politics of Politeness: High Sociometric Status Is Associated with Expectation-Consistent Behavior

Research examining face-to-face status hierarchies suggests that individuals attain respect and admiration by engaging in behavior that influences others'' judgments of their value to the group. Building on this research, we expected that high-status individuals would be less likely to engage in behaviors that violate group norms and expectations, relative to low-status individuals. Adolescent participants took part in an interaction in which they teased an opposite-gender friend (Study 1) or an experiment in which taunting or cheering expectations were manipulated (Study 2). Consistent with the hypothesis, high-status boys and girls engaged in teasing behaviors consistent with their gender roles, relative to their low status counterparts (Study 1). In Study 2, high-status boys engaged in more direct provocation and off-record commentary while taunting, and more affiliative behavior while cheering on their partner, relative to low-status boys. Discussion focused on how expectation-consistent actions help individuals maintain elevated status.     

Effect of N-homocysteinylation on physicochemical and cytotoxic properties of amyloid β-peptide

Abstract Hyperhomocysteinemia has recently been identified as an important risk factor for Alzheimer's disease (AD). One of the potential mechanisms underlying harmful effects of homocysteine (Hcy) is site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HCTL). The accumulation of amyloid β-peptide (Aβ) in the brain is a neuropathological hallmark of AD. In the present study we were interested to investigate the effects of N-homocysteinylation on the aggregation propensity and neurotoxicity of Aβ(1-42). By coupling several techniques, we demonstrated that the homocysteinylation of lysine residues increase the neurotoxicity of the Aβ peptide by stabilizing soluble oligomeric intermediates.     

Magnetic drug targeting through a realistic model of human tracheobronchial airways using computational fluid and particle dynamics

Biomechanics and Modeling in Mechanobiology - Magnetic drug targeting (MDT) is a local drug delivery system which aims to concentrate a pharmacological agent at its site of action in order to...