A counter-swirl design concept for dry powder inhalers.

A swirling airflow is incorporated in several dry powder inhalers (DPIs) for effective powder de-agglomeration. This commonly requires the use of a flow-straightening grid in the DPI to reduce drug deposition loss caused by large lateral spreading of the emerging aerosol. Here, we propose a novel grid-free DPI design concept that improves the aerosol flow characteristics and reduces the aforementioned drug loss.

Glycolysis as key regulatory step in FSH-induced rat Sertoli cell proliferation: Role of the mTORC1 pathway.

The definitive number of Sertoli cells (SCs), achieved during the proliferative periods, defines the spermatogenic capacity in adulthood. It is recognized that FSH is the main mitogen targeting SC and that it exerts its action, at least partly, through the activation of the PI3K/Akt/mTORC1 pathway. mTORC1 controls a large number of cellular functions, including glycolysis and cell proliferation.

Advances in soft mist inhalers.

Introduction: Soft mist inhalers (SMIs) are propellant-free inhalers that utilize mechanical power to deliver single or multiple doses of inhalable drug aerosols in the form of a slow mist to patients. Compared to traditional inhalers, SMIs allow for a longer and slower release of aerosol with a smaller ballistic effect, leading to a limited loss in the oropharyngeal area, whilst requiring little coordination of actuation and inhalation by patients. Currently, the Respimat® is the only commercially available SMI, with several others in different stages of preclinical and clinical development.

Unraveling the Kinematics of Sperm Motion by Reconstructing the Flagellar Wave Motion in 3D.

Sperm swim through the female reproductive tract by propagating a 3D flagellar wave that is self-regulatory in nature and driven by dynein motors. Traditional microscopy methods fail to capture the full dynamics of sperm flagellar activity as they only image and analyze sperm motility in 2D. Here, an automated platform to analyze sperm swimming behavior in 3D by using thin-lens approximation and high-speed dark field microscopy to reconstruct the flagellar waveform in 3D is presented.

CRISPs Function to Boost Sperm Power Output and Motility.

Fertilization requires sperm to travel long distances through the complex environment of the female reproductive tract. Despite the strong association between poor motility and infertility, the kinetics of sperm tail movement and the role individual proteins play in this process is poorly understood. Here, we use a high spatiotemporal sperm imaging system and an analysis protocol to define the role of CRISPs in the mechanobiology of sperm function.

Flagellar energetics from high-resolution imaging of beating patterns in tethered mouse sperm.

We demonstrate a technique for investigating the energetics of flagella or cilia. We record the planar beating of tethered mouse sperm at high resolution. Beating waveforms are reconstructed using proper orthogonal decomposition of the centerline tangent-angle profiles.

Improved Drainage Cannula Design to Reduce Thrombosis in Veno-Arterial Extracorporeal Membrane Oxygenation.

Thrombosis is a potentially life-threatening complication in veno-arterial extracorporeal membrane oxygenation (ECMO) circuits, which may originate from the drainage cannula due to unfavorable blood flow dynamics. This study aims to numerically investigate the effect of cannula design parameters on local fluid dynamics, and thus thrombosis potential, within ECMO drainage cannulas. A control cannula based on the geometry of a 17 Fr Medtronic drainage cannula concentrically placed in an idealized, rigid-walled geometry of the right atrium and superior and inferior vena cava was numerically modeled.

On the Use of Computational Fluid Dynamics (CFD) Modelling to Design Improved Dry Powder Inhalers.

Purpose: Computational Fluid Dynamics (CFD) simulations are performed to investigate the impact of adding a grid to a two-inlet dry powder inhaler (DPI). The purpose of the paper is to show the importance of the correct choice of closure model and modeling approach, as well as to perform validation against particle dispersion data obtained from in-vitro studies and flow velocity data obtained from particle image velocimetry (PIV) experiments.

Methods: CFD simulations are performed using the Ansys Fluent 2020R1 software package.

In-vitro and particle image velocimetry studies of dry powder inhalers.

Inhalation drug delivery has seen a swift rise in the use of dry powder inhalers (DPIs) to treat chronic respiratory conditions. However, universal adoption of DPIs has been restrained due to their low efficiencies and significant drug losses in the mouth-throat region. Aerosol efficiency of DPIs is closely related to the fluid-dynamics characteristics of the inhalation flow generated from the devices, which in turn are influenced by the device design.

The size dependant behaviour of particles driven by a travelling surface acoustic wave (TSAW).

The use of travelling surface acoustic waves (TSAW) in a microfluidic system provides a powerful tool for the manipulation of particles and cells. In a TSAW driven system, acoustophoretic effects can cause suspended micro-objects to display three distinct responses: (1) swirling, driven by acoustic streaming forces, (2) migration, driven by acoustic radiation forces and (3) patterning in a spatially periodic manner, resulting from diffraction effects. Whilst the first two phenomena have been widely discussed in the literature, the periodic patterning induced by TSAW has only recently been reported and is yet to be fully elucidated.

Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography.

Purpose: Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques.

Methods: We present a technique for obtaining quantitative measurements of spray density in pMDI sprays.

A novel high-speed imaging technique to predict the macroscopic spray characteristics of solution based pressurised metered dose inhalers.

Purpose: Non-volatile agents such as glycerol are being introduced into solution-based pMDI formulations in order to control mean precipitant droplet size. To assess their biopharmaceutical efficacy, both microscopic and macroscopic characteristics of the plume must be known, including the effects of external factors such as the flow generated by the patient's inhalation. We test the hypothesis that the macroscopic properties (e.

On the mechanism of elasto-inertial turbulence.

Elasto-inertial turbulence (EIT) is a new state of turbulence found in inertial flows with polymer additives. The dynamics of turbulence generated and controlled by such additives is investigated from the perspective of the coupling between polymer dynamics and flow structures. Direct numerical simulations of channel flow with Reynolds numbers ranging from 1000 to 6000 (based on the bulk and the channel height) are used to study the formation and dynamics of elastic instabilities and their effects on the flow.