Formative and Validation Human Factors studies of a new disposable autoinjector for subcutaneous delivery of chronic disease therapies.

BACKGROUND: Use-related risks related to autoinjector devices have been previously identified. To minimize these problems, the identification of potential use errors is a critical task during device development. METHODS: This article presents iterative human factor studies, which aim to assess user interaction with the tested push-on-skin BD Intevia™ 1 mL Disposable Autoinjector, across a wide range of indications, and a broad user population. RESULTS: Through the different human factor studies, use errors were recorded when the participants completed the critical tasks, but their occurrence continuously decreased. First, the incidence of use errors was reduced when the participants read the IFU. In addition, the IFU updates and design change implemented contributed to improve the usability performance. During the validation study, some use errors were still observed, mainly during the first uses. Nevertheless, providing a training to the participants almost fully eliminated the remaining use errors. CONCLUSION: Thus, these results demonstrated that this new autoinjector can be safely and efficiently used for its intended uses and under the expected use conditions by all tested user groups.

User experience for manual injection of 2 mL viscous solutions is enhanced by a new prefillable syringe with a staked 8 mm ultra-thin wall needle.

OBJECTIVES: User experience was compared between a new pre-fillable 2.25 mL glass syringe equipped with an ultra-thin-wall (UTW) 8 mm staked needle and a marketed BD Neopak™ syringe equipped with a special-thin-wall (STW) 12.7 mm staked needle. METHODS: Participants simulated subcutaneous injections with both syringes alone (formative Human Factors study) and in combination with a needlestick-prevention device (validation Human Factors study). RESULTS: Usability results of both studies showed higher success rates for delivering the full dose of 2 mL viscous solution (30 cP) with the 8mmUTW syringe than with the 12.7mmSTW one (63% vs. 42% in the formative study). The use of the 8mmUTW syringe demonstrated also better ease of use and acceptance results and 72% of formative study participants preferred this new syringe over the current one when delivering the viscous solution. Using a shorter needle also showed a benefit in decreasing the injection-related anxiety. Besides, in the case of a non-recommended injection technique, the calculated risk of accidental intramuscular injection is reduced by 2 to 13 times with the 8mmUTW syringe. CONCLUSION: Altogether, the results obtained demonstrated an improvement of the user experience with this new syringe compared to the current one in the manual delivery of 2 mL viscous solutions.

Small GTPases orchestrate cell-cell communication during collective cell movement.

Collective cell migration is a critical mechanism involved in cell movement during various physiological and pathological processes such as angiogenesis and metastasis formation. During collective movement, cells remain functionally connected and can coordinate individual cell behaviors to ensure efficient migration. A cell-cell communication process ensures this complex coordination. Although the mechanisms regulating cell-cell communication remain unclear, recent findings indicate that it is based on acto-myosin cytoskeleton tension transmission from cell to cell through adherens junctions. As for single cell migration, small GTPases of the Rho and Rab families have been shown to be critical regulators of collective motion. Here, we discuss our current understanding on how these small GTPases are themselves regulated and how they control cell-cell communication during collective migration. Moreover, we also shed light on the key role of cell-cell communication and RhoGTPases in the physiological context of endothelial cell migration during angiogenesis.

Myosin II governs collective cell migration behaviour downstream of guidance receptor signalling.

Border cell migration during Drosophila oogenesis is a potent model to study collective cell migration, a process involved in development and metastasis. Border cell clusters adopt two main types of behaviour during migration: linear and rotational. However, the molecular mechanism controlling the switch from one to the other is unknown. Here, we demonstrate that non-muscle Myosin II (NMII, also known as Spaghetti squash) activity controls the linear-to-rotational switch. Furthermore, we show that the regulation of NMII takes place downstream of guidance receptor signalling and is critical to ensure efficient collective migration. This study thus provides new insight into the molecular mechanism coordinating the different cell behaviours in a migrating cluster.

Heterologous regulation of Mu-opioid (MOP) receptor mobility in the membrane of SH-SY5Y cells.

The dynamic organization of G protein-coupled receptors in the plasma membrane is suspected of playing a role in their function. The regulation of the diffusion mode of the mu-opioid (MOP) receptor was previously shown to be agonist-specific. Here we investigate the regulation of MOP receptor diffusion by heterologous activation of other G protein-coupled receptors and characterize the dynamic properties of the MOP receptor within the heterodimer MOP/neuropeptide FF (NPFF2) receptor. The data show that the dynamics and signaling of the MOP receptor in SH-SY5Y cells are modified by the activation of α2-adrenergic and NPFF2 receptors, but not by the activation of receptors not described to interact with the opioid receptor. By combining, for the first time, fluorescence recovery after photobleaching at variable radius experiments with bimolecular fluorescence complementation, we show that the MOP/NPFF2 heterodimer adopts a specific diffusion behavior that corresponds to a mix of the dynamic properties of both MOP and NPFF2 receptors. Altogether, the data suggest that heterologous regulation is accompanied by a specific organization of receptors in the membrane.