In Silico Investigation of the Clinical Translatability of Competitive Clearance Glucose-Responsive Insulins.

The glucose-responsive insulin (GRI) MK-2640 from Merck was a pioneer in its class to enter the clinical stage, having demonstrated promising responsiveness in in vitro and preclinical studies via a novel competitive clearance mechanism (CCM). The smaller pharmacokinetic response in humans motivates the development of new predictive, computational tools that can improve the design of therapeutics such as GRIs. Herein, we develop and use a new computational model, IMPACT, based on the intersection of human and animal model glucoregulatory systems, to investigate the clinical translatability of CCM GRIs based on existing preclinical and clinical data of MK-2640 and regular human insulin (RHI).

Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations.

The U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD).

A review of movement disorders in chemotherapy-induced neurotoxicity.

Chemotherapy agents used in the standard treatments for many types of cancer are neurotoxic and can lead to lasting sensory and motor symptoms that compromise day-to-day movement functions in cancer survivors. To date, the details of movement disorders associated with chemotherapy are known largely through self-reported symptoms and functional limitations. There are few quantitative studies of specific movement deficits, limiting our understanding of dysfunction, as well as effective assessments and interventions.

Changes in shear wave propagation within skeletal muscle during active and passive force generation.

Muscle force can be generated actively through changes in neural excitation, and passively through externally imposed changes in muscle length. Disease and injury can disrupt force generation, but it can be challenging to separate passive from active contributions to these changes. Ultrasound elastography is a promising tool for characterizing the mechanical properties of muscles and the forces that they generate.

Shear Waves Reveal Viscoelastic Changes in Skeletal Muscles After Hemispheric Stroke.

We investigated alterations in material properties such as elasticity and viscoelasticity of stroke-affected muscles using ultrasound induced shear waves and mechanical models. We used acoustic radiation force to generate shear waves along fascicles of biceps muscles and measured their propagation velocity. The shear wave data were collected in muscles of 13 hemiplegic stroke survivors under passive conditions at 90°, 120°, and 150° elbow flexion angles.

Altered viscoelastic properties of stroke-affected muscles estimated using ultrasound shear waves - Preliminary data.

As a result of a brain injury such as stroke, the skeletal muscles may undergo numerous structural and functional alterations. These abnormal changes are linked to muscle weakness, joint contracture, and abnormal muscle tone and eventually, result in motor impairment. A subset of these alterations affects passive muscle stiffness, i.