Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.

Unlabelled: Development of an understanding of membrane nanodomains colloquially known as "lipid rafts" has been hindered by a lack of pharmacological tools to manipulate rafts and protein affinity for rafts. We screened 24,000 small molecules for modulators of the affinity of peripheral myelin protein 22 (PMP22) for rafts in giant plasma membrane vesicles (GPMVs). Hits were counter-screened against another raft protein, MAL, and tested for impact on raft, leading to two classes of compounds.

Neuromuscular transmission deficits in patients with CMT and ClC-1 inhibition in CMT animal models.

Objective: Charcot-Marie Tooth (CMT) is a hereditary neuropathy characterized by muscle weakness and fatigue with no approved therapies. Preclinical studies implicate neuromuscular junction (NMJ) transmission deficits in muscle dysfunction in CMT. This study aimed to evaluate NMJ function in patients with CMT types 1 and 2, and to determine whether enhancing NMJ transmission can improve muscle function in preclinical CMT models.

Safety, Pharmacokinetics, and Pharmacodynamics of a First-in-Class ClC-1 Inhibitor to Enhance Muscle Excitability: Phase I Randomized Controlled Trial.

NMD670 is a first-in-class inhibitor of skeletal muscle-specific chloride channel ClC-1, developed to improve muscle weakness and fatigue in neuromuscular diseases. Preclinical studies show that ClC-1 inhibition enhances muscle excitability, improving muscle contractility and strength. We describe the first-in-human, randomized, double-blind, placebo-controlled study, which evaluated the safety, pharmacokinetics, and pharmacodynamics of single and multiple doses of NMD670 in healthy male and female subjects.

Surface Plasmon Modulation in CuP Nanocrystals.

We demonstrate modulation of the surface plasmon resonance in nonstoichiometric copper phosphide nanocrystals using spectroelectrochemical methods. Application of an anodic potential resulted in a blue-shift of the surface plasmon resonance and an incremental increase in its extinction coefficient. Conversely, upon application of a cathodic potential, the surface plasmon band red-shifted and reduced in intensity.

In Pursuit of a Person-Centered Approach to Care Delivery: A Qualitative Descriptive Study of the Patient Experience of a Long-Term Conditions Clinic in General Practice.

Innovative ways of working are emerging in health care to meet the complex needs of people living with multiple long-term conditions. While these initiatives are often measured for their health and economic outcomes, few studies prioritize the patient experience. This qualitative descriptive study is one of a few studies exploring the patient experience of attending a dedicated long-term conditions annual review clinic in a primary care setting in England.