Pharmacologic Targeting of the C-Terminus of Heat Shock Protein 90 Improves Neuromuscular Function in Animal Models of Charcot Marie Tooth X1 Disease.

Charcot-Marie-Tooth X1 (CMTX1) disease is an inherited peripheral neuropathy that arises from loss-of-function mutations in the protein connexin 32 (Cx32). CMTX1 currently lacks a pharmacologic approach toward disease management, and we have previously shown that modulating the expression of molecular chaperones using novologue therapy may provide a viable disease-modifying approach to treat metabolic and demyelinating neuropathies. Cemdomespib is an orally bioavailable novologue that manifests neuroprotective activity by modulating the expression of heat shock protein 70 (Hsp70).

Synthesis and evaluation of 3'- and 4'-substituted cyclohexyl noviomimetics that modulate mitochondrial respiration.

KU-32 (2) and KU-596 (3), are first and second generation cytoprotective novologues that are derivatives of novobiocin (1), a heat shock protein 90 (Hsp90) C-terminal inhibitor. Although 2 and 3 improve mitochondrial bioenergetics and have demonstrated considerable cytoprotective activity, they contain a synthetically demanding noviose sugar. This issue was initially addressed by creating noviomimetics, such as KU-1202 (4), which replaced the noviose sugar with ether-linked cyclohexyl derivatives that retained some cytoprotective potential due to their ability to increase mitochondrial bioenergetics.

Effect of glandularity on the detection of simulated cancers in planar, tomosynthesis, and synthetic 2D imaging of the breast using a hybrid virtual clinical trial.

Purpose: The purpose of this study was to measure the threshold diameter of calcifications and masses for 2D imaging, digital breast tomosynthesis (DBT), and synthetic 2D images, for a range of breast glandularities. This study shows the limits of detection for each of the technologies and the strengths and weaknesses of each in terms of visualizing the radiological features of small cancers.

Methods: Mathematical voxel breast phantoms with glandularities by volume of 9%, 18%, and 30% with a thickness of 53 mm were created.

Sleep and Coping in Early Childhood During the COVID-19 Pandemic.

Sleep disturbances in early childhood are associated with mood and anxiety disorders. Children also exhibit sleep disruptions, such as nighttime awakenings, nightmares, and difficulties falling asleep, in conjunction with adverse events and stress. Prior studies have examined independently the role of sleep on adaptive processing, as well as the effects of stress on sleep.

Mindfulness-Based Stress Reduction Benefits Psychological Well-Being, Sleep Quality, and Athletic Performance in Female Collegiate Rowers.

Factors such as psychological well-being, sleep quality, and athletic coping skills can influence athletic performance. Mindfulness-based interventions, including mindfulness-based stress reduction (MBSR), have been shown to benefit these factors, suggesting they may, at least indirectly, benefit athletic performance. Moreover, while mindfulness training has been linked to better accuracy in some high-precision sports, whether it can improve non-precision elements of athletic performance is unclear.