Reliability of Trapezius Muscle Hardness Measurement: A Comparison between Portable Muscle Hardness Meter and Ultrasound Strain Elastography

Prolonged computer work and smartphone use can cause stiffness of the neck and shoulder muscles, including the trapezius muscle. Hence, muscle hardness quantification is clinically beneficial. The present study aimed to examine the reliability of trapezius muscle hardness measurement using a portable muscle hardness meter and ultrasound strain elastography. Overall, 20 healthy young men participated in this study. Prior to measurement, the participant’s subjective symptoms, particularly shoulder muscle stiffness, were rated using an 11-point verbal scale. Furthermore, hardness of the right and left upper trapezius muscles was assessed. In the strain elastography assessment, muscle hardness was evaluated using strain ratio. Results showed that, in quantifying upper trapezius muscle hardness, both portable muscle hardness meter and strain elastography had an excellent intra-tester reliability (>0.9). However, the correlation coefficients between muscle hardness values assessed using a muscle hardness meter and those evaluated with strain elastography did not significantly differ, and the scores for subjective shoulder stiffness did not correspond to muscle hardness values. Therefore, the hardness of the trapezius muscle does not directly reflect the subjective shoulder stiffness. Future studies should thoroughly examine the location of the shoulder stiffness, and check whether it is accompanied by local pain or tenderness

Allosteric Inhibition of c-Abl to Induce Unfolded Protein Response and Cell Death in Multiple Myeloma

Endoplasmic reticulum stress activates inositol-requiring enzyme 1α (IRE1α) and protein kinase, R-like endoplasmic reticulum kinase (PERK), the two principal regulators of the unfolded protein response (UPR). In multiple myeloma, adaptive IRE1α signaling is predominantly activated and regulates cell fate along with PERK. Recently, we demonstrated that GNF-2, an allosteric c-Abl inhibitor, rheostatically enhanced IRE1α activity and induced apoptosis through c-Abl conformational changes in pancreatic β cells. Herein, we analyzed whether the pharmacological modulation of c-Abl conformation resulted in anti-myeloma effects. First, we investigated the effects of GNF-2 on IRE1α activity and cell fate, followed by an investigation of the anti-myeloma effects of asciminib, a new allosteric c-Abl inhibitor. Finally, we performed RNA sequencing to characterize the signaling profiles of asciminib. We observed that both GNF-2 and asciminib decreased cell viability and induced XBP1 mRNA splicing in primary human myeloma cells and myeloma cell lines. RNA sequencing identified the induction of UPR- and apoptosis-related genes by asciminib. Asciminib re-localized c-Abl to the endoplasmic reticulum, and its combination with a specific IRE1α inhibitor, KIRA8, enhanced cell death with the reciprocal induction of CHOP mRNA expression. Together, the allosteric inhibition of c-Abl-activated UPR with anti-myeloma effects; this could be a novel therapeutic target for multiple myeloma