Chemotherapy is a leading intervention against cancer. Albeit highly effective, chemotherapy has a multitude of deleterious side-effects including skeletal muscle wasting and fatigue, which considerably reduces patient quality of life and survivability. As such, a defense against chemotherapy-induced skeletal muscle dysfunction is required. Here we investigate the effects of oxaliplatin (OXA) treatment in mice on the skeletal muscle and mitochondria, and the capacity for the Poly ADP-ribose polymerase (PARP) inhibitor, BGP-15, to ameliorate any pathological side-effects induced by OXA. To do so, we investigated the effects of 2 weeks of OXA (3 mg/kg) treatment with and without BGP-15 (15 mg/kg). OXA induced a 15% (p < 0.05) reduction in lean tissue mass without significant changes in food consumption or energy expenditure. OXA treatment also altered the muscle architecture, increasing collagen deposition, neutral lipid and Ca2+ accumulation; all of which were ameliorated with BGP-15 adjunct therapy. Here, we are the first to show that OXA penetrates the mitochondria, and, as a possible consequence of this, increases mtROS production. These data correspond with reduced diameter of isolated FDB fibers and shift in the fiber size distribution frequency of TA to the left. There was a tendency for reduction in intramuscular protein content, albeit apparently not via Murf1 (atrophy)- or p62 (autophagy)- dependent pathways. BGP-15 adjunct therapy protected against increased ROS production and improved mitochondrial viability 4-fold and preserved fiber diameter and number. Our study highlights BGP-15 as a potential adjunct therapy to address chemotherapy-induced skeletal muscle and mitochondrial pathology.

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Polyimide/silicon dioxide nanocomposites were tested for their dielectric strength against nanofiller concentrations between 0% and 14%. The sol-gel process was used for in situ generation of silicon dioxide nanoparticles in a polyamic acid host matrix. Spin-coated and imidized samples with approximately 15 μm in thickness were then subjected to dielectric breakdown measurements in accordance with ASTM standards. Results showed two distinct regimes of dielectric strength. Higher dielectric withstand capability of nearly 275 kV mm −1 was exhibited by samples with 0% and 2% silicon dioxide. Higher concentration samples were dielectrically weaker by approximately 45% at 150 kV mm −1 . Broken-down specimens were examined under optical and electron microscopes. An inverse relationship between nanoparticle concentration and breakdown perforation diameter was observed. Hole sizes decreased gradually from 140 to 40 μm as silicon dioxide content increased from 0% to 6% and ultimately settled near 30 μm with higher concentrations. The testing results, examined through failure analysis, were explained by breakdown behaviors and mechanisms at different size scales. The findings from this project, in context with previous works and theories, can help establish connections of dielectric strength, perforation diameter, and nanofiller concentration for future polymer nanocomposite research.

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