The Effect of Holmium Laser Fiber Bending Radius on Power Delivery During Flexible Ureteroscopy.

Introduction: Flexible ureteroscopy is a mainstay of upper urinary tract stone treatment. Holmium laser lithotripsy is a particularly common and notable technique for the dusting and fragmenting of renal stones. During ureteroscopy, optical fibers are subject to sharp bends in pursuit of stones, particularly those at the lower pole. Following from principles of fiber optics, subjecting these fibers to sharp bending angle has the potential to reduce the efficiency of power transmission at the fiber tip. Due to the potential implications this hypothesis could have on endourological practice and research, we aimed to explore the potential impact of fiber bending on end-fiber power output. Materials and Methods: Using a highly sensitive oscilloscope and a urological holmium laser, we assessed the end-fiber power output under a variety of bending conditions. To ensure maximal confidence in our results, the maximal bending conditions explored substantially exceeded any condition, which could occur during ureteroscopic surgery. Results: We found evidence that bending radius alone has a clinically insignificant impact on the light power transmission in the fiber. At certain bending conditions, we observed a clinically unimportant but statistically significant reduction in power transmission. This was verified using two commonly used delivery fiber types exposed to 8-second bursts for each bending condition.

Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production.

Rapamycin is a well-known inhibitor of the Target of Rapamycin (TOR) signaling cascade; however, the impact of this drug on global genome function and organization in normal primary cells is poorly understood. To explore this impact, we treated primary human foreskin fibroblasts with rapamycin and observed a decrease in cell proliferation without causing cell death. Upon rapamycin treatment chromosomes 18 and 10 were repositioned to a location similar to that of fibroblasts induced into quiescence by serum reduction. Although similar changes in positioning occurred, comparative transcriptome analyses demonstrated significant divergence in gene expression patterns between rapamycin-treated and quiescence-induced fibroblasts. Rapamycin treatment induced the upregulation of cytokine genes, including those from the Interleukin (IL)-6 signaling network, such as IL-8 and the Leukemia Inhibitory Factor (LIF), while quiescent fibroblasts demonstrated up-regulation of genes involved in the complement and coagulation cascade. In addition, genes significantly up-regulated by rapamycin treatment demonstrated increased promoter occupancy of the transcription factor Signal Transducer and Activator of Transcription 5A/B (STAT5A/B). In summary, we demonstrated that the treatment of fibroblasts with rapamycin decreased proliferation, caused chromosome territory repositioning and induced STAT5A/B-mediated changes in gene expression enriched for cytokines.