MicroRNA-210-mediated mtROS confer hypoxia-induced suppression of STOCs in ovine uterine arteries.

BACKGROUND AND PURPOSE: Hypoxia during pregnancy is associated with increased uterine vascular resistance and elevated blood pressure both in women and female sheep. A previous study demonstrated a causal role of microRNA-210 (miR-210) in gestational hypoxia-induced suppression of Ca2+ sparks/spontaneous transient outward currents (STOCs) in ovine uterine arteries, but the underlying mechanisms remain undetermined. We tested the hypothesis that miR-210 perturbs mitochondrial metabolism and increases mitochondrial reactive oxygen species (mtROS) that confer hypoxia-induced suppression of STOCs in uterine arteries. EXPERIMENTAL APPROACH: Resistance-sized uterine arteries were isolated from near-term pregnant sheep and were treated ex vivo in normoxia and hypoxia (10.5% O2 ) for 48 h. KEY RESULTS: Hypoxia increased mtROS and suppressed mitochondrial respiration in uterine arteries, which were also produced by miR-210 mimic to normoxic arteries and blocked by antagomir miR-210-LNA in hypoxic arteries. Hypoxia or miR-210 mimic inhibited Ca2+ sparks/STOCs and increased uterine arterial myogenic tone, which were inhibited by the mitochondria-targeted antioxidant MitoQ. Hypoxia and miR-210 down-regulated iron-sulfur cluster scaffold protein (ISCU) in uterine arteries and knockdown of ISCU via siRNAs suppressed mitochondrial respiration, increased mtROS, and inhibited STOCs. In addition, blockade of mitochondrial electron transport chain with antimycin and rotenone inhibited large-conductance Ca2+ -activated K+ channels, decreased STOCs and increased uterine arterial myogenic tone. CONCLUSION AND IMPLICATIONS: This study demonstrates a novel mechanistic role for the miR-210-ISCU-mtROS axis in inhibiting Ca2+ sparks/STOCs in the maladaptation of uterine arteries and provides new insights into the understanding of mitochondrial perturbations in the pathogenesis of pregnancy complications resulted from hypoxia.

Implementation of a Pediatric Orthopaedic Bundle to Reduce Surgical Site Infections.

Surgical site infections (SSIs) cost an estimated $27,288 per case. An analysis of the National Surgical Quality Improvement Program data at the University of Rochester Medical Center suggested that rates of SSIs could be lowered in comparison with both peers and baseline. The aim of this study was to reduce the number of SSIs to zero through the implementation of a "bundle" or a combination of practices. Meetings were held with the multidisciplinary care team that includes surgeons and staff from pediatric pharmacy, pediatric infectious diseases, anesthesia, and nursing to create a care bundle for all pediatric orthopaedic surgery patients. Bundle elements included use of chlorhexidine gluconate wipes the night before surgery and the day of surgery, use of preoperative nutrition screens, development and use of a prophylactic antibiotic dosing chart, use of methicillin-resistant Staphylococcus aureus screening, maintenance of normal patient temperature, and use of nasal swabs in the operating room. The SSI rate dropped from a baseline figure of 4% in 2013 (n = 154) and 3.2% in 2014 (n = 189) to 0.0% (n = 198) in 2015 after the bundles were implemented. Both compliance with the bundle and SSI rates must be monitored monthly. Staff and providers should be offered monthly feedback on SSI rates and care bundle compliance. If an SSI does occur, a root-cause analysis is performed with the multidisciplinary care team using a standardized review form.