Lack of Fibronectin Extra Domain A Alternative Splicing Exacerbates Endothelial Dysfunction in Diabetes

Glucose-induced changes of artery anatomy and function account for diabetic vascular complications, which heavily impact disease morbidity and mortality. Since fibronectin containing extra domain A (EDA\u2009+\u2009FN) is increased in diabetic vessels and participates to vascular remodeling, we wanted to elucidate whether and how EDA\u2009+\u2009FN is implicated in diabetes-induced endothelial dysfunction using isometric-tension recording in a murine model of diabetes. In thoracic aortas of EDA(-/-), EDA(+/+) (constitutively lacking and expressing EDA\u2009+\u2009FN respectively), and of wild-type mice (EDA(wt/wt)), streptozotocin (STZ)-induced diabetes impaired endothelial vasodilation to acetylcholine, irrespective of genotype. However STZ\u2009+\u2009EDA(-/-) mice exhibited increased endothelial dysfunction compared with STZ\u2009+\u2009EDA(+/+) and with STZ\u2009+\u2009EDA(wt/wt). Analysis of the underlying mechanisms revealed that STZ\u2009+\u2009EDA(-/-) mice show increased oxidative stress as demonstrated by enhanced aortic superoxide anion, nitrotyrosine levels and expression of NADPH oxidase NOX4 and TGF-\u3b21, the last two being reverted by treatment with the antioxidant n-acetylcysteine. In contrast, NOX1 expression and antioxidant potential were similar in aortas from the three genotypes. Interestingly, reduced eNOS expression in STZ\u2009+\u2009EDA(+/+) vessels is counteracted by increased eNOS coupling and function. Although EDA\u2009+\u2009FN participates to vascular remodelling, these findings show that it plays a crucial role in limiting diabetic endothelial dysfunction by preventing vascular oxidative stress

High-Fat Diet with Acyl-Ghrelin Treatment Leads to Weight Gain with Low Inflammation, High Oxidative Capacity and Normal Triglycerides in Rat Muscle

Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-µg s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P = NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity

A novel approach to navigated implantation of S2 alar iliac screws using inertial measurement units

The authors report on a novel method of intraoperative navigation with inertial measurement units (IMUs) for implantation of S-2 alar iliac (S2AI) screws in sacropelvic fixation of the human spine and its application in cadaveric specimens. METHODS Screw trajectories were planned on a multiplanar reconstruction of the preoperative CT scan. The pedicle finder and screwdriver were equipped with IMUs to guide the axial and sagittal tilt angles of the planned trajectory, and navigation software was developed. The entry points were chosen according to anatomical landmarks on the exposed spine. After referencing, the sagittal and axial orientation of the pedicle finder and screwdriver were wirelessly monitored on a computer screen and aligned with the preoperatively planned tilt angles to implant the S2AI screws. The technique was performed without any intraoperative imaging. Screw positions were analyzed on postoperative CT scans. RESULTS Seventeen of 18 screws showed a good S2AI screw trajectory. Compared with the postoperatively measured tilt angles of the S2AI screws, the IMU readings on the screwdriver were within an axial plane deviation of 0° to 5° in 15 (83%) and 6° to 10° in 2 (11%) of the screws and within a sagittal plane deviation of 0° to 5° in 15 (83%) and 6° to 10° in 3 (17%) of the screws. CONCLUSIONS IMU–based intraoperative navigation may facilitate accurate placement of S2AI screws

Inertial measurement unit-assisted implantation of thoracic, lumbar, and sacral pedicle screws improves precision of a freehand technique

OBJECTIVE:A method applying inertial measurement units (IMUs) was developed to implant pedicle screws in the thoracic and lumbosacral spine. This was compared with a freehand technique. METHODS:The study was done on 9 human cadavers. For each cadaver, a preoperative computed tomography (CT) scan was performed to measure the axial and sagittal tilt angles of the screw trajectories from T1 to S1. After the entry points were defined on the exposed spine, the IMU-equipped pedicle finder and screwdriver were used to reproduce these tilt angles and implant half of the screws. The other half was implanted with a freehand technique. Fluoroscopy was not used. The screw trajectories were analyzed on postoperative CTs. RESULTS:A hundred and sixty-two screws were placed with use of the IMUs and 162 screws were implanted by freehand. The IMU-guided technique matched the planned trajectories significantly better than the freehand technique (axial tilt P < 0.001, sagittal tilt P < 0.001). With IMU assistance, the mean offsets between the planned and postoperatively measured tilt angles of the screws were 3.3 degrees ± 3.5 degrees for the axial plane (median 2 degrees, range 0-23 degrees) and 3.4 degrees ± 3 degrees for the sagittal plane (median 3 degrees, range 0-13 degrees). For the freehand technique, the mean offsets between the planned and postoperatively measured tilt angles of the screws were 5.6 degrees ± 4.5 degrees for the axial plane (median 5 degrees, range 0-31 degrees) and 6.7 degrees ± 5.4 degrees for the sagittal plane (median 6 degrees, range 0-33 degrees). CONCLUSIONS:IMU-assisted implantation of pedicle screws may enhance the performance of a freehand technique in the thoracic and lumbosacral spin

A novel approach to navigated implantation of thoracic and lumbosacral pedicle screws using inertial measurement units

Introduction: A novel method of intraoperative navigation with inertial measurement units was developed to implant pedicle screws in the thoracic and lumbosacral human spine. This was compared with a freehand technique. IMUs house accelerometers and gyroscopes to measure acceleration and angular rotation. Among the many applications, IMUs control and detect motion and orientation of tablet computers and smartphones. Material and Methods: The study was done on 9 human cadavers. A preoperative CT was performed to measure the axial and sagittal tilt angles of the pedicle screw trajectories from T1 to S1. After defining the entry points on the exposed spine, the IMU-equipped pedicle finder and screwdriver were used to reproduce these tilt angles and implant one half of the screws. The other half was implanted with a freehand technique. Fluoroscopy was not used in any of the procedures. In addition to adhering to anatomic landmarks, the entry points of the last 216 screws of the study were found by intraoperatively reproducing the distance between the left and right pedicle with a divider. The screw trajectories were analyzed and compared on postoperative CTs. Results: 162 screws were implanted with use of the IMUs and 162 screws were implanted with a freehand technique. In relation to the preoperatively planned trajectories, the IMU-guided technique performed significantly better than the freehand technique (axial tilt p?=?0.000001, sagittal tilt p?=?0.0000000003): With the IMU-guided technique, the mean offsets between the planned and postoperatively measured tilt angles of the screws were for the axial plane 3.3?°?±3.5° (median 2°, range 0° - 23°) and for the sagittal plane 3.4?°?±3° (median 3°, range 0° - 13°). For the freehand techniques the mean offsets between the planned and postoperatively measured tilt angles of the screws were for the axial plane 5.6° ±4.5° (median 5°, range 0° - 31°) and for the sagittal plane 6.7° ±5.4° (median 6°, range 0° - 33°). Evaluation of the overall screw position showed that the IMU-guided technique in combination with the divider scored significantly better than the freehand technique plus divider (p?=?0.006). Conclusion: Inertial measurement unit?based intraoperative navigation may provide a more reliable implantation of pedicle screws in the thoracic and lumbosacral spine than a freehand technique. Furthermore, adding a divider to intraoperatively reproduce the interpedicular distance of a given level may further improve this novel technique. Translating this rather low-cost technology from consumer electronics to a clinical spine scenario may assist implanting thoracic and lumbar pedicle screws with minimal to no fluoroscopic guidance, yet at no loss of precision

Initial body weight (BW), body weight at the end of the one-month dietary treatment (before start of ghrelin or saline injection treatments), body weight changes before start of ghrelin or saline treatments, body weight changes during 4-day ghrelin or saline treatments, total 4-day caloric intake during 4-day ghrelin or saline treatment, retroperitoneal and epidydimal fat pad weights, plasma insulin, glucose and free fatty acids (FFA) concentrations in the three experimental groups.

<p>Data are Mean±SE. Different letters denote statistically significant differences: P<0.05 by ANOVA and post-hoc tests.</p