Citations

AbstractReducing the work of breathing during exercise improves locomotor muscle blood flow and reduces diaphragm and locomotor muscle fatigue and is thought to be the result of a sympathetically mediated reflex.AimThe aim of this study was to assess muscle sympathetic nerve activity (MSNA) when the work of breathing is experimentally lowered during dynamic exercise.MethodsHealthy subjects (n = 12; age = 29 ± 9 years) performed semi‐recumbent cycling trials at 40%, 60%, and 80% of peak workload. Exercise trials consisted of spontaneous breathing, reduced work of breathing (proportional assist ventilator), followed by further spontaneous breathing (post‐ventilator). MSNA was recorded from the median nerve.ResultsThere was no difference in work of breathing between PAV and post‐PAV at 40% peak work. At 60% peak work, the ventilator significantly (P < 0.05) reduced work of breathing (103 ± 39 vs 144 ± 47 J min−1), sympathetic nerve activity (35 ± 5 vs 42 ± 8 burst min−1), and (2.4 ± 0.5 vs 2.6 ± 0.5 L min−1) without influencing ventilation (86 ± 9 vs 82 ± 10 L min−1; P > 0.05), for PAV and post‐PAV respectively. During 80% peak work (n = 8), the ventilator significantly (P < 0.05) reduced work of breathing (235 ± 110 vs. 361 ± 150 J min−1), MSNA (48 ± 7 vs 54 ± 11 burst min−1), and (2.9 ± 0.6 vs 3.2 ± 0.7 L min−1) but not ventilation (121 ± 20 vs 123 ± 20 L min−1; P > 0.05), for PAV and post‐PAV respectively. There was a significant relationship between MSNA and (P < 0.0001) with a significant interaction due to the ventilator (P < 0.05).ConclusionLowering the normally occurring work of breathing during exercise results in commensurate reductions in MSNA. Our findings provide evidence of a sympathetically mediated vasoconstrictor effect emanating from respiratory muscles during exercise.

BackgroundAdamantinomas are rare bone tumors, commonly affecting the tibia. Due to the rare nature of disease, previous studies are small or from multiple centers. The purpose of this study is to investigate outcomes of patients with adamantinoma treated in a single institution.MethodsForty‐six histological confirmed adamantinomas of the extremities were reviewed at our institution between 1939 and 2012. Follow‐up data included clinical and radiographical information focusing on complications, local recurrence, metastasis, and overall survival after the treatment. The mean follow‐up was 16 years (range 2‐42 years).ResultsThe most common location was the tibia (n = 31). Patients commonly presented with pain and swelling. The mean age was 24 years (7‐79 years). Thirty‐seven patients were treated with limb salvage. The 39% of patients required a reoperation. The 10‐year disease specific‐ and recurrence free survival was 92% and 72%, with three patients having a recurrence over 15 years postoperative. Older (> 20 years) patients and males were at increased risk of local recurrence (P < 0.05).ConclusionTreatment of adamantinoma of the long bone consists of limb‐salvage surgery. Male patients should be cautioned on their increased risk of disease recurrence, and advocate for continued surveillance of patients even greater than 15‐years postoperatively due to late tumor recurrence.

Abstract UNC-45A, a highly conserved member of the UCS (UNC45A/CRO1/SHE4P) protein family of cochaperones, plays an important role in regulating cytoskeletal-associated functions in invertebrates and mammalian cells, including cytokinesis, exocytosis, cell motility, and neuronal development. Here, for the first time, UNC-45A is demonstrated to function as a mitotic spindle-associated protein that destabilizes microtubules (MT) activity. Using in vitro biophysical reconstitution and total internal reflection fluorescence microscopy analysis, we reveal that UNC-45A directly binds to taxol-stabilized MTs in the absence of any additional cellular cofactors or other MT-associated proteins and acts as an ATP-independent MT destabilizer. In cells, UNC-45A binds to and destabilizes mitotic spindles, and its depletion causes severe defects in chromosome congression and segregation. UNC-45A is overexpressed in human clinical specimens from chemoresistant ovarian cancer and that UNC-45A–overexpressing cells resist chromosome missegregation and aneuploidy when treated with clinically relevant concentrations of paclitaxel. Lastly, UNC-45A depletion exacerbates paclitaxel-mediated stabilizing effects on mitotic spindles and restores sensitivity to paclitaxel. Implications: These findings reveal novel and significant roles for UNC-45A in regulation of cytoskeletal dynamics, broadening our understanding of the basic mechanisms regulating MT stability and human cancer susceptibility to paclitaxel, one of the most widely used chemotherapy agents for the treatment of human cancers.

SummaryBackgroundChildren undergoing posterior spinal fusion experience high blood loss often necessitating transfusion. An appropriately activated coagulation system provides hemostasis during surgery, but pathologic dysregulation can cause progressive bleeding and increased transfusions. Despite receiving antifibrinolytics for clot stabilization, many patients still require transfusions.AimsWe sought to examine the association of dilutional coagulopathy with blood loss and blood transfusion in posterior spinal fusion for pediatric scoliosis patients.MethodsA retrospective, single institution study of children undergoing posterior spinal fusion >6 levels with a standardized, prospective anesthetic protocol utilizing antifibrinolytics. Blood loss was evaluated using a hematocrit‐based calculation. To evaluate transfusions, a normalized Blood Product Transfusion calculation was developed. Factors associated with blood loss and blood transfusions were determined by univariate analysis and multivariate regression modeling with multicollinearity and mediation analysis.ResultsPatients received 73.7 mL/kg (standard deviation ±30.8) of fluid poor in coagulation factors. Estimated blood loss was 42.6 mL/kg (standard deviation ±18.0). There was a significant association between estimated blood loss and total fluids delivered (Spearman's rho = 0.51, 95% confidence interval 0.33‐0.65, P < 0.001). Factors significantly associated with normalized Blood Product Transfusion in this cohort included age, weight, scoliosis type, levels fused, total osteotomies, pelvic fixation, total fluid, maximum prothrombin time, and minimum fibrinogen. Regression modeling showed the best combination of variables for modeling normalized Blood Product Transfusion included patient weight, number of levels fused, total fluid administered, and maximum prothrombin time.ConclusionBlood product transfusion remains a frustrating problem in pediatric scoliosis. Identifying and controlling dilutional coagulopathy in these patients may reduce blood loss and the need for blood transfusion.

Objective Over the last decade, electronic health records (EHRs) have shaped clinical practice. In this article, we investigated the perceived effects of EHR use on clinical workflow and meaningful use (MU) performance metrics. Materials and Methods Semistructured interviews were conducted with 20 (n = 20) physicians at two urban emergency departments. Interview questions focused on time spent on EHR use, changes in clinical practices with EHR use, and the effect of MU performance metrics on clinical workflow. Qualitative coding using grounded theory and descriptive analyses were performed to provide descriptive insights. Results Physicians reported that EHRs improved their clinical workflow, especially on MU-related activities including door-to-doctor time and admit decision time. EHR use also affected physicians work efficiency, quality of care provided, and overall patient safety. Conclusion Physicians' perception of EHRs is likely to influence their practices. With negative perceptions of EHR usability problems, positive aspects of EHR use, including the influence on MU performance metrics, may be overridden.