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Abstract Background NADPH-oxidases (Nox) and the related Dual oxidases (Duox) play varied biological and pathological roles via regulated generation of reactive oxygen species (ROS). Members of the Nox/Duox family have been identified in a wide variety of organisms, including mammals, nematodes, fruit fly, green plants, fungi, and slime molds; however, little is known about the molecular evolutionary history of these enzymes. Results We assembled and analyzed the deduced amino acid sequences of 101 Nox/Duox orthologs from 25 species, including vertebrates, urochordates, echinoderms, insects, nematodes, fungi, slime mold amoeba, alga and plants. In contrast to ROS defense enzymes, such as superoxide dismutase and catalase that are present in prokaryotes, ROS-generating Nox/Duox orthologs only appeared later in evolution. Molecular taxonomy revealed seven distinct subfamilies of Noxes and Duoxes. The calcium-regulated orthologs representing 4 subfamilies diverged early and are the most widely distributed in biology. Subunit-regulated Noxes represent a second major subdivision, and appeared first in fungi and amoeba. Nox5 was lost in rodents, and Nox3, which functions in the inner ear in gravity perception, emerged the most recently, corresponding to full-time adaptation of vertebrates to land. The sea urchin Strongylocentrotus purpuratus possesses the earliest Nox2 co-ortholog of vertebrate Nox1, 2, and 3, while Nox4 first appeared somewhat later in urochordates. Comparison of evolutionary substitution rates demonstrates that Nox2, the regulatory subunits p47phox and p67phox, and Duox are more stringently conserved in vertebrates than other Noxes and Nox regulatory subunits. Amino acid sequence comparisons identified key catalytic or regulatory regions, as 68 residues were highly conserved among all Nox/Duox orthologs, and 14 of these were identical with those mutated in Nox2 in variants of X-linked chronic granulomatous disease. In addition to canonical motifs, the B-loop, TM6-FAD, VXGPFG-motif, and extreme C-terminal regions were identified as important for Nox activity, as verified by mutational analysis. The presence of these non-canonical, but highly conserved regions suggests that all Nox/Duox may possess a common biological function remained in a long history of Nox/Duox evolution. Conclusion This report provides the first comprehensive analysis of the evolution and conserved functions of Nox and Duox family members, including identification of conserved amino acid residues. These results provide a guide for future structure-function studies and for understanding the evolution of biological functions of these enzymes.

This article describes the successful implementation of a structured UV light field, generated from a modified LCD projector, to excite pressure-sensitive paint (PSP) and measure surface shape simultaneously without the need to compromise the PSP by mechanical degradation of the coating. Using commercially available hardware, results were gathered in a Mach 5 wind tunnel, showing the expected pressure distribution around a cone model with a flare and the surface geometry without any prior knowledge or information. The demonstrated methodology can be used to measure aerodynamic models exhibiting elastic deformation under load during a wind tunnel measurement campaign, providing out-of-plane motions are small. The captured deformation and pressure results can be used to support validation of structural models and correct numerical simulation meshes to the actual shape investigated in the wind tunnel. [ABSTRACT FROM AUTHOR]

Human neutrophil elastase (HNE) is a proteolytic enzyme belonging to the serine protease family and is involved in a variety of pathologies. Thus, compounds able to inhibit HNE represent promising therapeutics for the treatment of inflammatory diseases. Here, we report the further elaboration of our previously reported 3‐methylisoxazolone derivatives, synthesizing a new series of 3‐nor‐derivatives bearing different substituents at the 4‐phenyl ring. The most potent compounds 3a, 3g, and 3h, had IC50 values of 16, 11, and 18 nM, respectively. Molecular modeling studies and molecular dynamic (MD) simulations demonstrated no substantial differences between the 3‐methylisoxazole derivatives previously tested and the corresponding 3‐unsubstituted derivatives in the snapshot conformations sampled during the MD simulations, which is consistent with their similar levels of HNE inhibitory activity. Thus, we conclude that the isoxazolone scaffold is a good scaffold for developing HNE inhibitors, as it tolerates several modifications when adhering to basic scaffold requirements, and the resulting derivatives are quite potent HNE inhibitors. [ABSTRACT FROM AUTHOR]

The survey of the prevalence and needs of exceptional students in Queensland (Australia) Catholic primary and secondary schools (N=235) had such findings as 3.13 percent of school children had disabilities, 12.8 percent had learning difficulties, more support services were needed, and principals and teachers expressed positive attitudes toward integration. (Author/DB)

Background: The surgical approach for total hip arthroplasty (THA) has the potential to affect the immediate postoperative recovery; however, there is limited published data comparing the 3 most common surgical approaches. The purpose of the study was to investigate postoperative pain and subsequent opioid consumption between surgical approaches (anterior-AA, lateral-LA, and posterior-PA) in those undergoing primary elective THA.Methods: A retrospective cohort study assessed patient demographics (age, sex, and body mass index), American Society of Anesthesiologists grade, opioid naivety, operative details (anesthetic method, fixation method, and local infiltration analgesia), pain scores, and length of stay. Statistical analysis was performed with a 1-way analysis of variance 3 × 1 table with a P value < .05.Results: A total of 560 patients were included in the analysis (335 females and 225 males). The cohort consisted of 179 AA, 178 LA, and 203 PA patients. The average postoperative opioid usage was 63.05 (standard deviation [SD] = 42.97), 79.81 (SD = 56.10), and 77.50 (SD = 54.52) oral morphine equivalent daily dose (oMEDD) for the AA, LA, and PA, respectively. The mean difference was 16.8 oMEDD lower in the AA compared with the LA (P < .01) and 14.5 oMEDD lower in the AA compared with the PA (P = .02).Conclusion: The direct anterior approach was associated with lower daily opioid usage and pain scores after elective THA in the early postoperative period. This represents a potential 21% reduction in daily opioid dosage when compared with LA patients and 18.7% reduction in PA patients. [ABSTRACT FROM AUTHOR]

Background: Acetabular fractures are associated with damage to the femoral head, acetabular cartilage and labrum and possible disruption of the femoral head blood supply. Treatment aims to provide the best opportunity for restoration of joint function and to prevent long-term complications. Surgical intervention, in the form of open reduction and internal fixation (ORIF), is often required. Where post-traumatic osteoarthritis develops after ORIF, total hip arthroplasty (THA) is often required. Our aim here has been to identify and highlight our experience with the key technical points associated with successful outcomes for THA in this setting. Methods: A single-centre retrospective review of patients with acetabular fractures treated with ORIF and subsequent THA over a 4-year period was undertaken. Demographics, mechanism of injury, complications, interval time between surgeries, intra-operative outcomes and post-operative outcomes were recorded. Particular emphasis is made to describe standard pre-operative and intra-operative protocols. Results: Twenty-five patients were identified, with a mean age of 51.1 years at time of first ORIF. 60% presented following RTA. 80% of fractures involved the posterior wall or column. Meantime to eventual THA was 2.3 years. Mean THA duration was 1.52 h, with mean intra-operative blood loss and length of stay of 585 ml and 5 days, respectively. 24% required intra-operative removal of metal, with only one patient suffering a complication post-THA. Conclusion: Acceptable post-operative outcomes were demonstrated throughout the case series. In describing the pre-operative work up, intra-operative findings and intra-operative and post-operative complications encountered, common important technical points associated with a successful surgical strategy are described. Furthermore, potential pitfalls that may be encountered can be anticipated. [ABSTRACT FROM AUTHOR]

Introduction: The increasing incidence of acetabular fractures in the elderly and the fracture complexity seen in this cohort represents one of the greatest challenges faced by trauma orthopaedic surgeons today. There are no formal guidelines of best practice in the treatment of these patients. Management options vary from non-operative, acute ORIF, and/or total joint replacement. Although surgical intervention allows for earlier mobilization and avoidance of the complications of prolonged bedrest, the patients ability to tolerate what is often major surgery is always of concern. This is in stark contrast to intracapsular hip fractures, (a fracture within the same joint), where acute surgery is recommended in virtually all cases.Objectives: This study was undertaken to evaluate the peri-operative outcomes for geriatric patients undergoing acetabular ORIF and hemiarthroplasty to assess if there is a significant difference in early outcome parameters.Design: This is a retrospective case-control study.Setting: This study was performed in the National Centre for Pelvic and Acetabular surgery.Patients: 42 age- and sex-matched patients with comparable ASA grades were included in each arm of the study. Patient selection in the acetabular ORIF group was consecutive patients managed operatively in the centre during the period 2010-2015. The selection for the hemiarthroplasty group was by random selection of age- and sex-matched patients undergoing hemiarthroplasty during the same period.Main Outcome Measurements: The primary outcomes that were proposed prior to the study being performed was perioperative mortality and post-op complications. Secondary outcomes were operating times, blood loss and need for ICU admission.Results: A significant difference between the two cohorts was observed with operative times, blood loss, need for transfusion, and need for ICU admission, all higher in the acetabular ORIF group. There was no significant difference in mortality or post-op infection.Conclusions: Our paper supports the concept that acute ORIF of acetabular fractures, with appropriate peri-operative support, can be undertaken safely. There is no difference in the major peri-operative outcomes of mortality or infection when compared with hip fracture patients requiring hemiarthroplasty. [ABSTRACT FROM AUTHOR]

Malignant melanoma cells spontaneously generate reactive oxygen species (ROS) that promote constitutive activation of the transcription factor nuclear factor-[kappa]B (NF-[kappa]B). Although antioxidants and inhibitors of NAD(P)H oxidases significantly reduce constitutive NF-[kappa]B activation and suppress cell proliferation (11), the nature of the enzyme responsible for ROS production in melanoma cells has not been determined. To address this issue, we now have characterized the source of ROS production in melanoma cells. We report that ROS are generated by isolated, cytosol-free melanoma plasma membranes, with inhibition by NAD(P)H oxidase inhibitors. The [p22.sup.phox], [gp91.sup.phox], and [p67.sup.phox] components of the human phagocyte NAD(P)H oxidase and the [gp91.sup.phox] homolog NOX4 were demonstrated in melanomas by RT-PCR and sequencing, and protein product for both [p22.sup.phox] and [gp91.sup.phox] was detected in cell membranes by immunoassay. Normal human epidermal melanocytes expressed only [p22.sup.phox] and NOX4. Melanoma proliferation was reduced by NAD(P)H oxidase inhibitors and by transfection of antisense but not sense oligonucleotides for [p22.sup.phox] and NOX4. Also, the flavoprotein inhibitor diphenylene iodonium inhibited constitutive DNA binding of nuclear protein to the NF-[kappa]B and cAMP-response element consensus oligonucleotides, without affecting DNA binding activity to activator protein-1 or OCT-1. This suggests that ROS generated in autocrine fashion by an NAD(P)H oxidase may play a role in signaling malignant melanoma growth. superoxide anion; diphenylene iodonium; [p22.sup.phox]; [gp91.sup.phox]; [p67.sup.phox]; NOX1; NOX4; nuclear factor-[kappa]B; cAMP response element; dicumarol