Solution Structural Ensembles of Substrate-Free Cytochrome P450_cam

Removal of substrate (+)-camphor from the active site of cytochrome P450_cam (CYP101A1) results in nuclear magnetic resonance-detected perturbations in multiple regions of the enzyme. The ¹H–¹⁵N correlation map of substrate-free diamagnetic Fe­(II) CO-bound CYP101A permits these perturbations to be mapped onto the solution structure of the enzyme. Residual dipolar couplings (RDCs) were measured for ¹⁵N–¹H amide pairs in two independent alignment media for the substrate-free enzyme and used as restraints in solvated molecular dynamics (MD) simulations to generate an ensemble of best-fit structures of the substrate-free enzyme in solution. Nuclear magnetic resonance-detected chemical shift perturbations reflect changes in the electronic environment of the NH pairs, such as hydrogen bonding and ring current shifts, and are observed for residues in the active site as well as in hinge regions between secondary structural features. RDCs provide information about relative orientations of secondary structures, and RDC-restrained MD simulations indicate that portions of a β-rich region adjacent to the active site shift so as to partially occupy the vacancy left by removal of the substrate. The accessible volume of the active site is reduced in the substrate-free enzyme relative to the substrate-bound structure calculated using the same methods. Both symmetric and asymmetric broadening of multiple resonances observed upon substrate removal as well as localized increased errors in RDC fits suggest that an ensemble of enzyme conformations are present in the substrate-free form

18F Fluorocholine Dynamic Time-of-Flight PET/MR Imaging in Patients with Newly Diagnosed Intermediate- to High-Risk Prostate Cancer: Initial Clinical-Pathologic Comparisons.

Purpose To investigate the initial clinical value of fluorine 18 (18F) fluorocholine (FCH) dynamic positron emission tomography (PET)/magnetic resonance (MR) imaging by comparing its parameters with clinical-pathologic findings in patients with newly diagnosed intermediate- to high-risk prostate cancer (PCa) who plan to undergo radical prostatectomy. Materials and Methods The institutional review board approved the study protocol, and informed written consent was obtained from all subjects for this HIPAA-compliant study. Twelve men (mean age ± standard deviation, 61.7 years ± 8.4; range, 46-74 years) with untreated intermediate- to high-risk PCa characterized according to Cancer of the Prostate Risk Assessment (CAPRA) underwent preoperative FCH dynamic PET/MR imaging followed by radical prostatectomy between April and November 2015. PET/MR imaging parameters including average and maximum K1 (delivery rate constant) and standardized uptake values (SUVs) and Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores were measured and compared with clinical-pathologic characteristics. For statistical analysis, the Spearman rank correlation and Mann-Whitney U tests were performed. Results Of the PET parameters, maximum SUV of primary tumors showed significant correlations with several clinical-pathologic parameters including serum prostate-specific antigen level (ρ = 0.71, P = .01), pathologic stage (ρ = 0.59, P = .043), and postsurgical CAPRA score (ρ = 0.72, P = .008). The overall PI-RADS score showed significant correlations with pathologic tumor volume (ρ = 0.81, P < .001), percentage of tumor cells with Gleason scores greater than 3 (ρ = 0.59, P = .02), and postsurgical CAPRA score (ρ = 0.58, P = .046). The high-risk postsurgical CAPRA score patient group had a significantly higher maximum SUV than did the intermediate-risk group. Combined PET and MR imaging showed improved sensitivity (88%) for prediction of pathologic extraprostatic extension compared with that with MR imaging (50%) and PET (75%) performed separately. Conclusion Maximum SUVs and PI-RADS scores from FCH PET/MR imaging show good correlation with clinical-pathologic characteristics, such as postsurgical CAPRA score, which are related to prognosis in patients with newly diagnosed intermediate- to high-risk PCa. © RSNA, 2016 Online supplemental material is available for this article

Grade 1 Internal Carotid Artery Blunt Cerebrovascular Injury Persistence Risks Stroke With Current Management: An EAST Multicenter Study.

BACKGROUND: Higher blunt cerebrovascular injury (BCVI) grade and lack of medical therapy are associated with stroke. Knowledge of stroke risk factors specific to individual grades may help tailor BCVI therapy to specific injury characteristics. METHODS: A post-hoc analysis of a 16 center, prospective, observational trial (2018-2020) was performed including grade 1 internal carotid artery (ICA) BCVI. Repeat imaging was considered the second imaging occurrence only. RESULTS: From 145 grade 1 ICA BCVI included, 8 (5.5%) suffered a stroke. Grade 1 ICA BCVI with stroke were more commonly treated with mixed anticoagulation and antiplatelet therapy (75.0% vs 9.6%, P DISCUSSION: While the stroke rate for grade 1 ICA BCVI is low overall, injury persistence appears to heighten stroke risk. Some strokes occurred despite initiation of medical therapy. Repeat imaging is needed in grade 1 ICA BCVI to evaluate for injury progression or resolution

Endovascular Intervention in Internal Carotid Artery Blunt Cerebrovascular Injury: An EAST Multicenter Study.

BACKGROUND: Use of endovascular intervention (EI) for blunt cerebrovascular injury (BCVI) is without consensus guidelines. Rates of EI use and radiographic characteristics of BCVI undergoing EI nationally are unknown. METHODS: A post-hoc analysis of a prospective, observational study at 16 U.S. trauma centers from 2018 to 2020 was conducted. Internal carotid artery (ICA) BCVI was included. The primary outcome was EI use. Multivariable logistic regression was performed for predictors of EI use. RESULTS: From 332 ICA BCVI included, 21 (6.3%) underwent EI. 0/145 (0%) grade 1, 8/101 (7.9%) grade 2, 12/51 (23.5%) grade 3, and 1/20 (5.0%) grade 4 ICA BCVI underwent EI. Stroke occurred in 6/21 (28.6%) ICA BCVI undergoing EI and in 33/311 (10.6%) not undergoing EI ( DISCUSSION: Pseudoaneurysm size is associated with use of EI for ICA BCVI. Stroke is more common in ICA BCVI with EI but did not occur after EI use

Grade 1 Internal Carotid Artery Blunt Cerebrovascular Injury Persistence Risks Stroke With Current Management: An EAST Multicenter Study.

BACKGROUND: Higher blunt cerebrovascular injury (BCVI) grade and lack of medical therapy are associated with stroke. Knowledge of stroke risk factors specific to individual grades may help tailor BCVI therapy to specific injury characteristics. METHODS: A post-hoc analysis of a 16 center, prospective, observational trial (2018-2020) was performed including grade 1 internal carotid artery (ICA) BCVI. Repeat imaging was considered the second imaging occurrence only. RESULTS: From 145 grade 1 ICA BCVI included, 8 (5.5%) suffered a stroke. Grade 1 ICA BCVI with stroke were more commonly treated with mixed anticoagulation and antiplatelet therapy (75.0% vs 9.6%, P DISCUSSION: While the stroke rate for grade 1 ICA BCVI is low overall, injury persistence appears to heighten stroke risk. Some strokes occurred despite initiation of medical therapy. Repeat imaging is needed in grade 1 ICA BCVI to evaluate for injury progression or resolution

Fire, Plant Invasions, and Erosion Events on Western Rangelands

Millions of hectares of rangeland in the western United States have been invaded by annual and woody plants that have increased the role of wildland fire. Altered fire regimes pose significant implications for runoff and erosion. In this paper we synthesize what is known about fire impacts on rangeland hydrology and erosion, and how that knowledge advances understanding of hydrologic risks associated with landscape scale plant community transitions and altered fire regimes. The increased role of wildland fire on western rangeland exposes landscapes to amplified runoff and erosion over short- and long-term windows of time and increases the risk of damage to soil and water resources, property, and human lives during extreme events. Amplified runoff and erosion postfire are a function of storm characteristics and fire-induced changes in site conditions (i.e., ground cover, soil water repellency, aggregate stability, and surface roughness) that define site susceptibility. We suggest that overall postfire hydrologic vulnerability be considered in a probabilistic framework that predicts hydrologic response for a range of potential storms and site susceptibilities and that identifies the hydrologic response magnitudes at which damage to values-at-risk are likely to occur. We identify key knowledge gaps that limit advancement of predictive technologies to address the increased role of wildland fire across rangeland landscapes. Our review of literature suggests quantifying interactions of varying rainfall intensity and key measures of site susceptibility, temporal variability in strength/influence of soil water repellency, and spatial scaling of postfire runoff and erosion remain paramount areas for future research to address hydrologic effects associated with the increased role of wildland fire on western rangelands.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

Does treatment delay for blunt cerebrovascular injury affect stroke rate?: An EAST multicenter study.

BACKGROUND: The purpose of this study was to analyze injury characteristics and stroke rates between blunt cerebrovascular injury (BCVI) with delayed vs non-delayed medical therapy. We hypothesized there would be increased stroke formation with delayed medical therapy. METHODS: This is a sub-analysis of a 16 center, prospective, observational trial on BCVI. Delayed medial therapy was defined as initiation \u3e24 hours after admission. BCVI which did not receive medical therapy were excluded. Subgroups for injury presence were created using Abbreviated Injury Scale (AIS) score \u3e0 for AIS categories. RESULTS: 636 BCVI were included. Median time to first medical therapy was 62 hours in the delayed group and 11 hours in the non-delayed group (p \u3c 0.001). The injury severity score (ISS) was greater in the delayed group (24.0 vs the non-delayed group 22.0, p \u3c 0.001) as was the median AIS head score (2.0 vs 1.0, p \u3c 0.001). The overall stroke rate was not different between the delayed vs non-delayed groups respectively (9.7% vs 9.5%, p = 1.00). Further evaluation of carotid vs vertebral artery injury showed no difference in stroke rate, 13.6% and 13.2%, p = 1.00 vs 7.3% and 6.5%, p = 0.84. Additionally, within all AIS categories there was no difference in stroke rate between delayed and non-delayed medical therapy (all N.S.), with AIS head \u3e0 13.8% vs 9.2%, p = 0.20 and AIS spine \u3e0 11.0% vs 9.3%, p = 0.63 respectively. CONCLUSIONS: Modern BCVI therapy is administered early. BCVI with delayed therapy were more severely injured. However, a higher stroke rate was not seen with delayed therapy, even for BCVI with head or spine injuries. This data suggests with competing injuries or other clinical concerns there is not an increased stroke rate with necessary delays of medical treatment for BCVI