Structure-based comparative analysis and prediction of N-linked glycosylation sites in evolutionarily distant eukaryotes

AbstractThe asparagine-X-serine/threonine (NXS/T) motif, where X is any amino acid except proline, is the consensus motif for N-linked glycosylation. Significant numbers of high-resolution crystal structures of glycosylated proteins allow us to carry out structural analysis of the N-linked glycosylation sites (NGS). Our analysis shows that there is enough structural information from diverse glycoproteins to allow the development of rules which can be used to predict NGS. A Python-based tool was developed to investigate asparagines implicated in N-glycosylation in five species: Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana and Saccharomyces cerevisiae. Our analysis shows that 78% of all asparagines of NXS/T motif involved in N-glycosylation are localized in the loop/turn conformation in the human proteome. Similar distribution was revealed for all the other species examined. Comparative analysis of the occurrence of NXS/T motifs not known to be glycosylated and their reverse sequence (S/TXN) shows a similar distribution across the secondary structural elements, indicating that the NXS/T motif in itself is not biologically relevant. Based on our analysis, we have defined rules to determine NGS. Using machine learning methods based on these rules we can predict with 93% accuracy if a particular site will be glycosylated. If structural information is not available the tool uses structural prediction results resulting in 74% accuracy. The tool was used to identify glycosylation sites in 108 human proteins with structures and 2247 proteins without structures that have acquired NXS/T site/s due to non-synonymous variation. The tool, Structure Feature Analysis Tool (SFAT), is freely available to the public at http://hive.biochemistry.gwu.edu/tools/sfat

Catamenial hemothorax in a patient with multiple sclerosis.

Stevenson, E. K., Sloan, K. A., Narsule, C. K., Kretschman, D. M., Sarita-Reyes, C. D., Steiling, K., & Ebright, M. I. (2014). Catamenial hemothorax in a patient with multiple sclerosis. American journal of respiratory and critical care medicine, 190(12), e69–e70. https://doi.org/10.1164/rccm.201407-1283I

Role of Vena Cava Filter in the Prophylaxis and Treatment of Venous Thromboembolism in Injured Adult Patients: A Systematic Review, Meta-Analysis, and Practice Management Guideline from the Eastern Association for the Surgery of Trauma

Injured patients are at an increased risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). Inferior vena cava (IVC) filters have been used in injured patients to prevent venous thromboembolism (VTE), but current evidence-based guidelines are lacking. Questions regarding IVC filter use in injured patients with clearly defined Population(s), Intervention(s), Comparison(s), and appropriately selected Outcomes (PICO) were formulated. The study sought to understand the evidence behind use of ultra short term IVC filters and use of IVC filters in injured patients with and without known VTE who are unable to receive therapeutic anticoagulation and chemoprophylaxis, respectively. A literature search and review was conducted, followed by meta-analysis. The quality of evidence was assessed per Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. There were twenty-one studies that were analyzed. Three studies were randomized controlled trials (RCTs), three were observational studies, and fifteen studies were retrospective studies. In injured patients without known acute VTE who cannot receive chemoprophylaxis, we recommend against placement of an IVC filter due to associated higher rate of mortality, DVT, PE, and length of stay. The quality of evidence was assessed to be low. In injured patients with known DVT who cannot receive chemoprophylaxis we conditionally recommend against placement of an IVC filter. The quality of evidence was assessed to be very low. No recommendations can be made with respect to placement of ultra short term IVC filters based upon available data. IVC filters should not be placed routinely for prophylaxis in injured adult patients without known VTE who cannot receive chemoprophylaxis. The taskforce conditionally recommends against the placement of IVC filter in injured adult patients with known DVT who cannot receive chemoprophylaxis. Guideline; Systematic review/meta-analysis, level IV

Efficacy of Ultrasonography in the Evaluation of Suspected Appendicitis in a Pediatric Population

The purpose of this study was to evaluate the efficacy of ultrasound (US) for the diagnosis of acute appendicitis in children. Patients and methods: We reviewed all sonograms for acute appendicitis in children suspected of having appendicitis from January 2009 to December 2012. Sonographic findings were positive when the largest axial diameters were >6 mm. The sonograms that were unable to find the appendix were classified into an other group and were considered separately. Sonographic findings were compared with surgical pathological findings or discharge diagnoses in cases of no surgery. Subgroup analysis in the surgical group, including patient age (<11 years or 11–16 years) and sex, was also performed. Results: The appendix was identified in 270/428 cases (63.1%). The overall sensitivity was 71.2% [95% confidence interval (CI): 56.9–82.9%], specificity 97.7% (95% CI: 94.7–99.3%), positive predictive value 88.1% (95% CI: 74.4–96.0%), negative predictive value 93.4% (95% CI: 89.4–96.3%), accuracy 92.6%, and receiver operating characteristic = 0.84. The specificity (47.1%), negative predictive value (61.5%), and accuracy (76.3%) were significantly lower in the surgical group. The efficacy of US between the sexes and age groups showed no significant difference, except the lower positive predictive values in the younger age group. Conclusion: US efficacy for the diagnosis of appendicitis in children is high enough to use as an imaging modality of first choice to reduce complications, hospital stay, and negative appendectomy rate