29), compared with never users. Neither were significant associations found between fracture and smoking, social class and parity. The findings did not vary materially with age or type of fracture.\n\nConclusion: Ever use of oral contraception was not associated with fracture in this study. (C) 2011 Elsevier Inc. All rights reserved.”
“New Delhi metallo-beta-lactmase-1 (NDM-1) is an enzyme that confers antibiotic resistance to bacteria and is thus a serious threat to human health. Almost all clinically available beta-lactam antibiotics can be hydrolyzed by NDM-1. To S63845 determine the mechanism behind the wide substrate diversity and strong catalytic ability of NDM-1, we explored the molecular interactions between

NDM-1 and different beta-lactam antibiotics using computational methods. Molecular dynamics simulations and binding free energy calculations were performed on enzyme-substrate (ES) complex

models of NDM-1-Meropenem, NDM-1-Nitrocefin, and NDM-1-Ampicillin constructed by molecular docking. Our computational results suggest that mutant residues Ile35 and Lys216, and active site loop L1 residues 65-73 in NDM-1 play crucial roles in substrate recognition and binding. The results of our study provide new insights into the mechanism behind the enhanced substrate binding and wider substrate spectrum of NDM-1 compared IPI-145 cost with its homologous enzymes CcrA and IMP-1. These insights may be useful in the discovery and design of specific and potent inhibitors against NDM-1. (C) 2013 Elsevier Inc. All rights reserved.”
“BACKGROUND: Patients with osteosarcoma and Ewing sarcoma have achieved longer survival over the past decades, but late side effects of chemotherapy and radiotherapy have become important concerns. METHODS: The authors reviewed all patients with localized osteosarcoma or Ewing sarcoma who had been enrolled in the Italian Sarcoma Group neoadjuvant protocols from 1983 through 2006. Data were updated in December 2010 to determine 3 endpoints: the NU7441 in vitro incidence of a secondary

primary cancer (designated as “second malignant neoplasm” [SMN]), infertility, and cardiotoxicity. RESULTS: Data were available on 883 patients with osteosarcoma and 543 patients with Ewing sarcoma. In the osteosarcoma group, there were 39 SMNs (4.4%) in 36 patients; in the Ewing sarcoma group, 15 patients (2.8%) experienced a single SMN each. The cumulative 10-year and 20-year incidence of an SMN (+/- standard error) was 4.9%+/- 0.9% and 6.1%+/- 1.2%, respectively, in the osteosarcoma group and 3.4%+/- 0.9% and 4.7%+/- 1.6%, respectively, in the Ewing sarcoma group. The most common SMN in the osteosarcoma group was breast cancer (n = 11), and the most common SMN in the Ewing sarcoma group was radiotherapy-induced osteosarcoma (n = 6). After 20 years, the risk of developing an SMN increased, whereas the risk of a recurrence of the primary tumor decreased. Permanent sterility was more common in males than in females.