17 research outputs found
Discovery of Leukotriene A4 Hydrolase Inhibitors Using Metabolomics Biased Fragment Crystallography†
The synthesis and structure-activity relationships of biologically active anthraquinones
Ph.D.Leon Zalko
2 Convenient Syntheses Of 2-Aryl-1-Cyano-1-Propenes From Quaternary Ammonium-Salts
Two readily available and different quaternary ammonium salts have been prepared by the alkylation of vinamidinium salt reduction products. These salts have been successfully converted to 2-aryl-1-cyano-1-propenes and this methodology represents a clean and efficient procedure for the construction of such systems
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National Evaluation of Needlestick Events and Reporting Among Surgical Residents.
BACKGROUND: Needlestick injuries pose significant health hazards; however, the nationwide frequency of needlesticks and reporting practices among surgical residents are unknown. The objectives of this study were to examine the rate and circumstances of self-reported needlestick events in US surgery residents, assess factors associated with needlestick injuries, evaluate reporting practices, and identify reporting barriers. STUDY DESIGN: A survey administered after the American Board of Surgery In-Training Examination (January 2017) asked surgical residents how many times they experienced a needlestick during the last 6 months, circumstances of the most recent event, and reporting practices and barriers. Factors associated with needlestick events were examined using multivariable hierarchical regression models. RESULTS: Among 7,395 resident survey respondents from all 260 US general surgery residency programs (99.3% response rate), 27.7% (n = 2,051) noted experiencing a needlestick event in the last 6 months. Most events occurred in the operating room (77.5%) and involved residents sticking themselves (76.2%), mostly with solid needles (84.7%). Self-reported factors underlying needlestick events included residents own carelessness (48.8%) and feeling rushed (31.3%). Resident-level factors associated with self-reported needlestick events included senior residents (PGY5 29.9% vs PGY1 22.4%; odds ratio 1.66; 95% CI 1.41 to 1.96), female sex (31.9% vs male 25.2%; odds ratio 1.31; 95% CI 1.18 to 1.46), or frequently working more than 80 hours per week (odds ratio 1.42; 95% CI 1.20 to 1.68). More than one-fourth (28.7%) of residents did not report the needlestick event to employee health. CONCLUSIONS: In this comprehensive national survey of surgical residents, needlesticks occurred frequently. Many needlestick events were not reported and numerous reporting barriers exist. These findings offer guidance in identifying opportunities to reduce needlesticks and encourage reporting of these potentially preventable injuries among trainees
Automated Process Research. An Example of Accelerated Optimization of the Friedel−Crafts Acylation Reaction, a Key Step for the Synthesis of Anti-HIV (+)-Calanolide A
Antagonists of the EP3 receptor for prostaglandin E2 are novel antiplatelet agents that do not prolong bleeding.
International audienceMyocardial infarction and stroke are caused by blood clots forming over a ruptured or denuded atherosclerotic plaque (atherothrombosis). Production of prostaglandin E(2) (PGE(2)) by an inflamed plaque exacerbates atherothrombosis and may limit the effectiveness of current therapeutics. Platelets express multiple G-protein coupled receptors, including receptors for ADP and PGE(2). ADP can mobilize Ca(2+) and through the P(2)Y(12) receptor can inhibit cAMP production, causing platelet activation and aggregation. Clopidogrel (Plavix), a selective P(2)Y(12) antagonist, prevents platelets from clotting but thereby increases the risk of severe or fatal bleeding. The platelet EP(3) receptor for PGE(2), like the P(2)Y(12) receptor, also inhibits cAMP synthesis. However, unlike ADP, facilitation of platelet aggregation via the PGE(2)/EP(3) pathway is dependent on co-agonists that can mobilize Ca(2+). We used a ligand-based design strategy to develop peri-substituted bicylic acylsulfonamides as potent and selective EP(3) antagonists. We show that DG-041, a selective EP(3) antagonist, inhibits PGE(2) facilitation of platelet aggregation in vitro and ex vivo. PGE(2) can resensitize platelets to agonist even when the P(2)Y(12) receptor has been blocked by clopidogrel, and this can be inhibited by DG-041. Unlike clopidogrel, DG-041 does not affect bleeding time in rats, nor is bleeding time further increased when DG-041 is co-administered with clopidogrel. This indicates that EP(3) antagonists potentially have a superior safety profile compared to P(2)Y(12) antagonists and represent a novel class of antiplatelet agents