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Keith P. Reber John D. Sivey Matthew Vollmuth Priyansh D. Gujarati 《Journal of labelled compounds & radiopharmaceuticals》2022,65(9):254-263
Parabens are antimicrobial additives found in a wide array of consumer products. However, the halogenated compounds formed from parabens during wastewater disinfection are a potential environmental concern. In order to identify these transformation products and investigate their mechanism of formation, a synthetic route to ethyl parabens labeled with the stable isotope carbon-13 at specific positions within the benzene ring was developed. This efficient two-step procedure starts from commercially available 13C-labeled phenols and involves (1) initial acylation of the phenol via a Houben–Hoesch reaction with trichloroacetonitrile followed by (2) a modified haloform reaction of the resulting trichloromethyl ketone to afford the corresponding 13C-labeled ethyl parabens in 65%–80% overall yield. The scope of the modified haloform reaction was also investigated, allowing for the synthesis of other parabens derived from primary or secondary alcohols, including 13C- and deuterium-labeled esters. In addition, 4-hydroxybenzoic acid can be formed directly from the common trichloromethyl ketone intermediate upon treatment with lithium hydroxide. This protocol complements existing methods for preparing 13C-labeled paraben derivatives and offers the specific advantages of exhibiting complete regioselectivity in the Houben–Hoesch reaction (to form the para-disubstituted product) and avoiding the need for protecting groups in the modified haloform reaction that forms the paraben esters. 相似文献
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Archie L. Overmann DesRaj M. Clark Panagiotis Tsagkozis Rikard Wedin Jonathan A. Forsberg 《Journal of orthopaedic research》2020,38(10):2149-2156
Treatment decisions in patients with metastatic bone disease rely on accurate survival estimation. We developed the original PATHFx models using expensive, proprietary software and now seek to provide a more cost-effective solution. Using open-source machine learning software to create PATHFx version 2.0, we asked whether PATHFx 2.0 could be created using open-source methods and externally validated in two unique patient populations. The training set of a well-characterized, database records of 189 patients and the bnlearn package within R Version 3.5.1 (R Foundation for Statistical Computing), was used to establish a series of Bayesian belief network models designed to predict survival at 1, 3, 6, 12, 18, and 24 months. Each was externally validated in both a Scandinavian (n = 815 patients) and a Japanese (n = 261 patients) data set. Brier scores and receiver operating characteristic curves to assessed discriminatory ability. Decision curve analysis (DCA) evaluated whether models should be used clinically. DCA showed that the model should be used clinically at all time points in the Scandinavian data set. For the 1-month time point, DCA of the Japanese data set suggested to expect better outcomes assuming all patients will survive greater than 1 month. Brier scores for each curve demonstrate that the models are accurate at each time point. Statement of Clinical Significance: we successfully transitioned to PATHFx 2.0 using open-source software and externally validated it in two unique patient populations, which can be used as a cost-effective option to guide surgical decisions in patients with metastatic bone disease. 相似文献
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Christopher J. Destache David J. Guervil Keith S. Kaye 《International journal of antimicrobial agents》2019,53(5):644-649
Background
The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the USA.Methods
Data, including patient demographics, medical history, risk factors, microbiological aetiology and clinical outcomes, were collected by review of patient charts between September 2013 and February 2015.Results
Patients (n=55) with Gram-positive endocarditis were treated with CPT-F. The most common risk factors were intravascular devices (43.6%), diabetes mellitus (40.0%) and injection drug use (38.2%). The most commonly isolated pathogens were meticillin-resistant Staphylococcus aureus (MRSA; 80%), meticillin-susceptible S. aureus (MSSA; 7.3%) and coagulase-negative staphylococci (7.3%). CPT-F was given as first-line therapy in 7.3% of patients and as second-line or later therapy in 92.7% of patients, and as monotherapy in 41.8% of patients and as concurrent therapy in 58.2% of patients. Clinical success was observed in 82.6% (19/23) of patients treated with CPT-F as monotherapy. In patients treated with CPT-F as first-line therapy or second-line or later therapy, 75.0% (3/4) and 70.6% (36/51) achieved success, respectively. Clinical success was observed in 77.3% (34/44) of patients with MRSA and 25% (1/4) of patients with MSSA. Two patients discontinued treatment with CPT-F due to an adverse event.Conclusions
CPT-F treatment was associated with a high rate of clinical success in patients with Gram-positive infective endocarditis, including those with risk factors and infections caused by MRSA. A high rate of clinical success was observed in patients treated with CPT-F used as first- line therapy or second-line or later therapy, or as monotherapy or in combination with other antibiotics. 相似文献9.
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Ali R. Cohen Thomas J.E. Clark Lynette M. Renner Pamela C. Carter Erin M. Shriver 《Canadian journal of ophthalmology. Journal canadien d'ophtalmologie》2019,54(3):355-358
ObjectiveDetermine the prevalence of intimate partner violence (IPV) as a mechanism of traumatic ocular injury in women, typical injury patterns, and the clinical course of affected patients. Encourage IPV screening and safety assessment in patients presenting with characteristic ocular trauma.MethodsMedical records of 211 female patients with traumatic ocular injuries evaluated at the University of Iowa Hospitals and Clinics between January 1995 and January 2015 were reviewed to determine the rate of IPV as a mechanism of ocular trauma. Twenty-one patients were excluded due to no documented trauma.ResultsLeading causes of traumatic ocular injuries in the 190 female patients included were accidental trauma with an inanimate object (n = 70/190, 36.8%), falls (n = 52/190, 27.4%), motor vehicle collisions (n = 21/190, 11.1%), and assault (n = 16/190, 8.4%). In 2.1% of cases (n = 4/190), no mechanism of traumatic injury was documented. Assault was the fourth leading mechanism of injury accounting for 8.4% of cases (n = 16/190), with IPV accounting for more than one third of cases with a documented perpetrator (n = 5/13). No perpetrator was documented in 18.8% (n = 3/16). All 5 patients with IPV-related injuries sustained scleral laceration or rupture; 4 out of 5 patients had no light perception vision and ultimately required enucleation.ConclusionIPV is an important mechanism of traumatic ocular injury. IPV-associated injuries tend to be severe in nature, as demonstrated by the high rate of globe laceration or rupture and subsequent enucleation in the study population. By appropriate screening and referral, ophthalmologists have an opportunity to redirect a potentially devastating course. 相似文献