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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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PurposeTwitter is an increasingly popular social media platform within the health care community. The objective of this analysis is to characterize the profile of radiation oncology–related tweets and Twitter users over the past 6 years.Methods and MaterialsUsing the web-based social media analytics platform Symplur Signals, we filtered tweets containing at least 1 of the following hashtags or key words: #radonc, #radiationoncology, "rad onc," or "radiation oncology." We evaluated radiation oncology–related Twitter activity between October 2014 and March 2020 for tweet frequency, tweet content, and individuals or groups posting tweets. We identified the most influential Twitter users contributing to radiation oncology–related tweets.ResultsFrom 2014 to 2020, the quarterly volume of radiation oncology–related tweets increased from 5027 to 29,763. Physicians contributed the largest growth in tweet volume. Academic radiation oncologists comprise 60% of the most influential Twitter accounts responsible for radiation oncology–related content. The number of radiation-oncology resident physicians on Twitter increased from 25 to 328 over the past 6 years, and 20% of radiation-oncology residency programs have a Twitter account. Seventy-one percent of radiation oncology–related tweets generated direct communication via mentions, and 59% of tweets contain links to external sources, including scientific articles.ConclusionsThe number of physicians contributing radiation oncology–related Twitter content has increased significantly in recent years. Academic radiation oncologists are the primary influencers of radiation oncology–related Twitter activity. Twitter is used by radiation oncologists to both professionally network and discuss findings related to the field. There remains the opportunity for radiation oncologists to broaden their audience on Twitter to encompass a more diverse community, including patients.  相似文献   
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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   
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This study examined the impact of childhood traumatic brain injury (TBI) on self-regulation and social and behavioral functioning, and the role of self-regulation as a predictor of children's social and behavioral functioning. Participants included 65 children with moderate to severe TBI and 65 children without TBI, all between 6 and 11 years of age. Self-regulation and social and behavioral functioning were assessed 2 to 5 years following injury. Children with TBI displayed deficits in self-regulation and social and behavioral functioning, after controlling for socioeconomic status (SES), although the magnitude of the deficits was not related to injury severity. Self-regulation accounted for significant variance in children's social and behavioral functioning, after controlling for SES and group membership. Self-regulation may be an important determinant of children's social and behavioral functioning following TBI.  相似文献   
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Development of autoimmune hepatitis in primary biliary cirrhosis.   总被引:1,自引:0,他引:1  
AIM/BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown aetiology. Up to 10% of patients with typical features of PBC will have additional features of autoimmune hepatitis (AIH). A subset, however, have no such features but go on to develop a 'sequential' AIH overlap syndrome. Objectives: Describe our experience with eight patients who developed AIH after the diagnosis of PBC was made. METHODS: We reviewed the charts of all PBC patients over a 9-year period (from 1996 to 2005). Only PBC patients with no features of AIH were included. RESULTS: There were 1476 patients with PBC. Of these, eight patients developed features of AIH overlap syndrome based on biochemical and histological parameters. Treatment included prednisone and azathioprine for 24 or more months. The majority of patients remained on ursodeoxycholic acid (UDCA) throughout treatment. Response to therapy was defined by improvement in enzymes, and was rapid for all patients. One patient was able to discontinue treatment with prednisone and azathioprine, while seven have continued on therapy to date. CONCLUSIONS: A 'sequential' overlap syndrome of AIH with PBC can occur. Treatment with prednisone and azathioprine may lead to a rapid improvement in aminotransferase levels.  相似文献   
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