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71.
Christopher Grimm Simona Pompei Kristina Egger Michael Fuchs Wolfgang Kroutil 《RSC advances》2023,13(9):5770
Lignin-derived aryl methyl ethers (e.g. coniferyl alcohol, ferulic acid) are expected to be a future carbon source for chemistry. The well-known P450 dependent biocatalytic O-demethylation of these aryl methyl ethers is prone to side product formation especially for the oxidation sensitive catechol products which get easily oxidized in the presence of O2. Alternatively, biocatalytic demethylation using cobalamin dependent enzymes may be used under anaerobic conditions, whereby two proteins, namely a methyltransferase and a carrier protein are required. To make this approach applicable for preparative transformations, fusion proteins were designed connecting the cobalamin-dependent methyltransferase (MT) with the corrinoid-binding protein (CP) from Desulfitobacterium hafniense by variable glycine linkers. From the proteins created, the fusion enzyme MT-L5-CP with the shortest linker performed best of all fusion enzymes investigated showing comparable and, in some aspects, even better performance than the separated proteins. The fusion enzymes provided several advantages like that the cobalamin cofactor loading step required originally for the CP could be skipped enabling a significantly simpler protocol. Consequently, the biocatalytic demethylation was performed using Schlenk conditions allowing the O-demethylation e.g. of the monolignol coniferyl alcohol on a 25 mL scale leading to 75% conversion. The fusion enzyme represents a promising starting point to be evolved for alternative demethylation reactions to diversify natural products and to valorize lignin.Lignin-derived aryl methyl ethers (e.g. coniferyl alcohol, ferulic acid) are demethylated under anaerobic conditions using a cobalamin dependent fusion enzyme, which combines the cobalamin carrier protein and the methyltransferase. 相似文献
72.
Lucas Morin Davide L. Vetrano Giulia Grande Laura Fratiglioni Johan Fastbom Kristina Johnell 《Journal of the American Medical Directors Association》2017,18(6):551.e1-551.e7
Objectives
To investigate the prevalence and factors associated with the use of medications of questionable benefit throughout the final year of life of older adults who died with dementia.Design
Register-based, longitudinal cohort study.Setting
Entire Sweden.Participants
All older adults (≥75 years) who died with dementia between 2007 and 2013 (n = 120,067).Measurements
Exposure to medications of questionable benefit was calculated for each of the last 12 months before death, based on longitudinal data from the Swedish Prescribed Drug Register.Results
The proportion of older adults with dementia who received at least 1 medication of questionable benefit decreased from 38.6% 12 months before death to 34.7% during the final month before death (P < .001 for trend). Among older adults with dementia who used at least 1 medication of questionable benefit 12 months before death, 74.8% remained exposed until their last month of life. Living in an institution was independently associated with a 15% reduction of the likelihood to receive ≥1 medication of questionable benefit during the last month before death (odds ratio 0.85, 95% confidence interval 0.88–0.83). Antidementia drugs accounted for one-fifth of the total number of medications of questionable benefit. Lipid-lowering agents were used by 8.3% of individuals during their final month of life (10.2% of community-dwellers and 6.6% of institutionalized people, P < .001).Conclusion
Clinicians caring for older adults with advanced dementia should be provided with reliable tools to help them reduce the burden of medications of questionable benefit near the end of life. 相似文献73.
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Sarah DeLozier Peter Speltz Jason Brito Leigh Anne Tang Janey Wang Joshua C Smith Dario Giuse Elizabeth Phillips Kristina Williams Teresa Strickland Giovanni Davogustto Dan Roden Joshua C Denny 《J Am Med Inform Assoc》2021,28(1):126
Identifying acute events as they occur is challenging in large hospital systems. Here, we describe an automated method to detect 2 rare adverse drug events (ADEs), drug-induced torsades de pointes and Stevens-Johnson syndrome and toxic epidermal necrolysis, in near real time for participant recruitment into prospective clinical studies. A text processing system searched clinical notes from the electronic health record (EHR) for relevant keywords and alerted study personnel via email of potential patients for chart review or in-person evaluation. Between 2016 and 2018, the automated recruitment system resulted in capture of 138 true cases of drug-induced rare events, improving recall from 43% to 93%. Our focused electronic alert system maintained 2-year enrollment, including across an EHR migration from a bespoke system to Epic. Real-time monitoring of EHR notes may accelerate research for certain conditions less amenable to conventional study recruitment paradigms. 相似文献
77.
Susan T. Laing M.D. M.S. Beverly Smulevitz B.S. Kristina P. Vatcheva M.S. Anne R. Rentfro Ph.D. R.N. David D. McPherson M.D. Susan P. Fisher‐Hoch M.D. Joseph B. McCormick M.D. 《Echocardiography (Mount Kisco, N.Y.)》2012,29(10):1224-1232
Background: Framingham risk scores (FRS) were validated in a mostly Caucasian population. Evaluation of subclinical atherosclerosis by carotid ultrasound may improve ascertainment of risk in nonwhite populations. This study aimed to evaluate carotid intima‐media thickness (cIMT) and carotid plaquing among Mexican Americans, and to correlate these markers with coronary risk factors and the FRS. Methods/Results: Participants (n = 141) were drawn from the Cameron County Hispanic Cohort. Carotid artery ultrasound was performed and cIMT measured. Carotid plaque was defined as areas of thickening >50% of the thickness of the surrounding walls. Mean age was 53.1 ± 11.7 years (73.8% female). Most were overweight or obese (88.7%) and more than half (53.2%) had the metabolic syndrome. One third (34.8%) had abnormal carotid ultrasound findings (either cIMT ≥75th percentile for gender and age or presence of plaque). Among those with abnormal carotid ultrasound, the majority were classified as being at low 10‐year risk for cardiovascular events. Carotid ultrasound reclassified nearly a third of the cohort as being at high risk. This discordance between 10‐year FRS and carotid ultrasound was noted whether risk was assessed for hard coronary events or global risk. Concordance between FRS and carotid ultrasound findings was best when long‐term (30‐year) risk was assessed and no subject with an abnormal carotid ultrasound was categorized as low risk by the 30‐year FRS algorithm. Conclusions: Integration of carotid ultrasound findings to coronary risk assessments and use of longer term prediction models may provide better risk assessment in this minority population, with earlier initiation of appropriate therapies. 相似文献
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Jonas Stålheim Kristina Berglund Ulf Berggren Jan Balldin Claudia Fahlke 《Alcoholism treatment quarterly》2018,36(3):387-398
There is a substantial co-occurrence between alcohol dependence and psychiatric symptoms. Moreover, research suggests that such symptoms, including psychotic experiences, are continuously distributed in the population. There is a lack of research concerning psychotic symptoms in otherwise non-psychiatric populations with alcohol dependence. The aim of this study was to investigate the prevalence of psychotic symptoms in this population, and to relate this to childhood trauma and management of alcohol dependence. From a population with alcohol dependence two sub-groups were extracted, with low and high levels of psychotic experiences respectively. These were compared concerning childhood trauma and management of dependence using ANOVA, and the resulting model was examined using binary logistic regression. There was a sub-group of 14,3% of the population with elevated levels of psychotic experiences. This group displayed higher degree of self-reported childhood trauma as well as difficulties in managing alcohol dependence, when compared to a sub-group with low levels of psychotic experiences. There may be a substantial sub-group in the otherwise non-psychiatric population with alcohol dependence, with significant difficulties concerning psychotic symptoms, trauma and management of dependence, where anxiety may have a mediating function. If so, this group calls for broader assessment and treatment than standard alcohol interventions. 相似文献