The isolation, purification and complete characterization of the diterpene forskolin from nutritional supplements.

Forskolin (1) is a diterpene found in the Coleus forskohlii plant that has been examined for its medical properties resulting from adenylyl cyclase activation. This article describes a straightforward purification method of 1 from commercially available weight loss capsules. In addition, there has been some ambiguity with respect to the use of the name 'forskolin' to describe 1 and related diterpenes, which this report serves to eliminate. Herein we detail the complete spectroscopic characterization of purified 1 as well as its single crystal X-ray structure.

Identifying patients likely to be readmitted after transcatheter aortic valve replacement.

Hospital readmission following transcatheter aortic valve replacement (TAVR) contributes considerably to the costs of care. Readmission rates following TAVR have been reported to be as high as 17.4% at 30 days and 53.2% at 1 year. Patient and procedural factors predict an increased likelihood of readmission including non-transfemoral access, acute and chronic kidney impairment, chronic lung disease, left ventricular systolic dysfunction, atrial fibrillation, major bleeding and prolonged index hospitalisation. Recent studies have also found the requirement for new pacemaker implantation and the severity of paravalvular aortic regurgitation and tricuspid regurgitation to be novel predictors of readmission. Post-TAVR readmission within 30 days of discharge is more likely to occur for non-cardiac than cardiac pathology, although readmission for cardiac causes, especially heart failure, predicts higher mortality than readmission for non-cardiac causes. To combat the risk of readmission and associated mortality, the routine practice of calculating and considering readmission risk should be adopted by the heart team. Furthermore, because most readmissions following TAVR occur for non-cardiac reasons, more holistic approaches to readmission prevention are necessary. Familiarity with the most common predictors and causes of readmission should guide the development of initiatives to address these conditions proactively.

Evaluation Following Staggered Implementation of the "Rethinking Critical Care" ICU Care Bundle in a Multicenter Community Setting.

OBJECTIVES: To evaluate process metrics and outcomes after implementation of the "Rethinking Critical Care" ICU care bundle in a community setting. DESIGN: Retrospective interrupted time-series analysis. SETTING: Three hospitals in the Kaiser Permanente Northern California integrated healthcare delivery system. PATIENTS: ICU patients admitted between January 1, 2009, and August 30, 2013. INTERVENTIONS: Implementation of the Rethinking Critical Care ICU care bundle which is designed to reduce potentially preventable complications by focusing on the management of delirium, sedation, mechanical ventilation, mobility, ambulation, and coordinated care. Rethinking Critical Care implementation occurred in a staggered fashion between October 2011 and November 2012. MEASUREMENTS AND MAIN RESULTS: We measured implementation metrics based on electronic medical record data and evaluated the impact of implementation on mortality with multivariable regression models for 24,886 first ICU episodes in 19,872 patients. After implementation, some process metrics (e.g., ventilation start and stop times) were achieved at high rates, whereas others (e.g., ambulation distance), available late in the study period, showed steep increases in compliance. Unadjusted mortality decreased from 12.3% to 10.9% (p < 0.01) before and after implementation, respectively. The adjusted odds ratio for hospital mortality after implementation was 0.85 (95% CI, 0.73-0.99) and for 30-day mortality was 0.88 (95% CI, 0.80-0.97) compared with before implementation. However, the mortality rate trends were not significantly different before and after Rethinking Critical Care implementation. The mean duration of mechanical ventilation and hospital stay also did not demonstrate incrementally greater declines after implementation. CONCLUSIONS: Rethinking Critical Care implementation was associated with changes in practice and a 12-15% reduction in the odds of short-term mortality. However, these findings may represent an evaluation of changes in practices and outcomes still in the midimplementation phase and cannot be directly attributed to the elements of bundle implementation.

Successful oral ciprofloxacin therapy of Neisseria elongata endocarditis.

OBJECTIVE: To report successful oral ciprofloxacin therapy for Neisseria elongata endocarditis. CASE SUMMARY: A patient with N elongata endocarditis refused parenteral therapy, but his infection completely resolved with 7 weeks of oral ciprofloxacin. DISCUSSION: This patient's refusal of parenteral therapy prompted the use of oral ciprofloxacin because it is well absorbed and was expected to be very active against his organism. His infection resolved and did not relapse. Although successful oral therapy has been reported for endocarditis caused by Staphylococcus aureus, primarily in injection drug users, completely oral therapy for other organisms has not been previously described. CONCLUSIONS: When parenteral therapy is not possible, oral administration of highly active, well-absorbed antibiotics may be effective for selected cases of endocarditis caused by susceptible organisms.

Neuro magnetic resonance spectroscopy using wavelet decomposition and statistical testing identifies biochemical changes in people with spinal cord injury and pain.

Spinal cord injury (SCI) can be accompanied by chronic pain, the mechanisms for which are poorly understood. Here we report that magnetic resonance spectroscopy measurements from the brain, collected at 3T, and processed using wavelet-based feature extraction and classification algorithms, can identify biochemical changes that distinguish control subjects from subjects with SCI as well as subdividing the SCI group into those with and without chronic pain. The results from control subjects (n=10) were compared to those with SCI (n=10). The SCI cohort was made up of subjects with chronic neuropathic pain (n=5) and those without chronic pain (n=5). The wavelet-based decomposition of frequency domain MRS signals employs statistical significance testing to identify features best suited to discriminate different classes. Moreover, the features benefit from careful attention to the post-processing of the spectroscopy data prior to the comparison of the three cohorts. The spectroscopy data, from the thalamus, best distinguished control subjects without SCI from those with SCI with a sensitivity and specificity of 0.9 (Percentage of Correct Classification). The spectroscopy data obtained from the prefrontal cortex and anterior cingulate cortex both distinguished between SCI subjects with chronic neuropathic pain and those without pain with a sensitivity and specificity of 1.0. In this study, where two underlying mechanisms co-exist (i.e. SCI and pain), the thalamic changes appear to be linked more strongly to SCI, while the anterior cingulate cortex and prefrontal cortex changes appear to be specifically linked to the presence of pain.