Aims Vascular calcification is common in diabetic patients. Warfarin has been associated with renovascular calcification and worsening renal function; rivaroxaban may provide renopreservation by decreasing vascular inflammation. We compared the impact of rivaroxaban and warfarin on renal outcomes in diabetic patients with non-valvular atrial fibrillation (NVAF). Methods and results Using United States IBM MarketScan data from January 2011 to December 2017, we identified adults with both NVAF and diabetes, newly-initiated on rivaroxaban or warfarin with ≥12-month insurance coverage prior to anticoagulation initiation. Patients with Stage 5 chronic kidney disease (CKD) or undergoing haemodialysis at baseline were excluded. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weighting (IPTW) based on propensity scores (absolute standardized differences <0.1 achieved for all after adjustment). Outcomes included incidence rates of emergency department/hospital admissions for acute kidney injury (AKI) and the composite of the development of Stage 5 CKD or need for haemodialysis. Patients were followed until an event, index anticoagulant discontinuation/switch, insurance disenrollment, or end-of-data availability. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression. We assessed 10 017 rivaroxaban (22.6% received a reduced dose) and 11 665 warfarin users. In comparison to warfarin, rivaroxaban was associated with lower risks of AKI (HR = 0.83, 95% CI = 0.74–0.92) and development of Stage 5 CKD or need for haemodialysis (HR = 0.82, 95% CI = 0.70–0.96). Sensitivity and subgroup analyses had similar effects as the base-case analysis. Conclusion Rivaroxaban appears to be associated with lower risks of undesirable renal outcomes vs. warfarin in diabetic NVAF patients.
DWI is a reliable tool for characterising focal breast lesions.
Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) may be used to identify blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG event. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI-BOLD cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 9 subjects during eyes-open condition inside a 1.5 T magnetic resonance (MR) scanner using a MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. For EEG data analysis we used the event-related-synchronization/desynchronization (ERS/ERD) approach to investigate where movement-related decreases in alpha and beta power are located. For image statistical analysis we used a general linear model (GLM) approach. There was a significant correlation between the positive-negative ratio of BOLD signal peaks and ERD values in the electrodes over the region of activation. We conclude that combined EEG-fMRI may be used to investigate movement-related oscillations of the human brain inside an MRI scanner and the movement-related changes in the EMG or EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.
Overexpression of inducible nitric oxide synthase causes the production of high levels of nitric oxide, which, under pathological conditions, leads to immunosuppression and tissue damage. The results recently obtained using peptide nucleic acids, rather than traditional oligonucleotides as antigen and antisense molecules, prompted us to test their efficacy in the regulation of nitric oxide production, thereby overcoming the obstacle of cellular internalization. The cellular permeability of four inducible nitric oxide synthase antisense peptide nucleic acids of different lengths was evaluated. These peptide nucleic acids were covalently linked to a hydrophobic peptide moiety to increase internalization and to a tyrosine to allow selective 125 I radiolabelling. Internalization experiments showed a 3^25-fold increase in the membrane permeability of the modified peptide nucleic acids with respect to controls. inducible nitric oxide synthase inhibition experiments on intact stimulated macrophages RAW 264.7 after passive permeation of the two antisense peptide nucleic acids 3 and 4 demonstrated a significant decrease (43^44%) in protein enzymatic activity with respect to the controls. These data offer a basis for developing a good alternative to conventional drugs directed against inducible nitric oxide synthase overexpression.z 1999 Federation of European Biochemical Societies.
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