ß-amyloid model core peptides: Effects of hydrophobes and disulfides.

The mechanism by which a disordered peptide nucleates and forms amyloid is incompletely understood. A central domain of ß-amyloid (Aß21-30) has been proposed to have intrinsic structural propensities that guide the limited formation of structure in the process of fibrillization. In order to test this hypothesis, we examine several internal fragments of Aß, and variants of these either cyclized or with an N-terminal Cys. While Aß21-30 and variants were always monomeric and unstructured (circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMRS)), we found that the addition of flanking hydrophobic residues in Aß16-34 led to formation of typical amyloid fibrils. NMR showed no long-range nuclear overhauser effect (nOes) in Aß21-30, Aß16-34, or their variants, however. Serial 1 H-15 N-heteronuclear single quantum coherence spectroscopy, 1 H-1 H nuclear overhauser effect spectroscopy, and 1 H-1 H total correlational spectroscopy spectra were used to follow aggregation of Aß16-34 and Cys-Aß16-34 at a site-specific level. The addition of an N-terminal Cys residue (in Cys-Aß16-34) increased the rate of fibrillization which was attributable to disulfide bond formation. We propose a scheme comparing the aggregation pathways for Aß16-34 and Cys-Aß16-34, according to which Cys-Aß16-34 dimerizes, which accelerates fibril formation. In this context, cysteine residues form a focal point that guides fibrillization, a role which, in native peptides, can be assumed by heterogeneous nucleators of aggregation.

Incidence, risk factors, and complications of postoperative delirium in elderly patients undergoing radical cystectomy.

OBJECTIVE: To identify the risk factors for, and complications associated with, the development of delirium after radical cystectomy. MATERIALS AND METHODS: From July 2008 to December 2009, 59 patients, aged ≥65 years and undergoing radical cystectomy, were prospectively enrolled. The baseline cognitive status was assessed using the Mini-Mental Status Examination. Postoperative delirium was assessed using the Confusion Assessment Method. RESULTS: A total of 49 patients completed the surgery and all assessments. The incidence of postoperative delirium was 29%, with duration of 1-5 days. On univariate analysis, older age and preoperative Mini-Mental Status Examination score were associated with postoperative delirium. On multivariate analysis, only age was associated with postoperative delirium (odds ratio 1.52, 95% confidence interval 1.04-2.22, P=.03). The 2 groups did not differ in pathologic stage, length of surgery, intraoperative and postoperative narcotic usage, body mass index, age-adjusted Charlson comorbidity index, activities of daily living scores, smoking history, preoperative hematocrit, estimated blood loss, urinary tract infection, interval to a regular diet, or length of hospital stay. The patients who developed postoperative delirium were more likely to undergo readmission (odds ratio 10.7, 95% confidence interval 2.2-51.8, P=.01) and reoperation (odds ratio 9.2, 95% confidence interval 1.5-55.3, P=.03) but did not differ in the 90-day and 1-year mortality rates or incidence of postoperative complications. CONCLUSION: In patients aged≥65 years, a lower preoperative Mini-Mental Status Examination score and older age were significantly associated with the development of postcystectomy delirium, as measured using the Confusion Assessment Method. The patients who developed delirium were more likely to undergo readmission and reoperation. Larger studies with multiple surgeons are needed to validate these findings.

Active Crohn's disease in the small bowel: evaluation by diffusion weighted imaging and quantitative dynamic contrast enhanced MR imaging.

PURPOSE: To determine relative diagnostic value of MR diffusion and perfusion parameters in detection of active small bowel inflammation in patients with Crohn's disease (CD). MATERIALS AND METHODS: We reviewed 18 patients with active CD of terminal ileum (TI) who underwent MR enterography (MRE; including dynamic contrast enhanced MRI and diffusion-weighted MRI). Conventional MRI findings of TI were recorded. Regions of interest were drawn over TI and normal ileum to calculate apparent diffusion coefficient (ADC), the volume transfer constant (K(trans)) and the contrast media distribution volume (v(e)). Receiver operating characteristic analysis was used to determine their diagnostic performance. RESULTS: Among conventional MR findings, mural thickening and increased enhancement were present in all actively inflamed small bowel. K(trans), v(e), and ADC values differed significantly between actively inflamed TI and normal ileum (0.92 s(-1) versus 0.36 s(-1); 0.31 versus 0.15 ± 0.08; 0.00198 mm(2)/s versus 0.00311 mm(2)/s; P < 0.001). Area under the curve (AUC) for K(trans), v(e), and ADC values ranged from 0.88 to 0.92 for detection of active inflammation. Combining K(trans) and ADC data provided an AUC value of 0.95. CONCLUSION: Dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) provide quantitative measures of small bowel inflammation that can differentiate actively inflamed small bowel segments from normal small bowel in CD. DWI provides better sensitivity compared with DCE-MRI and combination of ADC and K(trans) parameters for analysis can potentially improve specificity.