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OBJECTIVES: Acoustic noise emission from MRI scanners is considered a major factor of patient discomfort during routine MRI examinations. We prospectively evaluated the impact of acoustic noise reduction using software implementations in routine clinical MRI on subjective patient experience and image quality. METHODS: Two-hundred consecutive patients undergoing one of four MRI examinations (brain, lumbar spine, shoulder, and knee) at a single center were prospectively randomized into two groups at a 1 to 1 ratio: standard MRI examination and MRI examination with acoustic noise reduction. After the examination, patients were asked to complete a questionnaire aimed at defining their subjective experience (primary endpoint). Two readers assessed subjective image quality of all patient studies in consensus (secondary endpoint). Nonparametric tests and logistic regression models were used for statistical analysis. RESULTS: Hundred-seventy-four patients were included in the final study. Patients in the intervention group felt less discomforted by the acoustic noise (p = 0.01) and reported increased audibility of music through the headphones (p = 0.03). No significant difference in subjective image quality was found. CONCLUSION: Our study indicates that the effects of acoustic noise reduction in routine clinical MRI can be translated into reduced patient discomfort from acoustic noise and improved audibility of music. Acoustic noise reduction thus significantly contributes to increased patient comfort during MRI examinations.

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Tumor-derived vesicles (TDV) have been recently implicated in immunosuppression by transporting specific proteins, including Fas ligand (FasL) and TRAIL, to immune cells. We hypothesized that TDVs carrying miRNAs with immunological function could interfere with the translational machinery of immune cells and lead to TDV-mediated immunosuppression in cancer. We show that TDVs from human tumor cells indeed contain multiple miRNA species with known roles in lymphocyte development and function: hsa-miR-146a, miR-29a, and miR-21. Quantification by RT-PCR shows that the amount of miR-21 within TDVs isolated from the breast cancer cell line HCC1806 is at physiologically relevant levels. Additionally, we show that these miRNAs carried by TDVs copurify with argonaute proteins. This observation corroborates the idea that the machinery of microvesicle secretion and that of RNA interference are interconnected.

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When measuring the properties of fluids from biological sources, sample volumes in the micro-liter range are often desired as higher volumes may not be available or are very expensive. Miniaturized viscosity and density sensors based on a vibrating cantilever fulfill this requirement. In this paper, the possibility of measuring viscosity and density of DNA solutions at the same time using such a sensor is shown. The sensor requires a sample volume of 10 µl. By doing a titration of a solution containing 110 bp long strands of DNA in the diluted, Newtonian regime, the intrinsic viscosity can be determined to be 0.047 ml mg(-1) using the cantilever sensor. The cantilever is also tested with solutions of 10 kbp long strands with concentrations in the semi-dilute, non-Newtonian regime. The comparably small change in resonance frequency and damping observed using these solutions at 12.5 kHz is attributed to shear thinning, which is expected when extrapolating results from other groups.

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Amyloid accumulation in the brain of Alzheimer's patients results from altered processing of the 39- to 43-amino acid amyloid ß protein (Aß). The mechanisms for the elevated amyloid (Aß(1-42)) are considered to be over-expression of the amyloid precursor protein (APP), enhanced cleavage of APP to Aß, and decreased clearance of Aß from the central nervous system (CNS). We report herein studies of Aß stimulated effects on endothelial cells. We observe an interesting and as yet unprecedented feedback effect involving Aß(1-42) fibril-induced synthesis of APP by Western blot analysis in the endothelial cell line Hep-1. We further observe an increase in the expression of Aß(1-40) by flow cytometry and fluorescence microscopy. This phenomenon is reproducible for cultures grown both in the presence and absence of serum. In the former case, flow cytometry reveals that Aß(1-40) accumulation is less pronounced than under serum-free conditions. Immunofluorescence staining further corroborates these observations. Cellular responses to fibrillar Aß(1-42) treatment involving eNOS upregulation and increased autophagy are also reported.

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The use of molecular editing in the elucidation of the mechanism of action of amphotericin B is presented. A modular strategy for the synthesis of amphotericin B and its designed analogues is developed, which relies on an efficient gram-scale synthesis of various subunits of amphotericin B. A novel method for the coupling of the mycosamine to the aglycone was identified. The implementation of the approach has enabled the preparation of 35-deoxy amphotericin B methyl ester. Investigation of the antifungal activity and efflux-inducing ability of this amphotericin B congener provided new clues to the role of the 35-hydroxy group and is consistent with the involvement of double barrel ion channels in causing electrolyte efflux.

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The interaction of the beta-amyloid peptide (Abeta) with neuronal membranes could play a key role in the pathogenesis of Alzheimer's disease. Recent studies have focused on the interactions of Abeta oligomers to explain the neuronal toxicity accompanying Alzheimer's disease. In our study, we have investigated the role of lipid interactions with soluble Abeta(28-35) (wild-type) and its mutants A30G and A30I in their aggregation and conformational preferences. CD and Trp fluorescence spectroscopic studies indicated that, immediately on dissolution, these peptides adopted a random coil structure. Upon addition of negatively charged 1,2-dipalmitoyl-syn-glycero-3-phospho-rac-(glycerol) sodium salt (PG) lipid, the wild-type and A30I mutant underwent reorganization into a predominant beta-sheet structure. However, no conformational changes were observed in the A30G mutant on interaction with PG. In contrast, the presence of zwitterionic 1,2-dipalmitoyl-syn-glycero-3-phosphatidylcholine (PC) lipid had no effect on the conformation of these three peptides. These observations were also confirmed with atomic force microscopy and the thioflavin-T assay. In the presence of PG vesicles, both the wild-type and A30I mutant formed fibrillar structures within 2 days of incubation in NaCl/P(i), but not in their absence. Again, no oligomerization was observed with PC vesicles. The Trp studies also revealed that both ends of the three peptides are not buried deep in the vesicle membrane. Furthermore, fluorescence spectroscopy using the environment-sensitive probe 1,6-diphenyl-1,3,5-hexatriene showed an increase in the membrane fluidity upon exposure of the vesicles to the peptides. The latter effect may result from the lipid head group interactions with the peptides. Fluorescence resonance energy transfer experiments revealed that these peptides undergo a random coil-to-sheet conversion in solution on aging and that this process is accelerated by negatively charged lipid vesicles. These results indicate that aggregation depends on hydrophobicity and propensity to form beta-sheets of the amyloid peptide, and thus offer new insights into the mechanism of amyloid neurodegenerative disease.

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