Comparison of the diagnostic accuracy of diffusion-weighted and dynamic contrast-enhanced MRI with 18F-FDG PET/CT to differentiate osteomyelitis from Charcot neuro-osteoarthropathy in diabetic foot.

PURPOSE: To compare the diagnostic accuracy of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) involving two region of interest (ROI) sizes with 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to differentiate diabetic foot osteomyelitis (DFO) from Charcot neuro-osteoarthropathy (CN). METHOD: Thirty-one diabetic patients were included in this prospective study. Two readers independently evaluated DWI (apparent diffusion coefficient [ADC] and high-b-value signal pathological-to-normal bone ratio [DWIr]) and DCE-MRI parameters (Ktrans, Kep, Ve, internal area under the gadolinium curve at 60 s [iAUC60] and time intensity curve [TIC]) using two different ROI sizes, and 18F-FDG PET/CT parameters (visual assessment, SUVmax, delayed SUVmax, and percentage changes between SUVmax and delayed SUVmax). Techniques were compared by univariate analysis using the area under the receiver operating characteristic curve [AUC]. Reliability was analyzed with Kappa and Intraclass correlation [ICC]. RESULTS: DWIr, Ktrans and iAUC60 showed better diagnostic accuracy (AUC = 0.814-0.830) and reliability (ICC > 0.9) for large than for small ROIs (AUC = 0.736-0.750; ICC = 0.6 in Ktrans, 0.8 in DWIr and iAUC60). TIC showed moderate diagnostic performance (AUC = 0.739-0.761) and reliability (κ 0.7). Visual assessment of 18F-FDG PET/CT demonstrated a significantly higher accuracy (AUC = 0.924) than MRI parameters. Semi-quantitative 18F-FDG PET/CT parameters did not provide significant improvement over visual analysis (AUC = 0.848-0.903). CONCLUSION: DWIr, Ktrans and iAUC60 allowed reliable differentiation of DFO and CN, particularly for large ROIs. Visual assessment of 18F-FDG PET/CT was the most accurate technique for differentiation.

A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.

Recognition of Neisseria meningitidis by the long pentraxin PTX3 and its role as an endogenous adjuvant.

Long pentraxin 3 (PTX3) is a non-redundant component of the humoral arm of innate immunity. The present study was designed to investigate the interaction of PTX3 with Neisseria meningitidis. PTX3 bound acapsular meningococcus, Neisseria-derived outer membrane vesicles (OMV) and 3 selected meningococcal antigens (GNA0667, GNA1030 and GNA2091). PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions. Ptx3-deficient mice had a lower antibody response in vaccination protocols with OMV and co-administration of PTX3 increased the antibody response, particularly in Ptx3-deficient mice. Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis. These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium.

Values and preferences for oral antithrombotic therapy in patients with atrial fibrillation: physician and patient perspectives.

BACKGROUND: Exploration of values and preferences in the context of anticoagulation therapy for atrial fibrillation (AF) remains limited. To better characterize the distribution of patient and physician values and preferences relevant to decisions regarding anticoagulation in patients with AF, we conducted interviews with patients at risk of developing AF and physicians who manage patients with AF. METHODS: We interviewed 96 outpatients and 96 physicians in a multicenter study and elicited the maximal increased risk of bleeding (threshold risk) that respondents would tolerate with warfarin vs. aspirin to achieve a reduction in three strokes in 100 patients over a 2-year period. We used the probabilistic version of the threshold technique. RESULTS: The median threshold risk for both patients and physicians was 10 additional bleeds (10 P = 0.7). In both groups, we observed large variability in the threshold number of bleeds, with wider variability in patients than clinicians [patient range: 0-100, physician range: 0-50]. We observed one cluster of patients and physicians who would tolerate <10 bleeds and another cluster of patients, but not physicians, who would accept more than 35. CONCLUSIONS: Our findings suggest wide variability in patient and physician values and preferences regarding the trade-off between strokes and bleeds. Results suggest that in individual decision making, physician and patient values and preferences will often be discordant; this mandates tailoring treatment to the individual patient's preferences.

Analytical ultracentrifugation studies of oligomerization and DNA-binding of TtCarH, a Thermus thermophilus coenzyme B12-based photosensory regulator.

Thermus thermophilus transcriptional factor TtCarH belongs to a newly discovered class of photoreceptors that use 5'-deoxyadenosylcobalamin (AdoB12) as the light-sensing chromophore. Photoregulation relies on the repressor activity of AdoB12-bound oligomers in the dark, which light counteracts by oligomer disruption due to AdoB12 photolysis. In this study, we investigated TtCarH self-association and binding to DNA in the dark and in the light using analytical ultracentrifugation (AUC) methods, both sedimentation velocity (SV) as well as equilibrium (SE). From a methodological point of view, this study shows that AUC can provide hydrodynamic insights in cases where light is a crucial determinant of solution properties. For the light-sensitive TtCarH, absorbance as well as interference AUC data yielded comparable results. Sedimentation coefficients and whole-body hydrodynamic analysis from SV experiments indicate that in solution apo-TtCarH and light-exposed AdoB12-TtCarH are predominantly aspherical, ellipsoidal monomers, in accord with SE data. By comparison, AdoB12-TtCarH exists as a more compact tetramer in the dark, with smaller forms such as dimers or monomers remaining undetected and low levels of larger oligomers appearing at higher protein concentrations. AUC analyses indicate that in the dark AdoB12-TtCarH associates as a tetramer with DNA but forms smaller complexes in the apo form or if exposed to light. The self-association and DNA-binding properties of TtCarH deduced from AUC are consistent with data from size-exclusion and DNA-binding gel-shift assays. AUC analyses together with hydrodynamic modeling provide insights into the AdoB12- and light-dependent self-association and DNA-binding of TtCarH.

Mujer de 67 años con dolor, parestesias y debilidad progresiva en las extremidades / A 67 year-old woman with pain, paresthesia and progressive weakness of the limbs

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