Quality-assured training in the evaluation of cochlear implant electrode position: a prospective experimental study

Background The objective of this study was to demonstrate the utility of an approach in training predoctoral medical students, to enable them to measure electrode-to-modiolus distances (EMDs) and insertion-depth angles (aDOIs) in cochlear implant (CI) imaging at the performance level of a single senior rater. Methods This prospective experimental study was conducted on a clinical training dataset comprising patients undergoing cochlear implantation with a Nucleus® CI532 Slim Modiolar electrode (N = 20) or a CI512 Contour Advance electrode (N = 10). To assess the learning curves of a single medical student in measuring EMD and aDOI, interrater differences (senior-student) were compared with the intrarater differences of a single senior rater (test-retest). The interrater and intrarater range were both calculated as the distance between the 0.1th and 99.9th percentiles. A "deliberate practice" training approach was used to teach knowledge and skills, while correctives were applied to minimize faulty data-gathering and data synthesis. Results Intrarater differences of the senior rater ranged from - 0.5 to 0.5 mm for EMD and - 14° to 16° for aDOI (respective medians: 0 mm and 0°). Use of the training approach led to interrater differences that matched this after the 4th (EMD) and 3rd (aDOI) feedback/measurement series had been provided to the student. Conclusions The training approach enabled the student to evaluate the CI electrode position at the performance level of a senior rater. This finding may offer a basis for ongoing clinical quality assurance for the assessment of CI electrode position

Dual-Source CT Angiography of Peripheral Arterial Stents: In Vitro Evaluation of 22 Different Stent Types

Purpose. To test different peripheral arterial stents using four image reconstruction approaches with respect to lumen visualization, lumen attenuation and image noise in dual-source multidetector row CT (DSCT) in vitro. Methods and Materials. 22 stents (nitinol, steel, cobalt-alloy, tantalum, platinum alloy) were examined in a vessel phantom. All stents were imaged in axial orientation with standard parameters. Image reconstructions were obtained with four different convolution kernels. To evaluate visualization characteristics of the stent, the lumen diameter, intraluminal density and noise were measured. Results. The mean percentage of the visible stent lumen diameter from the nominal stent diameter was 74.5% ± 5.7 for the medium-sharp kernel, 72.8% ± 6.4 for the medium, 70.8% ± 6.4 for the medium-smooth and 67.6% ± 6.6 for the smooth kernel. Mean values of lumen attenuation were 299.7HU ± 127 (medium-sharp), 273.9HU ± 68 (medium), 270.7HU ± 53 (medium-smooth) and 265.8HU ± 43. Mean image noise was: 54.6 ± 6.3, 20.5 ± 1.7, 16.3 ± 1.7, 14.0 ± 2 respectively. Conclusion. Visible stent lumen diameter varies depending on stent type and scan parameters. Lumen diameter visibility increases with the sharpness of the reconstruction kernel. Smoother kernels provide more realistic density measurements inside the stent lumen and less image noise

Activated complement C3: A potentially novel predictor of progressive IgA nephropathy

Activated complement C3: A potentially novel predictor of progressive IgA nephropathy. In the search for a serologic marker of disease activity, we measured concentrations of activated C3 (actC3, that is, neoantigens developing after C3 activation on breakdown products), C4-C3 complexes and soluble C5b-9 (sC5b-9) in one or two plasma samples from adult patients with IgA nephropathy (IgAN, N = 50) or Henoch-Schönlein purpura (HSP, N = 4). As controls, 20 patients with non-immune renal disease, but comparable age, degree of proteinuria, renal dysfunction and prevalence of hypertension were studied. Compared to controls, actC3 levels were elevated in 30% of the patients with IgAN and one of the HSP patients. C4-C3 complexes were elevated in only 8% of the IgAN patients, and sC5b-9 levels were within the control range in all IgAN and HSP patients. In IgAN patients with elevated actC3 levels, proteinuria and hematuria were more pronounced than in those with normal levels. Elevated plasma concentrations of actC3 at the first presentation correlated with subsequent deterioration of renal function both in patients with initially normal and already impaired renal function (r = -0.56, N = 44, P = 0.003). The five IgAN patients with elevated actC3 on both occasions of obtaining plasma showed the most rapid loss of renal function. We conclude that mainly alternative pathway complement activation can be demonstrated in patients with IgAN and HSP. In IgAN patients the presence of complement activation is associated with more severe renal disease. Further studies are warranted to examine the clinical usefulness of actC3 as a predictor of the subsequent course of IgAN

MR Angiography of Peripheral Arterial Stents: In Vitro Evaluation of 22 Different Stent Types

Purpose. To evaluate stent lumen visibility of a large sample of different peripheral arterial (iliac, renal, carotid) stents using magnetic resonance angiography in vitro. Materials and Methods. 21 different stents and one stentgraft (10 nitinol, 7 316L, 2 tantalum, 1 cobalt superalloy, 1 PET + cobalt superalloy, and 1 platinum alloy) were examined in a vessel phantom (vessel diameters ranging from 5 to 13 mm) filled with a solution of Gd-DTPA. Stents were imaged at 1.5 Tesla using a T1-weighted 3D spoiled gradient-echo sequence. Image analysis was performed measuring three categories: Signal intensity in the stent lumen, lumen visibility of the stented lumen, and homogeneity of the stented lumen. The results were classified using a 3-point scale (good, intermediate, and poor results). Results. 7 stents showed good MR lumen visibility (4x nitinol, 2x tantalum, and 1x cobalt superalloy). 9 stents showed intermediate results (5x nitinol, 2x 316L, 1x PET + cobalt superalloy, and 1x platinum alloy) and 6 stents showed poor results (1x nitinol, and 5x 316L). Conclusion. Stent lumen visibility varies depending on the stent material and type. Some products show good lumen visibility which may allow the detection of stenoses inside the lumen, while other products cause artifacts which prevent reliable evaluation of the stent lumen with this technique

Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer's Disease

Lipids play an important role as risk or protective factors in Alzheimer's disease (AD). Previously it has been shown that plasmalogens, the major brain phospholipids, are altered in AD. However, it remained unclear whether plasmalogens themselves are able to modulate amyloid precursor protein (APP) processing or if the reduced plasmalogen level is a consequence of AD. Here we identify the plasmalogens which are altered in human AD postmortem brains and investigate their impact on APP processing resulting in Aβ production. All tested plasmalogen species showed a reduction in γ-secretase activity whereas β- and α-secretase activity mainly remained unchanged. Plasmalogens directly affected γ-secretase activity, protein and RNA level of the secretases were unaffected, pointing towards a direct influence of plasmalogens on γ-secretase activity. Plasmalogens were also able to decrease γ-secretase activity in human postmortem AD brains emphasizing the impact of plasmalogens in AD. In summary our findings show that decreased plasmalogen levels are not only a consequence of AD but that plasmalogens also decrease APP processing by directly affecting γ-secretase activity, resulting in a vicious cycle: Aβ reduces plasmalogen levels and reduced plasmalogen levels directly increase γ-secretase activity leading to an even stronger production of Aβ peptides

Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipid de novo synthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic AD postmortem brains, suggesting that SPT is involved in AD pathology

Integrated microfluidics for at-line culture monitoring of proteins and metabolites

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Nanofluidic Immobilization and Growth Detection of Escherichia coli in a Chip for Antibiotic Susceptibility Testing

Infections with antimicrobial resistant bacteria are a rising threat for global healthcare as more and more antibiotics lose their effectiveness against bacterial pathogens. To guarantee the long-term effectiveness of broad-spectrum antibiotics, they may only be prescribed when inevitably required. In order to make a reliable assessment of which antibiotics are effective, rapid point-of-care tests are needed. This can be achieved with fast phenotypic microfluidic tests, which can cope with low bacterial concentrations and work label-free. Here, we present a novel optofluidic chip with a cross-flow immobilization principle using a regular array of nanogaps to concentrate bacteria and detect their growth label-free under the influence of antibiotics. The interferometric measuring principle enabled the detection of the growth of Escherichia coli in under 4 h with a sample volume of 187.2 µL and a doubling time of 79 min. In proof-of-concept experiments, we could show that the method can distinguish between bacterial growth and its inhibition by antibiotics. The results indicate that the nanofluidic chip approach provides a very promising concept for future rapid and label-free antimicrobial susceptibility tests