Explore the vast range of titles available.

This study aimed at evaluating the performance of a battery of morphological and functional tests for the assessment of small nerve fiber loss in asymptomatic diabetic neuropathy (DNP). Patients diagnosed for ≥10 years with type 1 ( n  = 10) or type 2 ( n  = 13) diabetes mellitus (DM) without conventional symptoms or signs of DNP were recruited and compared with healthy controls ( n  = 18) and patients with overt DNP ( n  = 5). Intraepidermal nerve fiber density (IENFd) was measured with PGP9.5 immunostaining on punch skin biopsies performed at the distal leg. Functional tests consisted of quantitative sensory testing (QST) for light-touch, cool, warm and heat pain detection thresholds and brain-evoked potentials with electrical (SEPs) and CO 2 laser stimulation [laser-evoked potentials (LEPs)] of hand dorsum and distal leg using small (0.8 mm 2 ) and large (20 mm 2 ) beam sizes. Results confirmed a state of asymptomatic DNP in DM, but only at the distal leg. Defining a critical small fiber loss as a reduction of IENFd ≤−2 z scores of healthy controls, this state prevailed in type 2 (30%) over type 1 DM (10%) patients despite similar disease duration and current glycemic control. LEPs with the small laser beam performed best in terms of sensitivity (91%), specificity (83%) and area-under-the ROC curve (0.924). Although this performance was not statically different from that of warm and cold detection threshold, LEPs offer an advantage over QST given that they bypass the subjective report and are therefore unbiased by perceptual factors.

Background In this study we explored the possibility of automating the PGP9.5 immunofluorescence staining assay for the diagnosis of small fiber neuropathy using skin punch biopsies. The laboratory developed test (LDT) was subjected to a validation strategy as required by good laboratory practice guidelines and compared to the well-established gold standard method approved by the European Federation of Neurological Societies (EFNS). To facilitate automation, the use of thinner sections. (16 µm) was evaluated. Biopsies from previously published studies were used. The aim was to evaluate the diagnostic performance of the LDT compared to the gold standard. We focused on technical aspects to reach high-quality standardization of the PGP9.5 assay and finally evaluate its potential for use in large scale batch testing. Results We first studied linear nerve fiber densities in skin of healthy volunteers to establish reference ranges, and compared our LDT using the modifications to the EFNS counting rule to the gold standard in visualizing and quantifying the epidermal nerve fiber network. As the LDT requires the use of 16 µm tissue sections, a higher incidence of intra-epidermal nerve fiber fragments and a lower incidence of secondary branches were detected. Nevertheless, the LDT showed excellent concordance with the gold standard method. Next, the diagnostic performance and yield of the LDT were explored and challenged to the gold standard using skin punch biopsies of capsaicin treated subjects, and patients with diabetic polyneuropathy. The LDT reached good agreement with the gold standard in identifying small fiber neuropathy. The reduction of section thickness from 50 to 16 µm resulted in a significantly lower visualization of the three-dimensional epidermal nerve fiber network, as expected. However, the diagnostic performance of the LDT was adequate as characterized by a sensitivity and specificity of 80 and 64 %, respectively. Conclusions This study, designed as a proof of principle, indicated that the LDT is an accurate, robust and automated assay, which adequately and reliably identifies patients presenting with small fiber neuropathy, and therefore has potential for use in large scale clinical studies.

Oil spills in estuaries are less studied and less understood than their oceanic counterparts. To address this gap, we present a detailed analysis of estuarine oil spill transport. We develop and analyse a range of simulations for the Humber Estuary, using a coupled hydrodynamic and oil spill model. The models were driven by river discharge at the river boundaries and tidal height data at the offshore boundary. Satisfactory model performance was obtained for both model calibration and validation. Some novel findings were made: (a) there is a statistically significant (p < 0.05) difference in the influence of hydrodynamic conditions (tidal range, stage and river discharge) on oil slick transport; and (b) because of seasonal variation in river discharge, winter slicks released at high water did not exhibit any upstream displacement over repeated tidal cycles, while summer slicks travelled upstream into the estuary over repeated tidal cycles. The implications of these findings for operational oil spill response are: (i) the need to take cognisance of time of oil release within a tidal cycle; and (ii) the need to understand how the interaction of river discharge and tidal range influences oil slick dynamics, as this will aid responders in assessing the likely oil trajectories.

Assessment of attenuation (measured in Hounsfield units, HU) of human coronary plaques was performed using multislice computed tomography (MSCT) in an ex vivo model. In three ex vivo specimens of left coronary arteries in oil, MSCT was performed after intracoronary injection of four solutions of contrast material (400 mgI/ml iomeprol). The four solutions were diluted as follows: 1/infinity, 1/200, 1/80, and 1/20. All scans were performed with the following parameters: slices/collimation 16/0.75 mm, rotation time 375 ms. Each specimen was scored for the presence of atherosclerotic plaques. In each plaque the attenuation was measured in four regions of interest for lumen, plaque (non-calcified thickening of the vessel wall), calcium, and surrounding (oil surrounding the vessel). The results were compared with a one-way analysis of variance test and were correlated with Pearson's test. There were no significant differences in the attenuation of calcium and oil in the four solutions. The mean attenuation in the four solutions for lumen (35+/-10, 91+/-7, 246+/-18, 511+/-89 HU) and plaque (22+/-22, 50+/-26, 107+/-36, 152+/-67 HU) was significantly different between each decreasing dilution (p<0.001). The mean attenuation of lumen and plaque of coronary plaques showed high correlation, while the values were significantly different (r=0.73; p<0.001). Intracoronary attenuation modifies significantly the attenuation of plaques assessed with MSCT.

Sandbanks, the largest of bed patterns in shallow sandy seas, pose a potential risk to shipping. They are also valuable elements of natural coastal protection, dissipating the energy of waves. In the Southern Bight of the North Sea, several sandbank areas have been reported in the literature. However, based on an objective crest–trough analysis of the bathymetry of the Dutch continental shelf, the present study shows that sandbanks are more widespread than commonly considered. These banks are relatively low, presumably explaining why they have not been documented before. This widespread occurrence of sandbanks in the North Sea is in agreement with theoretical predictions based on stability analysis techniques. The possible interference between large-scale human activity and low-amplitude open-shelf ridges implies that one should be careful not to overlook these patterns if none should appear in a preliminary (visual) assessment. The only part of the Southern Bight in which no ridges can be seen is a circular area with a diameter of about 50 km near the mouth of the river Rhine. Here, freshwater outflow affects the direction of tidal ellipses and residual flow, and suppresses the formation of open ridges.

Attenuation variability (measured in Hounsfield Units, HU) of human coronary plaques using multislice computed tomography (MSCT) was evaluated in an ex vivo model with increasing convolution kernels. MSCT was performed in seven ex vivo left coronary arteries sunk into oil followingthe instillation of saline (1/infinity) and a 1/50 solution of contrast material (400 mgI/ml iomeprol). Scan parameters were: slices/collimation, 16/0.75 mm; rotation time, 375 ms. Four convolution kernels were used: b30f-smooth, b36f-medium smooth, b46f-medium and b60f-sharp. An experienced radiologist scored for the presence of plaques and measured the attenuation in lumen, calcified and noncalcified plaques and the surrounding oil. The results were compared by the ANOVA test and correlated with Pearson's test. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The mean attenuation values were significantly different between the four filters (p < 0.0001) in each structure with both solutions. After clustering for the filter, all of the noncalcified plaque values (20.8 +/- 39.1, 14.2 +/- 35.8, 14.0 +/- 32.0, 3.2 +/- 32.4 HU with saline; 74.7 +/- 66.6, 68.2 +/- 63.3, 66.3 +/- 66.5, 48.5 +/- 60.0 HU in contrast solution) were significantly different, with the exception of the pair b36f-b46f, for which a moderate-high correlation was generally found. Improved SNRs and CNRs were achieved by b30f and b46f. The use of different convolution filters significantly modifief the attenuation values, while sharper filtering increased the calcified plaque attenuation and reduced the noncalcified plaque attenuation.

The detection of DNA fragmentation by the use of the TUNEL technique has become a standard technique for the detection of apoptosis in tissue sections. DNA cleavage, detected by the TUNEL technique, is the last irreversible stage of the apoptosis cascade. When the nuclear DNA is cleaved in oligonucleosomal-sized fragments, processes such as transcription are completely abolished. The values of apoptotic cell death that were obtained for atherosclerotic plaques by the TUNEL technique ranged from less than 2% up to 60%. The latter value would indicate that plaques are in an imminent state of collapse, which is certainly not the case. Other factors that could result in TUNEL labeling have to be considered. Therefore, we developed a co-localization system and studied TUNEL labeling together with markers of RNA transcription and splicing. The present study demonstrates that, besides apoptotic nuclei, non-apoptotic nuclei that show signs of active gene transcription are labeled by the TUNEL technique. The fact that the TUNEL technique is not specific for the executive phase of apoptosis is not surprising, as the technique is only selective (rather than specific) for apoptotic nuclei as these contain a far greater degree of DNA fragmentation than non-apoptotic nuclei. Therefore, we think that the TUNEL technique should be combined with additional techniques, such as markers of transcription and morphological criteria.

Varicose veins are characterized by dilated and thickened vein walls. This study examined whether the changes that occur in varicose veins are associated with smooth muscle cell (SMC) hypertrophy, cellular proliferation or apoptosis. Moreover, the association between SMC hypertrophy and the expression of the estrogen receptor-β (ERβ) was investigated. Varicose veins were obtained from male patients during vascular stripping surgery (n = 11) and nonvaricose veins during coronary bypass surgery, also from male subjects (n = 12). The cellular volume of the SMC in both the longitudinal and circular layer of the vessel wall was measured using stereological methods. Apoptosis was detected using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) technique. SMC proliferation and ERβ expression were investigated by immunohistochemistry. Neither in the longitudinal nor in the circular layer of the varicose vein wall were signs of apoptosis or proliferation present. However, the mean cellular volume of the SMC in the circular layer of the varicose veins was strongly increased (5,291 ± 363 µm 3 ) as compared to non-varicose veins (2,812 ± 212 µm 3 , p < 0.001). Moreover, ERβ expression in the circular layer of varicose veins (63 ± 4%) significantly differed from nonvaricose veins (39 ± 4%; p = 0.001). Interestingly, the SMC volume correlated with ERβ expression (r = 0.71, p < 0.001). These data show that cell death or proliferation of SMC do not, or only rarely, occur in varicose veins. However, remodeling of varicose veins can mainly be attributed to increased volumes of the SMC of the circular layer and this increase correlates with ERβ expression.

This review highlights three morphodynamics modelling approaches, used for offshore marine aggregate extraction impact assessment. These approaches are based upon examples of (1) full process-based models; (2) idealised processbased models; and (3) conceptual models. Illustrated also is the way in which these models, applied for extractions on flat bed or sandbanks, can complement each other, towards the estimation of Coastal State Indicators (CSIs). This review leads to the conclusion that, for an optimal environment assessment, there are two main approaches: (1) either combine and couple the models, in order to simulate the full morphodynamics of the system over a long time-scale, taking into account also short-term events, or (2) use a set of existing models, knowing precisely their applicability to the CSI's and the reliability of their predictions, rather than using only the best model, available presently.

The present study describes the histopathologic aspects of varicose (n=29; mean age, 52 ± 12 years) and normal saphenous veins (n=17; mean age, 51 ± 12 years) of patients from a similar age group. We focused on the changes that occur in the circular layer of the venous wall. We examined the venous walls by light microscopy and transmission electronmicroscopy. A semiquantitative grading system was used to assess the smooth muscle cell (SMC) hypertrophy and the change that occurs in the elastin pattern. The volume densities (Vv) of SMC and collagen were measured as well as the diameter of the SMC, and the nuclei of SMC per fixed area were counted. The varicose vein wall differed from the normal saphenous vein by the presence of hypertrophic SMC as well as disor ganized elastin patterns. A correlation between the hypertrophic SMC and an abnormal elastin pattern was observed (r=0.658, p<0.001). Ultrastructurally, the SMC show prominent microherniations and vesicles that bud from the cell. These vesicles contain microfilaments and microtubuli, although no other organelles could be detected. The elastin fibers are disrupted from the hypertrophic SMC. No significant difference could be detected in both the Vv of SMC and the Vv of collagen. The diameter of the SMC in the varicose vein (d=9.45 ± 1.22 μm) differs significantly from that in the normal saphenous vein (d=6.22 ± 1.47 μm) (p<0.001). Also, the nuclei of SMC per fixed area differs signif icantly between the varicose (87 ± 18) and nonvaricose (117 ±24) veins (p<0.001). We conclude that the cellular hypertrophy of the SMC and the microherniations could be the basis for disruption of the elastin fibers connected to the SMC in varicose veins. Disrupted connections between SMC and elastin fibers could in turn induce the weakness of the venous wall observed in varicose vein disease.