Association of serum-soluble heat shock protein 60 with carotid atherosclerosis: clinical significance determined in a follow-up study

BACKGROUND AND PURPOSE: Previous work has shown that soluble heat shock protein 60 (HSP60; sHSP60), present in circulating blood, is associated with carotid atherosclerosis. In the current evaluation, we tested the hypothesis that sHSP60 levels are associated with the progression of carotid arteriosclerosis, prospectively. METHODS: The association of sHSP60 with early atherogenesis (5-year development and progression of nonstenotic carotid plaques) was investigated as part of the population-based prospective Bruneck Study. The current study focused on the follow-up period between 1995 and 2000 and, thus, included 684 subjects. RESULTS: sHSP60 levels measured in 1995 and 2000 were highly correlated (r=0.40; P<0.001), indicating consistency over a 5-year period. Circulating HSP60 levels were significantly correlated with antilipopolysaccharide and anti-HSP60 antibodies. It was also elevated in subjects with chronic infection (top quintile group of HSP60, among subjects with and without chronic infection: 23.8% versus 17.0%; P=0.003 after adjustment for age and sex). HSP60 levels were significantly associated with early atherogenesis, both in the entire population (multivariate odds ratio, for a comparison between quintile group V versus I+II: 2.0 [1.2 to 3.5] and the subgroup free of atherosclerosis at the 1995 baseline: 3.8 [1.6 to 8.9]). The risk of early atherogenesis was additionally amplified when high-sHSP60 and chronic infection were present together. CONCLUSIONS: Our study provides the first prospective data confirming an association between high levels of sHSP60 and early carotid atherosclerosis. This possibly indicates an involvement of sHSP60 in activating proinflammatory processes associated with early vessel pathology

Robust Models for Optic Flow Coding in Natural Scenes Inspired by Insect Biology

The extraction of accurate self-motion information from the visual world is a difficult problem that has been solved very efficiently by biological organisms utilizing non-linear processing. Previous bio-inspired models for motion detection based on a correlation mechanism have been dogged by issues that arise from their sensitivity to undesired properties of the image, such as contrast, which vary widely between images. Here we present a model with multiple levels of non-linear dynamic adaptive components based directly on the known or suspected responses of neurons within the visual motion pathway of the fly brain. By testing the model under realistic high-dynamic range conditions we show that the addition of these elements makes the motion detection model robust across a large variety of images, velocities and accelerations. Furthermore the performance of the entire system is more than the incremental improvements offered by the individual components, indicating beneficial non-linear interactions between processing stages. The algorithms underlying the model can be implemented in either digital or analog hardware, including neuromorphic analog VLSI, but defy an analytical solution due to their dynamic non-linear operation. The successful application of this algorithm has applications in the development of miniature autonomous systems in defense and civilian roles, including robotics, miniature unmanned aerial vehicles and collision avoidance sensors

Motion sensitivity in the nucleus of the basal optic root of the pigeon

1. Single-unit responses to large-field movement (angular velocity, w = 0.25-42 degrees/s) of sine-wave gratings of different spatial wavelength (lambda = 5.2-41 degrees) and contrast have been recorded in the nucleus of the basal optic root (nBOR) of the accessory optic system (AOS) of the pigeon. 2. The steady-state response to moving sine-wave gratings increases with increasing contrast to reach a saturation level at 25%. 3. Generally the steady-state responses of the cells passed through a maximum when stimulated at various velocities. In 12 of the 15 cells tested with six different velocities and four different spatial wavelengths, the location of the response maximum on the velocity scale depended on the spatial wavelength (lambda) used. That is, in these cells the response depends on the temporal frequency (tf = w/lambda) of the stimulus and not on its velocity alone. This is in agreement with the prediction of the theory of motion detection according to the basic version of the correlation scheme. 4. The temporal frequency for maximal response of individual cells shifts to higher values when the contrast of the sine-wave gratings is reduced to 5%. 5. The steady-state response of 16 of the recorded directional selective cells (53) is modulated with the temporal frequency of the stimulus, regardless of the phase of the grating at the beginning of its movement. 6. In phasic-tonically responding cells, the phasic response peak decays to the steady-state level with a time constant that becomes shorter as the temporal frequency of the stimulus increases. 7. The basic version of the correlation scheme includes only the time constant of one low-pass filter. Therefore the phasic response is expected to decay to the steady-state level with one and the same time constant, and the position of the maximal response on the temporal frequency scale should not be influenced by a change of pattern contrast. According to the model, phase-dependent modulations of the steady-state response should occur only when the spatial wavelength of the stimulus pattern is large compared with the sampling base of the underlying detector. Consequently the results given in points 4-6 cannot be described by a basic version of the correlation scheme

Cortical oscillations and the origin of express saccades

The latencies of visually guided saccadic eye movements can form bimodal distributions. The 'express saccades' associated with the first mode of the distribution are thought to be generated via an anatomical pathway different from that for the second mode, which comprises regular saccades. The following previously published observations are the basis for a new alternative model of these effects: (i) visual stimuli can cause oscillations to appear in the electroencephalogram; (ii) visual stimuli can cause a negative shift in the electroencephalogram that lasts for several hundreds of milliseconds; and (iii) negativity in the electroencephalogram can be associated with reduced thresholds of cortical neurons to stimuli. In the new model both express and regular saccades are generated by the same anatomical structures. The differences in saccadic latency are produced by an oscillatory reduction of a threshold in the saccade-generating pathway that is transiently produced under certain stimulus paradigms. The model has implications regarding the functional significance of spontaneous and stimulus-induced oscillations in the central nervous system

The pigeon's eye viewed through an ophthalmoscopic microscope: Orientation of retinal landmarks and significance of eye movements

The retina of live, anaesthetized pigeons was inspected with an ophthalmoscopic microscope mounted on a goniometer. Retinal landmarks (optic axis, pecten, fovea, border between the yellow and red field) and the ora terminalis were projected into the visual field of the eye and related to existing data. The resting position of the eye is determined by an orientation of the pecten 45° to the horizontal plane and the optic axis pointing to the horizon with an azimuth angle of 70° relative to the bill. The binocular overlap is maximal (≈ 30°) some 15° above the eye-bill axis. In the resting position of the eye the red field is directed to the lower frontal visual field with only marginal binocular overlap. Binocular overlap of the area donalis with the red field, however, during frontal fixation is brought about by eye movements in the range we have demonstrated. The fixation point is 10° below the eye-bill axis

Association between vascular cell adhesion molecule 1 and atrial fibrillation

IMPORTANCE Accumulating evidence links inflammation and atrial fibrillation (AF).OBJECTIVE To assess whether markers of systemic and atrial inflammation are associated with incident AF in the general population.DESIGN, SETTING, AND PARTICIPANTS The Bruneck Study is a prospective, population-based cohort study with a 20-year follow-up (n = 909). The population included a random sample of the general community aged 40 to 79 years. Levels of 13 inflammation markers were measured at baseline in 1990. Findings were replicated in a case-control sample nested within the prospective Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study (n = 1770). Data analysis was performed from February to May 2016.EXPOSURES Levels of 13 inflammation markers.MAIN OUTCOMES AND MEASURES Incident AF over a 20-year follow-up period in the Bruneck Study.RESULTS Of the 909 participants included in the Bruneck Study, mean [SD] age was 58.8 (11.4) years and 448 (49.3%) were women. Among the 880 participants free of prevalent AF (n = 29) at baseline, 117 developed AF during the 20-year follow-up period (incidence rate, 8.2; 95% CI, 6.8-9.6 per 1000 person-years). The levels of soluble vascular cell adhesion molecule 1 (VCAM-1) and osteoprotegerin were significantly associated with incident AF (hazard ratio [HR], 1.49; 95% CI, 1.26-1.78; and 1.46; 95% CI, 1.25-1.69, respectively; P &lt;.001 with Bonferroni correction for both), but osteoprotegerin lost significance after age and sex adjustment (HR, 1.05; 95% CI, 0.87-1.27; P &gt;.99 with Bonferroni correction). Matrix metalloproteinase 9, metalloproteinase inhibitor 1, monocyte chemoattractant protein-1, P-selectin, fibrinogen, receptor activator of nuclear factor-.B ligand, high-sensitivity C-reactive protein, adiponectin, leptin, soluble intercellular adhesion molecule 1, and E-selectin all fell short of significance (after Bonferroni correction in unadjusted and age-and sex-adjusted analyses). The HR for a 1-SD higher soluble VCAM-1 level was 1.34 (95% CI, 1.11-1.62; Bonferroni-corrected P =.03) in a multivariable model. The association was of a dose-response type, at least as strong as that obtained for N-terminal pro-B-type natriuretic peptide (multivariable HR for a 1-SD higher N-terminal pro-B-type natriuretic peptide level, 1.15; 95% CI, 1.04-1.26), internally consistent in various subgroups, and successfully replicated in the SAPHIR Study (age-and sex-adjusted, and multivariable odds ratios for a 1-SD higher soluble VCAM-1 level, 1.91; 95% CI, 1.24-2.96, P =.003; and 2.59; 95% CI, 1.45-4.60; P =.001).CONCLUSIONS AND RELEVANCE Levels of soluble VCAM-1, but not other inflammation markers, are significantly associated with new-onset AF in the general community. Future studies should address whether soluble VCAM-1 is capable of improving AF risk classification beyond the information provided by standard risk scores