Interaction of oxidative stress and misfolded proteins in the mechanism of neurodegeneration

Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the most important steps in the pathology underlying a wide spectrum of neurodegenerative disorders, including the two most common ones—Alzheimer's and Parkinson's disease. Activity and toxicity of these proteins depends on the stage and form of aggregates. Excessive production of free radicals, including reactive oxygen species which lead to oxidative stress, is proven to be involved in the mechanism of pathology in most of neurodegenerative disorders. Both reactive oxygen species and misfolded proteins play a physiological role in the brain, and only deregulation in redox state and aggregation of the proteins leads to pathology. Here, we review the role of misfolded proteins in the activation of ROS production from various sources in neurons and glia. We discuss if free radicals can influence structural changes of the key toxic intermediates and describe the putative mechanisms by which oxidative stress and oligomers may cause neuronal death

Multimodal optical diagnostics of the microhaemodynamics in upper and lower limbs

The introduction of optical non-invasive diagnostic methods into clinical practice can substantially advance in the detection of early microcirculatory disorders in patients with different diseases. This paper is devoted to the development and application of the optical non-invasive diagnostic approach for the detection and evaluation of the severity of microcirculatory and metabolic disorders in rheumatic diseases and diabetes mellitus. The proposed methods include the joint use of laser Doppler flowmetry, absorption spectroscopy and fluorescence spectroscopy in combination with functional tests. This technique showed the high diagnostic importance for the detection of disturbances in peripheral microhaemodynamics. These methods have been successfully tested as additional diagnostic techniques in the field of rheumatology and endocrinology. The sensitivity and specificity of the proposed diagnostic procedures have been evaluated.<br/

Application of deep convolutional and long short-term memory neural networks to red blood cells motion detection and velocity approximation

The paper deals with processing data obtained using nailfold high-speed videocapillaroscopy. To detect the red blood cells velocity two approaches are used. The deterministic approach is based on pixel intensities analysis for object detection and calculation of the displacement and velocity of red blood cells in a capillary. The obtained data formulate targets for the second approach. The stochastic approach is based on a sequence of artificial neural networks. The semantic segmentation network UNet is used for capillary detection. Then, the classification network GoogLeNet or ResNet is used as a feature extractor to convert masked video frames to a sequence of feature vectors. And finally, the long short-term memory network is used to approximate the red blood cells velocity. The results demonstrated that the accuracy of the mean velocity approximation in the time range of several seconds is up to 0.96. But the accuracy at each specific time moment is less accurate. So, the proposed algorithm allows the determination of the RBCs mean velocity but it doesn't allow determination of the RBCs pulsations accurate enough

Blood flow oscillations as a signature of microvascular abnormalities

Laser Doppler flowmetry (LDF) was utilized for blood ow measurements. Wavelet analysis was used to identify spectral characteristics of the LDF signal in patients with rheumatic diseases and diabetes mellitus. Baseline measurements were applied for both pathological groups. Blood flow oscillations analyses were performed by means of the wavelet transform. Higher baseline perfusion was observed in both pathological groups in comparison to controls. Differences in the spectral properties between the groups studied were revealed. The results obtained demonstrated that spectral properties of the LDF signal collected in basal conditions may be the signature of microvasculature functional state

Fibre-optic probe for fluorescence diagnostics with blood influence compensation

To minimise the influence of blood content on the fluorescence measurements in vivo, a fibre optical probe combining fluorescence and diffuse reflectance measurements was developed. For the inverse solution of the blood content recovery, a set of neural networks trained by the Monte Carlo generated learning set was used. An approach of fluorescence measurements triggered by simultaneous real-time measurements of blood content in living tissue during moderate changes in contact pressure of the optic probe is proposed. The method allows one to decrease the necessary pressure on the probe as well as increase the repeatability of the measurements. The developed approach was verified in a series of experiments on volunteers with fluorescence excitation at 365 nm and 450 nm. The proposed technology is of particular interest in the development of new fluorescence-based optical biopsy systems

Assessment of tissue ischemia of nail fold precapillary zones using a fluorescence capillaroscopy

An optical instrument for nailfold fluorescence capillaroscopy and image registration has been developed. With this instrument, an effect of increasing fluorescence intensity in the spectral range of NADH fluorescence during ischemia was detected

Evaluation of microvascular disturbances in rheumatic diseases by analysis of skin blood flow oscillations

Laser Doppler flowmetry (LDF), tissue reflectance oximetry (TRO) and pulse oximetry (PO) and cold pressor test (CPT) were used to assess the microcirculation parameters and the activation of regulatory mechanisms. LDF and TRO samples wavelet transform in the frequency bands 0.01-2 Hz was used to evaluate microvascular disturbances in rheumatic diseases and to assess the vascular involvement in the pathological process. The spectral components of LDF and TRO signals associated with endothelial, adrenergic, intrinsic smooth muscle, respiratory and cardiac activities were analyzed. Significant difference between healthy and rheumatology subjects was identified in perfusion parameters. Spectral analysis of the LDF signal revealed significant difference between two group of high (<0.1 Hz) frequency pulsations. Based on the analysed of the perfusion and amplitudes oscillation in the frequency band the decision rule for detection microvascular disturbances were synthesized. The perfusion parameter and amplitude oscillation associated with cardiac activities included in the decision rule. Based on the measured parameters and the result of wavelet transform LDF- and TRO-signals the parameters for detection of complications associated with microvascular disturbances and their possible causes were proposed

Direct optical generation of singlet oxygen in the regulation of vascular tone

An approach to visualization of the vascular bed with the possibility of assessing changes in blood filling and identifying diagnostically significant periodic changes in the signal by analyzing speckle images is proposed. The effect of singlet oxygen by direct excitation of an oxygen molecule by 1267 nm laser radiation on changes in the vascular bed parameters was studied using this approach

Incremental residual polarization of human skin caused by aging

Significance The study of the effect of aging on the optical properties of biological tissues, in particular polarization, is important in the development of new diagnostic approaches. Aim This work aims to provide a comprehensive analysis of the factors and mechanisms that contribute to the alteration of skin polarization properties caused by aging, using polarization-sensitive hyperspectral imaging measurements and Monte Carlo simulation. Approach Our investigation involved both experimental studies of in vivo human skin of volunteers of different ages and computational modeling that accounted for changes in the absorption and scattering properties of the skin model. Specifically, we analyzed alterations in the degree of linear polarization (DOLP) to better understand the impact of aging on skin polarization properties. Results A statistically significant increase in the DOLP was found for the elderly group. At the same time, there was no correlation between changes in polarization and the calculated blood volume fraction parameter for different ages. According to the simulation results, it was also found that a change in the scattering properties of biological tissues has a more significant effect on the change in polarizing light compared to the change in absorption. Conclusions The results of the work prove that the sensitivity of polarization imaging to age- or pathological-related skin changes may be primarily due to changes in scattering, which in turn is associated with changes in the collagen fibers of the dermis. The proposed technique shows promise for in vivo non-invasive real-time assessment of age-associated skin changes and can also be extended to monitor changes associated with the development of age-related pathologies