[The significance of glymphatic pathway in the relationship between the sleep-wake cycle and neurodegenerative diseases]. / Rol' glimfaticheskogo klirensa v mekhanizmakh svyazi tsikla «son­bodrstvovanie¼ i razvitiya neirodegenerativnykh protsessov.

Selective and progressive death of neurons is a characteristic feature of the process of neurodegeneration and leads to corresponding neuronal dysfunctions. Neurodegenerative diseases represent a heterogeneous group of clinically distinct disorders with similar molecular mechanisms of pathogenesis. They are based on the processes of abnormal aggregation of proteins, the formation of fibrillary insoluble structures and their deposition in the form of histopathological inclusions in the tissues of the nervous system. Disturbance of homeostatic functions that regulate neuronal ion and energy metabolism, biosynthesis and degradation of proteins and nucleotides, chronic hypoxia and the penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause metabolic changes associated with age and disorders in the sleep-wake cycle, but also contribute to the development of neurodegenerative diseases. In animal studies, clearance pathways have been identified in which solutes and specific tracers are excreted perivascular into the meningeal lymphatics. The glymphatic pathway promotes the removal of metabolites, including Aß amyloid and tau protein, from the parenchymal extracellular space of the brain. The glymphatic system is discussed to be more efficient during natural sleep, and fluid dynamics through this pathway exhibit daily fluctuations and are under circadian control. This review systematizes the key aspects and scientific data of recent studies on the role of the glymphatic pathway and astroglial AQP-4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, in particular in relation to the regulatory role of the sleep-wake cycle and in development of neurodegeneration.

[Changes in sleep patterns and the doom-scrolling (doom-surfing) phenomenon as modifiable risk factors for anxiety due to continuous stress of the COVID-19 pandemic]. / Izmeneniya rezhima sna i potreblenie informatsii s negativnym kontentom v internete («dumskrolling¼, «dumserfing¼) kak upravlyaemye faktory riska razvitiya trevogi v usloviyakh stressa pandemii COVID-19.

OBJECTIVE: To evaluate the modifiable daily behavior patterns associated with increased anxiety indicators in the general population in response to the COVID-19 pandemic. MATERIAL AND METHODS: The study examined the characteristics of the Russian population (n=7777) of the international multicenter project COMET-G. In particular, variables were targeted to describe deviations in the behavior of adults during the period of application of measures of social isolation in connection with the pandemic, and revealing a relationship with the total score on the Spielberger State Anxiety Scale (STAI-S). Among these variables, experts selected those that could potentially be subject to change in the short term, that is, act as manageable or modifiable risk factors for the development of anxiety. The selected variables were analyzed in a statistical PLS-model to identify indicators that make the most significant contribution to the increase in the total anxiety score. RESULTS: Our statistical model explained 48.4% of the variability in the STAI-S anxiety total scores related to changes in daily life habits. In particular, doom-scrolling/doom-surfing about the spread of the virus and the COVID-19 pandemic, changes in sleep patterns and usual daily life activities due to social isolation measures presented as factors significantly contributing to the increase of state anxiety. CONCLUSION: Given the manageable or modifiable risk factors that we have identified, public awareness and therapeutic recommendations, pointing to the need to (I) control the amount of time spent in the internet and monitor their internet-based content consumption, (II) regulate sleep-wake patterns, (III) maintain daily habits and household activities, may reduce the likelihood of developing anxiety disorders in the context of the impact of a global chronic stress due to the COVID-19 pandemic and associated social isolation measures.

Electrically driven kinklike distorting waves in microsized liquid crystals.

Electrically driven kinklike distortion regimes in a microsized liquid crystal channel have been investigated both experimentally and analytically. Kinklike distortion waves were excited by the interaction between the electric field E and the gradient ∇n[over ̂] of the director field in a homogeneously aligned liquid crystal (HALC) channel. Having obtained the evolution of the normalized light intensity, which was recorded by the high-speed camera, the process of excitation and evolution of the traveling wave in the HALC channel was visualized for the first time. It was shown, based on a nonlinear extension of the classical Ericksen-Leslie theory, that in the case when the electric field E≫E_{th}, the flow of liquid crystal material completely stops and a new mechanism for converting the electric field arises in the form of the electrically driven distorting traveling kinklike wave, which can be excited in the LC channel, composed of 4-n-pentyl-4^{'}-cyanobiphenyl molecules.

[The significance of the glymphatic pathway in the relationship between the sleep-wake cycle and neurodegenerative diseases]. / Rol' glimfaticheskogo klirensa v mekhanizmakh vzaimosvyazi tsikla «son­bodrstvovanie¼ i razvitiya neirodegenerativnykh protsessov.

Selective and progressive death of neurons is a characteristic feature of the process of neurodegeneration and leads to corresponding neuronal dysfunctions. Neurodegenerative diseases represent a heterogeneous group of clinically distinct disorders with similar molecular mechanisms of pathogenesis. They are based on the processes of abnormal aggregation of proteins, the formation of fibrillary insoluble structures and their deposition in the form of histopathological inclusions in the tissues of the nervous system. Disturbance of homeostatic functions that regulate neuronal ion and energy metabolism, biosynthesis and degradation of proteins and nucleotides, chronic hypoxia and the penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause metabolic changes associated with age and disorders in the sleep-wake cycle, but also contribute to the development of neurodegenerative diseases. In animal studies, clearance pathways have been identified in which solutes and specific tracers are excreted perivascular into the meningeal lymphatics. The glymphatic pathway promotes the removal of metabolites, including Aß amyloid and tau protein, from the parenchymal extracellular space of the brain. The glymphatic system is discussed to be more efficient during natural sleep, and fluid dynamics through this pathway exhibit daily fluctuations and are under circadian control. This review systematizes the key aspects and the data of recent research on the role of the glymphatic pathway and astroglial AQP-4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, in particular in relation to the regulatory role of the sleep-wake cycle and in development of neurodegeneration.

Water/organic liquid interface properties with amine, carboxyl, thiol, and methyl terminal groups as seen from MD simulations.

Molecular dynamics simulations were performed to study structural and dynamic properties of polar butanamine/water/butanamine, pentanoic acid/water/pentanoic acid, butanethiol/water/butanethiol, and nonpolar pentane/water/pentane systems. The mass density profiles along the interface normal to the organic liquid/water system, the difference in the local structure of H 2 O molecules in bulk and in the vicinity of interface, as well as the diffusion behavior of water molecules at the interface with above-mentioned organic liquids have been investigated. Our MD simulation has shown that the diffusion of water molecules across the water/organic liquid interface is influenced by the hydrogen bonds n HB between water molecules and the terminal groups of organic liquids. It was found that the loss of the hydrogen bonds n HB in the nonpolar organic liquid leads to a decrease in the value of the normal component of the diffusion coefficient D z , while the tangential diffusion coefficients, both D x and D y , increase.

Skeletal photoinduced rearrangement of diarylethenes: ethene bridge effects.

A skeletal photorearrangement involving UV-induced 6π-electrocyclization of diarylethenes with various ethene bridges has been studied. It has been found that deprotonation is the predominant step among the three possible alternative reaction pathways (radical abstraction, deprotonation, or sigmatropic shift) following 6π-electrocyclization, and incorporation of an electronegative carbonyl group into the geminal position to the phenyl residue results in a reduction in the reaction time and an increase in the yield of the desired product. The significant increase in the reaction time in less polar solvents (toluene, TCM) also indicates a large contribution of the deprotonation step to the skeletal photorearrangement of diarylethenes. Performing the reaction in toluene in the presence of tertiary amines leads to a reduction in the reaction time and an increase in the yield of the desired product. The best results were achieved when the reaction was carried out in toluene in the presence of DIPEA. The experimental results are in good agreement with the DFT calculations.

Charge Fluctuations on a Flat Interface between Dielectric and Electrolyte or Dense Plasma.

An interface between a dielectric and a medium containing charge carriers with moderate mobility is considered. In equilibrium, stochastic fluxes of positive and negative particles toward the surface have equal average current density j0, and we suppose that the surface absorbs all falling charges. All over the surface, this results in the emergence of oppositely charged spots of various sizes D fluctuating and interacting with each other. Fourier expansion reduces this collection of interacting spots to the ensemble of independently fluctuating charge density waves. An exact solution of the Poisson equation for a single wave on a flat surface was obtained and provided strict proof that a fluctuating electric field is quite strong just above each charge spot but diminishes exponentially with the distance from the plane. The lifetime τ of a charge spot is inversely proportional to the density j0 of the stochastic current while proportional to j0τ fluctuation's amplitudes independent of j0. The fluctuation's parameter dependence on the charge spot's size D can vary according to the conducting medium properties.

[Study of the effectiveness of neuroprotective therapy in restoring motor function in patients during the acute period of ischemic stroke]. / Issledovanie effektivnosti neiroprotektivnoi terapii pri vosstanovlenii dvigatel'noi funktsii u patsientov v ostrom periode ishemicheskogo insul'ta.

OBJECTIVE: The purpose of the work was to study the effect of neuroprotective therapy with Cellex on the features of recovery of movement disorders in patients in the acute period of ischemic stroke. MATERIAL AND METHODS: A single-center randomized study was conducted to assess the efficacy and safety of the use of neuroprotective therapy with Cellex in patients in the acute period of ischemic stroke. The study included 60 patients with a stroke duration of no more than 3 days in the middle cerebral artery area and vertebrobasillar area with moderate and severe central hemiparesis. Patients of the study group received 1 ml of Cellex. subcutaneously 1 time per day for 10 days. All patients received drug therapy and rehabilitation measures within the framework of the standard of care for patients with ischemic stroke. RESULTS: Against the background of the therapy, by the end of the study on days 14-21, the study and control groups showed a significant improvement according to clinical scales: NIHSS, mRS, RMI. The patients of the study group showed a more pronounced recovery of motor function, relative to the comparison group, according to motor scales: «A-D¼ FMA (54 [53; 62] and 42 [34; 51], p=0.03), «E-F¼ FMA (29 [28; 33] and 25 [18; 27], p=0.03), ARAT (47 [48; 57], 32 [24; 48], p=0.046). Among the patients of the study group, by the end of the study, the severity of mild stroke was 67%, relative to the comparison group 11% (χ21df=6.48; p=0.01). The use of neuroprotective therapy in the form of Cellex had a positive effect on both the prognostic score and the long-term assessment according to the SSS scale, due to the regression of motor disorders of the upper and lower extremities. CONCLUSION: The study has demonstrated the effectiveness of the use of neuroprotective therapy in the treatment of movement disorders in patients in the acute period of ischemic stroke. Therapy with Cellex helped to reduce the severity of stroke, and had a positive effect on the prognosis of the disease.

[Motor rehabilitation of patients in the acute period of stroke using virtual reality technology]. / Dvigatel'naya reabilitatsiya patsientov v ostrom periode insul'ta s ispol'zovaniem tekhnologii virtual'noi real'nosti.

OBJECTIVE: To study an effect of adjuvant rehabilitation using implicit virtual reality on the dynamics of the motor function of the lower extremities in patients in the acute period of ischemic stroke. MATERIALS AND METHODS: The study was carried out to assess the effectiveness and safety of rehabilitation using virtual reality in 60 patients with lower central paresis in the acute period of ischemic stroke, lasting from 3 to 5 days. Patients of the study group additionally received rehabilitation using the hardware-software complex ReviVR, which allows to stimulate the patient's plantar surface by means of pneumo cuffs synchronously with the step of his animated body. Animation of movement was demonstrated to the patient using virtual reality glasses. The duration of the classes was 10 days, 20-25 minutes each. The total duration of rehabilitation measures in the study and comparison groups was 3-4 hours. RESULTS: A significant regression on NIHSS (3 [-4; -1] and -1 [-2; 0], p<0.001) and a progress on RMI (3 [1; 3] and 2 [0; 2], p<0.001, respectively), between the study group and the control group were found. Changes on FMA-LE section (E-F) occurred on day 10, between the study and comparison groups (9 [5; 16] and 4 [0; 7], respectively, p=0.04). The improvement in FMA-LE out of synergy, in the standing position, indicated an increased readiness of the patient to form an independent walk. CONCLUSION: The study has shown that the use of virtual reality rehabilitation increases the effectiveness of motor rehabilitation in patients with lower central paresis in the acute period of stroke.

[Sleep disorders in synucleinopathy]. / Narushenie sna pri sinukleinopatiyakh.

The article highlights the current state of the problem of sleep disorders in various neurodegenerative diseases. The clinical picture and diagnosis of these disorders are described in detail. Separately, the emphasis is made on the mechanisms underlying development of these disorders and their features in various forms of synucleinopathies. The mediator and physiological changes that underlie sleep disorders in various nosological units of synucleinopathies are discussed in detail. The current attitude to certain sleep disorders as predictors of neurodegenerative diseases is evaluated. The role of the glymphatic system in the development of these disorders is considered. Also, modern therapeutic strategies for sleep disorders in neurodegenerative diseases are discussed.

Electrically driven nematic flow in microfluidic capillary with radial temperature gradient.

An electrically driven fluid pumping principle and a mechanism of kinklike distortion of the director field n[over ̂] in the microsized nematic volume has been described. It is shown that the interactions, on the one hand, between the electric field E and the gradient of the director's field ∇n[over ̂], and, on the other hand, between the ∇n[over ̂] and the temperature gradient ∇T arising in a homogeneously aligned liquid crystal microfluidic channel, confined between two infinitely long horizontal coaxial cylinders, may excite the kinklike distortion wave spreading along normal to both cylindrical boundaries. Calculations show that the resemblance to the kinklike distortion wave depends on the value of radially applied electric field E and the curvature of these boundaries. Calculations also show that there exists a range of parameter values (voltage and curvature of the inner cylinder) producing a nonstandard pumping regime with maximum flow near the hot cylinder in the horizontal direction.

Electrically driven nematic flow in microfluidic devices containing a temperature gradient.

Fluid pumping principle has been developed utilizing the interaction, on the one hand, between the electric field E and the gradient ∇n[over ̂] of the director's field, and, on the other hand, between the ∇n[over ̂] and the temperature ∇T gradient arising in a homogeneously aligned liquid crystal (HALC) microfluidic channel. Calculations, based upon the nonlinear extension of the classical Ericksen-Leslie theory, with accounting the entropy balance equation, show that due to the coupling among the ∇T, ∇n,[over ̂] and E in the HALC microfluidic channel the horizontal flow v=v_{x}i[over ̂]=ui[over ̂] may be excited. The direction and magnitude of v is influenced both by the heat flux q across the microfluidic channel and the strength of the electric field E. The results of calculations showed that the dependence of the maximum value of the equilibrium velocity distribution |u_{max}(E/E_{th})| across the LC channel versus electric field E/E_{th} is characterized by maximum value at E/E_{th}=2.0. In the case when the electric field E≫E_{th}, the horizontal flow of the LC material completely stops and a novel mechanism of converting of the electric field in the form of the kinklike wave reorientation of the director field n[over ̂] can be excited in the LC channel.

Nonmechanical principle for producing a flow in a homogeneously aligned microfluidic nematic channel.

Nonmechanical fluid pumping principle has been developed utilizing the interactions of both the director [Formula: see text] and velocity v fields and temperature T redistribution across a two-dimensional homogeneously-aligned nematic (HAN) microfluidic channel under the influence both of a heat flux [Formula: see text] and the surface electric field E0, originating from the surface charge density [Formula: see text]. The heat flux [Formula: see text] is caused by the laser beam pulse focused on the channel's boundary, whereas the normally directed electric field is due to electric double layers, that is naturally created within the liquid crystal near a charged surface. Calculations, based upon the nonlinear extension of the classical Ericksen-Leslie theory, with accounting the entropy balance equation, show that due to the coupling between the [Formula: see text] and [Formula: see text], in the HAN microfluidic channel the vortical flow [Formula: see text] may be excited. The direction and magnitude of [Formula: see text] is influenced by [Formula: see text] and E0, as well as by the thickness of the HAN microfluidic channel.

Photochemical rearrangement of diarylethenes: synthesis of functionalized phenanthrenes.

A novel protocol for the synthesis of functionalized phenanthrenes through photocyclization of diarylethenes (DAE) under UV irradiation is proposed. The reaction proceeds through 6π-electrocyclization with the formation of a cyclic (closed) intermediate that undergoes a rearrangement affording unsymmetrical phenanthrenes in good yields. However, in contrast to benzene derivatives, the photocyclization of naphthalene diarylethenes proceeds more slowly, which is confirmed by DFT calculations. The transformation was performed on a 1 mmol scale. The scalability showed that the diarylethenes bearing oxazole, thiazole, pyrazole and imidazole as aryl moieties are more prone to photorearrangement and can be used in preparative organic synthesis.

Intracellular Acidification Suppresses Synaptic Vesicle Mobilization in the Motor Nerve Terminals.

Intracellular protons play a special role in the regulation of presynaptic processes, since the functioning of synaptic vesicles and endosomes depends on their acidification by the H+-pump. Furthermore, transient acidification of the intraterminal space occurs during synaptic activity. Using microelectrode recording of postsynaptic responses (an indicator of neurotransmitter release) and exo-endocytic marker FM1-43, we studied the effects of intracellular acidification with propionate on the presynaptic events underlying neurotransmitter release. Cytoplasmic acidification led to a marked decrease in neurotransmitter release during the first minute of a 20-Hz stimulation in the neuromuscular junctions of mouse diaphragm and frog cutaneous pectoris muscle. This was accompanied by a reduction in the FM1-43 loss during synaptic vesicle exocytosis in response to the stimulation. Estimation of the endocytic uptake of FM1-43 showed no disruption in synaptic vesicle endocytosis. Acidification completely prevented the action of the cell-membrane permeable compound 24-hydroxycholesterol, which can enhance synaptic vesicle mobilization. Thus, the obtained results suggest that an increase in [H+]in negatively regulates neurotransmission due to the suppression of synaptic vesicle delivery to the sites of exocytosis at high activity. This mechanism can be a part of the negative feedback loop in regulating neurotransmitter release.

Kinklike pressure wave in the microsized twisted nematic volume.

We have described a novel mechanism of the kinklike pressure P(z-vt) response of the microsized twisted nematic volume under the effect of externally applied electric field E directed parallel to the restricted surfaces and induced by a strong local disturbance of the director field n[over ̂]. It is found that the torques acting on the director n[over ̂] may excite the pressure traveling wave spreading along the normal to both boundaries, whose resemblance to a kink-like wave increases with increasing the value of the applied electric field greater than some critical value E_{cr}.

[Disorders of arousal: the mechanism of occurrence, neurophysiological features]. / Parasomnii, sviazannye s narusheniem probuzhdeniia iz medlennogo sna: mekhanizm vozniknoveniia, neirofiziologicheskie osobennosti.

The article covers the current state of the problem of disorders of arousal (DOAs). The clinical features and diagnostics of the disease are described in detail. Separately, emphasis is placed on the mechanisms of the occurrence of DOAs and the characteristic changes in the central nervous system. The question of neurophysiological changes preceding the clinical manifestation of DOAs and the concept of local sleep as a physiological basis for the occurrence of DOAs are considered. Current therapeutic approaches in the treatment of these forms of parasomnias are reviewed.

Structural and optical properties of free-standing smectic films.

We have carried out a complex numerical study of the structural, thermodynamic and optical properties of the partially fluorinated 5-n -alkyl-2-(4-n-(perfluoroalkyl-metheleneoxy)phenyl) free-standing smectic film in air under the action of the external electric field [Formula: see text]. Calculations, based upon the extended McMillan's mean-field theory with anisotropic forces, show a stepwise reduction of the value of the Helmholtz free energy and the reflectivity of the partially fluorinated smectic film in air, as the temperature is raised above the bulk smectic-A-isotropic transition value. It has been shown, by solving the self-consistent nonlinear equations for the orientational and translational order parameters, that the electric field [Formula: see text] may not only affect the layer-thinning transition sequences, but also change the first multilayer jump in the film thickness, whereas practically does not affect the reflectivity R(N) of the partially fluorinated N -layer smectic film in air. In the range of film thicknesses investigated, the reduction of the R(N) is, at least, qualitatively in agreement with the experimentally observed decrease of the optical reflectivity with the decrease of N.

Nature of thermally excited vortical flow in a microsized nematic volume.

The theoretical description of the reorientational dynamics in the case of a hybrid-oriented two-dimensional (2D) liquid crystal (LC) cell, under the influence of a temperature gradient ∇T, caused by a heat flux q directed at an angle α across the lower bounding surface with the orientational defect, has been presented. Our calculations, based on the appropriate nonlinear extension of the classical Ericksen-Leslie theory, show that due to interaction between ∇T and the gradient of the director field ∇n[over ̂] in the LC sample a thermally excited vortical fluid flow is maintained in the bulk of the nematic volume. In order to elucidate the role of both the orientational defect and the heat flux q in formation of the vortical flow in the microsized LC volume, we have analyzed the response of the LC material confined in the microsized 2D volume on the effect of the laser beam focused on the bounding surface.

Photocyclization of diarylethenes: the effect of imidazole on the oxidative photodegradation process.

We have studied the photoreaction of 1,2-diarylethenes under aerobic conditions in the presence of various amines to prevent side processes promoted by singlet oxygen. It has been found that the most amines quite effectively deactivate processes associated with singlet oxygen, but primary and secondary amines unlike tertiary ones, react with substrates resulting in various side products. Among the studied amines, the most effective additive for preventing side processes, including those associated with singlet oxygen is imidazole, which is practically not consumed in photoreaction. It was shown that imidazole can also prevents the photodegradation of organic photochromes in solutions. The results obtained can be used in various branches of science, technology and medicine to improve the photostability of photosensitive organics (dyes).