Multi-target neural network model of anxiolytic activity of chemical compounds using correlation convolution of multiple docking energy spectra.

Anxiety disorders are one of the most common mental health pathologies in the world. They require searc h and development of novel effective pharmacologically active substances. Thus, the development of new approaches to the search for anxiolytic substances by artificial intelligence methods is an important area of modern bioinformatics and pharmacology.

Post-compression of powerful femtosecond pulses after second harmonic generation.

A proof-of-principle experiment of highly efficient (38%) second harmonic generation was implemented at a ∼1 / intensity of a 45 fs pulse in a composite nonlinear sample-a 1 mm KDP crystal glued onto a 1 mm fused silica substrate. The attenuated replica of the second harmonic pulse (455 nm) was compressed down to 28.6 fs by means of dispersive mirrors, with a significant reduction in both the wings and the far temporal contrast.

[Drug-induced cognitive impairment and dementia].

One of the reasons for the development or worsening of cognitive impairment (CI) may be the use of a number of drugs: non-steroidal anti-inflammatory drugs, antiarrhythmics, antidepressants, glucocorticosteroids, antitumor drugs and a number of others. The negative effect of drugs on cognitive functions is realized due to many pathophysiological mechanisms: disruption of hormonal regulation, decreased neuronal excitability, increased activity of gamma-aminobutyric acid receptors, decreased cerebral circulation, atrophic changes in the brain; many mechanisms have not been fully established. Risk factors for the development of drug-induced CIs are: old age or childhood, brain damage, chronic diseases, genetic factors, the patient's initial CI, polypharmacy, dose and duration of drug use, acute infectious diseases, metabolic disorders, dehydration, acute urinary retention, etc.

Computational Analysis of CD46 Protein Interaction with SARS-CoV-2 Structural Proteins: Elucidating a Putative Viral Entry Mechanism into Human Cells.

This study examines an unexplored aspect of SARS-CoV-2 entry into host cells, which is widely understood to occur via the viral spike (S) protein's interaction with human ACE2-associated proteins. While vaccines and inhibitors targeting this mechanism are in use, they may not offer complete protection against reinfection. Hence, we investigate putative receptors and their cofactors.

Consensus Ensemble Multitarget Neural Network Model of Anxiolytic Activity of Chemical Compounds and Its Use for Multitarget Pharmacophore Design.

A classification consensus ensemble multitarget neural network model of the dependence of the anxiolytic activity of chemical compounds on the energy of their docking in 17 biotargets was developed. The training set included compounds thathadalready been tested for anxiolytic activity and were structurally similar to the 15 studied nitrogen-containing heterocyclic chemotypes. Seventeen biotargets relevant to anxiolytic activity were selected, taking into account the possible effect on them of the derivatives of these chemotypes.

Small-scale fluctuations of laser beam fluence at the large B-integral in ultra-high intensity lasers.

Analytical expressions for the spatial spectrum of fluence fluctuations of a laser pulse propagating in a medium with Kerr nonlinearity have been obtained. It is shown that inhomogeneities with a spatial scale much larger than the critical scale of self-focusing grow insignificantly even at large values of the B-integral. Experiments using BK7 glass and a KDP crystal as a nonlinear medium confirm the obtained theoretical results.

Improving focusability of post-compressed PW laser pulses using a deformable mirror.

The use of the post-compression technique ensures gain in laser pulse peak power but at the same time degrades beam focusability due to the nonlinear wavefront distortions caused by a spatially nonuniform beam profile. In this paper a substantial focusability improvement of a post-compressed laser pulse by means of adaptive optics was demonstrated experimentally. The Strehl ratio increase from 0.

Combined In Silico, Ex Vivo, and In Vivo Assessment of L-17, a Thiadiazine Derivative with Putative Neuro- and Cardioprotective and Antidepressant Effects.

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c- immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches.

Synthesis and Pharmacological Evaluation of Novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-]benzimidazole Derivatives as Promising Anxiolytic and Analgesic Agents.

A number of novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-]benzimidazole derivatives were obtained by alkylation mainly in the 1-tautomeric form of 2,3,4,5-tetrahydro[1,3]diazepino[1,2-]benzimidazole or its 8,9-dimethyl-substituted analog 4-chlorobenzyl bromide, 4-chloroacetic acid fluoroanilide, and 4-tert-butylphenacyl bromide in neutral medium. Compounds 3 were cyclized and synthesized earlier with 11-phenacyl-substituted diazepino[1,2-]benzimidazoles upon heating in conc. HBr.

11 fs, 1.5 PW laser with nonlinear pulse compression.

The PEARL laser output pulse with a duration of 60-70 fs was compressed to 11 fs after passing through a 5-mm thick silica plate and reflecting from two chirping mirrors with a total dispersion of -250 fs. The experiments were carried out for the B-integral values up to 19 without damage of the optical elements, which indicates that small-scale self-focusing was suppressed. The results obtained show the possibility of further nonlinear compression scaling to multipetawatt power in pulses with duration commensurate with the field period.

[What do we Mean by "Ideal" Blood Pressure Control?].

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications.

[Consensus ensemble neural network multitarget model of RAGE inhibitory activity of chemical compounds].

RAGE signal transduction via the RAGE-NF-κB signaling pathway is one of the mechanisms of inflammatory reactions that cause severe complications in diabetes mellitus. RAGE inhibitors are promising pharmacological compounds that require the development of new predictive models. Based on the methodology of artificial neural networks, consensus ensemble neural network multitarget model has been constructed.

Protection and Active Decontamination of Dairy Cattle Heifers against Lipophilic Toxins (PCBs) from Diet.

We studied the effects of a hydrophobized reversed-phase feed adsorbent in the form of a polyoctylated polysilicate hydrogel (POPSH) on productivity indicators, metabolic adaptation, and on the level of polychlorinated biphenyls (PCBs) in the blood of growing Holsteinized black-and-white heifers during the transition period. Two groups of two-month-old heifers of 20 head each were used. The experimental group received POPSH in addition to the main diet.

Searching for new anxiolytic agents among derivatives of 11-dialkylaminoethyl-2,3,4,5-tetrahydrodiazepino[1,2-a]benzimidazole.

A study on the anxiolytic activity of the new derivatives of 11-dialkylaminoethyl-2,3,4,5-tetrahydrodiazepino[1,2-a]benzimidazole, containing privileged scaffolds of benzodiazepine and benzimidazole in their structure, was conducted. The cytotoxic properties of low levels of six compounds were preliminary determined in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. The screening of these substances for anxiolytic activity was conducted using elevated plus maze (EPM) test in vivo, and DAB-21 was found to be the most active compound.

Low-Level Laser Therapy in Prevention of the Development of Endothelial Dysfunction and Clinical Experience of Treatment and Rehabilitation of COVID-19 Patients.

Objectives: The aim of the article is to justify the application of low-level laser therapy (LLLT) to prevent the development of endothelial dysfunction in COVID-19 patients. The results of treating and rehabilitating patients with COVID-19 and prevention of the disease using low-level laser therapy (LLLT) are evaluated.

Methods: A literature review is conducted on mechanisms of vascular homeostasis regulation, biomodulating effect of laser light, and LLLT methods for preventing endothelial dysfunction.

Bornyl Derivatives of -(Benzyloxy)Phenylpropionic Acid: In Vivo Evaluation of Antidiabetic Activity.

A series of bornyl derivatives of -(benzyloxy)phenylpropionic acid were prepared, and their hypoglycemic activities were examined by an oral glucose tolerance test in mice. The results of this test revealed two compounds, and , that can reduce the blood level of glucose similarly to reference compound vildagliptin. Both compounds were tested in an experiment on mice with metabolic disorders: the C57BL/6 strain.

Effect of Perindopril/Indapamide on Cerebral Blood Flow in Middle-Aged, Treatment-Naïve Patients with Hypertension.

Introduction: The relationship between blood pressure (BP) and cerebral blood flow (CBF) is not fully understood. This study evaluated the impact of a perindopril arginine/indapamide (Pa/I) single-pill combination (SPC) on CBF in middle-aged patients.

Methods: A total of 22 treatment-naïve patients with essential hypertension and at least one hypertension-mediated organ damage and 41 healthy controls were enrolled.

[The relationship between the combined use of various proton pump inhibitors with antiplatelet drugs and the risk of cardiovascular complications].

In the article the problem of the combined use of clopidogrel and various proton pump inhibitors (PPIs) in terms of cardiovascular complications risk and stent thrombosis is considered. The results of meta - analyses and a systematic reviews affecting this issue are represented in detail. The inter - drug interactions mechanisms of various PPIs with clopidogrel based on the characteristics of the metabolism in the liver cytochromes system are discussed.

[Hypertension and insomnia].

Insomnia is frequently detected in patients with arterial hypertension (AH): from 19% to 47.9% of all cases according to epidemiological studies. On the other hand, the frequency of hypertension in patients with insomnia ranges from 21.

[Treatment of chronic heart failure: is deprescribing possible?].

Deprescribing is a scheduled withdrawal, dose reduction, or replacement of a medicine with a safer one. Several groups of medicinal products (MPs) are used simultaneously in the treatment of chronic heart failure. This increases the risk of adverse drug reactions, particularly in elderly and senile patients.

[Drug-induced seizures: prevalence, risk factors, treatment and prevention].

There is a growing interest to the problem of drug-induced epileptic seizures (ES) due to their relatively high prevalence, poor prognosis, a large number of different drugs associated with the development of drug-induced ES, and low awareness among general practitioners. Drug-induced ES are most often associated with the use of antidepressants, antipsychotics, antiepileptic drugs (overdose or as a result of discontinuation), antibiotics, immunosuppressants and immunomodulators, antitumor agents, analgesics, central nervous system stimulators, anesthetics etc. The prevalence of drug-induced ES varies with different drugs.

[Mechanisms for the Development of Blood Pressure Variability and the Potential of Antihypertensive Drugs in Their Correction].

Blood pressure variability (BPV) is the fluctuations of blood pressure over a certain period of time under the influence of various factors. The issue of increased BPV is of particular clinical importance due to high predictive value of this parameter as a risk factor for fatal and non-fatal cardiovascular, cerebrovascular and renal events. It is proved that in the BPV increasing, the key role is played by impairments in arterial baroreflexes, which, in turn, are mediated by increased vascular stiffness, impact of angiotensin II and the sympathetic nervous system, endothelial dysfunction, nitric oxide deficiency and aging, including the vascular aging.

Vascular cognitive impairment: pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments.

Vascular cognitive impairment (VCI) and vascular dementia are the most common forms of cognitive disorder associated with cerebrovascular disease and related to increased morbidity and mortality among the older population. Growing evidence suggests the contribution of blood-pressure variability, cardiac arrhythmia, hyperactivation of the renin-angiotensin-aldosterone system, endothelial dysfunction, vascular remodeling and stiffness, different angiopathies, neural tissue homeostasis, and systemic metabolic disorders to the pathophysiology of VCI. In this review, we focus on factors contributing to cerebrovascular disease, neurovascular unit alterations, and novel approaches to cognitive improvement in patients with cognitive decline.

[Single Pill Indapamide and Perindopril Arginine Combination: Optimal Coupling of Vascular Protection and Hemodynamic Risk Factors Reduction in Patients with Essential Arterial Hypertension].

Objective: to investigate the impact of indapamide / perindopril single-pill combination (I / P SPC) on arterial stiffness parameters, blood pressure (BP) level and BP variability (BPV) in middle-aged patients with stage II grade 1-2 essential arterial hypertension (EAH). Materials and methods. We retrospectively formed a group of patients with stage II grade 1-2 EAH who had not previously received regular antihypertensive therapy (AHT) (n=52, mean age 52.