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Background/Objectives: One of the hallmarks of Alzheimer's disease (AD) is the accumulation of aggregated beta-amyloid (Aβ) protein in the form of senile plaques within brain tissue. Senile plaques contain various post-translational modifications of Aβ, including prevalent isomerization of Asp7 residue. The Asp7 isomer has been shown to exhibit increased neurotoxicity and induce amyloidogenesis in brain tissue of transgenic mice. The toxicity of Aβ peptides may be partly mediated by their structure and morphology. In this respect, in this study we analyzed the structural and aggregation characteristics of the Asp7 isoform of Aβ42 and compared them to those of synthetic Aβ42. We also investigated the effects of intracerebroventricular (i.c.v.) administration of these peptides, a method often used to induce AD-like symptoms in rodent models. Methods: Atomic force microscopy (AFM) was conducted to compare the morphological and aggregation properties of Aβ42 and Asp7 iso-Aβ42. The effects of i.c.v. stereotaxic administration of the proteins were assessed via behavioral analysis and reactive oxygen species (ROS) estimation in vivo using a scanning ion-conductance microscope with a confocal module. Results: AFM measurements revealed structural differences between the two peptides, most notably in their soluble toxic oligomeric forms. The i.c.v. administration of Asp7 iso-Aβ42 induced spatial memory deficits in rats and elevated oxidative stress levels in vivo, suggesting a potential of ROS in the pathogenic mechanism of the peptide. Conclusions: The findings support the further investigation of Asp7 iso-Aβ42 in translational research on AD and suggest its involvement in neurodegenerative processes. [ABSTRACT FROM AUTHOR]

Given the high growth rates of cognitive decline among the elderly population and the lack of effective etiological treatments, early diagnosis of cognitive impairment progression is an imperative task for modern science and medicine. It is of particular interest to identify predictors of an unfavorable subsequent course of cognitive disorders, specifically, rapid progression. Our study assessed the informative role of various risk factors on the dynamics of cognitive impairment among mild cognitive impairment (MCI) patients. The study included patients with MCI (N = 338) who underwent neuropsychological assessment, magnetic resonance imaging (MRI) examination, blood sampling for general and biochemical analysis, APOE genotyping, and polygenic risk score (PRS) evaluation. The APOE ε4/ε4 genotype was found to be associated with a diminished overall cognitive scores initial assessment and negative cognitive dynamics. No associations were found between cognitive changes and the PRS. The progression of cognitive impairment was associated with the width of the third ventricle and hematological parameters, specifically, hematocrit and erythrocyte levels. The absence of significant associations between the dynamics of cognitive decline and PRS over three years can be attributed to the provided suitable medical care for the prevention of cognitive impairment. Adding other risk factors and their inclusion in panels assessing the risk of progression of cognitive impairment should be considered. [ABSTRACT FROM AUTHOR]

Chemotherapy is among the main classical approaches to the treatment of oncologic diseases. Its efficiency has been comprehensively proven by clinical examinations; however, the low selectivity of chemotherapeutic agents limits the possibilities of this method, making it necessary to search for new approaches to the therapy of oncologic diseases. Photodynamic therapy is the least invasive method and a very efficient alternative for the treatment of malignant tumors; however, its efficiency depends on the depth of light penetration into the tissue and on the degree of oxygenation of the treatment zone. In this work, a hitherto unknown conjugate of a natural bacteriochlorin derivative and doxorubicin was obtained. In vitro and in vivo studies showed a more pronounced activity of the conjugate against MCF-7 and 4T1 cells and its higher tumorotropicity in animal tumor-bearing animals compared to free anthracycline antibiotic. The suggested conjugate implements the advantages of photodynamic therapy and chemotherapy and has great potential in cancer treatment. [ABSTRACT FROM AUTHOR]

The development of animal models of mental disorders is an important task since such models are useful for studying the neurobiological mechanisms of psychopathologies and for trial of new therapeutic drugs. One way to model pathologies of the nervous system is to impair fetal neurodevelopment through stress of the pregnant future mother, or prenatal stress (PS). The use of variable frequency ultrasound (US) in rodents is a promising method of imitating psychological stress, to which women in modern society are most often subjected. The aim of our study was to investigate the effect of PS induced by exposure to variable frequency ultrasound (US PS) throughout the gestational period on the adult rat offspring, namely, to identify features of behavioral alterations and neurochemical brain parameters that can be associated with certain mental disorders in humans, to determine the possibility of creating a new model of psychopathology. Our study included a study of some behavioral characteristics of male and female rats in the elevated plus maze, open-field test, object recognition test, social interaction test, sucrose preference test, latent inhibition test, Morris water maze, forced swimming test, acoustic startle reflex, and prepulse inhibition tests. We also determined the activity of the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems in the hippocampus and frontal cortex by HPLC-ED. Concentration of norepinephrine, dopamine, DOPAC, serotonin, and HIAA, as well as DOPAC/dopamine and HIAA/serotonin ratios were determined. A correlation analysis of behavioral and neurochemical parameters in male and female rats was performed based on the data obtained. The results of the study showed that US PS altered the behavioral phenotype of the rat offspring. US PS increased the level of anxious behavior, impaired orientation-research behavior, increased grooming activity, decreased the desire for social contacts, shifted behavioral reactions from social interaction to interaction with inanimate objects, impaired latent inhibition, and decreased the startle reflex. US PS activated the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems of the rat frontal cortex and hippocampus. A correlation between neurochemical and behavioral parameters was revealed. Our study showed that US PS leads to a certain dysfunction on behavioral and neurochemical levels in rats that is most closely associated with symptoms of schizophrenia or autism. We hypothesize that this could potentially be an indicator of face validity for a model of psychopathology based on neurodevelopmental impairment. [ABSTRACT FROM AUTHOR]

The article presents the authors’ methodology for studying technical ignition causes of cars, with the establishment of the initial fire based on the signs and nature of temperature damage. What is more, subsequent development of the main scenario of fire occurrence is introduced. Modern control system is becoming larger and more complicated day by day and probability of system outage increases with it, so people urgently need to personalize the system of failure diagnostics to conduct real-time monitoring and malfunction diagnosis in production system and take necessary steps to improve its overall reliability and maintainability. According to the presented method of fire research, determination of the ignition causes is carried out by the method of successive elimination. Based on the functional features of the researchable object (a motor vehicle), established by expertise as an initial fire, the ignition of flammable liquid because of leakage from the fuel system, thermal development of the processes accompanying the emergency operation mode of the power grid could be possible ignition causes of the car. The authors pay special attention to the fire hazard of the electric system of a vehicle, which is determined by the fact that its individual elements can serve as a source of burning in case of an emergency in some functional chain. Establishment of initial fire causes increased complexity in connection with relatively small size of cars (especially light cars), fleetness of fires in vehicles and in case of failure to take recovery measures for burning in the initial stage and its development for the entire volume of the car. The results of applying the methodology were positively evaluated by independent expert companies.

Danger is a key concept of life safety it is, constantly being transforming and taking on new forms at the present time. Information and information technologies play an important role in the modern world, which causes the need for further research in this area, including to ensure the safety of various aspects of life. In modern research, it is presented that information flows are characterized by an information, energy component. Theodore van Houen, the creator of the theory of quantum entropy logic, showed in his theory that information flows have material properties, information is a material form of matter. The development of energy information technologies or methods of nonlinear forecasting, which is based on quantum entropy logic, currently opens up unlimited possibilities for obtaining information. These technologies are widely used in foreign countries for various purposes: for medical purposes for diagnosing diseases, as well as for the study of events in time and space. These technologies are being actively developed in our country in private laboratories and institutes and are used for preventive analysis in order to prevent unfavorably developing events.

Advantages of light-optical devices (LEDs) were investigated in the article. Based on the research, special attention is paid to the prospects of development of led headlights. Complicacy of car electrical equipment leads to increase of indicated efficiency and energy storage capacity and electric generators, yield increase, decrease of labor intensity maintenance operation and reconstruction. On the other hand, innovations in scientific-technological progress in electronic engineering sphere lead to rise in reluctances, so more than 30% of these reluctances account for electrical equipment. Analysis of current requirements to automobile components of lighting devices has been carried out. LEDs as automobile light sources are gaining rapid popularity. Currently, LEDs are widely used as internal light sources (instrument illumination, indicator lamps) and external ones (tail lights, additional brake lights, daytime running lights). Since 2007, white LEDs have been used as dipped- and main-beam sources. Light sources are characterized by such parameters as voltage, light power and luminous power. Derivative of these parameters is the luminous efficiency (luminous power per unit of light power), that acts as a kind of lamp’s performance and economy indicator. This article has been made in relation to the study of auto technical expertise in Moscow and Moscow Region.

This paper presents a systematic review of empirical research on the phenomenon of discrimination on sharing economy platforms. Sharing platforms such as Airbnb, Uber, and BlaBlaCar have recently become notorious as hotbeds of digital discrimination. Difficult to detect and deter, digital discrimination describes the state when an online transaction is influenced by the race, gender, age, or other non-business characteristics of providers or consumers. Four key themes emerged from our analysis: forms of discrimination, domains (industries), outcomes and coping strategies. There is strong evidence of bias on both the demand side (consumers, guests) and the supply side (providers, hosts) and across domains such as accommodation sharing, ridesharing, skills sharing, and peer-to-peer lending. We propose a framework to organize the existing studies and guide future research and practical solutions to reduce inequality on online platforms. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases are extremely common throughout the world. However, in most cases, it is asymptomatic at the initial stage. Therefore, it is important to develop non-invasive diagnostic methods that allow identification of the IBD risks in a timely manner. It is well known that gastrointestinal microbiota secrete volatile compounds (VOCs) and their composition may change in IBD. We propose a non-invasive method to identify the dynamics of IBD development in the acute and remission stage at the level of VOCs in model of dextran sulfate sodium (DSS) with chemically induced colitis measured by headspace GC/MS (HS GC/MS). Methods: VOCs profile was identified using a headspace GC/MS (HS GC/MS). GC/MS data were processed using MetaboAnalyst 5.0 and GraphPad Prism 8.0.1 software. The disease activity index (DAI) and histological method were used to assess intestinal inflammation. The peak of intestinal inflammation activity was reached on day 7, according to the disease activity index. Histological examination data showed changes in the intestine due to different stages of inflammation. As the acute inflammation stage was reached, the metabolomic profile also underwent changes, especially at the short-fatty acids level. A higher relative amounts of acetic acid (p value < 0.025) and lower relative amounts of propanoic acid (p value < 0.0005), butanoic acid (p value < 0.005) and phenol 4-methyl- (p value = 0.053) were observed in DSS7 group on day 7 compared to the control group. In remission stage, disease activity indexes decreased, and the histological picture also improved. But metabolome changes continued despite the withdrawal of the DSS examination. A lower relative amounts of propanoic acid (p value < 0.025), butanoic acid (p value < 0.0005), pentanoic acid (p value < 0.0005), and a significant de-crease of hexanoic acid (p value < 0.0005) relative amounts were observed in the DSS14 group compared to the control group on day 14. A model of DSS-induced colitis in rats was successfully implemented for metabolomic assessment of different stages of inflammation. We demonstrated that the ratios of volatile compounds change in response to DSS before the appearance of standard signs of inflammation, determined by DAI and histological examination. Changes in the volatile metabolome persisted even after visual intestine repair and it confirms the high sensitivity of the microbiota to the damaging effects of DSS. The use of HS GC/MS may be an important addition to existing methods for assessing inflammation at early stages. [ABSTRACT FROM AUTHOR]

The effectiveness of tumor therapy, especially immunotherapy and oncolytic virotherapy, critically depends on the activity of the host immune cells. However, various local and systemic mechanisms of immunosuppression operate in cancer patients. Tumor-associated immunosuppression involves deregulation of many components of immunity, including a decrease in the number of T lymphocytes (lymphopenia), an increase in the levels or ratios of circulating and tumor-infiltrating immunosuppressive subsets [e.g., macrophages, microglia, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs)], as well as defective functions of subsets of antigen-presenting, helper and effector immune cell due to altered expression of various soluble and membrane proteins (receptors, costimulatory molecules, and cytokines). In this review, we specifically focus on data from patients with glioblastoma/glioma before standard chemoradiotherapy. We discuss glioblastoma-related immunosuppression at baseline and the prognostic significance of different subsets of circulating and tumor-infiltrating immune cells (lymphocytes, CD4+ and CD8+ T cells, Tregs, natural killer (NK) cells, neutrophils, macrophages, MDSCs, and dendritic cells), including neutrophil-to-lymphocyte ratio (NLR), focus on the immune landscape and prognostic significance of isocitrate dehydrogenase (IDH)-mutant gliomas, proneural, classical and mesenchymal molecular subtypes, and highlight the features of immune surveillance in the brain. All attempts to identify a reliable prognostic immune marker in glioblastoma tissue have led to contradictory results, which can be explained, among other things, by the unprecedented level of spatial heterogeneity of the immune infiltrate and the significant phenotypic diversity and (dys)functional states of immune subpopulations. High NLR is one of the most repeatedly confirmed independent prognostic factors for shorter overall survival in patients with glioblastoma and carcinoma, and its combination with other markers of the immune response or systemic inflammation significantly improves the accuracy of prediction; however, more prospective studies are needed to confirm the prognostic/predictive power of NLR. We call for the inclusion of dynamic assessment of NLR and other blood inflammatory markers (e.g., absolute/total lymphocyte count, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, and systemic immune response index) in all neuro-oncology studies for rigorous evaluation and comparison of their individual and combinatorial prognostic/ predictive significance and relative superiority. [ABSTRACT FROM AUTHOR]

Despite significant advances in our knowledge regarding the genetics and molecular biology of gliomas over the past two decades and hundreds of clinical trials, no effective therapeutic approach has been identified for adult patients with newly diagnosed glioblastoma, and overall survival remains dismal. Great hopes are now placed on combination immunotherapy. In clinical trials, immunotherapeutics are generally tested after standard therapy (radiation, temozolomide, and steroid dexamethasone) or concurrently with temozolomide and/or steroids. Only a minor subset of patients with progressive/recurrent glioblastoma have benefited from immunotherapies. In this review, we comprehensively discuss standard therapy-related systemic immunosuppression and lymphopenia, their prognostic significance, and the implications for immunotherapy/oncolytic virotherapy. The effectiveness of immunotherapy and oncolytic virotherapy (viro-immunotherapy) critically depends on the activity of the host immune cells. The absolute counts, ratios, and functional states of different circulating and tumor-infiltrating immune cell subsets determine the net immune fitness of patients with cancer and may have various effects on tumor progression, therapeutic response, and survival outcomes. Although different immunosuppressive mechanisms operate in patients with glioblastoma/gliomas at presentation, the immunological competence of patients may be significantly compromised by standard therapy, exacerbating tumor-related systemic immunosuppression. Standard therapy affects diverse immune cell subsets, including dendritic, CD4+, CD8+, natural killer (NK), NKT, macrophage, neutrophil, and myeloid-derived suppressor cell (MDSC). Systemic immunosuppression and lymphopenia limit the immune system's ability to target glioblastoma. Changes in the standard therapy are required to increase the success of immunotherapies. Steroid use, high neutrophil-to-lymphocyte ratio (NLR), and low post-treatment total lymphocyte count (TLC) are significant prognostic factors for shorter survival in patients with glioblastoma in retrospective studies; however, these clinically relevant variables are rarely reported and correlated with response and survival in immunotherapy studies (e.g., immune checkpoint inhibitors, vaccines, and oncolytic viruses). Our analysis should help in the development of a more rational clinical trial design and decision-making regarding the treatment to potentially improve the efficacy of immunotherapy or oncolytic virotherapy. [ABSTRACT FROM AUTHOR]

Prenatal stress (PS) affects the development and functioning of the central nervous system, but the exact mechanisms underpinning this effect have not been pinpointed yet. A promising model of PS is one based on chronic exposure of pregnant rodents to variable-frequency ultrasound (US PS), as it mimics the PS with a psychic nature that most adequately captures the human stressors in modern society. The aim of this study was to investigate the effects of US PS on the brain neurotransmitter, neuropeptide, and neurotrophic systems of newborn Wistar rats. We determined the concentration of neurotransmitters and their metabolites (serotonin, HIAA, dopamine, DOPAC, and norepinephrine), neuropeptides (α-MSH, β-endorphin, neurotensin, oxytocin, and substance P), and the neurotrophin brain-derived neurotrophic factor (BDNF) in rat brain tissues by HPLC-ED, ELISA, and multiplex ELISA. Correlation analysis and principal component analysis (PCA) were used to get a sense of the relationship between the biochemical parameters of the brain. The results demonstrated that US PS increases the concentration of serotonin (p = 0.004) and DOPAC (p = 0.04) in the hippocampus has no effect on the neurotransmitter systems of the frontal cortex, reduces the concentration of BDNF in the entirety of the brain of males (p = 0.008), and increases the neuropeptides α-MSH (p = 0.02), β-endorphin (p = 0.01), oxytocin (p = 0.008), and substance P (p < 0.001) in the entire brain. A degree of complexity in the neurotransmitter system network in the frontal cortex and network change in the hippocampus after exposure to US PS have been observed. PCA revealed a similar pattern of neurotransmitter system interactions in the frontal cortex and hippocampus in males and females after exposure to US PS. We suggest that US PS can alter neurodevelopment, which is mediated by changes in the studied neurochemical systems that thus affect the behavioral phenotype in animals. [ABSTRACT FROM AUTHOR]

The prevalence of mental disorders and how they are diagnosed represent some of the major problems in psychiatry. Modern genetic tools offer the potential to reduce the complications concerning diagnosis. However, the vast genetic diversity in the world population requires a closer investigation of any selected populations. In the current research, four polymorphisms, namely rs6265 in BDNF, rs10835210 in BDNF, rs6313 in HTR2A, and rs1800955 in DRD4, were analyzed in a case–control study of 2393 individuals (1639 patients with mental disorders (F20-F29, F30-F48) and 754 controls) from the European part of Russia using the TaqMan SNP genotyping method. Significant associations between rs6265 BDNF and rs1800955 DRD4 and mental impairments were detected when comparing the general group of patients with mental disorders (without separation into diagnoses) to the control group. Associations of rs6265 in BDNF, rs1800955 in DRD4, and rs6313 in HTR2A with schizophrenia in patients from the schizophrenia group separately compared to the control group were also found. The obtained results can extend the concept of a genetic basis for mental disorders in the Russian population and provide a basis for the future improvement in psychiatric diagnostics. [ABSTRACT FROM AUTHOR]

Lipids are a crucial component of the human brain, serving important structural and functional roles. They are involved in cell function, myelination of neuronal projections, neurotransmission, neural plasticity, energy metabolism, and neuroinflammation. Despite their significance, the role of lipids in the development of mental disorders has not been well understood. This review focused on the potential use of lipids as blood biomarkers for common mental illnesses, such as major depressive disorder, anxiety disorders, bipolar disorder, and schizophrenia. This review also discussed the impact of commonly used psychiatric medications, such as neuroleptics and antidepressants, on lipid metabolism. The obtained data suggested that lipid biomarkers could be useful for diagnosing psychiatric diseases, but further research is needed to better understand the associations between blood lipids and mental disorders and to identify specific biomarker combinations for each disease. [ABSTRACT FROM AUTHOR]

Simple Summary: To achieve the highest ethical standards in laboratory research, animal discomfort and the risk of health complications at the identification stage should be minimized. This requires the development of new bioethical yet reliable identification methods or the use of a combination of established non-invasive methods. Reliable methods for identifying rodents play an important role in ensuring the success of preclinical studies. However, animal identification remains a trivial laboratory routine that is not often discussed, despite the fact that more than 6 million rodents are used in animal studies each year. Currently, there are extensive regulations in place to ensure adequate anesthesia and to reduce animal suffering during experiments. At the same time, not enough attention is paid to the comfort of rodents during routine identification procedures, which can be painful and cause some complications. In order to achieve the highest ethical standards in laboratory research, we must minimize animal discomfort during the identification phase. In this article, we discuss traumatic methods of identification and describe several painless methods for marking in long-term experimental studies. The use of non-traumatic and non-invasive methods requires the renewal of marks as they fade and additional handling of the rodents. Laboratory personnel must be trained in stress-minimizing handling techniques to make mark renewal less stressful. [ABSTRACT FROM AUTHOR]

The polygenic risk score (PRS), together with the ɛ4 allele of the APOE gene (APOE-ɛ4), has shown high potential for Alzheimer's disease (AD) risk prediction. The aim of this study was to validate the model of polygenic risk in Russian patients with dementia. A microarray-based assay was developed to identify 21 markers of polygenic risk and ɛ alleles of the APOE gene. This case–control study included 348 dementia patients and 519 cognitively normal volunteers. Cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau protein levels were assessed in 57 dementia patients. PRS and APOE-ɛ4 were significant genetic risk factors for dementia. Adjusted for APOE-ɛ4, individuals with PRS corresponding to the fourth quartile had an increased risk of dementia compared to the first quartile (OR 1.85; p-value 0.002). The area under the curve (AUC) was 0.559 for the PRS model only, and the inclusion of APOE-ɛ4 improved the AUC to 0.604. PRS was positively correlated with tTau and pTau181 and inversely correlated with Aβ42/Aβ40 ratio. Carriers of APOE-ɛ4 had higher levels of tTau and pTau181 and lower levels of Aβ42 and Aβ42/Aβ40. The developed assay can be part of a strategy for assessing individuals for AD risk, with the purpose of assisting primary preventive interventions. [ABSTRACT FROM AUTHOR]

Many studies aim to detect the early phase of dementia. One of the major ways to achieve this is to identify corresponding biomarkers, particularly immune blood biomarkers. The objective of this study was to identify such biomarkers in patients with mild cognitive impairment (MCI) in an experiment that included cognitive training. A group of patients with MCI diagnoses over the age of 65 participated in the study (n = 136). Measurements of cognitive functions (using the Mini-Mental State Examination scale and Montreal Cognitive Assessment) and determination of 27 serum biomarkers were performed twice: on the first visit and on the second visit, one year after the cognitive training. APOE genotypes were also determined. Concentrations of EGF (F = 17; p = 0.00007), Eotaxin (F = 7.17; p = 0.008), GRO (F = 13.42; p = 0.0004), IL-8 (F = 8.16; p = 0.005), MCP-1 (F = 13.46; p = 0.0001) and MDC (F = 5.93; p = 0.016) increased after the cognitive training in MCI patients. All these parameters except IL-8 demonstrated a weak correlation with other immune parameters and were poorly represented in the principal component analysis. Differences in concentrations of IP-10, FGF-2, TGFa and VEGF in patients with MCI were associated with APOE genotype. Therefore, the study identified several immune blood biomarkers that could potentially be associated with changes in cognitive function. [ABSTRACT FROM AUTHOR]

This article presents a study on the effectiveness of using smart devices in teaching foreign languages. The research involved conducting an experiment with students (N=195), allowing for a comparison of learning outcomes between groups of those using smart devices in the process of learning a foreign language and those without them. The results demonstrate the benefits of practically using smart devices in foreign language acquisition, significantly improving the quality of instructional material presentation and its absorption by students, enriching the educational process, increasing motivation for language learning, fostering closer collaboration between teachers and students, introducing variation in homework and independent student work, and thereby creating new conditions for self-education and individual learning trajectories. The authors conclude that smart technologies eliminate the limitations inherent in traditional methods, taking teaching and learning beyond the classroom. Implementing smart technologies in students' practical activities in professionally oriented foreign language classes promotes the development of all four language skills – reading, writing, speaking, and listening, improves communicative abilities, and helps foreign language learners adapt to international testing. [ABSTRACT FROM AUTHOR]

The purpose of the study is the development of methods of identification of vehicles. These methods based on the system of identification their optical images for organization of movement and reducing the number of road accidents. There is a way of mathematical processing of signals in this method. These signals are registered with the help of optical-electronic sensors for the rapid decision-making based on computer technology. As a result, there is a confirmation of the method’s operability in real conditions. Digital signal processing lets to determine the intensity, speed and density of traffic flow automatically. At the same time, multiplicative method is a method of multidimensional analysis in a multidimensional space of numerical criteria. It divides the traffic flow by classes. This technology opens a lot of great opportunities for optimizing traffic management and helps to improve the safety of vehicles. The results of the survey are proposed for using in smart city systems.

There is a strategy of the E-95 road «Pskov» infrastructure improvement and some practical recommendations for implementation of the plan in this work. The main purpose of the article is infrastructure improvement of the section of the Federal highway, for example, some new workplaces can be created, moreover, comfort and safety increasing can improve people’s quality of life. Such objects as petrol-filling stations and service stations are essential elements for the modernization of the roadside infrastructure at this highway. It is offered to apply a typical business plan and calculate the cost of every type of such constructions taking into account the requirements of regulatory documents. There is a necessity for the construction of 2 new service stations and 9 new petrolfilling stations, in accordance with the analysis of the roadside infrastructure. Amount and nomenclature of technological equipment of stations are thoroughly worked out and calculated by the authors of the statement, moreover, writers calculate power and transportation and installation cost. The results of the survey have practical importance and they can be recommended for improving the roadside structure. The results of the survey are optimal service delivery project for the road users in case of the transport load on the section of the Federal highway.

One of the most significant factors for age-related macular degeneration (AMD) development is considered to be aging, the processes of which are closely associated with telomere shortening. The different forms, indicators of aggressiveness, and intensities of AMD can be observed in the same age group, confirming the need to find a biomarker for early diagnosis and be capable of monitoring the progression of the pathological process. Therefore, we investigated whether the relative telomere length (RTL) has any connection with the risk of development of disease and its progression. RTL was measured using RT-PCR in 166 people, including 96 patients with AMD. RTL was significantly lower in patients with AMD. Women were more likely to develop AMD than men (odds ratio (OR) = 9.53 × 106 vs. OR = 1.04 × 108, respectively). The decrease in RTL in patients reliably correlated with the progression of AMD, and the smallest RTL was observed in late-stage patients. RTL < 0.8 is a significant risk factor for disease progression. The results of our research showed that RTL may be considered as a potential biomarker and a promising predictor of disease progression in patients with early AMD. [ABSTRACT FROM AUTHOR]

The detection of specific markers of dementia and mild cognitive decline (MCI) could be the key to disease prevention and forehanded treatment. Female gender is one of the major risk factor for dementia. The aim of our study was to compare serum concentration of some factors related to lipid metabolism and the immune system in patients with MCI and dementia. The study was performed on women >65 years old: controls (n = 75), diagnosed with dementia (n = 73) and MCI (n = 142). Patients were evaluated using Mini-Mental State Examination, Clock Drawing Test and Montreal Cognitive Assessment scales in the period 2020–2021. The level of Apo A1 and HDL was significantly decreased in patients with dementia; the level of Apo A1 was also decreased in MCI. EGF, eotaxin-1, GRO-α, and IP-10 were elevated in patients with dementia compared to the controls. IL-8, MIP-1β, sCD40L, and TNF-α levels were decreased in MCI patients and increased in patients with dementia compared to the control. Serum VEGF levels were decreased in MCI and dementia patients in comparison with the control. We hypothesize that no single marker can indicate a neurodegenerative process. Future research should focus on identifying markers to determine possible diagnostic combinations that can reliably predict neurodegeneration. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death worldwide. Despite substantial progress in the understanding of tumor biology, and the appearance of new generations of targeted drugs and treatment techniques, the success achieved in this battle, with some notable exceptions, is still only moderate. Photodynamic therapy (PDT) is a successful but still underestimated therapeutic modality for treating many superficial cancers. In this paper, we focus on the extensive investigation of the monocationic chlorin photosensitizer (PS), considered here as a new photosensitizing agent for both antitumor and antimicrobial PDT. This monocationic chlorin PS (McChl) obtained from methylpheophorbide a (MPh) via a two-step procedure is well soluble in water in the physiological temperature range and forms stable complexes with passive carriers. McChl generates singlet oxygen with a good quantum yield in a lipid-like environment and binds mainly to low- and high-density lipoproteins in a vascular system. A comparison of the photodynamic activity of this agent with the activity of the well-established photosensitizer chlorin e6 (Chl e6) clearly indicates that McChl provides a much more efficient photoinactivation of malignant and microbial cells. The pilot PDT treatment of M1 sarcoma-bearing rats with this PS demonstrates its good potential for further preclinical investigations. [ABSTRACT FROM AUTHOR]

This paper presents a methodological and conceptual replication of Stieglitz and Dang-Xuan's (2013) investigation of the role of sentiment in information-sharing behavior on social media. Whereas Stieglitz and Dang-Xuan (2013) focused on Twitter communication prior to the state parliament elections in the German states Baden-Wurttemberg, Rheinland-Pfalz, and Berlin in 2011, we test their theoretical propositions in the context of the state parliament elections in Saxony-Anhalt (Germany) 2021. We confirm the positive link between sentiment in a political Twitter message and its number of retweets in a methodological replication. In a conceptual replication, where sentiment was assessed with the alternative dictionary-based tool LIWC, the sentiment was negatively associated with the retweet volume. In line with the original study, the strength of association between sentiment and retweet time lag insignificantly differs between tweets with negative sentiment and tweets with positive sentiment. We also found that the number of an author's followers was an essential determinant of sharing behavior. However, two hypotheses supported in the original study did not hold for our sample. Precisely, the total amount of sentiments was insignificantly linked to the time lag to the first retweet. Finally, in our data, we do not observe that the association between the overall sentiment and retweet quantity is stronger for tweets with negative sentiment than for those with positive sentiment. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is currently regarded as a promising method for the treatment of oncological diseases. However, it involves a number of limitations related to the specific features of the method and the specific characteristics of photosensitizer molecules, including tumor hypoxia, small depth of light penetration into the tumor tissue, and low accumulation sensitivity. These drawbacks can be overcome by combining PDT with other treatment methods, for example, chemotherapy. In this work, we were the first to obtain agents that contain bacteriopurpurinimide as a photodynamic subunit and complexes of gold(I) that implement the chemotherapy effect. To bind the latter agents, N-heterocyclic carbenes (NHC) based on histidine and histamine were obtained. We considered alternative techniques for synthesizing the target conjugates and selected an optimal one that enabled the production of preparative amounts for biological assays. In vitro studies showed that all the compounds obtained exhibited high photoinduced activity. The C-donor Au(I) complexes exhibited the maximum specific activity at longer incubation times compared to the other derivatives, both under exposure to light and without irradiation. In in vivo studies, the presence of histamine in the NHC-derivative of dipropoxy-BPI (7b) had no significant effect on its antitumor action, whereas the Au(I) metal complex of histamine NHC-derivative with BPI (8b) resulted in enhanced antitumor activity and in an increased number of remissions after photodynamic treatment. [ABSTRACT FROM AUTHOR]

The nasal drug delivery route has distinct advantages, such as high bioavailability, a rapid therapeutic effect, non-invasiveness, and ease of administration. This article presents the results of a study of the processes for obtaining chitosan aerogel particles that are promising as nasal or inhalation drug delivery systems. Obtaining chitosan aerogel particles includes the following steps: the preparation of a chitosan solution, gelation, solvent replacement, and supercritical drying. Particles of chitosan gels were obtained by spraying and homogenization. The produced chitosan aerogel particles had specific surface areas of up to 254 m2/g, pore volumes of up to 1.53 cm3/g, and porosities of up to 99%. The aerodynamic diameters of the obtained chitosan aerogel particles were calculated, the values of which ranged from 13 to 59 µm. According to the calculation results, a CS1 sample was used as a matrix for obtaining the pharmaceutical composition "chitosan aerogel—clomipramine". X-ray diffraction (XRD) analysis of the pharmaceutical composition determined the presence of clomipramine, predominantly in an amorphous form. Analysis of the high-performance liquid chromatography (HPLC) data showed that the mass loading of clomipramine was 35%. Experiments in vivo demonstrated the effectiveness of the pharmaceutical composition "chitosan aerogel—clomipramine" as carrier matrices for the targeted delivery of clomipramine by the "Nose-to-brain" mechanism of nasal administration. The maximum concentration of clomipramine in the frontal cortex and hippocampus was reached 30 min after administration. [ABSTRACT FROM AUTHOR]

Objectives: In the current study, we compared the effects of a single intranasal administration of clomipramine with effects of four neuropeptides, melatonin, oxytocin, orexin, and neuropeptide Y, to compare them in an acute stress model. Methods: The anti-stress effect was evaluated in the sucrose preference and forced swimming tests. Serum corticosterone level in rats was measured to evaluate the stress response. Results: Neuropeptide Y reduced immobilization time in the Porsolt test and decreased corticosterone levels, but increased the anhedonia. Orexin had no positive effect on animal behavior, but decreased corticosterone levels. Oxytocin decreased immobilization time, maintained anhedonia at the level of control, but did not affect corticosterone levels. Melatonin demonstrated no positive effects in any of the tests. Conclusion: The intranasal administered neuropeptide Y could be a promising compound for the treatment of stress disorders. [ABSTRACT FROM AUTHOR]

Mental disorders represent common brain diseases characterized by substantial impairments of social and cognitive functions. The neurobiological causes and mechanisms of psychopathologies still have not been definitively determined. Various forms of brain proteinopathies, which include a disruption of protein conformations and the formation of protein aggregates in brain tissues, may be a possible cause behind the development of psychiatric disorders. Proteinopathies are known to be the main cause of neurodegeneration, but much less attention is given to the role of protein impairments in psychiatric disorders' pathogenesis, such as depression and schizophrenia. For this reason, the aim of this review was to discuss the potential contribution of protein illnesses in the development of psychopathologies. The first part of the review describes the possible mechanisms of disruption to protein folding and aggregation in the cell: endoplasmic reticulum stress, dysfunction of chaperone proteins, altered mitochondrial function, and impaired autophagy processes. The second part of the review addresses the known proteins whose aggregation in brain tissue has been observed in psychiatric disorders (amyloid, tau protein, α-synuclein, DISC-1, disbindin-1, CRMP1, SNAP25, TRIOBP, NPAS3, GluA1, FABP, and ankyrin-G). [ABSTRACT FROM AUTHOR]

(1) Background: Older people suffer from cognitive decline; several risk factors contribute to greater cognitive decline. We used acquired (COVID-19 infection) and non-modifiable (presence of APOE rs429358 and rs7412 polymorphisms) factors to study the progression of subjective cognitive impairment while observing patients for one year. Cognitive training was used as a protective factor. (2) Methods: Two groups of subjects over the age of 65 participated in the study: group with subjective cognitive decline receiving cognitive training and individuals who did not complain of cognitive decline without receiving cognitive training (comparison group). On the first visit, the concentration of antibodies to COVID-19 and APOE genotype was measured. At the first and last point (1 year later) the Mini-Mental State Examination scale and the Hospital Anxiety and Depression Scale were performed. (3) Results: COVID-19 infection did not affect cognitive function. A significant role of cognitive training in improving cognitive functions was revealed. Older adults with APOE-ε4 genotype showed no positive effect of cognitive training. (4) Conclusions: Future research should focus on cognitive dysfunction after COVID-19 in long-term follow-up. Attention to the factors discussed in our article, but not limited to them, are useful for a personalized approach to maintaining the cognitive health of older adults. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an effective treatment for a number of solid malignancies. In this work, the antitumor efficacy of photodynamic therapy for murine B16 melanoma with intravenous administration of a new photosensitizer (PS) based on the chlorin e6 conjugate with a prostate-specific membrane antigen (PSMA) was studied in vivo. We have previously published the data obtained in the first part of the study: the dynamics of PS accumulation in the tumor and surrounding tissues and the antitumor efficacy of the photodynamic therapy, which was evaluated by the regression parameters and morphological characteristics of the tumors—including by the complete regression of the tumors, the absolute growth rate of the tumors among the mice with continued tumor growth, and an increase in life expectancy compared to the control. The criterion for a complete cure was the absence of signs of tumor recurrence within 90 days after therapy. The conducted studies demonstrated the high efficiency of the new photosensitizer for the photodynamic therapy of B16 melanoma. This article presents a continuation of this work, including histological studies of the zones exposed to laser irradiation on the 21st day after treatment and an assessment of the therapeutic potential of photodynamic therapy for the destruction of tumor cells. Pathological studies in the zones of photodynamic exposure revealed that the effectiveness of the PDT depended on the PS dose and the laser irradiation parameters. [ABSTRACT FROM AUTHOR]

We have previously described the LCGA-17 peptide as a novel anxiolytic and antidepressant candidate that acts through the α2δ VGCC (voltage-gated calcium channel) subunit with putative synergism with GABA-A receptors. The current study tested the potential efficacy of acute and chronic intranasal (i.n.) LCGA-17 (0.05 mg/kg and 0.5 mg/kg) in rats on predator odor-induced conditioned place aversion (POCPA), a model of post-traumatic stress disorder (PTSD), and chronic unpredictable stress (CUS) that produce a range of behavioral and physiological changes that parallel symptoms of depression in humans. CUS and LCGA-17 treatment effects were tested in the sucrose preference (SPT) social interaction (SI), female urine sniffing (FUST), novelty-suppressed feeding (NSFT), and forced swim (FST) tests. Analysis of the catecholamines content in brain structures after CUS was carried out using HPLC. The efficacy of i.n. LCGA-17 was also assessed using the Elevated plus-maze (EPM) and FST. Acute LCGA-17 administration showed anxiolytic and antidepressant effects in EPM and FST, similar to diazepam and ketamine, respectively. In the POCPA study, LCGA-17 significantly reduced place aversion, with efficacy greater than doxazosin. After CUS, chronic LCGA-17 administration reversed stress-induced alterations in numerous behavioral tests (SI, FUST, SPT, and FST), producing significant anxiolytic and antidepressant effects. Finally, LCGA-17 restored the norepinephrine levels in the hippocampus following stress. Together, these results support the further development of the LCGA-17 peptide as a rapid-acting anxiolytic and antidepressant. [ABSTRACT FROM AUTHOR]

Aim: Schizophrenia manifests differently in women and men. This disease starts at a young age, leads to disability at working age. The aim of our work was to study sex differences, association between social factors and different parameters of the clinical picture and the course of the disease. Methods: This study was performed using population of Russian patients (men: 345, women: 310). Patients were examined using DSM‐V, Bush‐Francis catatonia rating scale (BFCRS), Positive and Negative Syndrome Scale (PANSS), 4‐Items Negative Symptoms Assessment (NSA‐4) and Frontal Assessment Battery (FAB). Results: Sex differences were mainly shown through negative symptoms, which were more severe in male patients. Men were shown to experience a decrease in social functioning and earlier age of onset. A positive family history further influenced negative symptoms and age of onset. When comparing scores before and after inpatient treatment (4 weeks), sex differences were not so pronounced. Female patients and patients with high levels of education, no conflictual relationship with family and active labour activity showed a later age of onset of the prodromal events and manifestation age. The decrease in the number of social contacts correlated with lower age of disability. The association between social factors and the severity of psychotic symptoms was shown across DSM‐V, PANSS, NSA‐4 and FAB, but not for BFCRS. Social factors were associated with negative symptoms of schizophrenia, but not with positive. Conclusion: For successful treatment of patients with schizophrenia, the discussed factors must be considered and schizophrenia treatment methods should be primarily aimed at improving social functioning. [ABSTRACT FROM AUTHOR]

We investigated the associations of DRD3 rs6280, HTR1A rs6295, BDNF rs6265, SCL6A4 rs16965628, and 5HT2A rs7322347 with schizophrenia in a case–control study, and associations of these genetic variants with several clinical features. We also investigated markers of inflammatory response (C-reactive protein, IL-2, IL-6, IL-10), the activity of leukocytic elastase (LE) and α1-proteinase inhibitor (a1-PI), antibodies to S100B and myelin basic protein (MBP) in schizophrenia. Clinical symptoms were assessed on three scales: Positive and Negative Syndrome Scale, The Bush – Francis Catatonia Rating Scale and Frontal Assessment Battery. All SNPs were typed using predesigned TaqMan SNP genotyping assays. The biomarkers related to the immune system were routinely tested using ELISA kits. The association with schizophrenia was found for DRD3 rs6280 (p = 0.05) and HTR2A rs7322347 (p = 0.0013). We found differences between groups by parameters of LE and a1-PI and LE/a1-PI (p < 0.001). And IL-6 was evaluated in the schizophrenia group (p < 0.001). We showed that patients with the TT allele (BDNF rs6265) had more severe impairments in frontal lobe function. a1-PI can serve as a marker for assessing the severity of frontal lobe damage in patients with frontal dementia. We found some biological parameters reflecting the severity of frontal dysfunction in schizophrenia. [ABSTRACT FROM AUTHOR]