Application of concentration-weighted trajectory approach to identify sources with high anthropogenic mercury emissions in the East Asia.

The study evaluates the applicability of the CWT method for identifying mercury sources in a region with high anthropogenic emissions. Analysis is conducted to compare results on grids of 1 × 1°, 0.5 × 0.5°, and 0.1 × 0.1°. New data on atmospheric atomic mercury concentrations over the Sea of Japan and the East China Sea are compared, with higher resolution enabling clearer source localization. Results show increased mercury concentrations in winter, likely due to the heating season, yet they remain lower than previous values. Comparing grid resolutions indicates higher resolution can better pinpoint sources and disregard some emissions. The analysis also confirms transboundary transfer of atomic mercury from northeast China to the southeast Korean Peninsula.

Tackling APOE's structural challenges via in silico modeling in the era of neural networks: Can AlphaFold II help circumvent the problem of lacking full-length protein structure?

The APOE gene, encoding apolipoprotein E, is a predictor of longevity and age-related diseases. Despite numerous genetic studies, the data on molecular mechanisms by which apolipoprotein E affects the human phenotype remain incomplete due to the structural properties of the protein. Recently, a number of studies have used in silico drug discovery techniques based on protein-ligand docking, further highlighting the issue of lacking 3D structure of apolipoprotein E. Using molecular dynamics simulation, we found that AlphaFold II models of apolipoprotein E conformationally significantly differ both from the only available NMR structure, 2L7B, and structures obtained through circular dichroism spectroscopy: the ε4 isoform lacks the salt bridge between R61 and E255, while the ε2 and ε3 isoforms have extensive networks of interdomain interactions. Our findings challenge the benefits of using AlphaFold II for obtaining starting conformations for molecular docking.

Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein.

Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options. Methods: We assessed cognitive status in long-living adults aged 90+ (n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression). Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein. Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults.

[An effect of antipsychotic and anticholinergic treatment on cognitive function in patients with schizophrenia]. / Vliyanie antipsikhoticheskoi i antikholinergicheskoi terapii na kognitivnye funktsii u bol'nykh shizofreniei.

OBJECTIVE: To reveal the relationships between antipsychotic and anticholinergic drugs and cognitive functions in patients with schizophrenia. MATERIAL AND METHODS: The observational prospective study was conducted at the Bekhterev National Medical Center of Psychiatry and Neurology. The study involved 41 patients (22 men and 19 women) with paranoid schizophrenia, according to ICD 10 criteria, aged 30.12±8.24 years on stable antipsychotic monotherapy or in combination with anticholinergic drug (trihexiphenidyl). Cognitive functions were assessed using the «Brief Assessment of Cognitive Function in Patients with Schizophrenia¼ (BACS) scale, severity of mental state and extrapyramidal disturbances were measured using the «Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Scale for Assessment of Extrapyramidal Side Effects (SAS). All examination procedures were performed twice at weeks 2 and 8 of therapy. Patients were divided into 2 groups according to the type of antipsychotic therapy. Twelve patients received first generation antipsychotics (FGAs) (group 1), 29 patients received second generation antipsychotics (SGAs) (group 2). RESULTS: Patients receiving SGAs had a significant decrease in the overall SAS score at week 8 of therapy compared with data at week 2, and there was an improvement in cognitive function, unlike patients receiving FGAs. There were also changes on BACS tests the digit sequencing (V=51.5, p=0.007), token motor task (V=75.5, p=0.007) and Tower of London (V=52, p=0.027) only in patients of group 2. CONCLUSION: The improved tolerance to the drug, as well as cognitive measures, was shown in patients taking SGAs by week 8. Our study confirms the importance of adhering to the minimum effective dose of antipsychotic drugs for the treatment of schizophrenia to prevent cognitive impairment, and to give preference to SGAs in the choice of treatment.

Mercury geochemistry of marine sediments from the eastern Laptev Sea: The spatial distribution, levels, and contamination assessment.

Twenty-seven sediment samples from the eastern Laptev Sea were analyzed for mercury and total organic carbon as well as grain-size distribution. The average total mercury (THg) concentrations in sediments are 29 ± 14 µg kg-1. A significant correlation of THg content with total organic carbon and clay and silt fractions was shown. The 210Pb-dated sediment core was used to evaluate the contamination degree and flux of THg in sediments from the eastern Laptev Sea. The average sedimentation rate for the all dated intervals was 0.17 cm/year. The THg flux increased from 20 to 28 µg/m2/year in the period of 1892-1950 to 53-59 µg/m2/year in the modern period of 2011-2015. According to various indices, the ecological risk from THg in studied sediment was low.

Epidemiological Screening for the Risk of Mental, Behavioral and Developmental Disorders, Including Autism, in Early Childhood: Data for Russia 2017-2019.

We aimed to screen children aged 18-48 months in the general population of nine Russian regions for risk of mental, behavioral and developmental disorders (MBDDs) including autism spectrum disorders (ASD) using an original screening tool. The prevalence of the risk for MBDDs is 1307:10,000 (13.07%), the prevalence of clinically verified cases of MBDDs is 151:10,000 (1.51%), whereas the prevalence of ASD among them is 18:10,000 (0.18%). Basing on our results, the screening procedures are already integrated into the Russian primary care system since the end of 2019. Screening of the risk for MBDDs including ASD in Russia among children in the general pediatric population is a promising area of preventive medicine.

Distribution and assessment of trace metals in modern bottom sediments in the southwestern Chukchi Sea.

Sediment samples from 53 stations of the southwestern Chukchi sea were investigated to the spatial distributions and assess the state of trace metals contamination using ecological indices. The mean concentrations (mg kg-1) in sediments were: Cr (70.5), Ni (41.0), Cu (16.5), Zn (82.7), As (15.90), Cd (0.27), Pb (15.96), Hg (32.0 µg kg-1). The spatial distribution pattern of trace metals was similar with maximum values in the northern of the Chukchi Sea in the outer shelf sediments, while the high values of Cd were noted at stations located in the southern part of the sea where a strong influence of the Pacific waters penetrating through the Bering Strait. The ecological indices indicated no signs of anthropogenic pollution in the study sediments of the Chukchi Sea. Received data are of value for detecting and tracking future chemical changes in the sediments of the Chukchi sea, particularly in light of environmental changes.

CRAC (Clinical Relevance of Alterations in Cancer): a Knowledge Base for the Selection of Molecularly Matched Therapy for Solid Tumors.

Multigene testing using NGS (next-generation sequencing) provides a large amount of information and can detect multiple molecular alterations. Subsequent clinical interpretation is a time-consuming process necessary to select a treatment strategy. Existing databases often contain inconsistent information and are not regularly updated. The use of ESCAT levels of evidence requires a deep understanding of the nature of alterations and does not answer the question of which therapy option to select when multiple biomarkers with the same level of evidence are detected. To address these issues, we created the Clinical Relevance of Alterations in Cancer (CRAC) database on the relevance of detected alterations in specific genes, which are often analyzed as part of NGS panels. The team of oncologists and biologists assigned a CRAC score from 1 to 10 to each biomarker (a type of genomic alteration characteristic of specific genes) for 15 malignancies; an average score was entered into the database. CRAC scores are a numerical reflection of the following factors: therapy availability and the prospects of drug treatment with experimental drugs for patients with a particular type of tumor. A total of 134 genes and 15 of the most common tumor types have been selected for CRAC. The biomarker-nosology associations with CRAC scores in the range of 1-3 are the most frequent (n=2719 out of 3495; 77.8%), the least frequent ones (n=52 out of 3495; 1.5%) are with the highest CRAC scores 9 and 10. To estimate the practical effectiveness of the CRAC database, 208 reports on comprehensive molecular profiling were retrospectively analyzed; the applicability of CRAC was compared with the ESCAT level of evidence system. The highest CRAC scores corresponded to the ESCAT maximum levels of evidence: the range of scores 8-10 corresponded to evidence levels I and II. No biomarker within the same level of evidence was represented by the same CRAC score; the largest range of CRAC scores was observed for biomarkers of levels evidence IIIA and IV - from 2 to 10 and from 1 to 9, respectively. The use of CRAC scores allowed to identify additional 95 alterations with CRAC scores of 1-5 in the studied patients. The developed database is available at: https://crac.oncoatlas.ru/.

[The relationship between visual dysfunction and cognitive deficit in schizophrenia]. / Disfunktsiya zritel'nogo analizatora pri shizofrenii i ee svyaz' s kognitivnym defitsitom.

OBJECTIVE: To investigate whether visual processing abnormalities are the result of visual dysfunction involving cognitive impairment or independent abnormalities and to identify the relationship of visual impairments with cognitive functions and severity of psychopathological symptoms. MATERIAL AND METHODS: We compared results of visual size perception and actions on objects (motor assessment) in patients with schizophrenia (n=37), including patients with non-resistant schizophrenia (n=19) and healthy individuals (n=20). Cognitive impairments were assessed with BACS. Severity of schizophrenia symptoms was assessed with PANSS. RESULTS: The error in the visual size perception test was smaller in healthy controls compared with non-resistant patients (p<0.03). There are no significant differences between non-resistant patients and other groups. Also, there are no significant differences in motor assessment between healthy controls and patients with schizophrenia. In the visual size perception test, the amount of error correlates with cognitive impairments (r= -0.84, p<0.001), and the severity of psychotic symptoms on PANSS (r=0.55, p<0.05). CONCLUSION: Changes in visual threshold in patients with schizophrenia are correlated with cognitive dysfunction and reflect dysfunction in the parvocellular system.

[Contemporary methods of non-drug therapy for depression]. / Sovremennye metody nelekarstvennoi terapii depressii.

The review presents information on the most effective current non-drug methods of treatment of depression used in practice. A review of publications in PubMed and PsycINFO and Cochrane Library over the past 10 years was conducted. Non-drug biological therapies demonstrate high efficacy in the reduction of depressive symptoms in patients with recurrent depressive disorder. The use of non-drug therapy does not preclude the continuation of pharmacological therapy. In order to choose an optimal method of treatment, the psychophysical state of a patient, severity of depressive symptoms, response to drug therapy, and possibility of prescribing pharmacological therapy should be taken into account, and the principles of evidence-based medicine should be taken into consideration when making a decision.

[Models of clinical and social management of patients with autism spectrum disorders]. / Kliniko-sotsial'nye modeli vedeniya patsientov s rasstroistvami autisticheskogo spektra.

OBJECTIVE: To develop clinical and social models and management routes for patients with autism spectrum disorders (ASD). MATERIAL AND METHODS: A clinical follow-up study was performed for 254 patients, aged 4-17 years (average age 7.3 years), who represented the main forms of ASD. Psychopathological, clinical-follow-up, psychological and statistical methods were used. RESULTS AND CONCLUSION: Five management models for patients with different forms of ASD are described; differentiation of routes for interagency monitoring of patients is proposed. The effectiveness of the integrated use of drug and non-drug therapeutic approaches for the management of patients with ASD in the clinical-age aspect is shown. Timely diagnosis of ASD makes it possible to develop differentiated routes of patient management within the framework of interdepartmental interaction and achieve positive results in the clinical and age aspect.

Immunomorphological Changes in Neuronal and Non-Neuronal Structures in the Rat Intestine in a Toxin-Induced Model of Parkinsonism.

The damage to the enteric nervous system structures and the localization of total and phosphorylated α-synuclein, the main pathomorphological marker of parkinsonism, were studied by immunomorphological methods on small intestine wholemounts from rats with parkinsonism induced by systemic administration of paraquat. Reduced density of neurons in the myenteric ganglia and degenerative changes with accumulation of phosphorylated α-synuclein in sympathetic afferents to the small intestine were revealed. Phosphorylated α-synuclein was also found in non-neuronal cells located outside the ganglia. The revealed changes presumably reflect the initial stage of spreading of the pathological process during the development of Parkinson's disease.

[Screening of the risk of mental and developmental disorders in children of early age in the Russian population (2017-2019)]. / Skrining riska vozniknoveniya narushenii psikhicheskogo razvitiya u detei rannego vozrasta (dannye po 9 regionam Rossii v 2017­2019 gg.).

OBJECTIVE: Screening of children 18-48 months of age at risk of mental and developmental disorders in the general population. MATERIAL AND METHODS: The survey was conducted by a continuous epidemiological method in primary health care institutions in the nine largest regions of Russia. For the period 2017-2019, 595 691 parents of children, aged 18-48 months, were surveyed. RESULTS AND CONCLUSION: The prevalence risk rate for mental and developmental disorders was determined as 1.307:10 000. The prevalence rate for mental and behavioural disorders (ICD-10) was 151:10 000. The analysis of the structure of mental and behavioural disorders was carried out. An increase in cases of pervasive developmental disorders (item F84) was detected - autism spectrum disorders (ASD) with an increase in the age of children. The prevalence of ASD under the age of 48 months was found to be 18:10 000, compared with 2015-2016 - 5:10 000 under the age of 24 months.

[Morphochemical changes in human striatum during aging.]

Age-related neurodegenerative diseases, including Parkinson's disease, are characterized by a number of pathomorphological signs, such as neuron loss in certain brain structures, gliosis, iron accumulation. However, the literature indicates that these signs can also be observed during normal (physiological) aging. The aim of our work was to evaluate qualitative and quantitative morphochemical changes in neurons and neuroglia, and also to localize iron (II) compounds in the human striatum during physiological aging. In the old age group, compared with the mature one, the size of the neuron bodies was significantly smaller, the neuronal distribution density did not differ, but the distribution density of both the overall glia and astrocytes was significantly higher. In the old age group, the accumulation of iron (II) compounds were seen along the walls of the vessels, as well as inside the cytoplasm of neurons and glial cells. We conclude that the results obtained may serve as a basis for the comparative study of the neurodegenerative process and for the earlier and more accurate diagnosis of neurodegenerative diseases associated with aging, including Parkinson's disease.

[Electroconvulsive therapy in treatment of resistant schizophrenia: biological markers of efficacy and safety]. / Primenenie élektrosudorozhnoi terapii pri rezistentnoi shizofrenii: biologicheskie pokazateli éffektivnosti i bezopasnosti.

AIM: To evaluate clinical and biological efficacy and safety of electroconvulsive therapy (ECT) in patients with treatment-resistant paranoid schizophrenia. MATERIAL AND METHODS: Determination of CNS specific biological markers (BDNF, NSE, S100B), together with markers of inflammation and CNS alteration (IL-2, CPK, CPK-MB), and clinical evaluation were performed in two groups of patients: the ECT + antipsychotic treatment group (n=66) and the antipsychotic treatment group (n=32). RESULTS AND CONCLUSION: In the ECT + antipsychotic treatment group, the more pronounced reduction of psychotic symptoms has been revealed compared with subjects on antipsychotic treatment as monotherapy. Patients receiving ECT showed no increase in plasma levels of inflammation and CNS alteration biomarkers (NSE, S100B, CPK, CPK-MB, IL-2). The plasma level of BDNF, capable to characterize both the efficacy and safety of antipsychotic therapy, had a more pronounced upward trend in subjects with combined electroconvulsive and antipsychotic treatment, which may indicate good tolerability and high effectiveness of ECT.

Brain Proteome of Drosophila melanogaster Is Enriched with Nuclear Proteins.

The brain proteome of Drosophila melanogaster was characterized by liquid chromatography/high-resolution mass spectrometry and compared to the earlier characterized Drosophila whole-body and head proteomes. Raw data for all the proteomes were processed in a similar manner. Approximately 4000 proteins were identified in the brain proteome that represented, as expected, the subsets of the head and body proteomes. However, after thorough data curation, we reliably identified 24 proteins unique for the brain proteome; 13 of them have never been detected before at the protein level. Fourteen of 24 identified proteins have been annotated as nuclear proteins. Comparison of three used datasets by label-free quantitation showed statistically significant enrichment of the brain proteome with nuclear proteins. Therefore, we recommend the use of isolated brain preparations in the studies of Drosophila nuclear proteins.

[The epidemiologic study of the risk of autism spectrum disorders in children of 16-24 months in Russia, 2015-2016]. / Épidemiologiia riska vozniknoveniia rasstroistv autisticheskogo spektra u detei 16-24 mesiatsev zhizni (dannye po Rossii za 2015-2016 gg.).

AIM: To screen infants of the general population for the risk of autism spectrum disorders (ASD). MATERIAL AND METHODS: The survey was conducted by a total epidemiological method in primary health care facilities in the three largest regions in Russia (Volgograd, Novosibirsk, Chelyabinsk regions). For the period 2015-2016, 74191 parents of children aged 16-24 months were questioned. RESULTS AND CONCLUSION: The prevalence of risk of ASD (a condition of a pre-illness) was 103.5 cases per 1000 of children aged 16-24 months. Some of the children at ASD risk had a preventive consultation with a psychiatrist, 36 children (0.5 per 1000 peers) had severe clinical disorders classified as F84 - 'Pervasive developmental disorders' of ICD-10 (F84.0; F84.1; F84.8). From the perspective of predicative and preventive medicine, children at risk require complex measures to prevent the onset of a mental disorder or worsening of the mental state of the child.

Identification of Single Amino Acid Substitutions in Proteogenomics.

An important aim of proteogenomics, which combines data of high throughput nucleic acid and protein analysis, is to reliably identify single amino acid substitutions representing a main type of coding genome variants. Exact knowledge of deviations from the consensus genome can be utilized in several biomedical fields, such as studies of expression of mutated proteins in cancer, deciphering heterozygosity mechanisms, identification of neoantigens in anticancer vaccine production, search for RNA editing sites at the level of the proteome, etc. Generation of this new knowledge requires processing of large data arrays from high-resolution mass spectrometry, where information on single-point protein variation is often difficult to extract. Accordingly, a significant problem in proteogenomic analysis is the presence of high levels of false positive results for variant-containing peptides in the produced results. Here we review recently suggested approaches of high quality proteomics data processing that may provide more reliable identification of single amino acid substitutions, especially contrary to residue modifications occurring in vitro and in vivo. Optimized methods for assessment of false discovery rate save instrumental and computational time spent for validation of interesting findings of amino acid polymorphism by orthogonal methods.

[Autism spectrum disorders in children and adults: the experience of reserches from different countries]. / Rasstroistva autisticheskogo spektra u detei i vzroslykh: podkhody k probleme v raznykh stran.

Current studies on the development autism spectrum disorders (ASD) at different ages are reviewed. The review highlights the increasing interest to this problem and converging positions of researchers from different countries, encouraged by the development of international and other classifications of mental diseases, on the terminology, classification and prevalence of ASD in children. An important feature of the present stage is to draw attention to an understudied problem of ASD in adults, including elderly, and provision of medical and social care to these patients.

Immunomorphological Changes in the Olfactory Bulbs of Rats after Intranasal Administration of Rotenone.

Changes in the structure of the olfactory bulbs after long-term intranasal administration of pesticide rotenone, a classical inductor of parkinsonism, to rats were studied by the methods of immunomorphology. In rats intranasally receiving rotenone in a dose of 2.5 mg/kg every other day over 2 weeks, a decrease in the density of dopaminergic neurons and the area of astrocyte processes in the olfactory bulbs, activation of microglia in the glomerular layer, and enhanced α-synuclein phosphorylation and its accumulation in the bodies of mitral layer neurons were observed. The observed changes agree with the hypothesis on pathological α-synuclein transport via the olfactory route in Parkinson's disease and confirm relevance of the rotenone model of Parkinson's disease for studies of the pathological accumulation of α-synuclein.