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Subject. Anatomical and functional disorders of the mucogingival complex. Objectives. To evaluate microcirculatory, clinical and radiological changes in periodontal tissues in various variants of mucogingival complex disorders. Methodology. The study was conducted at the Department of Therapeutic Dentistry of ASMU. In the course of the study, 80 patients (49 women, 31 men) aged 18 to 35 years were examined with a ratio of dentition close to orthognathic bite in the presence of maximum occlusion. Three groups were formed depending on the anatomical and functional state of the mucogingival complex. In the clinical part of the study, an objective assessment of the condition of periodontal tissues was carried out on the basis of a dental examination with a comprehensive analysis of the periodontal status. The X-ray examination included the analysis and description of cone-beam computed tomograms for patients of clinical groups. To assess microcirculation in periodontal tissues, the method of ultrasonic Dopplerography with functional probe breakdown was used. Results. In the studied groups, the level of oral hygiene was characterized as good, and the indicators of hygiene indices did not differ significantly, periodontal indices indicated the absence or minimal degree of inflammation in periodontal tissues. Carrying out a functional tension test made it possible to divide patients into subgroups according to the type of reaction: normal, compensated, subcompensated, decompensated. According to the results of the study of CBCT in the comparison group, pathological changes in the bone tissue of the alveolar process of the studied areas were not recorded, in patients of the first clinical group, in most cases (80.2%), pathological changes in the bone tissue of the alveolar process were not observed, in the rest (19.8%), a low level of alveolar bone was noted. In patients of the second clinical group, the phenomena of osteoporosis and an increase in the distance from the dental enamel-cement border to the edge of the outer cortical plate were recorded. Conclusions. X-ray changes in bone tissue most often corresponded to the already existing clinical symptoms of periodontal tissue damage against the background of mucogingival pathology. The predictors of prenosological diagnosis in anatomical and functional disorders of the mucogingival complex were changes in microcirculation indicators.

Intellectual development disorder (IDD) is characterized by a general deficit in intellectual and adaptive functioning. In recent years, there has been a growing interest in studying the genetic structure of IDD. Of particular difficulty are patients with non-specific IDD, for whom it is impossible to establish a clinical diagnosis without complex genetic diagnostics. We examined 198 patients with non-specific IDD from 171 families using whole-exome sequencing and chromosome microarray analysis. Hereditary forms of IDD account for at least 35.7% of non-specific IDD, of which 26.9% are monogenic forms. Variants in the genes associated with the BAF (SWI/SNF) complex were the most frequently identified. We were unable to identify phenotypic features that would allow differential diagnosis of monogenic and microstructural chromosomal rearrangements in non-specific IDD at the stage of clinical examination, but due to its higher efficiency, exome sequencing should be the diagnostic method of the highest priority study after the standard examination of patients with NIDD in Russia.

Purpose: To elucidate the novel molecular cause in families with a new autosomal recessive neurodevelopmental disorder. Methods: A combination of exome sequencing and gene matching tools was used to identify pathogenic variants in 17 individuals. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and subcellular localization studies were used to characterize gene expression profile and localization. Results: Biallelic variants in the TMEM222 gene were identified in 17 individuals from nine unrelated families, presenting with intellectual disability and variable other features, such as aggressive behavior, shy character, body tremors, decreased muscle mass in the lower extremities, and mild hypotonia. We found relatively high TMEM222 expression levels in the human brain, especially in the parietal and occipital cortex. Additionally, subcellular localization analysis in human neurons derived from induced pluripotent stem cells (iPSCs) revealed that TMEM222 localizes to early endosomes in the synapses of mature iPSC-derived neurons. Conclusion: Our findings support a role for TMEM222 in brain development and function and adds variants in the gene TMEM222 as a novel underlying cause of an autosomal recessive neurodevelopmental disorder.

International audience; The ALF transcription factor paralogs, AFF1, AFF2, AFF3, and AFF4, are components of the transcriptional super elongation complex that regulates expression of genes involved in neurogenesis and development. We describe an autosomal dominant disorder associated with de novo missense variants in the degron of AFF3, a nine amino acid sequence important for its binding to ubiquitin ligase, or with de novo deletions of this region. The sixteen affected individuals we identified, along with two previously reported individuals, present with a recognizable pattern of anomalies, which we named KINSSHIP syndrome (KI for horseshoe kidney, NS for Nievergelt/Savarirayan type of mesomelic dysplasia, S for seizures, H for hypertrichosis, I for intellectual disability, and P for pulmonary involvement), partially overlapping the AFF4-associated CHOPS syndrome. Whereas homozygous Aff3 knockout mice display skeletal anomalies, kidney defects, brain malformations, and neurological anomalies, knockin animals modeling one of the microdeletions and the most common of the missense variants identified in affected individuals presented with lower mesomelic limb deformities like KINSSHIP-affected individuals and early lethality, respectively. Overexpression of AFF3 in zebrafish resulted in body axis anomalies, providing some support for the pathological effect of increased amount of AFF3. The only partial phenotypic overlap of AFF3-and AFF4-associated syndromes and the previously published transcriptome analyses of ALF transcription factors suggest that these factors are not redundant and each contributes uniquely to proper development.

The system of the research institute’s library information resources is described. The electronic resources generated both by the institute itself and other producers are characterized as the most dynamic system component. Collection development profile relevant to researchers’ current information needs and designed to form uniform document and information environment of the Institute is suggested.

The ALF transcription factor paralogs,AFF1, AFF2, AFF3andAFF4, are components of the transcriptional super elongation complex that regulates expression of genes involved in neurogenesis and development. We describe a new autosomal dominant disorder associated withde novomissense variants in the degron of AFF3, a nine amino acid sequence important for its degradation. Consistent with a causative role ofAFF3variants, the mutated AFF3 proteins show reduced clearance. Ten affected individuals were identified, and present with a recognizable pattern of anomalies, which we named KINSSHIP syndrome (KI for horseshoeKIdney, NS forNievergelt/Savarirayan type of mesomelic dysplasia, S forSeizures, H forHypertrichosis, I forIntellectual disability and P forPulmonary involvement), partially overlapping theAFF4associated CHOPS syndrome. An eleventh individual with a microdeletion encompassing only the transactivation domain and degron motif ofAFF3exhibited overlapping clinical features. A zebrafish overexpression model that shows body axis anomalies provides further support for the pathological effect of increased amount of AFF3 protein.Whereas homozygousAff3knockout mice display skeletal anomalies, kidney defects, brain malformation and neurological anomalies, knock-in animals modeling the microdeletion and the missense variants identified in affected individuals presented with lower mesomelic limb deformities and early lethality, respectively.Transcriptome analyses as well as the partial phenotypic overlap of syndromes associated withAFF3andAFF4variants suggest that ALF transcription factors are not redundant in contrast to what was previously suggested

Gene mutations occur with high frequency in children with mental retardation. Standard diagnostic methods, such as TMS, Sanger's sequencing of individual genes, MLPA analysis of deletions, and investigation of methylation status in Martin-Bell syndrome are not informative in the majority of cases that hampered further diagnostic efforts. Massive parallel sequencing (MPS) allowed physicians to continue diagnostic search in previously undiagnosed cases and to find molecular causes of disease. MPS permits to discover a large number of new genes and understand the pathogenesis of mental retardation and brain development more deeply. It became possible to perform prenatal and pre-implantation diagnostics. However, big data generate big problems with their interpretation the genetic counselor faces with. This review reflects the advantages and disadvantages of MPS. Different variants of MPS, including gene panels, whole exome and whole genome sequencing as well as sequencing of trios, are described. In addition, the authors discuss the difficulties of interpretation of the results and recommendations for obtaining the most accurate results.Генные мутации с высокой частотой встречаются у детей с умственной отсталостью (УО). Стандартные методы диагностики, такие как секвенирование по Сэнгеру отдельных генов или поиск делеций методом MLPA, ТМС и определение метилирования при синдроме Мартина-Белл, в большинстве случаев оказываются неэффективными, и врачи были вынуждены останавливаться в диагностическом поиске. В настоящее время для указанной цели применяется метод массового параллельного секвенирования (МПС). Благодаря ему открывается огромное количество новых генов, что позволяет глубже понимать патогенез УО и механизмы развития мозга. Открывается возможность пренатальной и предимплантационной диагностики. Однако в связи с большим объемом получаемых данных возникает ряд сложностей, с которыми сталкивается врач-генетик. В данном обзоре отражены преимущества и недостатки МПС. Описаны разновидности МПС, включающие секвенирование панели генов, полноэкзомное и полногеномное секвенирование, а также секвенирование 'трио' родители - пробанд. Кроме того, отражены сложности интерпретации получаемых результатов и рекомендации для получения максимально точных результатов.

The article deals with the Chinese global strategy the Silk Road Economic Belt and the possibility of involving Ukraine in it. The authors pay special attention to the implementation of the China-Ukraine-EU High-Speed Railway Project within the framework of the Silk Road Strategy. The geopolitical position of Ukraine allows the authors to state that Ukraine may represent a special interest for the Celestial Empire as a logistical hub and a kind of “window” to Europe, as the central axis of the international transport corridors passes through Ukraine. The authors analyze the direct economic, as well as external economic and social effects of the construction of High-Speed Railways in Ukraine.

Depression is the most common form of mental disability in the world. Depressive episodes may be precipitated by severe acute stressful events or by mild chronic stressors. Studies on the mechanisms of depression require both appropriate experimental models (most of them based on the exposure of animals to chronic stressors), and appropriate tests for assessment of depressive states. In this study male Wistar rats were exposed to two different chronic stress paradigms: an eight-week chronic unpredictable mild stress or a two-week combined chronic stress. The behavioral effects of stress were evaluated using sucrose preference, forced swim and open field tests. After the exposure to chronic unpredictable mild stress, anhedonia was developed, activity in the open field increased, while no changes in the duration of passive floating could be detected. After chronic combined stress, anhedonia was also evident, whereas behavior in the open field and forced swim test did not change. The levels of corticosterone in the blood and brain structures involved in stress-response did not differ from control in both experiments. The absence of significant changes in corticosterone levels and passive floating may be indicative of the adaptation of animals to chronic stress. Anhedonia appears to be a more sensitive indicator of depressive-like behavioral effects of chronic stress as compared to behavior in the forced swim or open field tests.