Quantification of attenuation and speckle features from endoscopic OCT images for the diagnosis of human brain glioma.

Application of optical coherence tomography (OCT) in neurosurgery mostly includes the discrimination between intact and malignant tissues aimed at the detection of brain tumor margins. For particular tissue types, the existing approaches demonstrate low performance, which stimulates the further research for their improvement. The analysis of speckle patterns of brain OCT images is proposed to be taken into account for the discrimination between human brain glioma tissue and intact cortex and white matter. The speckle properties provide additional information of tissue structure, which could help to increase the efficiency of tissue differentiation. The wavelet analysis of OCT speckle patterns was applied to extract the power of local brightness fluctuations in speckle and its standard deviation. The speckle properties are analysed together with attenuation ones using a set of ex vivo brain tissue samples, including glioma of different grades. Various combinations of these features are considered to perform linear discriminant analysis for tissue differentiation. The results reveal that it is reasonable to include the local brightness fluctuations at first two wavelet decomposition levels in the analysis of OCT brain images aimed at neurosurgical diagnosis.

Quantitative polarization-sensitive super-resolution solid immersion microscopy reveals biological tissues' birefringence in the terahertz range.

Terahertz (THz) technology offers a variety of applications in label-free medical diagnosis and therapy, majority of which rely on the effective medium theory that assumes biological tissues to be optically isotropic and homogeneous at the scale posed by the THz wavelengths. Meanwhile, most recent research discovered mesoscale ([Formula: see text]) heterogeneities of tissues; [Formula: see text] is a wavelength. This posed a problem of studying the related scattering and polarization effects of THz-wave-tissue interactions, while there is still a lack of appropriate tools and instruments for such studies. To address this challenge, in this paper, quantitative polarization-sensitive reflection-mode THz solid immersion (SI) microscope is developed, that comprises a silicon hemisphere-based SI lens, metal-wire-grid polarizer and analyzer, a continuous-wave 0.6 THz ([Formula: see text] µm) backward-wave oscillator (BWO), and a Golay detector. It makes possible the study of local polarization-dependent THz response of mesoscale tissue elements with the resolution as high as [Formula: see text]. It is applied to retrieve the refractive index distributions over the freshly-excised rat brain for the two orthogonal linear polarizations of the THz beam, aimed at uncovering the THz birefringence (structural optical anisotropy) of tissues. The most pronounced birefringence is observed for the Corpus callosum, formed by well-oriented and densely-packed axons bridging the cerebral hemispheres. The observed results are verified by the THz pulsed spectroscopy of the porcine brain, which confirms higher refractive index of the Corpus callosum when the THz beam is polarized along axons. Our findings highlight a potential of the quantitative polarization THz microscopy in biophotonics and medical imaging.

Сell clusters isolation in glioblastomas and their functional and molecular characterization using new morphometric approaches.

BACKGROUND: Digital pathology has come a long way in terms of creating tools to improve existing diagnostic approaches. However, several pathology fields, such as neuropathology, are still characterized by low coverage from machine learning tools and neural network analysis, which may be due to the complexity of the internal cellular and molecular structure of the corresponding neoplasms, including glioblastomas. METHOD: In the framework of this study, using advanced proprietary tools for obtaining images of histological slides and their deep morphometric analysis, we studied samples of 198 patients with glioblastoma with the selection of morphometric cell clusters. Also, cells of each cluster were isolated, and their proliferative, migratory, invasive activity, survival ability, aerobic glycolysis activity, and chemo- and radioresistance were studied. RESULTS: Four morphometric clusters were identified, including small-cell cluster, paracirculonuclear cluster, hypochromic cluster, and macronuclear cluster, which significantly differed in morphometric parameters and functional parameters. Hypochromic cluster cells demonstrated the highest proliferation activity; macronuclear cluster was the most active glucose consumer; paracirculonuclear cluster had the most prominent migratory and invasive activity and hypoxia resistance; small-cell cluster demonstrated predominantly average values of all parameters. Moreover, additional analysis revealed the presence of a separate subcluster of stem cell elements that correspond in their molecular properties to glioma stem cells and are present in all four clusters. It also turned out that several key molecular parameters of glioblastoma, such as mutational modifications in the EGFR, PDGFRA, and NF1 genes, along with the molecular GBM subtype, are significantly correlated with the identified cell clusters. CONCLUSIONS: Thus, the results represent an up-and-coming innovation in the practical field of digital pathology and fundamental questions of glioma carcinogenesis.

[Detection of SARS-CoV-2 RNA in the mucosa of the appendices of children with COVID-19]. / Vyyavlenie RNK SARS-CoV-2 v slizistoi obolochke cherveobraznogo otrostka u detei s COVID-19.

Background. The novel coronavirus infection (COVID-19) often manifests in children as diarrhea, vomiting, abdominal pain, and some children develop acute appendicitis. To elucidate the role of SARS-CoV-2 in the development of acute appendicitis, a more detailed study of the presence of its genetic material in the tissue of the appendix. OBJECTIVE: Determination of SARS-CoV-2 RNA in appendices of children with COVID-19 by fluorescence in situ hybridization (FISH). MATERIAL AND METHODS: A retrospective analysis of case histories and morphological analysis using FISH of appendices of pediatric patients with established clinical diagnosis of acute appendicitis and confirmed infection with SARS-CoV-2 was performed. The material was divided into 3 groups: 1st -appendices obtained during appendectomy in children with established clinical diagnosis of «coronavirus infection¼ (COVID-19, PCR+) (n=42; mean age 10.8 years); 2nd - appendices of children (n=55; mean age 9.7 years) with acute appendicitis obtained before the onset of the COVID-19 pandemic; 3rd (control) group (n=38; mean age 10.3 years) - autopsy material of the appendices (intact). RESULTS: In all samples of the appendices of the 1st group, a positive SARS-CoV-2 viral RNA signal was noted in the cytoplasm of most epithelial cells and single immunocompetent cells. The signal intensity remained the same in all slides, regardless of age. In all samples obtained from patients without COVID-19 (groups 2 and 3), confocal microscopy did not reveal a signal, which indicates successful adaptation of the FISH method in this study and excludes the false positive results. CONCLUSION: In the epithelium of the appendices of children of different age with COVID-19, the FISH method revealed SARS-CoV-2 RNA, which does not exclude the association between viral invasion and the development of acute appendicitis.

[NMDA receptors expression activity in anaplastic astrocytomas]. / Aktivnost' ekspressii NMDA-retseptorov glutamata v anaplasticheskikh astrotsitomakh.

OBJECTIVE: To study the relationship of NMDA receptors expression activity with proliferative activity and genetic properties of anaplastic astrocytomas, as well as the survival of patients with this disease. MATERIAL AND METHODS: To solve this problem, we compared the expression activity of the least studied NMDA receptors in the context under consideration, detected using immunofluorescent studies and polymerase chain reaction, with the results of histological and molecular studies, the proliferative activity of neoplasms, and the survival of patients. RESULTS: The expression activity of NMDA receptors is higher in astrocytomas, grade 3, which do not carry mutations in IDH1 and IDH2 genes. In addition, the activity of NMDA receptors expression directly correlates with proliferative activity in the tumors. The activity of NMDA receptor expression has a significant impact on the prognosis of disease-free survival. CONCLUSION: We have shown for the first time the significant role of NMDA receptors in the progression of diffuse astrocytomas, which can become the basis for creating new therapeutic and diagnostic tools.

DNA methylation inhibition participates in the anterograde amnesia key mechanism through the suppression of the transcription of genes involved in memory formation in grape snails.

The study of the amnesia mechanisms is of both theoretical and practical importance. The mechanisms of anterograde amnesia are the least studied, due to the lack of an experimental model that allows studying this amnesia type molecular and cellular mechanisms. Previously, we found that conditional food aversion memory reconsolidation impairment in snails by NMDA glutamate receptor antagonists led to the amnesia induction, in the late stages of which (>10 days) repeated training did not cause long-term memory formation. In the same animals, long-term memory aversion to a new food type was formed. We characterized this amnesia as specific anterograde amnesia. In the present work we studied the role of epigenetic DNA methylation processes as well as protein and mRNA synthesis in the mechanisms of anterograde amnesia and memory recovery. DNMT methyltransferase inhibitors (iDNMT: zebularine, RG108 (N-Phthalyl-1-tryptophan), and 5-AZA (5-Aza-2'-deoxycytidine)) were used to alter DNA methylation. It was found that in amnesic animals the iDNMT administration before or after shortened repeated training led to the rapid long-term conditional food aversion formation (Ebbinghaus saving effect). This result suggests that amnestic animals retain a latent memory, which is the basis for accelerated memory formation during repeated training. Protein synthesis inhibitors administration (cycloheximide) before or immediately after repeated training or administration of RNA synthesis inhibitor (actinomycin D) after repeated training prevented memory formation under iDNMT action. The earlier protein synthesis inhibitor effect suggests that the proteins required for memory formation are translated from the pre-existing, translationally repressed mRNAs. Thus, we have shown for the first time that the anterograde amnesia key mechanism is DNMT-dependent suppression of the transcription of genes involved in memory mechanisms. Inhibition of DNMT during repeated training reversed these genes expression blockade, opening access to them by transcription factors synthesized during training from the pre-existing mRNAs.

Comparative Study of the Effect of a DNA Methyltransferase Inhibitor and a Histone Deacetylase Inhibitor on Memory Formation Processes in Anterograde Amnesia.

The participation of DNA methylation and histone acetylation in the mechanisms of anterograde amnesia and memory recovery was studied on grape snails trained in conditioned food aversion. Anterograde amnesia developed 10 days after memory reconsolidation impairment with an NMDA glutamate receptor antagonist and was characterized by long-term memory formation impairment upon repeated training. DNA methyltransferase inhibitor injections to snails 1 h before repeated training, as well as 15 min or 4 h after repeated training, caused rapid formation of memory that persisted for at least 10 days. Injections of histone deacetylase inhibitor before repeated training also induced the formation of a stable long-term memory. However, administration of histone deacetylase inhibitor 15 min after repeated training initiated a temporary memory recovery. Injections of the inhibitor 4 h after repeated training were ineffective. These results indicate that histone-dependent chromatin remodeling and DNA methylation are selectively involved in the mechanisms of anterograde amnesia and memory recovery.

The Role of DNA Methylation and Activity of Neurotransmitter Receptors in the Mechanisms of Specific Anterograde Amnesia and Memory Recovery.

Impairment of reconsolidation of conditioned food aversion memory led to the development of a specific anterograde amnesia: repeated training of amnestic snails did not induce long-term memory formation. DNA demethylation caused by injections of DNA methyltransferase inhibitor (DNAMT) during repeated training led to long-term memory formation. Injections of an NMDA glutamate receptor antagonist or a serotonin receptor antagonist prevented memory formation induced by administration of DNAMT inhibitor and repeated training. We hypothesize that methylation-dependent repression of neuronal genes underlies anterograde amnesia. Demethylation eliminated the blockade of these genes and created conditions for long-term memory formation, the induction mechanisms of which involve neurotransmitter receptors.

3D pCASL-perfusion in preoperative assessment of brain gliomas in large cohort of patients.

The aim of the study was to evaluate the role of pseudocontinuous arterial spin labeling perfusion (pCASL-perfusion) in preoperative assessment of cerebral glioma grades. The study group consisted of 253 patients, aged 7-78 years with supratentorial gliomas (65 low-grade gliomas (LGG), 188 high-grade gliomas (HGG)). We used 3D pCASL-perfusion for each patient in order to calculate the tumor blood flow (TBF). We obtained maximal tumor blood flow (maxTBF) in small regions of interest (30 ± 10 mm2) and then normalized absolute maximum tumor blood flow (nTBF) to that of the contralateral normal-appearing white matter of the centrum semiovale. MaxTBF and nTBF values significantly differed between HGG and LGG groups (p < 0.001), as well as between patient groups separated by the grades (grade II vs. grade III) (p < 0.001). Moreover, we performed ROC-analysis which demonstrated high sensitivity and specificity in differentiating between HGG and LGG. We found significant differences for maxTBF and nTBF between grade III and IV gliomas, however, ROC-analysis showed low sensitivity and specificity. We did not observe a significant difference in TBF for astrocytomas and oligodendrogliomas. Our study demonstrates that 3D pCASL-perfusion as an effective diagnostic tool for preoperative differentiation of glioma grades.

Terahertz dielectric spectroscopy and solid immersion microscopy of ex vivo glioma model 101.8: brain tissue heterogeneity.

Terahertz (THz) technology holds strong potential for the intraoperative label-free diagnosis of brain gliomas, aimed at ensuring their gross-total resection. Nevertheless, it is still far from clinical applications due to the limited knowledge about the THz-wave-brain tissue interactions. In this work, rat glioma model 101.8 was studied ex vivo using both the THz pulsed spectroscopy and the 0.15λ-resolution THz solid immersion microscopy (λ is a free-space wavelength). The considered homograft model mimics glioblastoma, possesses heterogeneous character, unclear margins, and microvascularity. Using the THz spectroscopy, effective THz optical properties of brain tissues were studied, as averaged within the diffraction-limited beam spot. Thus measured THz optical properties revealed a persistent difference between intact tissues and a tumor, along with fluctuations of the tissue response over the rat brain. The observed THz microscopic images showed heterogeneous character of brain tissues at the scale posed by the THz wavelengths, which is due to the distinct response of white and gray matters, the presence of different neurovascular structures, as well as due to the necrotic debris and hemorrhage in a tumor. Such heterogeneities might significantly complicate delineation of tumor margins during the intraoperative THz neurodiagnosis. The presented results for the first time pose the problem of studying the inhomogeneity of brain tissues that causes scattering of THz waves, as well as the urgent need to use the radiation transfer theory for describing the THz-wave - tissue interactions.

[Magnetic resonance relaxometry in high-grade glioma subregion assessment - neuroimaging and morphological correlates]. / Magnitno-rezonansnaya relaksometriya v otsenke subregionov gliom golovnogo mozga vysokoi stepeni zlokachestvennosti ­ neirovizualizatsionnye i morfologicheskie korrelyaty.

OBJECTIVE: To analyze the differences of high-grade glioma subregions using magnetic resonance relaxometry with compilation of images (MAGiC) and arterial spin labeling (ASL), as well as to compare quantitative measurements of these techniques with morphological data. MATERIAL AND METHODS: The study enrolled 35 patients with newly diagnosed supratentorial gliomas (23 - grade IV, 12 - grade III). We measured relaxometric values (T1, T2, proton density), tumor blood flow (TBF) in glioma subregions and normal-appearing brain matter. Neuronavigation was intraoperatively used to obtain tissue samples from active tumor growth zone, perifocal infiltrative edema zone and adjacent brain matter along surgical approach. RESULTS: ASL perfusion revealed higher tumor blood flow (TBF) in active tumor growth region compared to perifocal infiltrative edema zone (p<0.01). Relaxometric values (T1, T2, proton density) in perifocal zone were higher (p<0.01) compared to adjacent intact white matter along surgical approach. However, there were no differences in TBF between these zones. Proton density in tumor-adjacent intact white matter was higher (p<0.01) compared to normal-appearing white matter in ipsilateral hemisphere. There was inverse correlation between T2 and TBF in active tumor growth zone (Spearman rank R= -0.58; p=0.0016). We found inverse correlation between T2 and Ki67 proliferative index and direct correlation between TBF and Ki67 in this zone. Nevertheless, these relationships were insignificant after multiple test adjustment. CONCLUSION: Our study advocates for complementary power of ASL perfusion and MR relaxometry in assessment of high-grade brain glioma subregions. More malignant tumor zones tend to have higher TBF and shorter T2. Further investigation is needed to prove the capability of MAGiC to reveal foci of increased relaxometric values in tumor-adjacent normal-appearing white matter.

Protein synthesis inhibitor administration before a reminder caused recovery from amnesia induced by memory reconsolidation impairment with NMDA glutamate receptor antagonist.

Memory recovery in amnestic animals is one of the most poorly studied processes. In this paper, we examine the role of protein synthesis and a reminder in the mechanisms of amnesia and memory recovery in grape snails trained to conditioned food aversion. Amnesia was induced by the impairment of memory reconsolidation using NMDA (N-methyl d-aspartate) glutamate receptor antagonists. In an early stage of amnesia (day 3), injections of protein synthesis inhibitors into animals combined with a reminder by a conditioned stimulus (CS) led to the recovery of aversive reactions to its presentation. Two types of changes in reactions to CS were revealed. In most animals, a persistent recovery of memory retrieval was found that lasted for at least 10 days. In other snails, aversive responses to CS persisted for 24 h. Isolated injections of inhibitors, injections of inhibitors and a reminder by the learning environment (without presenting a CS), usage of a differentiating stimulus instead of a CS, or inhibitor injections after the reminder did not affect the development of amnesia. The administration of protein synthesis inhibitors and a reminder in the late period after amnesia induction (10 days) did not affect its development or caused a short-term memory recovery. We suggest that amnesia is an active process that develops over time. The reminder induces the reactivation of the amnesia process dependent on protein synthesis, while the administration of protein synthesis inhibitors leads to the impairment of amnesia reactivation and recovery of the state formed before amnesia induction (i.e., recovery of conditioned food aversion memory).

Terahertz dielectric spectroscopy of human brain gliomas and intact tissues ex vivo: double-Debye and double-overdamped-oscillator models of dielectric response.

Terahertz (THz) technology offers novel opportunities in the intraoperative neurodiagnosis. Recently, the significant progress was achieved in the study of brain gliomas and intact tissues, highlighting a potential for THz technology in the intraoperative delineation of tumor margins. However, a lack of physical models describing the THz dielectric permittivity of healthy and pathological brain tissues restrains the further progress in this field. In the present work, the ex vivo THz dielectric response of human brain tissues was analyzed using relaxation models of complex dielectric permittivity. Dielectric response of tissues was parametrized by a pair of the Debye relaxators and a pair of the overdamped-oscillators - namely, the double-Debye (DD) and double-overdamped-oscillator (DO) models. Both models accurately reproduce the experimental curves for the intact tissues and the WHO Grades I-IV gliomas. While the DD model is more common for THz biophotonics, the DO model is more physically rigorous, since it satisfies the sum rule. In this way, the DO model and the sum rule were, then, applied to estimate the content of water in intact tissues and gliomas ex vivo. The observed results agreed well with the earlier-reported data, justifying water as a main endogenous label of brain tumors in the THz range. The developed models can be used to describe completely the THz-wave - human brain tissues interactions in the frameworks of classical electrodynamics, being quite important for further research and developments in THz neurodiagnosis of tumors.

Learning against the Background of DNA Methyltransferase Inhibition Leads to the Formation of Memory That Is Resistant to Reactivation and Impairment.

The involvement of DNA methylation in the mechanisms of formation of conditioned food aversion memory was studied on Helix lucorum snails. The dynamics of aversion formation in snails injected with DNA methyltransferase inhibitor RG108 did not differ from that in control snails. The memory was retained for more than one month after training following RG108 injection and the duration of memory persistence did not differ from that in control animals. However, the characteristics of memory in control and experimental snails differed significantly. In control snails, injections of glutamate NMDA-receptor antagonist or protein synthesis inhibitor before memory retrieval caused disorders in the memory reconsolidation and development of amnesia 2 days after training. By contrast, injections of these substances before retrieval to snails trained against the background of RG108 treatment caused no memory disorders. We hypothesized that inhibition of DNA methylation processes led to the formation of strong memory, not reactivated after retrieval and not transformed into a labile state sensitive to amnesic agents.

Identification of different cell clusters in the endothelium of atherosclerotic vessels and determination of inter-cluster gradient of proliferative and inflammatory activity as new diagnostic markers.

To characterize atherogenesis functionally, we studied the functional heterogeneity of endotheliocytes in carotid vessels with atherosclerotic plaques and identified several distinct cell clusters. We measured the Ki-67 labeling index (Ki-67 LI), percentage of Bcl-2 cells (CP) and expression of CCL5, IL 6 and VCAM1 in each cell cluster. We also investigated how these indicators change when the plaque becomes unstable and how they affect the risk of adverse cerebrovascular events in patients. We evaluated the inter-cluster gradient of marker activity and its relation to patient prognosis. We identified five endothelial clusters: the under plaque cluster (UPC), peripheral cluster (PC), marginal cluster (MC), transient cluster (TC) and outside plaque cluster (OC). The UPC exhibited the greatest proliferative, proinflammatory and adhesive activity, but low anti-apoptotic activity. The PC exhibited the second greatest proliferative, adhesive and proinflammatory activity. Progression of atherosclerosis and transition of a stable atherosclerotic plaque to an unstable one was accompanied by increased expression of nearly all markers. The proliferative activity in the UPC, PC and OC, and the pro-inflammatory activity in UPC and anti-apoptotic activity in the PC, were correlated with prognosis. Also, two gradients of proliferative activity and a gradient of pro-inflammatory activity were associated with risk of adverse events.

Capability of physically reasonable OCT-based differentiation between intact brain tissues, human brain gliomas of different WHO grades, and glioma model 101.8 from rats.

Optical coherence tomography (OCT) of the ex vivo rat and human brain tissue samples is performed. The set of samples comprises intact white and gray matter, as well as human brain gliomas of the World Health Organization (WHO) Grades I-IV and glioma model 101.8 from rats. Analysis of OCT signals is aimed at comparing the physically reasonable properties of tissues, and determining the attenuation coefficient, parameter related to effective refractive index, and their standard deviations. Data analysis is based on the linear discriminant analysis and estimation of their dispersion in a four-dimensional principal component space. The results demonstrate the distinct contrast between intact tissues and low-grade gliomas and moderate contrast between intact tissues and high-grade gliomas. Particularly, the mean values of attenuation coefficient are 7.56±0.91, 3.96±0.98, and 5.71±1.49 mm-1 for human white matter, glioma Grade I, and glioblastoma, respectively. The significant variability of optical properties of high Grades and essential differences between rat and human brain tissues are observed. The dispersion of properties enlarges with increase of the glioma WHO Grade, which can be attributed to the growing heterogeneity of pathological brain tissues. The results of this study reveal the advantages and drawbacks of OCT for the intraoperative diagnosis of brain gliomas and compare its abilities separately for different grades of malignancy. The perspective of OCT to differentiate low-grade gliomas is highlighted by the low performance of the existing intraoperational methods and instruments.

[The role of lipids in the classification of astrocytoma and glioblastoma using MS tumor profiling]. / Rol' lipidov pri klassifikatsii astrotsitomy i glioblastomy pri pomoshchi mass-spektrometricheskogo profilirovaniia opukholei.

Express MS identification of biological tissues has become a much more accessible research method due to the application of direct specimen ionization at atmospheric pressure. In contrast to traditional methods of analysis employing GC-MS methods for determining the molecular composition of the analyzed objects it eliminates the influence of mutual ion suppression. Despite significant progress in the field of direct MS of biological tissues, the question of mass spectrometric profile attribution to a certain type of tissue still remains open. The use of modern machine learning methods and protocols (e.g., "random forests") enables us to trace possible relationships between the components of the sample MS profile and the result of brain tumor tissue classification (astrocytoma or glioblastoma). It has been shown that the most pronounced differences in the mass spectrometric profiles of these tumors are due to their lipid composition. Detection of statistically significant differences in lipid profiles of astrocytoma and glioblastoma may be used to perform an express test during surgery and inform the neurosurgeon what type of malignant tissue he is working with. The ability to accurately determine the boundaries of the neoplastic growth significantly improves the quality of both surgical intervention and postoperative rehabilitation, as well as the duration and quality of life of patients.

[Primary sellar neuroblastoma (clinical case and literature review)]. / Pervichnaya sellyarnaya neiroblastoma. Klinicheskoe nablyudenie i obzor literatury.

Neuroblastoma is a malignancy developing from the embryonic neuroblasts of sympathetic nervous system. Primary sellar neuroblastomas are extremely rare (there are currently only 11 case reports in the literature). Possible development of neuroblastoma in sellar region expands differential diagnosis of local processes due to inclusion of neuroblastoma into the spectrum of suspected tumors. We report a literature review and description of a patient with primary sellar neuroblastoma.

Long-term memory consolidation or reconsolidation impairment induces amnesia with key characteristics that are similar to key learning characteristics.

According to a common perspective, amnesia is a passive consequence of memory consolidation or reconsolidation impairment. The results of our own study, as well as literature data, allowed us to offer an interpretation of amnesia. Amnesia is an active process whose key characteristics are similar to those of other long-term plastic rearrangements of the brain, including learning processes. In accordance with this hypothesis, the review considers the data we obtained on the mechanisms of amnesia induction and development caused by impairment of conditioned food aversion memory consolidation or reconsolidation. In particular, experimental data indicating the dependence of amnesia induction on protein and RNA syntheses are described. After amnesia induction, a time-dependent reorganization of its processes is shown to occur. In early amnesia stages (< 10 days), a gradual decrease in the possibility of memory formation during a second training was observed. In late stages of amnesia (10 days or more), an unusual physiological phenomenon was revealed-the second training did not lead to the formation of long-term memory. This effect was specific, as memory for a new type of food could possibly be formed in these animals. The described properties of amnesia facilitate its characterization as specific anterograde amnesia. In addition, at an early but not late amnesia stages, reminder presentation caused amnesia reactivation, impairment of which by DNA methyltransferase inhibitors caused memory recovery. The results obtained allow us to characterize amnesia as a specific, time-dependent, separate process. In conclusion, the potential biological significance of the described type of amnesia is considered, and we discuss the possible molecular mechanisms underlying it.

[Primary pineal melanocytoma: clinical case and literature review]. / Pervichnaia melanotsitoma pineal'noi oblasti: klinicheskii sluchai i obzor literatury.

Primary pineal melanocytomas are extremely rare pathologies and predominantly are clinically manifested by nonspecific symptoms of a pineal affect, which could be characteristic for tumors of different histological nature located in the same region. Also these tumors differ from other melanocytic tumors by their slow growth and relatively favorable clinical prognosis.