Development of Supervised Speaker Diarization System Based on the PyAnnote Audio Processing Library.

Diarization is an important task when work with audiodata is executed, as it provides a solution to the problem related to the need of dividing one analyzed call recording into several speech recordings, each of which belongs to one speaker. Diarization systems segment audio recordings by defining the time boundaries of utterances, and typically use unsupervised methods to group utterances belonging to individual speakers, but do not answer the question "who is speaking?" On the other hand, there are biometric systems that identify individuals on the basis of their voices, but such systems are designed with the prerequisite that only one speaker is present in the analyzed audio recording. However, some applications involve the need to identify multiple speakers that interact freely in an audio recording. This paper proposes two architectures of speaker identification systems based on a combination of diarization and identification methods, which operate on the basis of segment-level or group-level classification. The open-source PyAnnote framework was used to develop the system. The performance of the speaker identification system was verified through the application of the AMI Corpus open-source audio database, which contains 100 h of annotated and transcribed audio and video data. The research method consisted of four experiments to select the best-performing supervised diarization algorithms on the basis of PyAnnote. The first experiment was designed to investigate how the selection of the distance function between vector embedding affects the reliability of identification of a speaker's utterance in a segment-level classification architecture. The second experiment examines the architecture of cluster-centroid (group-level) classification, i.e., the selection of the best clustering and classification methods. The third experiment investigates the impact of different segmentation algorithms on the accuracy of identifying speaker utterances, and the fourth examines embedding window sizes. Experimental results demonstrated that the group-level approach offered better identification results were compared to the segment-level approach, and the latter had the advantage of real-time processing.

Craniopharyngiomas: Surgery and Radiotherapy.

Taking into account the benign nature of craniopharyngiomas, the main method of treatment is the resection of the tumor. However, the tendency of these tumors to invade critical structures (such as optic pathways, the hypothalamic-pituitary system, the Willis circle vessels) often limits the possibility of a radical surgery.Craniopharyngiomas of the third ventricle represent the greatest challenge for surgery. After radical surgery, hypothalamic disorders often occur, including not only obesity but also cognitive, emotional, mental, and metabolic disturbances. Metabolic disorders associated with damage to the hypothalamus progress after surgery and lead to impaired functions of the internal organs. This process is irreversible and, in many cases, becomes the direct cause of mortality. The life expectancy of patients with the surgically affected hypothalamus is significantly shorter than in patients with preserved diencephalic function. The incidence of hypothalamic disorders after surgery can reach 40%.Even with macroscopically total resection, craniopharyngiomas can recur in 10-30% of cases, and in the presence of tumor remnants and with no further radiation treatment, the risk of recurrence significantly increases to up to 50-85% according to various studies. For this reason, the observation of patients with residual tumors after surgery is an incorrect strategy.Radiation therapy significantly improves progression-free survival (PFS), and the use of stereotactic irradiation techniques ensures conformity of irradiation of tumor remnants with a complicated shape and location (Iwata H et al., J Neurooncol 106(3):571-577, 2012; Aggarwal et al., Pituitary 16(1):26-33, 2013; Savateev et al., Zh Vopr Neirokhir Im N N Burdenko 81(3):94-106; 2017), which potentially reduces the risk of undesirable postradiation effects. Therefore, the quality of life in patients with craniopharyngiomas infiltrating the hypothalamus is significantly higher after non-radical operations with subsequent stereotactic radiation than after a total or subtotal removal.

Treatment of Pediatric Glioblastoma with Combination Olaparib and Temozolomide Demonstrates 2-Year Durable Response.

For pediatric patients with high-grade gliomas, standard-of-care treatment includes surgery, chemotherapy, and radiation therapy; however, most patients ultimately succumb to their disease. With advances in genomic characterization of pediatric high-grade gliomas, the use of targeted therapies in combination with current treatment modalities offer the potential to improve survival in this patient population. In this report, we present the case of a 3-year-old girl with glioblastoma who continues to experience an exceptional and durable response (>2 years) to the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib. Our patient presented with persistent and progressive seizure activity that upon workup was the result of a large heterogeneously enhancing, mixed cystic and solid mass in the left frontal-parietal-temporal region. Histopathologic analysis of resected tumor tissue confirmed the diagnosis of glioblastoma, and comprehensive genomic profiling demonstrated absence of any BRAF or H3F3A mutations. Genomic profiling, however, did reveal a probable germline heterozygous BRCA2 Lys3326Ter (K3226*) nonsense variant. After debulking surgery, the patient received standard-of-care treatment with radiation and temozolomide. Nine months later the PARP inhibitor olaparib was administered in combination with temozolomide for 16 cycles. This regimen was well tolerated by the patient and serial imaging showed reduction in tumor size. Since completion of the regimen, the patient remains neurologically intact with no evidence of tumor recurrence. To our knowledge, this represents the first case of a pediatric glioblastoma that maintains a durable response to a therapeutic strategy that included the PARP inhibitor olaparib and more generally highlights the potential clinical utility of incorporating these agents into the treatment of pediatric high-grade gliomas. KEY POINTS: Germline mutations detected in pediatric gliomas may represent a cancer predisposition syndrome. Integrating molecular testing into routine clinical care for pediatric patients with glioma is critical to identify therapeutic targets and patients with a cancer predisposition syndrome. Patients with glioma with defects in DNA repair pathway components (e.g., BRCA1/2) may show increased responsiveness to poly (ADP-ribose) polymerase (PARP) inhibitors. Combining PARP inhibitors with temozolomide (standard-of-care treatment) revealed no adverse events or toxicities over the course of 18 months.

Diclofenac sodium aqueous systems at low concentrations: Interconnection between physicochemical properties and action on hydrobionts.

Diclofenac sodium (DS) is a widely used nonsteroidal anti-inflammatory drug (NSAIDs). NSAIDs are poorly removed during standard wastewater treatment. The consequences of the presence of NSAIDs in rivers and lakes at 10-11-10-8 mol/L are not yet established; therefore, ecotoxicologists have focused their efforts on studying the effect of low-concentration NSAIDs on fish and hydrobionts, and also on predicting the potential risks to humans. Literature provides some information about the bioeffects of some NSAID solutions in low concentrations but there is no physicochemical explanation for these phenomena. Studying the physicochemical patterns of DS solutions in the low range of concentrations and establishing an interconnection between the solutions' physicochemical properties and bioeffects can provide a conceptually new and important source of information regarding the unknown effects of DS. The physicochemical properties and action of DS solutions on Ceriodaphnia affinis cladocerans, Paramecium caudatum infusoria, Chlorella vulgaris unicellular green algae, as well as on the growth of the roots of Triticum vulgare wheat seeds, were studied in the calculated concentration range of 1 × 10-3-1 × 10-18 mol/L. The relationship between these phenomena was established using the certified procedures for monitoring the toxicity of natural water and wastewater. It was shown for the first time that water solutions of DS are dispersed systems in which the dispersed phase undergoes a rearrangement with dilution, accompanied by changes in its size and properties, which affects the nonmonotonic dependences of the system's physicochemical properties and could cause nonmonotonic changes in action on hydrobionts in the low concentration range.

Tb(III)-doped silica nanoparticles for sensing: effect of interfacial interactions on substrate-induced luminescent response.

The present work introduces the easy modification of the water-in-oil microemulsion procedure aimed at the doping of the Tb(III) complexes within core or shell zones of the silica nanoparticles (SNs), which are designated as "core-shell", "shell", and "core". The dye molecules, chelating ligands, and copper ions were applied as the quenchers of Tb(III)-centered luminescence through dynamic or/and static mechanisms. The binding of the quenchers at the silica/water interface results in the quenching of the Tb(III) complexes within SNs, which, in turn, is greatly dependent on the synthetic procedure. The luminescence of "core" SNs remains unchanged under the binding of the quenchers at the silica/water interface. The quenching through dynamic mechanism is more significant for "core-shell" and "shell" than for "core" SNs. Thus, both "core-shell" and "shell" SNs have enough percentage of the Tb(III) complexes located close to the interface for efficient quenching through the energy transfer. The quenching through the ion or ligand exchange is most efficient for "core-shell" SNs due to the greatest percentage of the Tb(III) complexes at the silica/water interface, which correlates with the used synthetic procedure. The highlighted regularities introduce the applicability of "core-shell" SNs used as silica beads for phosphatidylcholine bilayers in sensing their permeability toward the quenching ions.

Nanoassociate formation in highly diluted water solutions of potassium phenosan with and without permalloy shielding.

Diluted water solutions of anti-oxidant potassium phenosan, kept before explorations in "usual" conditions and in conditions of "permalloy container", i.e. shielding of solution from the influence of external low-frequency electromagnetic and/or geomagnetic fields, were studied. It is shown that in solutions kept in shielded conditions in the area of high dilution with a concentration of solutions lower than "threshold", nanoobjects called "nanoassociates", are not formed, and anomalous physicochemical and biological properties observed in solutions kept in "usual" conditions, are not found. We conclude that anomalous physicochemical and biological properties of highly diluted water solutions of potassium phenosan made under "usual" conditions are determined by "nanoassociates", in which an external low-frequency electromagnetic and/or geomagnetic field is a necessary condition of the formation.

Controlling the size and morphology of supramolecular assemblies of viologen-resorcin[4]arene cavitands.

A novel class of self-assembling nanoparticles is formed with viologen-resorcin[4]arene cavitands; the association model is strongly controlled by their hydrophobicity. Interestingly, the cavitand assemblies are designed through click chemistry to form self-assembled noncovalently connected aggregates through counterion displacement. The iodide and benzoate ions are utilized as strongly polarizable counterions to induce cavitand self-assembly. The counterion-mediated decrease in hydrophilicity of the viologen-resorcin[4]arenes is the underlying trigger to induce particle formation. These particles can be used as nanocontainers and find their applications in delivery systems.

Langmuir monolayers and thin films of amphifilic thiacalix[4]arenes. Properties and matrix for the immobilization of cytochrome c.

Formation and properties of Langmuir films of thiacalix[4]arene (TCA) derivatives containing N-donor groups on the lower rim (Y═O(CH2)3CN; OCH2CN; NH2; OCH2ArCN-p) in 1,3-alternate conformation on aqueous subphase and solid substrates have been studied. Only tetra-cyanopropoxy-p-tert-butylthiacalix[4]arene 1 forms a typical monomolecular layer with perpendicular orientation of the macrocycle relative to the water-air interface that is able to immobilize cytochrome c in the entire range of the surface pressure. Obtained monolayers were transferred by Langmuir-Schaefer technique onto quartz, indium-tin oxide (ITO), and silicon. It was demonstrated that protein activity is retained after immobilization on the substrate.

Supramolecular design of biocompatible nanocontainers based on amphiphilic derivatives of a natural compound isosteviol.

Two diterpenoid surfactants with ammonium head groups and bromide (S1) or tosylate (S2) counterions have been synthesized. Exploration of these biomimetic species made it possible to demonstrate that even minor structural changes beyond their chemical nature may dramatically affect their solution behavior. While their aggregation thresholds differ inconsiderably, morphological behavior and affinity to lipid bilayer are strongly dependent on the counterion nature. Compound S2 demonstrates properties of typical surfactants and forms small micelle-like aggregates above critical micelle concentration. For surfactant S1, two critical concentrations and two types of aggregates occur. Structural transitions have been observed between small micelles and aggregates with higher aggregation numbers and hydrodynamic diameter of ca. 150 nm. Unlike S2, surfactant S1 is shown to integrate with liposomes based on dipalmitoylphosphatidylcholine, resulting in a decrease of the temperature of the main phase transition. Both surfactants demonstrate an effective complexation capacity toward oligonucleotide (ONu), which is supported by recharging the surfactant-ONu complexes and the ethidium bromide exclusion at a low N/P ratio. Meanwhile, a very weak complexation of plasmid DNA with the surfactants has been revealed in the gel electrophoresis experiment. The DNA transfer to bacterial cells mediated by the surfactant S1 is shown to depend on the protocol used. In the case of the electroporation, the inhibition of the cell transformation occurs in the presence of the surfactant, while upon the chemical treatment no surfactant effect has been observed. The variability in the morphology, the biocompatibility, the nanoscale dimension and the high binding capacity toward the DNA decamer make it possible to nominate the designed surfactants as promising carriers for biosubstrates or as a helper surfactant for the mixed liposome-surfactant nanocontainers.

Median trans-atlanto-occipital membrane microsurgical approach to the posterior cranial fossa without craniotomy.

Minimally invasive approaches are becoming increasingly popular and contributing to improving the results of the surgical treatment of a wide variety of intracranial pathologies. Fifteen patients with posterior cranial fossa tumors underwent microsurgery through the atlanto-occipital membrane without resection of any bone structures. Tumors were localized in the brainstem in 8 patients and in the fourth ventricle in 7 patients. According to preoperative MRI and CT scans, the distance between the posterior arch of the atlas and the opisthion ranged from 9.9 to 16.5 mm (median 13 mm). The surgery was performed with the patient in the prone position and the head flexed. The trajectory of the surgical approach was directed from the skin incision located above the C2 spinous process 3.5-4 cm rostral along the midline. Total tumor resection was performed in 10 patients, subtotal resection in 2 patients, partial resection in 1 patient, and open biopsy in 2 patients. Surgical complications occurred in only 1 patient (meningoencephalitis). This minimally invasive trans-atlanto-occipital membrane approach for posterior cranial fossa tumors provides adequate visualization of the caudal part of the fourth ventricle and brainstem when the anthropometric parameters of the patient are suitable.

Complex formation of d-metal ions at the interface of Tb(III)-doped silica nanoparticles as a basis of substrate-responsive Tb(III)-centered luminescence.

The complex formation of d-metal ions at the interface of Tb(III)-doped silica nanoparticles modified by amino groups is introduced as a route to sensing d-metal ions and some organic molecules. Diverse modes of surface modification (covalent and noncovalent) are used to fix amino groups onto the silica surface. The interfacial binding of d-metal ions and complexes is the reason for the Tb(III)-centered luminescence quenching. The regularities and mechanisms of quenching are estimated for the series of d-metal ions and their complexes with chelating ligands. The obtained results reveal the interfacial binding of Cu(II) ions as the basis of their quantitative determination in the concentration range 0.1-2.5 µM by means of steady-state and time-resolved fluorescence measurements. The variation of chelating ligands results in a significant effect on the quenching regularities due to diverse binding modes (inner or outer sphere) between amino groups at the interface of nanoparticles and Fe(III) ions. The applicability of the steady-state and time-resolved fluorescence measurements to sense both Fe(III) ions and catechols in aqueous solution by means of Tb(III)-doped silica nanoparticles is also introduced.

Supramolecular systems based on novel mono- and dicationic pyrimidinic amphiphiles and oligonucleotides: a self-organization and complexation study.

Novel mono- and dicationic pyrimidinic surfactants are synthesized and their aggregation behavior is studied by methods of tensiometry and nuclear magnetic resonance (NMR) self-diffusion. To estimate their potentiality as gene delivery agents, the complexation with oligonucleotides (ONus) is explored by dynamic light scattering (DLS) and zeta-potential titration methods and ethidium bromide exclusion experiments. Bola-type pyrimidinic amphiphile (BPM) demonstrates rather a weak affinity to ONus. Although it induces mixed associations with ONus, only slight charge compensation changes occur at a large excess of bola, with no recharging reached. Similarly, the ethydium bromide exclusion study reveals a slow increase in the binding capacity toward an ONu with an increment in BPM concentration. The monocationic pyrimidinic surfactant (MPM) and its gemini analogue (GPM-1) are ranked as intermediates in both their aggregative activity and complexing properties toward ONus. They both form mixed associates with ONus well below the critical micelle concentrations (cmcs) of 2 and 15 mM respectively. However, GPM-1 has a much lower isoelectric point at the molar ratio surfactant/ONu r~1 compared to r~3 for MPM. This probably indicates a larger electrostatic contribution to the ONu complexation in the case of GPM-1. The most hydrophobic pyrimidinic surfactant (GPM-2), bearing three alkyl tails, demonstrates enhanced aggregative activity and binding capacity toward ONus as compared to former pyrimidinic surfactants. Due to effective aggregative (low cmc of 0.04 mM) plus binding properties (fraction of bound ONu ß=0.76 at r=2.5), GPM-2 may be ranked as a promising agent for wider biological applications.

Pineal cyst management: A single-institution experience spanning two decades.

Background: Pineal cysts (PCs) are benign lesions commonly found on intracranial imaging. Despite their high prevalence, there is no clear consensus on the most appropriate management of patients with PCs, especially those with symptomatic nonhydrocephalic cysts. Methods: A retrospective analysis was performed on 142 patients with PCs (103 surgical cases and 39 conservatively managed cases). Data were examined, including clinical presentation, imaging findings, ophthalmological status, natural course, postoperative outcomes, and complications. Results: Surgical group: the most common symptom was headache (92%), followed by signs of intracranial hypertension due to hydrocephalus (22%). New radiological feature of PCs was found in 11 patients. From 71 patients with long-term follow-up, headache completely resolved in 44 (62%) patients; marked improvement was observed in 20 (29%); in 7 (9%) - headache remained unchanged. The most common postoperative complication was neuro-ophthalmological disorders (23%), with a tendency for resolution in the long-term follow-up period. Neuro-ophthalmological symptoms at last follow-up included upward gaze palsy (6%) and skew deviation (5%), followed by convergence disorders (3%) and eyelid-retraction (2%). Natural course group: PC size remained stable in 34 (87%) patients during the follow-up period. The patient's gender or age was not a significant predictor of cyst growth (P = 0.4, P = 0.56). Conclusion: The majority of patients with a newly diagnosed PC remain clinically and radiologically stable. Patients with nonhydrocephalic PCs and intractable headaches experience significant relief in headache symptoms, but are at risk of mild to moderate neuro-ophthalmological disorders. The natural course of PCs and factors promoting their growth still remains poorly defined.

ExhauFS: exhaustive search-based feature selection for classification and survival regression.

Feature selection is one of the main techniques used to prevent overfitting in machine learning applications. The most straightforward approach for feature selection is an exhaustive search: one can go over all possible feature combinations and pick up the model with the highest accuracy. This method together with its optimizations were actively used in biomedical research, however, publicly available implementation is missing. We present ExhauFS-the user-friendly command-line implementation of the exhaustive search approach for classification and survival regression. Aside from tool description, we included three application examples in the manuscript to comprehensively review the implemented functionality. First, we executed ExhauFS on a toy cervical cancer dataset to illustrate basic concepts. Then, multi-cohort microarray breast cancer datasets were used to construct gene signatures for 5-year recurrence classification. The vast majority of signatures constructed by ExhauFS passed 0.65 threshold of sensitivity and specificity on all datasets, including the validation one. Moreover, a number of gene signatures demonstrated reliable performance on independent RNA-seq dataset without any coefficient re-tuning, i.e., turned out to be cross-platform. Finally, Cox survival regression models were used to fit isomiR signatures for overall survival prediction for patients with colorectal cancer. Similarly to the previous example, the major part of models passed the pre-defined concordance index threshold 0.65 on all datasets. In both real-world scenarios (breast and colorectal cancer datasets), ExhauFS was benchmarked against state-of-the-art feature selection models, including L1-regularized sparse models. In case of breast cancer, we were unable to construct reliable cross-platform classifiers using alternative feature selection approaches. In case of colorectal cancer not a single model passed the same 0.65 threshold. Source codes and documentation of ExhauFS are available on GitHub: https://github.com/s-a-nersisyan/ExhauFS.

Reconstruction of fluorophore absorption and fluorescence lifetime using early photon mesoscopic fluorescence molecular tomography: a phantom study.

Significance: Fluorescence molecular lifetime tomography (FMLT) plays an increasingly important role in experimental oncology. The article presents and experimentally verifies an original method of mesoscopic time domain FMLT, based on an asymptotic approximation to the fluorescence source function, which is valid for early arriving photons. Aim: The aim was to justify the efficiency of the method by experimental scanning and reconstruction of a phantom with a fluorophore. The experimental facility included the TCSPC system, the pulsed supercontinuum Fianium laser, and a three-channel fiber probe. Phantom scanning was done in mesoscopic regime for three-dimensional (3D) reflectance geometry. Approach: The sensitivity functions were simulated with a Monte Carlo method. A compressed-sensing-like reconstruction algorithm was used to solve the inverse problem for the fluorescence parameter distribution function, which included the fluorophore absorption coefficient and fluorescence lifetime distributions. The distributions were separated directly in the time domain with the QR-factorization least square method. Results: 3D tomograms of fluorescence parameters were obtained and analyzed using two strategies for the formation of measurement data arrays and sensitivity matrices. An algorithm is developed for the flexible choice of optimal strategy in view of attaining better reconstruction quality. Variants on how to improve the method are proposed, specifically, through stepped extraction and further use of a posteriori information about the object. Conclusions: Even if measurement data are limited, the proposed method is capable of giving adequate reconstructions but their quality depends on available a priori (or a posteriori) information. Further research aims to improve the method by implementing the variants proposed.

Cascade and commutative self-assembles of nanoscale three-component systems controlled by the conformation of thiacalix[4]arene.

In this work, the formation of two- and three-component supramolecular systems based on cone, partial cone, 1,3-alternate stereoisomers of heteroditopic "hosts": p-tert-butylthiacalix[4]arene containing 4-amidopyridine fragments with silver(I) cations and dicarboxylic acids in liquid and solid phases were studied by UV spectroscopy, dynamic light scattering, and atomic force microscopy methods. It has been shown that these macrocycles are coreceptors, capable of simultaneously binding silver(I) cations, dicarboxylic acids (oxalic, malonic, succinic, maleic, fumaric acids), and hydroxyl acids (glycol, tartaric acids). For the first time, by the dynamic light scattering method, it has been shown that the conformation of p-tert-butyl thiacalix[4]arenes significantly affects the type of three-component system formed: cone is characterized by the formation of cascade systems; for partial cone, intermediate systems; and for the 1,3-alternate stereoisomers, three types of three-component systems (cascade, intermediate, and commutative) were observed.

p-tert-Butyl thiacalix[4]arenes functionalized at the lower rim by amide, hydroxyl and ester groups as anion receptors.

New p-tert-butyl thiacalix[4]arenes differently substituted at the lower rim with amide, hydroxyl and ester groups were synthesized. Binding properties of the compounds toward some tetrabutylammonium salts n-Bu(4)NX (X = F(-), Cl(-), Br(-), I(-), CH(3)CO(2)(-), H(2)PO(4)(-), NO(3)(-)) were studied by UV spectroscopy. It was found that the stoichiometry of the complexes, generally, is 1 : 1, and the association constants are in the range of 10(3)-10(5) M(-1). The p-tert-butyl thiacalix[4]arenes containing secondary amide groups trisubstituted at the lower rim bind the studied anions most effectively. Selective receptors for fluoride and dihydrogen phosphate salts of tetrabutylammonium were found.

Novel self-assembling system based on resorcinarene and cationic surfactant.

Mixed association of calix[4]resorcinarene with ethyl sulfonate groups on the lower rim and dimethylaminomethyl groups on the upper rim (CR) and cationic surfactant 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide (DABCO-16) is studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy at fixed CR concentration and varied surfactant concentration. Beyond ca. 0.4 mM of DABCO-16, mixed aggregates enriched by CR are proved to be formed due to electrostatic forces, while beyond ca. 5 mM, aggregates enriched by surfactant occur due to the hydrophobic effect. Spectrophotometry monitoring of the solubilization of a hydrophobic dye, Orange OT, demonstrated that only the second type of mixed aggregate enriched by DABCO-16 is capable of binding the organic probe, while the mixed system where the surfactant is a minor component shows no binding capacity towards Orange OT. This finding can be used for the design of nanocontainers with controllable binding/release properties.

Diluted Aqueous Dispersed Systems of 4-Aminopyridine: The Relationship of Self-Organization, Physicochemical Properties, and Influence on the Electrical Characteristics of Neurons.

A variety of physicochemical methods were used to examine the self-organization, physicochemical, UV absorption, and fluorescent properties of diluted aqueous solutions (calculated concentrations from 1·10-20 to 1·10-2 M) of the membrane voltage-dependent potassium channels blocker 4-aminopyridine (4-AP). Using the dynamic light scattering method, it was shown that 4-AP solutions at concentrations in the range of 1·10-20-1·10-6 M are dispersed systems in which domains and nanoassociates of hundreds of nm in size are formed upon dilution. An interrelation between the non-monotonic concentration dependencies of the size of the dispersed phase, the fluorescence intensity (λ ex 225 nm, λ em 340 nm), specific electrical conductivity, and pH has been established. This allows us to predict the bioeffects of the 4-AP systems at low concentrations. The impact of these diluted aqueous systems on the electrical characteristics of identified neurons of Helix lucorum snails was studied. Incubation of neurons in the 4-AP systems for which the formation of domains and nanoassociates had been established lead to a nonmonotonic decrease of the resting potential by 7-13%. An analysis of the obtained results and published data allows for a conclusion that a consistent change in the nature and parameters of the dispersed phase, as well as the pH of the medium, apparently determines the nonmonotonic nature of the effect of the 4-AP systems in a 1·10-20-1·10-6 M concentration range on the resting membrane potential of neurons. It was found that the pre-incubation of neurons in the 4-AP system with a concentration of 1·10-12 M led to a 17.0% synergistic decrease in the membrane potential after a subsequent treatment with 1·10-2 M 4-AP solution. This finding demonstrates a significant modifying effect of self-organized dispersed systems of 4-AP in low concentrations on the neurons' sensitivity to 4-AP.