Effect of (R)-2-Amino-6-(1R,2S)-1,2-Dihydroxypropyl)-5,6,7,8-Tetrahydropterin-4(3H)-One and Its Structural Analogues on the Temperature Stability of Tryptophan Hydroxylase 2 with the P447R Mutation.

The enzyme tryptophan hydroxylase 2 (TPH2) catalyzes the hydroxylation of L-tryptophan to L-5-hydroxytryptophan (5-HTP), the first and the key step in 5-HT synthesis in the mammalian brain. Mutations in the human Tph2 gene reducing enzyme activity increase the risk of psychopathology. Pharmacological chaperones are small molecules that can specifically bind to mutant protein molecules, restore their disturbed 3D structure to the native state, and increase their stability and functional activity. The chaperone activity of (R)-2-amino-6-(1R,2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one (BH4) is expressed by increasing the in vitro thermal stability of mutant tyrosine hydroxylase and phenylalanine hydroxylase molecules which are similar to TPH2 in their structure and characteristics. The P447R substitution in the mouse TPH2 molecule results in a 2-fold decrease in enzyme activity in their brains. We studied the effect of this mutation on the TPH2 thermal stability, as well as on the ability of BH4 and its 8 structural analogues to increase the thermal stability of the mutant TPH2 from midbrain extracts of BALB/C mice. Temperature stability was studied by the decrease in enzyme activity during its heating for 2 min at increasing temperatures and was evaluated by the T50 value that is the temperature at which the enzyme activity decreased by half. For the mutant TPH2, the T50 value was decreased compared to the wild type enzyme. BH4 and its closest structural analogue, 6-methyl-5,6,7,8-tetrahydropterin, increased the T50 value, i.e., exhibited chaperone activity. Other close BH4 analogs, 6,7-dimethyl-5,6,7,8-tetrahydropterin and folic acid, were not effective. It can be assumed that BH4 can be effective in the treatment of mental disorders caused by mutations in the Tph2 gene.

[On the Draft Regulations on Districts of Sanitary (Mountain Sanitary) Protection of Natural Medicinal Resources: Comments, Suggestions]. / O proekte Polozheniya ob okrugakh sanitarnoi (gorno-sanitarnoi) okhrany prirodnykh lechebnykh resursov: zamechaniya, predlozheniya.

The purpose of the article is to attract the attention of specialists in the resort business in the document being developed - the Decree of the Government of the Russian Federation «On Approval of the Regulations on the Districts of Sanitary (Mining and Sanitary) Protection of Natural Medicinal Resources¼, the draft of which is proposed for discussion. The article presents all the comments on the discussed draft Regulation and proposals for making appropriate changes with their reasoned justification. The proposals put forward to change the wording of specific paragraphs of the Regulation are aimed at protecting and preserving the wealth of our country - natural healing factors that form the basis of sanatorium treatment. The proposals made to edit the paragraphs of the Regulation will undoubtedly guarantee the preservation of Russia's natural healing resources in order to use them for the prevention, treatment and rehabilitation of the population of our country and the successful development of the resort industry.

[Effects of thymus tissue transplantation on the survival of mice exposed to a lethal X-Ray dose.]

During the radiation exposure of the body, processes similar to those characteristic of the natural aging of mammals occur. This phenomenon is most often referred to as accelerated aging. By transplanting the thymus tissue, it is possible to achieve a normalization of food and water consumption, a stabilization of weight gain, and a significant increase in the life expectancy of experimental animals, even after their lethal irradiation.

[Ocular complications in intense pulsed light therapy (case study)]. / Glaznye oslozhneniya intensivnoi fototerapii (klinicheskoe nablyudenie).

A 24-year-old female patient with photophobia, discoria, redness and dryness in her right eye after intense pulsed light (IPL) therapy applied for posttraumatic subcutaneous hemorrhage received a comprehensive ophthalmic examination including optical coherence tomography (OCT) and OCT angiography of the anterior eye segment. Her best corrected visual acuity was 20/20 in both eyes. Medically induced mydriasis revealed discoria with paresis of pupil dilatator in the left eye (pupil size 4.2 mm and 6.6 mm in the right and left eye, respectively). Anterior segment OCT showed anterior chamber cytosis and increased iris vascularity. The patient was prescribed topical 1.0% tropicamide 2 times per day and 1.0% dexamethasone 4 times per day for two weeks. Examination performed after 3 months showed no restoration of pupil dilatator function in the left eye. The case demonstrates potential ocular complications of IPL therapy, which may include iris burn with iritis and persistent pupil dilatator dysfunction.

Synthesis of a tetranitrosyl iron complex with unique structure and properties as an inhibitor of phosphodiesterases.

A novel neutral tetranitrosyl iron complex {[Fe(H2O)4]2+[FeR2(NO)2]22-}·4H2O (1) with R = 5-(3-pyridyl)-4H-1,2,4-triazole-3-thiolyls (C7H5N4S), which is a supramolecular ensemble, has been synthesized and studied. As follows from X-ray diffraction analysis, this is an octahedral Fe2+complex (Lewis acid) with two monoanionic dinitrosyl groups [FeR2(NO)2]- (Lewis base) and 4 water molecules as the ligands. As follows from Mössbauer spectra, the coordinating Fe2+ ion is in a low-spin state S = 0, and the dinitrosyl Fe+ ion is in a low-spin state S = 1/2. According to the data of EPR spectroscopy, mass-spectrometry and amperometry, complex 1 in solution forms dinitrosyl particles of [Fe(C7H6N4S-H)2(NO)2]- composition, which are responsible for NO generation. In addition, complex 1 was shown to be a 5-6 times more efficient phosphodiesterase (PDE) inhibitor at 5 × 10-5 M and 10-4 M concentrations than its thioligand. Probable binding sites of the [FeR2(NO)2]- ligand for the bovine PDE1B model have been determined by molecular docking and quantum-chemical calculations.

Effect of Prolonged Exposure to Short Daylight and a Tryptophan Hydroxylase Inhibitor on the Behavior and Brain Serotonin System in Danio rerio.

We studied the effect of reduced tryptophan hydroxylase (TPH) activity and short daylight exposure on the behavior and the 5-HT system of the brain in D. rerio. Male and female D. rerio were exposed for 30 days to standard (12:12 h light:dark) and short (4:20 h light:dark) photoperiods in the presence or absence of TPH inhibitor (p-chlorophenylalanine, pCPA, 5 mg/liter). On day 31, the fish behavior in the "novel tank diving" test, their sex and body weight were determined, and the levels of pCPA, 5-HT, and its metabolite 5-HIAA were measured by HPLC; the levels of the key genes encoding metabolism enzymes (Tph1a, Tph1b, Tph2, and Mao) and receptors of 5-HT (Htr1aa, Htr2aa) were assessed by real-time PCR with reverse transcription. The short daylight exposure caused masculinization of females, reduced body weight, and motor activity in the "novel tank diving" test, but did not affect the 5-HT system of the brain. Long-term pCPA treatment had no effect on sex and body weight, significantly reduced the 5-HIAA level, but increased Tph1a and Tph2 gene expression in the brain. No effects of the interaction of short daylight and pCPA exposure on the sex, body weight, behavior, and 5-HT system of the brain were found. Thus, a moderate decrease in TPH activity cannot potentiate the negative effects of short daylight exposure on the sex, body weight, behavior, and 5-HT system of D. rerio.

[The first application of intraoperative mri for analysis of cerebral perfusion in surgical brain revascularization]. / Pervoe primenenie intraoperatsionnoi MRT dlya issledovaniya tserebral'noi perfuzii pri khirurgicheskoi revaskulyarizatsii golovnogo mozga.

BACKGROUND: Effectiveness of surgical revascularization in patients with chronic cerebral ischemia depends on restoration of circulation in the damaged artery. Modern methods do not take into account dynamic changes in cerebral perfusion after extra-intracranial microvascular anastomosis (EICMA) and do not allow timely localizing the areas of persistent perfusion deficit. We propose a new method for determining the tactics of surgical cerebral revascularization based on intraoperative MRI (iMRI) perfusion data. This method provides the earliest information on intraoperative brain reperfusion. OBJECTIVE: To develop the principles of dynamic assessment of cerebral blood flow using intraoperative ASL perfusion during surgical revascularization in patients with chronic cerebral ischemia and to determine the indications for additional anastomoses. MATERIAL AND METHODS: Surgical revascularization with intraoperative MRI perfusion was performed in 27 patients between March 2022 and April 2023. There were 10 patients with post-thrombotic occlusion of internal carotid artery, 4 patients with occlusion of middle cerebral artery and 13 patients with moyamoya disease. All patients underwent MRI before surgery. After imposing the first EICMA, all patients underwent ASL perfusion for analysis of residual hypoperfusion zones, signs of local hyperperfusion and indications or contraindications for additional revascularization with the second donor branch. RESULTS: In all cases, iMRI made it possible to determine the tactics of brain revascularization using one or two EICMA. In 17 cases, ASL perfusion confirmed the targeted improvement of cerebral blood flow (CBF) in the entire hemisphere or middle cerebral artery basin. Only one EICMA was imposed in these cases. In 10 cases, a single anastomosis was insufficient for restoration of blood flow. These patients underwent additional revascularization with the second donor branch (35.7%). In all cases, we achieved significant quantitative improvement in CBF and volume of brain tissue with restored blood flow (ASPECTS scale). A single EICMA was followed by increase in CBF and areas of restored blood flow by almost 2 times (22.7±9.6 ml/100 g/min and 4.7±1.8 scores (ASPECTS) before surgery vs. 39.4±16.4 ml/100 g/min and 4.7±1.8 scores after EICMA). In the double EICMA group, these parameters increased by almost 3 times (18±3.1 ml/100 g/min and 3.8±0.9 scores before surgery vs. 57±11.4 ml/100 g/min and 7.7±1.5 scores after double EICMA). All patients had no complications. Neurological status improved immediately after surgery in 9 patients (33.3%), stable postoperative period was observed in 12 cases (44.4%). Six (22.2%) patients had transient neurological deficit associated with hyperperfusion syndrome that regressed within a few days after surgery. There were no persistent ischemic complications. CONCLUSION: Intraoperative ASL perfusion is an effective and informative tool for determining the degree of restoration of blood flow. We can timely adjust surgical strategy, determine the indications or contraindications for additional revascularization and exclude early ischemic complications using this method.

Long-Term Continuous Computer Registration and Analysis of Motor Activity of a Group of Zebrafish Danio rerio.

A new algorithm for long-term continuous computer recording and analysis of motor activity of a group of zebrafish in the home tank has been developed. The movements of a group of Danio rerio during the entire light period and for several days are recorded at a frequency of 1 frame/sec in the form of short (15 min) files. Then these files are analyzed by the unique DanioStudo software, which, using a threshold algorithm and appropriate masks, calculates for each frame the sum of pixels associated with fish (the sum of fish silhouettes), and for two consecutive frames, the sum of altered pixels (the sum of altered fish silhouettes). The following indexes are calculated: the rate of sum of silhouettes alteration as the ratio of the sum of altered silhouettes to the sum of silhouettes (1) and the time spent in the selected area of the home tank as the ratio of the sum of silhouettes in this area to the sum of silhouettes in the entire tank (2). The mean rate of silhouette alteration correlates to the length of the path travelled by the fish and, therefore, serves as a correct measure of the motor activity of a group of fish. Using these algorithms, completely new data were obtained: it was shown that the motor activity of fish remains constant throughout the entire light period, but depends on the size of the home tank. The proposed approach, together with the DanioStudio software, can be effective in studying the dynamics of changes in the behavior of fish under long-term exposure to short daylight, drugs and toxic substances.

An Analysis of Genetic Predisposition to Hereditary Catalepsy in a Mouse Model of Neuropsychiatric Disorders Using Whole-Genome Sequencing Data.

Catalepsy is a behavioral condition that is associated with severe psychopathologies, including schizophrenia, depression, and Parkinson's disease. In some mouse strains, catalepsy can be induced by pinching the skin at the scruff of the neck. The main locus of hereditary catalepsy in mice has recently been linked to the 105-115 Mb fragment of mouse chromosome 13 by QTL analysis. We performed whole-genome sequencing of catalepsy-resistant and catalepsy-prone mouse strains in order to pinpoint the putative candidate genes related to hereditary catalepsy in mice. We remapped the previously described main locus for hereditary catalepsy in mice to the chromosome region 103.92-106.16 Mb. A homologous human region on chromosome 5 includes genetic and epigenetic variants associated with schizophrenia. Furthermore, we identified a missense variant in catalepsy-prone strains within the Nln gene. Nln encodes neurolysin, which degrades neurotensin, a peptide reported to induce catalepsy in mice. Our data suggest that Nln is the most probable candidate for the role of major gene of hereditary, pinch-induced catalepsy in mice and point to a shared molecular pathway between catalepsy in mice and human neuropsychiatric disorders.

[Analysis of intraocular lens displacement relative to the haptic plane by ultrasound biomicroscopy data]. / Analiz smeshchenii opticheskoi chasti intraokulyarnoi linzy otnositel'no ploskosti gapticheskikh elementov po dannym ul'trazvukovoi biomikroskopii.

PURPOSE: This study analyzed cases with postoperative displacement of intraocular lens (IOL) relative to the haptic plane using ultrasound biomicroscopy (UBM). MATERIAL AND METHODS: The study analyzed biometry data of 231 patients (277 eyes) aged 72.39±7.77 years, among them 43.25% were males. IOL position and refraction were analyzed at 1, 3 and 6 months after standard phacoemulsification. RESULTS AND DISCUSSION: UBM was performed to analyze the position of the IOL. Stabilization of lens position was observed by the 3rd month of observation. Among the cases with displacement of the optical part relative to the haptic plane, the forward shift was determined in 24.85%, backward - in 16.67% of cases. Eyes with opposite IOL displacements differed significantly in lens diameter, ciliary sulcus diameter and the power of implanted IOL. IOL shift towards the retina produced significant hyperopic refractive error. A discriminant function was compiled using preoperative biometry data comprising the model for predicting backward IOL displacement with high probability. However, we failed to obtain a qualitative model for forward IOL displacements. CONCLUSION: Calculation error in modern formulas could occur because of IOL displacement, including the shift of the optical part relative to the haptic plane in postoperative period. Analysis of biometry data allows calculating IOL displacement towards the retina with a high probability, which could help avoid hyperopic refraction error postoperatively.

Comparison of Fluorometric and Chromatographic Methods of In Vitro Assay of Tryptophan Hydroxylase 2, the Key Enzyme of Serotonin Synthesis in the Brain.

We present rapid and sensitive assay of tryptophan hydroxylase 2 enzyme activity based on the fluorescence of the complex of 5-hydroxytryptophan (5-HTP) with o-phthalic aldehyde. This method was compared with the standard method based on chromatographic isolation of 5-HTP followed by its quantification using an electrochemical detector. High sensitivity of the developed fluorometric method and similarity of the results obtained by fluorometric and chromatographic methods were demonstrated. The use of this rapid, cheap, and effective fluorometric method can simplify and facilitate measurements of tryptophan hydroxylase 2 activity and can make this assay available for a wide range of neurochemical and pharmacological laboratories.

[Alterations in the Level of mRNA of TPH1, TPH2 Genes, Tryptophan Hydroxylase Activity and Serotonin Metabolism in Mouse Brain Five Days after Lipopolysaccharide Administration].

Tryptophan hydroxylases 1 and 2 (TPH1 and TPH2) play a key role in the synthesis of serotonin (5-HT), a hormone and neurotransmitter, in the peripheral organs and brain, respectively. The main aim of this study was to clarify the distribution of mRNA of the Tph1 and Tph2 genes in brain structures under normal conditions and after inflammation. The experiments were carried out on young (4 weeks old) male C57BL/6 mice. The animals were divided into three groups: intact, control, injected ip with saline, and injected ip with 2 mg/kg of bacterial lipopolysaccharide (LPS). Markers of inflammation, spleen mass and thymus mass were assayed 5 days after the saline or LPS administration. In the frontal cortex, hippocampus, striatum, hypothalamus, and midbrain the concentrations of 5-HT and its main metabolite, 5-hydroxyindole acetic acid (5-HIAA), and TPH activity were assayed using HPLC, while Tph1 and Tph2 mRNA were quantified using quantitative real-time RT-PCR. A dramatic increase of spleen mass and decrease of thymus mass 5 days after LPS administration was shown. A significant increase of 5-HT and 5-HIAA levels in the midbrain as well as decrease of 5-HIAA concentration and TPH activity in hypothalamus in mice treated with LPS and saline compared with intact animals was revealed. The highest concentration of Tph2 gene mRNA was observed in the midbrain in 5-HT neuron bodies, while this gene mRNA level was lower in 5-HT endings (cortex, hippocampus, striatum, and hypothalamus). Trace amounts of Tph1 mRNA was found in all studied brain structures in mice of the three groups. Thus, Tph1 gene expression in the mouse brain is too low to significantly affect 5-HT synthesis in normal conditions and during inflammation.

[Short-term experience of intravitreal brolucizumab in treatment of diabetic macular edema]. / Kratkosrochnyi opyt primeneniya brolutsizumaba v lechenii diabeticheskogo makulyarnogo oteka.

PURPOSE: This study examines the efficacy and safety of brolucizumab in the treatment of diabetic macular edema (DME) in real clinical practice in the Russian Federation. MATERIAL AND METHODS: The study included 14 consecutive treatment-naïve DME patients, among them 7 males and 7 females (21 eyes in total) with mean age of 65.1±8.0 years. Patients underwent standard ophthalmological examination and multimodal imaging, including optical coherence tomography. All patients received intravitreal injections of brolucizumab every 6 weeks. A total of 73 injections were performed. A data analysis was performed for 10 eyes of 10 patients 6 months after initiation of the treatment. RESULTS: After 4 injections of brolucizumab, best-corrected visual acuity (BCVA) increased statistically significantly from 35.8±13.7 to 41.5±11.9 ETDRS letters (p=0.03), central retinal thickness (CRT) and macular volume (MV) decreased from 411.5±107.4 to 280.2±64.6 microns (p=0.014) and from 7.39±0.92 to 6.16±7.37 mm3 (p=0.0006), respectively. The average gain of visual acuity was 5.7±7.0 letters, average decrease of CRT was -131.3±91.2, and average decrease of MV was -1.21±0.75 mm3. There were no adverse events associated with intraocular inflammation. CONCLUSION: Intravitreal injections of brolucizumab provide significant anatomical and functional improvement to DME patients in real clinical practice with results comparable to that of randomized clinical trials.

[A case of arrhythmogenic right ventricular cardiomyo-pathy associated with myocardial inflammation].

Recent years have been marked by a number of published reports that have shown a high frequency of signs of myocardial inflammation in patients with confirmed arrhythmogenic right ventricular cardiomyopathy (ARVC). This article presents a clinical case of typical phenotypic manifestations of ARVC associated with morphometric signs of subacute myocarditis. A 66-year-old man presented to the emergency department with signs of arrhythmogenic shock caused by ventricular tachycardia. Examination detected electrocardiographic signs of (ARVC), visualized signs of right ventricular dilatation, increased trabeculation, and wall fibrosis. Endomyocardial biopsy of the right ventricular wall showed degenerative alterations of cardiomyocytes with perivascular lymphocytic infiltration and areas of granulation tissue. New facts that evidence inflammatory alterations of the myocardium will still require specifying and reconsidering positions of expert consensuses on diagnostics and treatment of ARVC.

[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

[Questionnaire of the Ryzhikh National Medical Research Centre for Coloproctology is a new tool for assessing chronic pelvic pain and pelvic organ dysfunction]. / Oprosnik NMITs koloproktologii imeni A.N. Ryzhikh ­ novyi instrument otsenki khronicheskoi tazovoi boli i narusheniya funktsii tazovykh organov.

The article presents the work of a multidisciplinary team of experts from various fields of medicine to optimize the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ for use in clinical practice. The survey of respondents was conducted from June 28 to September 28, 2021. As a result of this survey, by repeatedly making edits and clarifications during communication with respondents, the final version was obtained, which allows assessing the patient's subjective sensations by the nature and localization of pelvic pain, sensitivity disorders and pelvic organ function. The main objective of this Questionnaire is to differentiate patients with neurogenic pain from a huge number of patients with chronic pelvic pain. This aspect will allow a more targeted approach to the diagnosis and pathogenetically justified treatment of patients, including after appropriate instrumental examinations. The work of a multidisciplinary team implies a higher degree of objectification and terminological accuracy of the Questionnaire under discussion. The presented version of the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ will be primarily used in coloproctological patients with pelvic pain problems and anal incontinence and obstructive defecation. Further studies will be directed to the clinical evaluation of the results of the work carried out.

[Particularities of thermoregulation in Parkinson's disease]. / Osobennosti termoregulyatsii u patsientov s bolezn'yu Parkinsona.

OBJECTIVE: To evaluate the topography of thermographic characteristics and compliance with the degree of asymmetry of motor and thermometric characteristics of patients with Parkinson's disease (PD). MATERIAL AND METHODS: The study enrolled 45 patients with PD (stage 1-3) according to the Hoehn and Yahr scale. The patients were divided into two groups: a right-sided group (n=27) and a left-sided one (n=18). The groups were matched for age, disease type and duration, and symptom severity. All the patients in the study group underwent thermography investigation. RESULTS: Lower temperature values were noted on the more affected side (p<0.05) only in patients with left-sided predominance of symptoms (p<0.05). CONCLUSION: This result may suggest that left-sided PD patients have more frequent thermoregulation dysfunction, but further research is needed to investigate the relationship between thermoregulation and motor asymmetry.

The Influence of Spatial Effects on the Dynamics of Solutions in Keynes' Mathematical Model of the Business Cycle.

We consider the special case of the mathematical model of Keynes' business cycle with the spatial interaction. In this model we assume that macroeconomic factors affect a certain geographical region and economic indicators. The dependence occurs on the spatial (geographical) coordinates in addition to the dependence on the temporal evolution, even if the economic subject is externally homogeneous in space. Spatial interaction led us to analyze a system of two differential equations of the 'reaction-diffusion' type, which replaces a system of two ordinary differential equations. This method is often used to analyze the dynamics of complex nonlinear systems and macroeconomic entities. An analysis of such a mathematical model is based on the use of modern methods of the theory of dynamical systems indicate the presence of new nonlinear effects in addition to those used in the traditional version of the Keynes model. We encountered the loss of stability of the homogeneous economic equilibrium state and the occurrence of economic cycles for some values of the parameters while investigating the characteristics of such a system. Meanwhile, another version of instability of a homogeneous economic equilibrium state with a different choice of parameters occurs, which in many cases leads to the appearance of a spatially non-homogeneous equilibrium state, which is characterized by the dependence of the corresponding economic indicators on the spatial (geographical) coordinates of the area in which the assigned macroeconomic entity is located.

[Eating behavior in children with autism spectrum disorder]. / Narusheniya pishchevogo povedeniya u detei s rasstroistvami autisticheskogo spektra.

OBJECTIVE: To study atypical eating behavior (AEB) in various variants of autism spectrum disorder (ASD) to determine the prognosis and therapeutic tactics. MATERIAL AND METHODS: One hundred and eighty patients (110 girls, 70 boys), aged 2 to 5 years (mean age 4 years), with a diagnosis of «Childhood autism¼ (F84.02), «Atypical autism¼ (F84.1), «Asperger Syndrome¼ (F84.5) and the presence of AEB were examined. RESULTS: Three clinical variants of ASD accompanied by AEB were identified: catatonic-regressive (n=75, 41%), catatonic (n=81, 45%) and hyperdynamic (n=24, 13%). The most pronounced AEB were in the catatonic-regressive variant, and the least in the hyperdynamic variant of ASD. The severity of AEB is associated with the severity of cognitive dysontogenesis. CONCLUSION: The characteristics of AEB are associated with the leading clinical syndrome of ASD. The severity of catatonia and regression affects the depth of AEB, which leads to secondary somatic disorders. Specialists of various profiles should participate in medical work for successful rehabilitation and prevention of somatic complications.

[Activity of the Russian antitumor compound chlonisol in models of eyelid tumors (experimental study)]. / Aktivnost' otechestvennogo protivoopukholevogo soedineniya khlonizol na modelyakh opukholei vek (eksperimental'noe issledovanie).

Eyelid tumors are the most common neoplasms in everyday ophthalmic practice and cover a wide range of benign and malignant lesions. Surgical methods, cryodestruction, laser therapy and radiation therapy are used in the treatment of malignant eyelid tumors. Chemotherapy does not occupy a prominent place in the treatment of malignant eyelid tumors, its use is limited to sensitive tumors. OBJECTIVE: To assess the antitumor activity of the Russian-developed chemical compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1.3-propandiol (chlonisol) on the models of transplantable tumors of various histogenesis implanted into the lower eyelid. MATERIAL AND METHODS: The study was carried out on 67 mice of lines 129/SN, BALB/c and C57BL/6 that had Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid. Tumor transplantation was done by injecting 0.05 ml of sterile sodium chloride solution containing 106 cells of Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1, or 10% suspension of tumor tissue of B16 melanoma. The injection was performed into the right lower eyelid in the direction from the outer towards the inner corner of the eye using a thin needle (29G). Chlonisol was administered at the maximum tolerated dose of 20 mg/kg or at the lower dose of 15 mg/kg intraperitoneally 24 hours after tumor transplantation. RESULTS: In mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and melanoma B16 transplanted under the skin of the lower eyelid, a single intraperitoneal injection of chlonisol at the dose of 20 or 15 mg/kg caused significant inhibition of tumor growth reaching 100%. Chlonisol significantly increased overall survival in animals with Ehrlich carcinoma (log rank test, p=0.0464), sarcoma 37 (log rank test, p<0.0001), lymphosarcoma LIO-1 (log rank test, p=0.0122) and B16 melanoma (log rank test, p<0.0001); the proportion of animals that were fully healed was 25, 78, 67 and 25%, respectively. CONCLUSION: Chlonisol has a pronounced antitumor effect in mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid.