[Targeting NMDAR/AMPAR: a promising pharmacotherapeutic approach for depressive disorders]. / Targetirovanie NMDAR/AMPAR ­ perspektivnyi podkhod farmakokorrektsii depressivnykh rasstroistv.

Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

Gamma-ray dose threshold for MAPbI3 solar cells.

In this work, we report on the effects observed in MAPbI3 polycrystalline films and solar cells under moderate gamma-ray doses of 3-21 kGy. We applied several instrumental techniques such as photoluminescence spectroscopy, time-resolved photoluminescence, Suns-VOC measurement, and impedance spectroscopy to characterize exposed samples. We observed a nonlinear dependency of such characteristics as PL intensity, career lifetime, ideality factor, and recombination resistance on the exposure dose. Small doses of 3-5 kGy annihilate some of the defect centers in the material, which results in improved carrier extraction and prolonged carrier lifetime, while with larger doses of 10 kGy and above, nonradiative recombination becomes predominant. In this way, we revealed a gamma-ray threshold for MAPbI3 films of around 10 kGy, above which it is not recommended to exploit this material. In space environment, yearly doses rarely exhibit 0.1 kGy (10 krad), and the MAPbI3 material has a sufficient margin of safety for space applications. Moreover, this unusual behaviour opens up the opportunity to use gamma-ray sources as an effective method to improve the quality of defective polycrystalline perovskite films before actual exploitation in an ionizing radiation-free environment.

[Methodological recommendations for surgical care in patients with hemophilia A receiving prophylactic therapy with emicizumab]. / Metodicheskie rekomendatsii po okazaniyu khirurgicheskoi pomoshchi u patsientov s gemofiliei A, poluchayushchikh profilakticheskuyu terapiyu emitsizumabom.

Methodological recommendations for surgical care in patients with hemophilia A receiving prophylactic therapy with emicizumab. Recommendations of the expert group. Moscow, 2024.

[Fixed ratio combinations GLP-1RA and basal insulin: literature review].

The progressive nature of type 2 diabetes mellitus leads to the need for insulin therapy in a significant proportion of patients. Very often start of insulin therapy in type 2 diabetes mellitus (T2DM) is associated with weight gain and a significant increase of hypoglycemia's risk. However, innovative options, such as fixed ratio combinations of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulin, minimize weight gain and hypoglycemia risks and allow a greater proportion of patients to achieve individual glycemic control goals without compromising safety parameters. This review includes a description of the randomized clinical trials, as well as the results of real clinical practice of the use of two currently existing fixed ration combinations of GLP-1RA and basal insulin - iDegLira and iGlarLixi.

Sorption behaviour of neptunium in marine and fresh water bottom sediments in Far East area of Russia (Lake Khanka and Amur Bay).

The concentration and sorption behavior of 237Np on the bottom sediments of water bodies in the Far East region of Russia (Lake Khanka and Peter the Great Bay) were studied for the first time. The 237Np concentrations vary from 1.06 × 10-6 to 4.43 × 10-5 mBq g-1 in the bottom sediments of Lake Khanka and from 1.05 × 10-4 to 2.52 × 10-3 mBq g-1 for Amur Bay. The experiment on the adsorption of Np on marine and lake sediment showed that it is sorbed through complexation with silicates (albite, leucite). The Np sorption isotherm on marine sediments is described by the Langmuir equation; the distribution coefficients (Kd) of Np vary from 57 to 588 mL g-1. For lake sediments, the isotherm is described by the Henry equation; the Kd value reaches 935 mL g-1.

[The effect of etiopathogenetic therapy of COVID-19 on the severity of the disease: results of a multicenter double-blind placebo-controlled randomized trial].

AIM: The search for etiopathogenetic agents to prevent the development of severe and extremely severe COVID-19 remains relevant. A placebo-controlled randomized clinical trial was conducted to evaluate the efficacy and safety of the antibody-based biological drug (Raphamin). MATERIALS AND METHODS: 785 outpatients 18-75 y.o. with laboratory confirmed mild COVID-19 were included within 24 hours from the disease onset. 771 patients were randomized to the group Raphamin (n=382) and the Placebo group (n=389). The study drug/placebo was prescribed for 5 days. The rate of progression to a more severe degree of COVID-19 by day 28 as well as the time to sustained clinical recovery and the frequency of hospitalization were evaluated. Safety was assessed taking into account adverse events, vital signs and laboratory parameters. RESULTS: The number of cases of progression to a more severe degree of COVID-19 in participants receiving Raphamin was 59 (15.5%) [52 (14.6%)] versus placebo - 89 (22.9%) [85 (23.7%)], ITT and [PP] analysis data are presented. The odds ratio between groups was OR=0.6157 [OR=0.5494], 95% confidence interval 0.4276-0.8866 [0.3750-0.8048], which meant a reduction in the chance of progression to a more severe degree by 38.4% [45.1%] or 1.48 [1.62] times; p=0.0088 [p=0.0019]. The time to sustained recovery in the Raphamin group was 4.5±2.4 [4.6±2.4] days, versus placebo - 5.8±4.7 [6.0±4.8] days; p=0.0025 [p=0.0036]. No adverse events with a certain relationship were registered. CONCLUSION: Raphamin reduces the risk of progression to a more severe degree of the COVID-19 and significantly shortens the duration of clinical symptoms.

Positron re-emission, reflection, and diffraction from W(100) surface at very low energies.

The energy distributions of scattered and re-emitted low-energy positrons from a W(100) surface were measured as a function of incident positron energy from 0 to 25 eV. Given that tungsten has a negative work function of about -3 eV for positrons, one can envisage three scenarios of very low-energy positron scattering from such a surface. First, a positron approaching the sample surface with energy say 1 eV above the vacuum level will see a potential barrier of about 2 eV height and will be reflected back to the vacuum. Second, when the energy of incident positrons increases up to the top of the surface potential barrier (positron work function), they start entering the solid and, therefore, the reflectivity of positrons from the surface reduces. Positrons entering the solid are thermalised within few picoseconds and have a chance to escape back to the vacuum with kinetic energy about 3 eV above the vacuum level undergoing so-calledre-emission. Third, coherent scattering of low-energy positrons may occur on the crystal surface, i.e. positron diffraction. All the three scenarios of low-energy positrons scattering are studied here experimentally. Measured spectra are very sensitive to the surface conditions of the sample: they change dramatically after surface oxidation or thin film deposition.

[Molecular methods for diagnosing novel coronavirus infection: comparison of loop-mediated isothermal amplification and polymerase chain reaction].

INTRODUCTION: Currently, the basis for molecular diagnostics of most infections is the use of reverse transcription polymerase chain reaction (RT-PCR). Technologies based on reverse transcription isothermal loop amplification (RT-LAMP) can be used as an alternative to RT-PCR for diagnostic purposes. In this study, we compared the RTLAMP and RT-PCR methods in order to analyze both the advantages and disadvantages of the two approaches. MATERIAL AND METHODS: For the study, we used reagent kits based on RT-PCR and RT-LAMP. The biological material obtained by taking swabs from the mucous membrane of the oropharynx and nasopharynx in patients with symptoms of a new coronavirus infection was used. RESULTS: We tested 381 RNA samples of the SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) from various patients. The obtained values of the threshold cycle (Ct) for RT-PCR averaged 20.0 ± 3.7 s (1530 ± 300 s), and for RT-LAMP 12.8 ± 3.7 s (550 ± 160 s). Proceeding from the theoretical assumptions, a linear relationship between values obtained in two kits was proposed as a hypothesis; the correlation coefficient was approximately 0.827. At the same time, for samples with a low viral load (VL), the higher Ct values in RT-LAMP did not always correlated with those obtained in RT-PCR. DISCUSSION: We noted a significant gain in time for analysis using RT-LAMP compared to RT-PCR, which can be important in the context of testing a large number of samples. Being easy to use and boasting short turnaround time, RT-LAMP-based test systems can be used for mass screening in order to identify persons with medium and high VLs who pose the greatest threat of the spread of SARS-CoV-2, while RT-PCR-based diagnostic methods are also suitable for estimation of VL and its dynamics in patients with COVID-19.

Structural Insight into Complexation Ability and Coordination of Uranyl Nitrate by 1,10-Phenanthroline-2,9-diamides.

Reprocessing of spent nuclear fuel (SNF) is an important task in a frame of ecology and rational use of natural resources. Uranium, as the main component of SNF (>95%), can be recovered for further use as fresh nuclear fuel. To minimize an amount of solid radioactive waste generated during SNF reprocessing, new extractants are under investigation. Diamides of 1,10-phenanthroline-2,9-dicarboxylic acid are perspective tetradentate N-donor ligands that form strong complexes with f-elements, which are soluble in polar organic solvents. As an example of three ligands of this class, we conducted a comparative study and showed how the substituent in the amide functional group affects the extraction ability toward uranyl nitrate from nitric acid media. We have performed a careful study (NMR, FT-IR, XRD, RMC-EXAFS) of the structures of synthesized complexes of new ligands with uranyl nitrate and used quantum mechanical calculations to explain the discovered regularities through.

[Kalmann syndrome in monozygous twins as an isolated manifestation of the SOX10 gene defect].

More than 30 genes are known to take part in hypothalamic-pituitary-gonadal axis development at the date and role of more than 10 other genes is studied. Despite it about 50% of isolated hypogonadotropic hypogonadism cases still have no molecular genetic explanation.A number of specific associations between iHH and different not-reproductive manifestations called syndromic forms are distinguished in general group of iHH. For example, the combination of Kalmann syndrome with sensorineural hearing loss is known as manifestation for defects of some genes encoding factors of neuronal migration; in patients with this phenotype CHD7, SOX10 genes defects are most frequent. However, defects in the genes of neuronal migration factors are characterized by a wide variability of phenotype, which is explained by the epigenetic mechanisms influence. Carriers of the mutation within the same family may lack some non-reproductive manifestations as well as hypogonadism.Here we present a case of Kalmann syndrome in monozygous twins, caused by a previously not described heterozygous mutation c.462C> G: p.I154M in the SOX10 gene in the absence of sensorineural hearing loss. The mutation was inherited from a father who has only isolated anosmia in the phenotype. This mutation was identified during full exome sequencing. This unique observation for Russia shows on the one hand expediency to check SOX10 sequence in addition to the other factors of neuronal migration and differentiation and, on the other hand, the prospect of full exome sequencing in a group of patients with undifferentiated iHH.

[A deep intronic mutation in AR gene causing androgen insensitivity syndrome: difficulties of diagnostics].

Partial androgen resistance syndrome (PAIS) is the most difficult form of disorders/differences of sex development 46,XY (DSD 46,XY) for choosing of patient management. To date, there are no clear biochemical criteria, especially before puberty, that allow differentiating PAIS from other PAIS-like forms of DSD 46, XY, and genetic verification of the partial form of AIS plays an important role. Meanwhile, according to the literature, mutations in the coding region of AR gene have not been identified in more than 50% of patients with suspected AIS. We performed an extensive analysis of the AR gene in a patient with clinical and laboratory signs of AIS and found a deep intron mutation in the AR gene (p. 2450-42G>A). This variant creates an alternative splice acceptor site resulted a disturbance of the AR function. These findings indicate the need for extensive genetic analysis in a cohort of patients with suspected CPA in the absence of mutations in the AR gene using standard methods of genetic diagnosis.

[Forensic aspects of the burning of human corpses]. / Sudebno-meditsinskie aspekty sozhzheniya trupov lyudei.

Objective - to outline the basic ideas about the conditions and results of the burning of human corpses and the potential possibilities of a forensic medical examination of the burned remains. It is impossible to burn the corpse of an adult to a state of only homogeneous ash not only on the fire, but also in special crematorium chambers. After the burning of the corpse, ash and bone fragments remain in a state of black, gray and white heat. The state of the cremated remains allows, at least, establishing the number of incinerated corpses, their species and anatomical affiliation. Reconstruction of the conditions of corpse burning is possible only within the framework of a comprehensive forensic examination with the participation of specialists in the field of fire-technical affairs and forensic medical experts. The exclusive competence of specialists in the field of fire-technical affairs is the verification of the conditions of combustion (type and volume of fuel, technical features of combustion, duration of cremation, etc.).

[Influence of chemosensional disorders on taste preferences in cancer patients who are receiving oral nutrition supplements].

Chemosensory disorders (CSD) such as disorders of taste and smell are one of the causes of malnutrition in cancer patients. The aim of the research was to evaluate the influence of CSD on taste preferences in cancer patients receiving oral nutritional supplements (ONS). Material and methods. The procedure involves 100 oncological patients (26 men, 74 women; 57.0±1.2 years old). The taste preferences in these patients were assessed using a digital rating scale during ONS. All patients had cancer outside the head and neck area and underwent specific treatment. The functional status on the ECOG scale was 0-II. All patients had indications for DPP (ESMO scale >2 points). Patients were offered a mixture of sweet (banana, coffee, vanilla) and unsweetened (vegetable, chicken soup) tastes in a disposable 30 ml container. The patient was asked to take a sip and evaluate the smell, taste, strength of taste and density (consistency) of the sample on a digital rating scale from 0 to 5 points, where 0 - I do not feel, 5 - I feel excellent. The maximum possible number of points for each sample was 20. Results. Signs of CSD (score <10) were detected in 69% of patients [95% confidence interval (CI) 59.5-77.7]. In this group, the frequency of choosing unsweetened tastes for ONS was 59.4% (95% CI 47.5-70.8), sweet - 40.6% (95% CI 29.2-52.5). In the group of patients without signs of CSD, the frequency of choosing savory tastes was 29.0% (95% CI 14.1-46.7), sweet - 71.0% (95% CI 53.3-85.9) (р=0.0049). Conclusion. The presence of CSD significantly affects the taste preferences of cancer patients and significantly increases the likelihood of choosing products for ONS with unsweetened taste (unsweetened foods).

[Antioxidant effect of cortexin, cerebrolysin and actovegin in rats with chronic cerebrovascular insufficiency]. / Antioksidantnoe deistvie Korteksina, Tserebrolizina i Aktovegina u zhivotnykh s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To compare the antioxidant effects of cortexin, cerebrolysin and actovegin in rats with chronic brain ischemia. MATERIAL AND METHODS: Chronic brain ischemia was modeled in male rats by 50% stenosis of the common carotid arteries. Forty days after surgery, the animals received 2 ten-day courses of therapy, separated by a break of 10 days. Placebo, cortexin (0.3, 1 and 3 mg/kg), cerebrolysin (0.8, 2.5 and 7.5 ml/kg) and actovegin (5 ml/kg) were administered to animals as treatment. The concentration of malondialdehyde (MDA) in the homogenates was determined by the reaction with thiobarbituric acid, the concentration of reduced glutathione was determined by the reduction reaction of 5.5-dithiobis- (2-nitrobenzoic acid); determination of catalase activity, as well as the content of lactate and pyruvate, by commercially available reagent kits. The activity of superoxide dismutase (SOD) was determined by the photometric method based on an assessment of the degree of inhibition of the epinephrine oxidation reaction. All reactions were carried out in triplicates. RESULTS: Modeling of chronic brain ischemia led to the statistically significant decrease in the content of lactate and pyruvate (p<0.001, when compared with the control group), which was not accompanied by a significant decrease in their ratio (p>0.05), as well as to the decrease in SOD, catalase activity, restored glutathione and increase in MDA concentrations. Compared with the control group, in the groups that received cortexin at a dose of 3 mg/kg/day, cerebrolysin at a dose of 7.5 ml/kg/day and actovegin at a dose of 5 ml/kg/day, there were an increase in the content of lactate and pyruvate (without a significant change in their ratio), restoration of glutathione levels and the activity of SOD and, to a lesser extent, catalase, combined with a decrease in the concentration of MDA. CONCLUSION: Course administration of cortexin (3 mg/kg), cerebrolysin (7.5 ml/kg) and, to a lesser extent, actovegin (5 ml/kg) has a positive effect on the state of the antioxidant system of the brain in rats with chronic brain ischemia.

[Clinical and molecular genetic features of 3 family cases of the central precocious puberty, due to MKRN3 gene defects].

Gonadotropin-dependent precocious puberty (central) is a condition resulting from the early (up to 8 years in girls and 9 years in boys) reactivation of the hypothalamic-pituitary-gonadal axis. An increase in the secretion of sex steroids by the gonads in this form is a consequence of the stimulation of the sex glands by gonadotropic hormones of the pituitary gland. In the absence of central nervous system abnormalities, CPP is classified as idiopathic and as familial in some cases, emphasizing the genetic origin of this disorder. Loss-of-function mutations in Makorin Ring Finger Protein 3 (MKRN3) are the most common identified genetic cause of central precocious puberty compared to sporadic cases. In the present study we performed the first descrition of 3 family cases of central precocious puberty duo to novel MKRN3 gene mutation detected by NGS in the Russian Federation.

[Clinical and molecular genetic features of cases of isolated hypogonadotropic hypogonadism, associated with defects in GNRHR genes].

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterised by lack of pubertal development and infertility, due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH). Clinically, there are variants of CHH with hypo-/anosmia (Kalman syndrome) and normosmic hypogonadotropic hypogonadism. Given a  growing list of gene mutations accounting for CHH, the application of next generation sequencing (NGS) comprises an excellent molecular diagnostic approach because it enables the simultaneous evaluation of many genes. Biallelic mutations in GNRHR gene lead to the development of hypogonadotropic hypogonadism with normosmia. In this paper, we describe 16 patients with proven GnRH resistance and estimate the frequency of pathogenic variants in the GNRHR gene in the Russian population.

[Familial case of hypogonadotropic hypogonadism as the CHARGE syndrome manifestation].

CHARGE syndrome is a rare autosomal dominant disease caused by CHD7 gene mutations. Individuals with CHARGE display a wide spectrum of clinical features. It might be presented only as a delay puberty, which does not require any hormone replacement therapy to severe CHARGE phenotype, requiring a multidisciplinary therapeutic approach. Wild spectrum of clinical presentation can be seen even among the patients with identical mutation. Diagnosis might be suspected by a combination of major and minor clinical criteria of this disorder, but molecular genetic analysis is mandatory for final verification. Accurate diagnosis is essential to informing patients about all possible clinical features, reproductive status and choosing the correct treatment approach. The most common endocrine abnormality in patients with CHARGE syndrome is the disturbance in gonadotropins function ranged from delay puberty to persistent hypogonadotropic hypogonadism with different olfactory phenotypes, resulted by specific role of CHD7 in GnRH neuronal embryogenesis.We describe a familial case of CHARGE syndrome with significant intrafamilial clinical heterogeneity due to CHD7 gene mutation.

LASER THERMAL ABLATION OF BENIGN THYROID NODULES AS AN EFFECTIVE, SAFE AND MINIMALLY INVASIVE METHOD FOR TREATING NODULAR GOITER (REVIEW).

To search for effective and safe methods aimed at reducing the frequency of surgical treatment for nodular thyroid pathology. 1999-2019 literature review conducted using NLM databases. There is more and more evidence in the literature on the efficacy and safety of minimally invasive treatments for thyroid nodular disease. Based on the literature data, it was revealed that the most effective technique for minimally invasive treatment is laser thermal ablation of thyroid nodules under visual control. This technique can be considered an alternative to surgical intervention in the treatment of benign thyroid nodules and, in most cases, leads to a decrease or complete disappearance of the nodule, clinical manifestations, or cosmetic defects. Unlike surgical treatment, it is practically devoid of the likelihood of formidable complications and, as a rule, passes without any threatening consequences for the patient. While the use of laser thermal ablation is expanding, the international medical community has begun to incorporate this technique into treatment guidelines and is making efforts to disseminate it in general clinical practice. Since the method of laser thermal ablation can be considered an effective alternative to surgical intervention for the treatment of benign thyroid nodules, it is necessary to widely introduce it into the general clinical practice in Russia and algorithms for providing medical care to patients with nodular goiter. The introduction of imaging-guided laser thermal ablation into clinical practice and its inclusion in the algorithms for the provision of medical care to patients with thyroid nodular pathology will significantly improve the quality and availability of medical care for patients with thyroid nodular pathology.

[Rapid diagnostics of novel coronavirus infection by loop-mediated isothermal amplification].

This review presents the basic principles of application of the loop-mediated isothermal amplification (LAMP) reaction for the rapid diagnosis of coronavirus infection caused by SARS-CoV-2. The basic technical details of the method, and the most popular approaches of specific and non-specific detection of amplification products are briefly described. We also discuss the first published works on the use of the method for the detection of the nucleic acid of the SARS-CoV-2 virus, including those being developed in the Russian Federation. For commercially available and published LAMP-based assays, the main analytical characteristics of the tests are listed, which are often comparable to those based on the method of reverse transcription polymerase chain reaction (RT-PCR), and in some cases are even superior. The advantages and limitations of this promising methodology in comparison to other methods of molecular diagnostics, primarily RT-PCR, are discussed, as well as the prospects for the development of technology for the detection of other infectious agents.

Diagnostics possibilities of erythrocytes analysis by the method of laser interference microscopy.

The morphofunctional state of erythrocytes significantly changes by the onset and progression of various diseases, as well as in critical conditions, injuries, accompanied by severe tissue damage. This leads to a violation of microcirculation and has an effect on hemorheology in general. In connection with this, there is a need for the development of adequate methods for assessing the functional activity of erythrocytes. The aim of the work was to study the possibilities of laser interference microscopy in the analysis of the functional state of erythrocytes. The results allowed us to quantify the state of the phase height and phase diameter of erythrocytes. Analysis of the surface nanostructure gave a qualitative assessment of the functional activity of cells. The following patterns were revealed: the action of adrenaline causes the appearance of echinocytes with an increase in phase height and decrease phase diameter and the appearance of spicules on the surface of cells. The action of cortisol leads to a decrease in the phase height and the phase diameter with the appearance of numerous loosening of the structure of the cell surface. Moreover, the traditional method of analyzing the distribution of erythrocytes in a population by morphology (discocytes, stomatocytes, and degeneratively altered cell forms) did not reveal statistically significant differences. Thus, the results indicate that the interference microscopy method allows a qualitative assessment of the morphofunctional activity of native cells. This increases the information content of the analysis and leads to the objectification of data on the functional capabilities of erythrocytes.