Effects of reprogrammed splenic CD8+ T-cells in vitro and in mice with spontaneous metastatic Lewis lung carcinoma.

BACKGROUND: Metastatic disease is a major and difficult-to-treat complication of lung cancer. Considering insufficient effectiveness of existing therapies and taking into account the current problem of lung cancer chemoresistance, it is necessary to continue the development of new treatments. METHODS: Previously, we have demonstrated the antitumor effects of reprogrammed CD8+ T-cells (rCD8+ T-cells) from the spleen in mice with orthotopic lung carcinoma. Reprogramming was conducted by inhibiting the MAPK/ERK signalling pathway through MEKi and the immune checkpoint PD-1/PD-L1. Concurrently, CD8+ T-cells were trained in Lewis lung carcinoma (LLC) cells. We suggested that rCD8+ T-cells isolated from the spleen might impede the development of metastatic disease. RESULTS: The present study has indicated that the reprogramming procedure enhances the survival and cytotoxicity of splenic CD8+ T-cells in LLC culture. In an LLC model of spontaneous metastasis, splenic rCD8 + T-cell therapy augmented the numbers of CD8+ T-cells and CD4+ T-cells in the lungs of mice. These changes can account for the partial reduction of tumors in the lungs and the mitigation of metastatic activity. CONCLUSIONS: Our proposed reprogramming method enhances the antitumor activity of CD8+ T-cells isolated from the spleen and could be valuable in formulating an approach to treating metastatic disease in patients with lung cancer.

Biological Activity of Artificial Plant Peptides Corresponding to the Translational Products of Small ORFs in Primary miRNAs and Other Long "Non-Coding" RNAs.

Generally, lncPEPs (peptides encoded by long non-coding RNAs) have been identified in many plant species of several families and in some animal species. Importantly, molecular mechanisms of the miPEPs (peptides encoded by primary microRNAs, pri-miRNAs) are often poorly understood in different flowering plants. Requirement for the additional studies in these directions is highlighted by alternative findings concerning positive regulation of pri-miRNA/miRNA expression by synthetic miPEPs in plants. Further extensive studies are also needed to understand the full set of their roles in eukaryotic organisms. This review mainly aims to consider the available data on the regulatory functions of the synthetic miPEPs. Studies of chemically synthesized miPEPs and analyzing the fine molecular mechanisms of their functional activities are reviewed. Brief description of the studies to identify lncORFs (open reading frames of long non-coding RNAs) and the encoded protein products is also provided.

[Clinical evaluation of the efficacy of innovative spread of a given fatty acid composition enriched by adaptogens].

Adaptogens are a group of substances capable to increase the nonspecific resistance of the organism to a wide range of harmful effects and stress. However, only limited data exist on their use in the composition of foods for special dietary uses. The aim of the study was to evaluate the effect of a diet that included vegetable-fat spread enriched with 5-hydroxytryptophan, L-theanine and γ-aminobutyric acid on memory, general well-being and emotional status of healthy volunteers. Material and methods. The single-center, single-blind randomized prospective trial that enrolled persons without signs of significant organic pathology have been performed. Participants were randomly allocated to receive either 45 g/day standard spread enriched with 5-hydroxytryptophan (0.67%), L-theanine (0.56%) and γ-aminobutyric acid (0.45%) (main group, MG) or 45 g/day standard spread (control group, CG) for 10 days. Beside this, all participants followed a standard diet. Initially, as well as on the 10th day after the start of using the diet, the emotional state was assessed using the HADS anxiety and depression scale and Beck's depression inventory (BDI), general well-being by SAN questionnaire, memory according to the Lurie method; reaction time and attention concentration were assessed using the Krepelin counting test and the Burdon correction test. A 5-point Likert visual-analogue scale was used to assess the palatability (pasting) of the product, the severity of feelings of hunger and satiety at the baseline and on the 10th day of the study. All tests were performed under the supervision of staff. During the study, daily monitoring of the presence of adverse events was performed. Results. There were 70 subjects in MG and 70 in CG. Lurie memory score significantly increased in the MG (59.9±6.7 vs 58.1±7.4 points at the baseline; p=0.001), but not in the CG (58.0±6.9 vs 57.3±7.3 points, p>0.05). According to the SAN questionnaire, significant increase of well-being values (46.9±13.4 vs 44.2±13.5 points; p=0.01) and mood (49.9±12.6 vs 47.4±12.9 points; p=0.01) was found in MG, while in CG there was an increase of the mood category only (54.4±10.8 vs 52.2±12.1, p=0.04). At the end of the study an increase of «Satiety¼ (60.3±22.8 vs 51.5±24.8, p=0.022) and decrease of «Hunger¼ score (24.1±19.8 vs 29.1±19.4, p=0.02) were revealed in CG but not in the CG. No significant change was found by the results of other tests, stool form and its frequency in both groups. Conclusion. Newly developed spread enriched with 5-hydroxytryptophan, L-theanine, γ-aminobutyric acid was well-tolerated, did not affect the feeling of hunger and satiety, and improved memory and well-being parameters.

The Role of Cancer and Somatic Stem Cells in the Anti-Inflammatory and Antitumor Effects of Aconitum baicalense Extract on Experimental Breast Cancer.

We studied the effects of the extract of the terrestrial part of Aconitum baicalense in BALB/c female mice at the early stages after the injection of N-methyl-N-nitrosourea (MNU). The extract reduced inflammatory activity and tumor growth in the mammary gland. The antitumor and anti-inflammatory effects of the extract are based on the inhibition of cancer stem cells, hematopoietic stem cells, and hematopoietic progenitor cells that promote inflammation. The extract of A. baicalense disrupted the recruitment of epithelial progenitor cells and angiogenesis precursors to the mammary gland preventing neovascularization and transformation of epithelial cells into tumor cells.

Effects of Age and Suntan on the Expression of Second Messenger Signaling Pathways of Necroptosis in Skin Cells during Facelifting Surgery.

We studied the effects of age and suntan on the expression of necroptosis signaling molecules (RIPK1, RIPK3, and MLKL kinases) and first TNF receptor (TNFR1) in isolated skin cells from women undergoing facelift surgery. In women above 50 years, the expression of the TNFR1, kinases RIPK1, RIPK3, and MLKL, the phosphorylated forms of these kinases was significantly (p<0.05) increased in comparison with the corresponding parameters in women under 30 years. The expression of all necroptosis proteins and TNFR1 in women with suntan was significantly (p<0.05) higher than in those without tan. Cells from the surgical material were incubated with TNFα to determine the level of induced necroptosis. In women aged >50 years and women with suntan, the expression of phosphorylated forms of kinases was significantly increased, which attested to necroptosis activation. This study allowed identifying the targets on skin cells for prevention of necrosis and inflammation after facelift surgery.

Age-Related Features of the Early Period of Liver Regeneration after Partial Hepatectomy in Rats.

Regenerative processes in the liver were studied in 3-month-old (young) and 9-month-old (aged) male Wistar rats on day 1 after 30 and 70% hepatectomy. Regardless of the resected liver volume, shifts in the biochemical parameters of the serum in aged rats were more pronounced than in young animals. After 30% hepatectomy, no age differences in the rate of hepatic regeneration were found, while after 70% liver resection this parameter was higher in young rats. Hepatectomy in young rats led to recruitment of MSC, hepatocyte precursors, endothelial and epithelial progenitor cells into the liver parenchyma and increased fluidity of the plasma and mitochondrial membranes of hepatocytes. In aged rats, the recruitment of MSC, hepatocyte precursors, and endothelial progenitor cells into the injured liver was impaired and the rigidity of the mitochondrial membranes of hepatocytes increased.

[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.

[Efficacy of newly developed kombucha-based specialized food product for treatment of constipation-predominant irritable bowel syndrome].

According to studies, the prevalence of constipation in the population can reach 27% due to the low intake of dietary fiber. Increasing dietary fiber intake can improve bowel movements. The aim of the study was to assess the efficacy of a non-alcoholic fermented pasteurized kombucha drink enriched with inulin and vitamins in patients with constipation-predominant irritable bowel syndrome (IBS). Material and methods. The study (NCT05164861) was approved by Local Ethics Committee and enrolled subjects with IBS (according to ROME IV). The subjects were randomized to receive either 220 ml of a non-alcoholic drink, based on pasteurized kombucha (KG), enriched with inulin (1.15 g/100 ml) or 220 ml water (control group, CG), for 10 days. Standard examination included evaluation of stool frequency (bowel movements per day), stool form (with the Bristol stool scale) and evaluation of concomitant symptoms (abdominal pain/discomfort, abdominal fullness, bloating, and feeling of incomplete bowel emptying) with the use of 5-point Likert scale before (BL) and 10 days after the start of intervention (EOT). Using visual analog scales (VAS), the palatability of the studied food was assessed at the beginning and end of the observation period. Results. Significant increase of stool frequency was found at the EOT compared to BL in KG (n=20), Mean±SD: 0.60±0.31 to 0.85±0.19 times/day; p=0.004, while there was no change in CG (n=20): 0.63±0.33 vs 0.72±0.28, p=0.6. Mean values of stool scale form increased in KG (3.0±1.2 to 4.4±1.0, p=0.001), while remained unchanged in CG (2.9±1.2 vs 3.4±1.2, p=0.6). Mean values of the Bristol stool scale in KG and CG differed significantly at EOT (p=0.018). Significant decrease in mean values of incomplete bowel emptying feeling was found in KG (1.88±0.78 at BL vs 1.41±0.56 points at EOT, p=0.015), but not in the control group. There were no statistically significant differences between patient's reports of the studied groups for other symptoms (bitterness and dryness in the mouth, heartburn, nausea, abdominal pain and heaviness in the stomach after eating). Conclusion. The effectiveness of a pasteurized fermented non-alcoholic drink based on kombucha enriched with inulin has been proven by reducing the intensity of complaints significant for constipation, normalizing the frequency and consistency of stools.

[Modification of dietary patterns in patients with non-alcoholic steatohepatitis].

AIM: To assess efficacy of dietary patterns modification with the use of specialized food in patients with non-alcoholic steatohepatitis (NASH). MATERIALS AND METHODS: We developed new specialized food (SPP2) based on literature data on the role of dietary patterns in pathogenesis of NASH. It contained -3 PUFAs, soluble dietary fiber, phospholipids, -lipoic acid, coenzyme Q10, L-carnitine, complex of vitamins. Patients with NASH (per EASL guidelines), were invited to participate in the study and were randomly assigned to receive either isocaloric diet (ICD) alone (based on the results of indirect calorimetry Cosmed, Italy) or isocaloric diet with specialized food (2 portions of SPP2 a day), for 14 days. Repeated examinations of body composition with phase angle analysis (InBody, Republic of Korea) and blood chemistry were performed at baseline (BL) and after 14 days (EOT). The patients were advised to follow usual physical activity during the study. Non-parametric statistics was used to compare BL and EOT characteristics in the groups. RESULTS: The groups did not differ by age, proportion of females, and baseline characteristics of body composition. Adherence to the diet was 87.5% in the ICD group and 88.2% in the ICD+SPP group (p=0.65). Compliance with the use of SPP was 100%. In the ICD+SPP group significant reduction of body weight was achieved (117.530.1 kg initially, vs 114.928.8 kg at EOT; p=0.007), whereas in the ICD group it was not statistically significant (106.722.1 kg at BL vs 104.016.8 kg at EOT, respectively; p=0.07). In contrast to the ICD group, in those who received ICD+SPP significant decrease in cholesterol (5.31.3 mmol/L at BL vs 4.61.3 mmol/L at EOT; p=0.003), LDL (3.71.0 mmol/L vs 3.31.0 mmol/L, respectively; p=0.009), alkaline phosphatase (132.699.1 vs 112.087.0 U/L; p=0.04), GGT (54.533.2 vs 37.519.7 U/L; p=0.04), insulin resistance index (6.13.2 vs 3.21.5, respectively; p=0.04) was detected. CONCLUSION: Modification of dietary patterns with the use of a specialized food in combination with low-calorie diet allows achieving significant reduction of weight and improve lipid and carbohydrate metabolism, reduce severity of cholestasis in patients with NASH.

Thin active region HgCdTe-based quantum cascade laser with quasi-relativistic dispersion law.

HgCdTe is promising as a material to solve a problem of the development of semiconductor sources with an operational frequency range of 6-10 THz due to the small optical phonon energies and electron effective mass. In this study, we calculate the dependence of the metal-metal waveguide characteristics on the number of cascades for the 3-well design HgCdTe-based quantum cascade laser at 8.3 THz. It is shown that four cascades are sufficient for lasing at a lattice temperature of 80 K due to the large gain in the active medium. The results of this study provide a way to simplify the fabrication of thin active region HgCdTe-based quantum cascade lasers for operation in the range of the GaAs phonon Reststrahlen band inaccessible to existing quantum cascade lasers.

[Efficacy of newly developed food for special dietary use in the diet of patients with non-alcoholic steatohepatitis].

Although diet plays a leading role in treatment of non-alcoholic fatty disease (and, in particular, non-alcoholic steatohepatitis), specialized foods for the treatment of these patients have not yet been developed. The aim of the study was to assess efficacy of the food for special dietary use (FSDU) in patients with non-alcoholic steatohepatitis. Material and methods. New FSDU contained (% of the RDAs): protein - 8%; fat - 7% (including ω-3 PUFA - 40%); soluble dietary fiber - 180%; phospholipids - 25%; alpha-lipoic acid - 33%; betaine - 10%; 12 mineral substances - 13-44%; 13 vitamins - 24-140%. The study (NCT04308980) was approved by local ethics committee and enrolled patients with diagnosis of NASH. Subjects were randomized to the following groups: those received iso-calorie diet (according to resting energy expenditures, by indirect calorimetry) alone (ICD) and iso-calorie diet + FSDU (2 portions per day, 14 days) (ICD + FSDU group). Safety was assessed based on clinical and laboratory data. Repeated measurements (baseline vs those on the 15th day of the study) of body composition assessed by bioelectrical impedance analysis, and blood chemistry were compared. Results. The results of complex examination of 20 subjects (12 in ICD + FSDU and 8 in ICD group) served as a source for the study. Initially, groups did not differ by age, sex, and body mass index (BMI). The product was well tolerated. In contrast to ICD group, those in ICD + FSDU group demonstrated greater decrease of weight: BMI initially (BMI0) (M±σ): 38.7±5.4 kg/m2 vs BMI at the end-point (BMIEOT) 36.7±5.1 kg/m2, p=0.003 in ICD + FSDU group, whereas in the ICD group BMI0=38.9±7.2 vs BMIEOT=38.9±7.3 kg/m2, p=0.08. These results were reached predominantly by a decrease of fat mass: body fat weight (BFW0) 50.2±10.7 vs BFWEOT=48.5±10.8 kg, p=0.002 in ICD + FSDU group, whereas BFW0=48.9±11.4 vs BFWEOT=47.8±11.6 kg, p=0.07 in ICD group. The activity of alanine and aspartate aminotransferase, gamma-glutamil transpeptidase and alkaline phosphatase decreased in ICD + FSDU group (р=<0.05), whereas in ICD group the difference between initial and control assessment was not significant (р=<0.10). Conclusion. The new FSDU is well tolerated by patients with NASH. In combination with iso-calorie diet, it may increase efficacy of weight loss, predominantly by fat.

Methodology for Conducting Post-Marketing Surveillance of Software as a Medical Device Based on Artificial Intelligence Technologies.

The aim of the study was to develop a methodology for conducting post-registration clinical monitoring of software as a medical device based on artificial intelligence technologies (SaMD-AI). Materials and Methods: The methodology of post-registration clinical monitoring is based on the requirements of regulatory legal acts issued by the Board of the Eurasian Economic Commission. To comply with these requirements, the monitoring involves submission of the review of adverse events reports, the review of developers' routine reports on the safety and efficiency of SaMD-AI, and the assessment of the system for collecting and analyzing developers' post-registration data on the safety and efficiency of medical devices. The methodology was developed with regard to the recommendations of the International Medical Device Regulators Forum and the documents issued by the Food and Drug Administration (USA). Field-testing of this methodology was carried out using SaMD-AI designed for diagnostic imaging. Results: The post-registration monitoring of SaMD-AI consists of three key stages: collecting user feedback, technical monitoring and clinical validation. Technical monitoring involves routine evaluation of SaMD-AI output data quality to detect and remove flaws in a timely manner, and to secure the product stability. Major outcomes include an ordered list of technical flaws in SaMD-AI and their classification using evidence from diagnostic imaging studies. The application of this methodology resulted in a gradual reduction in the number of studies with flaws due to timely improvements in artificial intelligence algorithms: the number of flaws decreased to 5% in various aspects during subsequent testing. Clinical validation confirmed that SaMD-AI is capable of producing clinically meaningful outputs related to its intended use within the functionality determined by the developer. The testing procedure and the baseline testing framework were established during the field testing. Conclusion: The developed methodology will ensure the safety and efficiency of SaMD-AI taking into account its specifics as intangible medical devices. The methodology presented in this paper can be used by SaMD-AI developers to plan and carry out the post-registration clinical monitoring.

[Technical decisions in surgical treatment of peripapillary duodenal ulcer]. / Tekhnicheskie resheniya v khirurgicheskom lechenii yazv dvenadtsatiperstnoi kishki okolososochkovoi lokalizatsii.

OBJECTIVE: To develop the surgical technology for prevention of duodenal, biliary and pancreatic hypertension after stomach resection for peripapillary duodenal ulcers. MATERIAL AND METHODS: The authors have an experience of 413 stomach resections for peptic ulcer disease. Major duodenal papilla was involved in destruction in 15 cases. The authors performed papillosphincterotomy, proximal duodenojejunostomy with involvement of major duodenal papilla into anastomosis or its transplantation into intestinal loop. RESULTS: Acute postoperative pancreatitis occurred in all patients (100%). Satisfactory immediate results were observed in 14 patients (93.3%). Postoperative acute pancreatitis was asymptomatic in these cases and therapy was effective. There was only 1 case (6.7%) of severe postoperative acute pancreatitis following by death from multiple organ failure. CONCLUSION: Immediate results confirm an effectiveness of surgical strategy for these patients.

[Adrenal imaging: anatomy and pathology (literature review)].

This literature review focuses on the normal adrenal gland anatomy and typical imaging features necessary to evaluate benign and malignant lesions. In particular, adenoma, pheochromocytoma, metastases and adrenocortical carcinoma were discussed as some of the most common lesions. For this purpose, a review of relevant local and international literature sources up to January 2021 was conducted.In many cases, adrenal incidentalomas have distinctive features allowing characterization using noninvasive methods. It is possible to suspect a malignant nature and promptly refer the patient for the necessary invasive examinations in some cases. -Computed tomography, especially with intravenous contrast enhancement, is the primary imaging modality because it enables differential diagnosis. Magnetic resonance tomography remains a sensitive method in lesion detection and follow-up but is not very specific for determining the malignant potential. Positron emission computed tomography also remains an additional method and is used mainly for differential diagnosis of malignant tumors, detecting metastases and recurrences after surgical treatment. Ultrasound has a limited role but is nevertheless of great importance in the pediatric population, especially newborns. Promising techniques such as radiomics and dual-energy CT can expand imaging capabilities and improve diagnostic accuracy.Because adrenal lesions are often incidentally detected by imaging performed for other reasons, it is vital to interpret such findings correctly. This review should give the reader a broad overview of how different imaging modalities can evaluate adrenal pathology and guide radiologists and clinicians.

A simplified cluster model and a tool adapted for collaborative labeling of lung cancer CT scans.

BACKGROUND AND OBJECTIVE: Lung cancer is the most common type of cancer with a high mortality rate. Early detection using medical imaging is critically important for the long-term survival of the patients. Computer-aided diagnosis (CAD) tools can potentially reduce the number of incorrect interpretations of medical image data by radiologists. Datasets with adequate sample size, annotation, and truth are the dominant factors in developing and training effective CAD algorithms. The objective of this study was to produce a practical approach and a tool for the creation of medical image datasets. METHODS: The proposed model uses the modified maximum transverse diameter approach to mark a putative lung nodule. The modification involves the possibility to use a set of overlapping spheres of appropriate size to approximate the shape of the nodule. The algorithm embedded in the model also groups the marks made by different readers for the same lesion. We used the data of 536 randomly selected patients of Moscow outpatient clinics to create a dataset of standard-dose chest computed tomography (CT) scans utilizing the double-reading approach with arbitration. Six volunteer radiologists independently produced a report for each scan using the proposed model with the main focus on the detection of lesions with sizes ranging from 3 to 30 mm. After this, an arbitrator reviewed their marks and annotations. RESULTS: The maximum transverse diameter approach outperformed the alternative methods (3D box, ellipsoid, and complete outline construction) in a study of 10,000 computer-generated tumor models of different shapes in terms of accuracy and speed of nodule shape approximation. The markup and annotation of the CTLungCa-500 dataset revealed 72 studies containing no lung nodules. The remaining 464 CT scans contained 3151 lesions marked by at least one radiologist: 56%, 14%, and 29% of the lesions were malignant, benign, and non-nodular, respectively. 2887 lesions have the target size of 3-30 mm. Only 70 nodules were uniformly identified by all the six readers. An increase in the number of independent readers providing CT scans interpretations led to an accuracy increase associated with a decrease in agreement. The dataset markup process took three working weeks. CONCLUSIONS: The developed cluster model simplifies the collaborative and crowdsourced creation of image repositories and makes it time-efficient. Our proof-of-concept dataset provides a valuable source of annotated medical imaging data for training CAD algorithms aimed at early detection of lung nodules. The tool and the dataset are publicly available at https://github.com/Center-of-Diagnostics-and-Telemedicine/FAnTom.git and https://mosmed.ai/en/datasets/ct_lungcancer_500/, respectively.

[Specialized products for dietary correction of the diet of patients with non-alcoholic steatohepatitis].

Non-alcoholic steatohepatitis (NASH) is a widespread disorder associated with a number of metabolic disorders. Lifestyle modification, including diet and physical activity are currently a first-line treatment for the disease. However, there is lack of specialized products (SP) with modified carbohydrate and fat composition, containing biologically active ingredients with proven physiological effects on the liver for this disorder. The aim of the paper is to summarize present knowledge on the biologically active ingredients with proven hepatoprotective effect and to describe the process of the development of two specialized products for clinical use in patients with NASH. Material and methods. Food ingredients containing soy and milk proteins, soluble dietary fiber, mono- and polyunsaturated fatty acids, vitamins, minerals, soy lecithin, L-carnitine, coenzyme Q10, α-lipoic acid, betaine, flavoring and aromatic additives were used in the development of SP formulations. The mass fraction of moisture in the SP was determined by the thermo-gravimetric method on a humidity analyzer, and the water activity was determined by measuring the dew point. The nutritional and energy value of the SP was calculated using data from chemical composition tables and information from manufacturers of food ingredients. Results and discussion. Taking into account the requirements for dietary therapy, the ingredient composition was scientifically justified and the formulations of two SP with a balanced amino acid composition were developed by using a combination of milk whey proteins, casein and soy protein isolate. The fat component included microencapsulated rapeseed oil, that is a source of mono- and polyunsaturated fatty acids (PUFAs) with the addition of ω-3 PUFAs. The carbohydrate composition was modified by eliminating mono- and disaccharides, traditionally used in sweet drinks, and adding maltodextrin in combination with sweeteners (polyols and natural sweeteners). Polydextrose, citrus pectin, inulin, and hydrolyzed guar gum are used as soluble dietary fibers. The SP included essential micronutrients (vitamins, mineral substances) and bioactive substances that have a proven physiological effect (coenzyme Q10, α-lipoic acid, L-carnitine, betaine hydrochloride, phospholipids). Technical documentation was developed and a pilot batch of SP-1 was developed for inclusion in the complex treatment of patients with NASH. Conclusion. The formulations and technology of SP (SP-1, SP-2) for therapeutic nutrition with a given chemical composition, designed to optimize the diet therapy of patients with NASH, have been developed. SP are sources of animal and vegetable proteins, soluble dietary fiber, mono- and polyunsaturated fatty acids, including ω-3 family, vitamins, minerals and trace elements, as well as bioactive substances with antioxidant, hepatoprotective and hypolipidemic effect. The technical documentation was developed and approved, according to which a pilot batch of SP-1 was produced to assess its effectiveness as a part of complex therapy of patients with NASH.

Chest MRI of patients with COVID-19.

During the pandemic of novel coronavirus infection (COVID-19), computed tomography (CT) showed its effectiveness in diagnosis of coronavirus infection. However, ionizing radiation during CT studies causes concern for patients who require dynamic observation, as well as for examination of children and young people. For this retrospective study, we included 15 suspected for COVID-19 patients who were hospitalized in April 2020, Russia. There were 4 adults with positive polymerase chain reaction (PCR) test for COVID-19. All patients underwent magnetic resonance imaging (MRI) examinations using MR-LUND PROTOCOL: Single-shot Fast Spin Echo (SSFSE), LAVA 3D and IDEAL 3D, Echo-planar imaging (EPI) diffusion-weighted imaging (DWI) and Fast Spin Echo (FSE) T2 weighted imaging (T2WI). On T2WI changes were identified in 9 (60,0%) patients, on DWI - in 5 (33,3%) patients. In 5 (33,3%) patients lesions of the parenchyma were visualized on T2WI and DWI simultaneously. At the same time, 4 (26.7%) patients had changes in lung tissue only on T2WI. (P(McNemar) = 0,125; OR = 0,00 (95%); kappa = 0,500). In those patients who had CT scan, the changes were comparable to MRI. The results showed that in case of CT is not available, it is advisable to conduct a chest MRI for patients with suspected or confirmed COVID-19. Considering that T2WI is a fluid-sensitive sequence, if imaging for the lung infiltration is required, we can recommend the abbreviated MRI protocol consisting of T2 and T1 WI. These data may be applicable for interpreting other studies, such as thoracic spine MRI, detecting signs of viral pneumonia of asymptomatic patients. MRI can detect features of viral pneumonia.

[Comparative Analysis of MPTP Neurotoxicity in Mice with a Constitutive Knockout of the α-Synuclein Gene].

Aggregated forms of α-synuclein are core components of pathohistological inclusions known as Lewy bodies in substantia nigra (SN) neurons of patients with Parkinson's disease (PD). The role of α-synuclein in selective loss of SN dopaminergic neurons (DNs) in PD is studied in mice knocked out in the α-synuclein gene. The new mouse strain delta flox KO with a constitutive knockout of the α-synuclein gene models the end point of in vivo deletion of the α-synuclein gene in mice with a conditional knockout and has no foreign sequence in the modified genomic locus, thus differing from all other α-synuclein knockout mouse strains. The effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is used to model PD, was compared between delta flox KO mice and mice of the well-known α-synuclein knockout strain AbKO. Subchronic MPTP administration, which models early PD, was found to reduce the dopamine content and to change the ratio of dopamine metabolites in the striatum to the same levels in delta flox KO, АbKO, and wild-type mice. Overt locomotor defects were not observed after MPTP treatment, but gait testing in a CatWalk XT (Noldus) system revealed identical gait deviations in mice of the two strains and control wild-type mice. Based on the findings, a similar mechanism of neurotoxic damage to DNs was assumed for delta flox KO and AbKO mice.

[State and prospects of legal regulation of telemedicine consultation in the patient-specialist format in children's psychiatric practice]. / Sostoyanie normativno-pravovogo regulirovaniya telemeditsinskogo konsul'tirovaniya i ego sovershenstvovanie v formate «patsient ­ spetsialist¼ v detskoi psikhiatricheskoi praktike.

INTRODUCTION: Remote interaction of medical workers with patients and (or) their legal representatives (the patient-doctor model) contains a large number of unresolved organizational and legal issues. OBJECTIVE: Analysis of the peculiarities of the organization and legal regulation of telemedicine counseling in child psychiatric practice and the development of recommendations for improving the legal and regulatory framework for remote interaction in the patient-specialist format. MATERIAL AND METHODS: The article analyzes the legal and regulatory requirements governing the use of telemedicine technologies in the process of providing psychiatric care. The material for the analysis was the experience of 1129 telemedicine consultations (TMC) in the patient-doctor model in the period from December 2019 to July 2020. RESULTS: Proposals have been formulated to improve the regulatory framework for TMC in psychiatric practice: consideration of the possibility of remote psychiatric examination within the framework of primary TMC; conducting remote medical commissions; elimination of conflicting regulatory requirements governing primary TMC. CONCLUSION: Conducting repeated TMC seems to be optimal as an effective tool for improving the quality and availability of medical care.

Constriction of endoplasmic reticulum tubules by the viral movement protein BMB2 is associated with local BMB2 anchorage at constriction sites.

Plant virus-encoded movement proteins (MPs) interact with endoplasmic reticulum (ER) membranes, the cytoskeleton, and plasmodesmata (PD) to mediate intracellular delivery of the virus genome to PD and its further transport through PD from infected to healthy cells. The Hibiscus green spot virus MP termed BMB2 has been shown to induce constrictions of ER tubules and to occur at highly curved membranes, thus showing properties similar to those of reticulons, a class of cellular proteins inducing membrane curvature and shaping the ER tubules. Consistent with this BMB2 function, mRFP-BMB2 localizes to discrete, constricted regions scattered along the ER tubules. Here, using BMB2-mRFP fusion protein as a BMB2 derivative with partially disabled functionality, we demonstrate that the focal localization of BMB2 to discrete sites along the ER tubules is insufficient to induce local tubule constrictions at these sites, suggesting that the formation of ER tubule constrictions represents a specific BMB2 function and is not simply a mechanistic consequence of its localization to the ER. The presented data suggest that the formation of ER-residing BMB2-containing distinct small aggregates, or protein platforms, can be uncoupled from BMB2-induced ER tubule constrictions, whereas the anchoring of platforms at particular ER sites appears to be linked to the constriction of ER tubules at these sites.