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Multiple sclerosis is a chronic autoimmune inflammatory disease that affects the brain and spinal cord. The most common form of this disease according to the type of its course is relapsing-remitting multiple sclerosis. Comorbidity in multiple sclerosis is an urgent problem of modern neurology, since it can influence such factors as the time of diagnosis, the rate of disease progression and the rate of patient disability, the number of exacerbations and the patient’s quality of life. The purpose of the work was to study and characterize comorbidity in patients with relapsing multiple sclerosis. To conduct this study 105 patients with a diagnosis of relapsing-remitting multiple sclerosis were enrolled. All patients were assessed using the Multiple Sclerosis Neurological Disability Severity Scale (EDSS). Study participants were divided into two groups – Group 1 and Group 2 – based on EDSS scores. Separately, study participants were divided into groups based on the principle of receiving pain-modifying therapy. In the 1st study group, concomitant diseases were in 57 (78.1%) patients, in the 2nd group – in 100% (p=0.010). In patients who did not receive pain-modifying therapy, 57 (98.3%) of those examined had concomitant diseases, in those who received such treatment – in 32 (68.1%), which was statistically significantly less (p

Background. Vibroacoustic therapy is used as a non-drug method of correcting respiratory disorders in various diseases, including acute poisoning. The effect of vibroacoustic therapy on blood cells currently remains unexplored.Objective. To evaluate the impact of vibroacoustic therapy on the morphofunctional rate of erythrocytes and platelets in patients with acute poisoning in patients with acute poisoning.Material and methods. Thirty eight patients with complicated acute poisoning transferred to the Toxicology Department of the N.V. Sklifosovsky Research Institute for Emergency Medicine were examined. In 19 patients, along with the standard therapy, a vibroacoustic therapy was performed using a VibroLUNG device (the main study group); the other 19 patients received only standard therapy (the comparison group). Vibroacoustic therapy began on the 2nd day after the patient admission to the Toxicology Department. The course of vibroacoustic therapy consisted of 2–9 procedures. Morphofunctional analysis of erythrocytes and platelets in all cases was performed before the start of the vibroacoustic therapy (before treatment) and before discharge from the hospital (1–2 days after completing the vibroacoustic therapy course).Results. In both groups, before treatment, we noted normal morphofunctional rate of erythrocytes and normal level of platelets with granules in the circulating blood. The level of severely damaged or altered platelets was only slightly higher than normal and did not differ between the groups. Meanwhile, in 50% of patients, platelets had a tendency to spontaneous activation and hyperactivation. Before discharge, the morph functional parameters of erythrocytes and platelets did not significantly change in both groups, while treatment with vibroacoustic therapy allowed to eliminate or reduce spontaneous platelet activation in 7 of 9 patients in the main study group. In the comparison group spontaneous platelet activation was absent in only 3 of 10 patients. In parallel, the time till pneumonia resolution turned statistically significantly reduced, by 1.5 times.Conclusions. In acute exogenous poisoning with complicated course, the risk of spontaneous platelet activation and hyperactivation increases. Vibroacoustic therapy does not violate the structural integrity of circulating erythrocytes and platelets. Vibroacoustic therapy, using the VibroLUNG device, reduces the tendency of platelets to spontaneous activation and hyperactivation, reduces the time for resolving pneumonia.

Relevance.The search for new methods of effective therapy for traumatic brain injury is one of the important tasks of modern biomedicine. One promising approach for treating traumatic brain injury is cell therapy. The aim of the work is to study the therapeutic effect of glial progenitor cells derived from induced pluripotent stromal cells in an experimental model of traumatic brain injury.Materials and Methods.Modeling of traumatic brain injury was carried out on mature male Wistar rats. The therapeutic group was administered asingle dose of 750*103cells/ml glial progenitor cells with avolume of 1 ml, and the control group — 1 ml of phosphate-­buffered saline. Administration was carried out intra-­arterially 24 hours after injury. To analyze the therapeutic effectiveness, an MRI study was performed on the 14th day, as well as alimb-placing test on the 1st, 3rd, 7th and 14th days. Histological examination was carried out on days 1, 3 and 7 after administration to assess the migration and distribution of stained cells (concentration 750*103cells/ml) by lipophilic dye PKH26 (Sigma, USA) at the rat’s brain tissues after traumatic brain injury. Measurements of injury volume and counts of PKH26-stained cells were performed using ImageJ software (Wayne Rasband, National Institute of Mental Health, Bethesda, MD, USA). The statistical analysis was carried out using GraphPad Prism 8.2.0 program (GraphPad Software, Inc., USA).Results and Discussion.Administration of GPCs led to decreasing the damage volume. Significant decrease in sensorimotor deficit was observed on days 3, 7 and 14 after injury compared with the control group. Intra-arterial administration resulted in successful delivery of glial progenitor cells to brain tissue. Cells were detected in the cerebral cortex, hippocampus, and striatum on day 1, and were not observed on days 3 and 7 after administration.Conclusion.Intra-arterial administration of GPCs leads to efficient migration of cells into brain tissue. Glial progenitor cells therapy promotes neurorecovery processes after traumatic brain injury. This therapy is apromising treatment for traumatic brain injury.

Objective: to evaluate the efficacy of a single or double administration of a preparation of high molecular weight hyaluronic acid (HLA) with chondroitin sulfate (CS) in post-traumatic knee osteoarthritis (OA). Material and methods. The study included 91 patients with stage III post-traumatic knee OA. All patients received intra-articular (i/a) injection of high molecular weight HLA with CS; 36 patients received the drug once (group 1) and 55 twice (group 2) with an average interval of 7±2 days. Before the start of treatment and 2 weeks, 1, 3, 6 and 12 months after i/a injection of HLA, pain intensity at rest and during movement was assessed using a visual analogue scale (VAS) and function was assessed using KOOS questionnaire (Knee injury and Osteoarthritis Outcome Score). Results and discussion. In general, patients receiving single and double i/a injections of HLA, pain during movement at baseline, and after 2 weeks, 1, 3, 6 and 12 months was 6.7±1.1; 4.0±0.7; 4.3±0.8; 4.6±1.0; 4.5±1.1 and 5.3±0.4 cm; pain at rest – 2.7±0.6; 1.5±0.2; 1.8±0.2; 2.1±0.5; 2.2±0.3 and 2.6±0.2 cm, and KOOS score was 35.9±13.6; 43.5±13.6; 49.2±17.6; 57.0±12.5; 51.5±11.7 and 40.3±10.2, respectively. In group 1, pain during movement at the same time line reached 6.7±1.2; 4.0±0.7; 4.3±1.1; 4.6±.08; 4.5±0.6 and 5.3±1.3 cm; pain at rest – 2.7±0.5; 1.5±0.3; 1.8±0.4; 2.1±0.4; 2.2±0.6 and 2.6±0.6 cm; KOOS score – 37.2±8.7; 39.1±10.1; 43.0±12.3; 47.0±13.6; 49.5±14.7 and 35.7±12.4, respectively.In the 2nd group, pain during movement was 6.1±1.5; 3.3±0.7; 3.6±0.6; 3.4±0.5; 3.7±0.4 and 4.4±0.3 cm; pain at rest was 2.6±0.3; 1.9±0.2; 1.1±0.2; 0.9±0.1; 0.7±0.1 and 1.7±0.3 cm; KOOS score was 34.7±9.4; 47.1±11.1; 59.3±11.5; 61.4±12.7; 57.2±14.3 and 45.7±12.4, respectively. Conclusion. In patients with stage III knee OA, double injections of HLA with HS were more effective. The maximum pain reduction and functional improvement were observed in the first 3 months after local injection therapy.

Abstract Background Among the non-traditional antibacterial agents in development, only a few targets critical Gram-negative bacteria such as carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii or cephalosporin-resistant Enterobacteriaceae. Endolysins and their genetically modified versions meet the World Health Organization criteria for innovation, have a novel mode of antibacterial action, no known bacterial cross-resistance, and are being intensively studied for application against Gram-negative pathogens. Methods The study presents a multidisciplinary approach, including genetic engineering of LysECD7-SMAP and production of recombinant endolysin, its analysis by crystal structure solution following molecular dynamics simulations and evaluation of antibacterial properties. Two types of antimicrobial dosage forms were formulated, resulting in lyophilized powder for injection and hydroxyethylcellulose gel for topical administration. Their efficacy was estimated in the treatment of sepsis, and pneumonia models in BALB/c mice, diabetes-associated wound infection in the leptin receptor-deficient db/db mice and infected burn wounds in rats. Results In this work, we investigate the application strategies of the engineered endolysin LysECD7-SMAP and its dosage forms evaluated in preclinical studies. The catalytic domain of the enzyme shares the conserved structure of endopeptidases containing a putative antimicrobial peptide at the C-terminus of polypeptide chain. The activity of endolysins has been demonstrated against a range of pathogens, such as Klebsiella pneumoniae, A. baumannii, P. aeruginosa, Staphylococcus haemolyticus, Achromobacter spp, Burkholderia cepacia complex and Haemophylus influenzae, including those with multidrug resistance. The efficacy of candidate dosage forms has been confirmed in in vivo studies. Some aspects of the interaction of LysECD7-SMAP with cell wall molecular targets are also discussed. Conclusions Our studies demonstrate the potential of LysECD7-SMAP therapeutics for the systemic or topical treatment of infectious diseases caused by susceptible Gram-negative bacterial species and are critical to proceed LysECD7-SMAP-based antimicrobials trials to advanced stages.

Aim of the study was to analyze the frequency and dynamics of schizophrenia, schizotypal disorder and autism in children and adolescents in Moscow and in the Kabardino-Balkarian Republic (KBR) for 2021–2022 to determine the need for appropriate support measures for this population group. Material and methods. The dynamics of primary and general morbidity of mental diseases, including children and adolescents, as well as primary and general morbidity of schizophrenia (F20), schizotypal disorder (F21) and autism among children and adolescents in Moscow and in the KBR for 2021–2022, corresponding to the ICD-10 codes, are considered. Results and discussion. There is an increase in the overall incidence of mental illness in 2021 and 2022 both in Moscow (an increase of 8.4 %) and in the KBR (an increase of 0.3 %), of which among the child population (10.9 and 2.2 %, respectively). An enhancement of the primary incidence of mental illness in Moscow was revealed with an increase of 23.7 %, in the KBR with an increase of 1.1 %, among the child population corresponding values were 29.4 and 10.6 %. The overall incidence of schizophrenia decreased by 1.1 % in Moscow and by 0.5 % in the KBR, among the child population – by 1.3 and 21.3 %, respectively. The overall incidence of schizotypal disorder enhanced by 9.1 % in Moscow, by 8.1 % in the KBR, among the child population – by 7.9 and 0 %, respectively. A decrease in the primary incidence of schizophrenia was revealed by 0.1 % in Moscow, by 91 % in the KBR. Among the child population it increased by 25.6 % in Moscow and decreased by 100 % in the KBR, as well as number of newly diagnosed cases of schizophrenia. The primary incidence of schizotypal disorder rose by 34.1 % in Moscow, by 16.7 % in the KBR, among the child population it decreased by 1 % and hasn’t changed, respectively. It is possible to note an increase in the total incidence of autism in 2021–2022 both in Moscow (by 21.1 %) and in the KBR (by 9.4 %), while the number of newly diagnosed cases of autism in Moscow increased by 26.3 %, then in the CBD it decreased by 66.8 %. Conclusions. A diagnostic bias was revealed – a decrease in the number of patients diagnosed with schizophrenia (F20) and a significant increase in the number of patients diagnosed with schizotypal disorder (F21). The statistical data obtained mainly indicate an improvement in the diagnosis of autism in childhood in Moscow and a decrease in the incidence of autism in the KBR.

Objective: to evaluate differences in the expression of genes associated with β-oxidation and de novo synthesis of fatty acids (FAs) in the blood of patients with the late stage of knee osteoarthritis (OA) before total knee arthroplasty (TA) depending on the development of postoperative pain (POP) in order to determine the molecular mechanisms responsible for the development of chronic POP. Material and methods. Blood of 50 patients with stage III–IV knee OA complaining of constant pain and joint dysfunction was analyzed prior to TA. The control group consisted of 26 healthy individuals. Pain intensity was assessed using a visual analogue scale (VAS) and the BPI questionnaire. In addition, pain, stiffness and physical functioning were assessed using WOMAC index and the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of POP was assessed 3 and 6 months after TA. Total RNA isolated from blood was used to determine the expression of ACLY, ACC1, MLYCD, FASN and CPT1A genes by real-time quantitative reverse transcriptase-polymerase chain reaction. Results and discussion. POP ≥ 30 mm by VAS was detected in 17 patients. Before TA, the expression of most of the analyzed genes was significantly increased compared to controls, while the expression of the FASN gene was comparable in patients with OA and healthy individuals. There were no differences in clinical and functional parameters between the groups of patients with and without POP. Before surgery, patients who subsequently developed POP had significantly higher expression of ACLY and CPT1A genes than patients who were satisfied with the results of TA. At the same time, no differences in the expression of ACC1, MLYCD and FASN were found in the groups analyzed. Conclusion. The development of POP is associated with an increased supply of FAs to the mitochondria caused by overexpression of the CPT1A gene, as well as with the accumulation of acetyl-CoA, a product of high expression of the ACLY gene, which can be measured in the blood of OA patients before TA.

Local injection therapy (LIT) with hyaluronic acid (HA) medications is one of the most promising methods for the treatment of periarticular soft tissue pathology (PASTP) caused by injury or overuse. Objective: to evaluate the efficacy and safety of LIT with HA medication with a molecular weight of 500–730 kDa in patients with various post-traumatic PASTP. Material and methods. The study included 30 patients with rotator cuff syndrome (RCS), lateral epicondylitis (LE) and plantar fasciitis (PF) after trauma. Inclusion criteria were the presence of moderate/severe pain (≥40 mm on a visual analogue scale (VAS)) over a 3-month period and the absence of effect of LIT with glucocorticoids. All patients were administered HA peritendinously three times (7 days apart) under ultrasound guidance. Treatment results were evaluated after 1 and 3 months based on the dynamics of pain intensity (VAS) and functional indicators using the ASES (American Shoulder and Elbow Surgical Evaluation), MES (Mayo Elbow Score) and FFI (Foot Functional Index) questionnaires. Results and discussion. In the general group, there was a statistically significant decrease in pain intensity after 1 and 3 months from a mean of 57.6 ± 14.7 to 37.0 ± 14.8 and 35.0 ± 14.3 mm according to VAS respectively (p < 0.05). In the patient groups with different PASTP, the average assessment of pain intensity and functional impairment at baseline and after 1 and 3 months was: for RCS (n = 11) 59.0 ± 15.1, 39.0 ± 15.7, 36.3 ± 16.2 mm according to VAS and 49.1 ± 14.3, 60.1 ± 13.7, 61.7 ± 3.8 according to ASES, respectively; with LE (n = 10) 54.0 ± 13.4, 35.0 ± 9.7, 34.0 ± 11.7 mm according to VAS and 71.5 ± 11.1, 78.3 ± 9.0, 81.5 ± 8.3 according to MES; with PF (n = 9) 61.0 ± 16.5, 36.6 ± 19.3, 34.4 ± 15.8 mm according to VAS and 47.2 ± 22.8, 39.6 ± 39.7, 39.0 ± 29.9 according to FFI. None of the patients experienced any adverse events during treatment. Conclusion. HA medication with a molecular weight of 500–730 kDa showed good efficacy and safety in LIT of PASTP of the shoulder, elbow joint and foot. Further studies are needed to evaluate the possibility of a broad use of the drug for the treatment of PASTP in real clinical practice.

This article describes the experience of using the type I interferon inhibitor anifrolumab (AFM) in a patient with a torpid course of systemic lupus erythematosus. The reason for prescribing AFM was the need for a quick achievement of low disease activity due to a planned hip replacement. Dynamic observational data over a six-month period confirmed that AFM enables a rapid achievement of low disease activity without increasing the dose of glucocorticoids, significantly improve the patient's quality of life and even prepare them for major surgery without exacerbating the underlying process.

Introduction. When performing osteoplastic craniotomy, there is a need to fill the diastasis between the skull bone and the explanted bone fragment. Grafts based on allogeneic bone chips and collagen (bone-plastic material) may be very effective for cranial bone repair in diastasis area.Aim. To evaluate the safety and clinical efficacy of osteoplastic material during the osteoplastic craniotomy.Material and methods. A retrospective and prospective clinical study was conducted at the N.V. Sklifosovsky Research Institute for Emergency Medicine and included 12 patients treated in Urgent Neurosurgery Department with diagnoses suggesting the need for craniotomy. Allogenic osteoplastic material was obtained from a 0.7-0.9% solution of type I collagen and spongy bone chips with a fraction size of 315-630 microns. Osteoplastic material grafts were used intraoperatively at the cranioplastic stage of the operation after the main stages had been completed. The efficacy and safety of the use of osteoplastic material were evaluated clinically and radiologically in the early postoperative period.Results. In the early postoperative period, the study patients had no pyo-septic complications, severe pain or soft tissue swelling. All patients were discharged from the hospital in satisfactory condition to be followed-up by the physician or neurologist at the out-patient facility. The computed tomography performed in the early postoperative period visualized the diastasis lines along the bone flap line in the comparison group patients (without osteoplastic material); and in the main group, the osteoplastic material was clearly visualized. At computed tomography of the skull performed after 6–9 months and after 2–18 months, the signs of bone tissue consolidation were visualized in the patients of the main group. The radiodensity of the autologous bone flap in both groups did not significantly change at any periods. In the diastasis area, the radiodensity of diastasis in the main group was significantly higher than in the comparison group. After 1-1.15 years the radiodensity values in the diastasis area increased by average of 1.95 times (p

Objective: to investigate the relationship between the expression of genes mediating cellular energy production and the development of chronic postoperative pain (CPP) after total knee arthroplasty (TKA) in patients with osteoarthritis (OA).Material and methods. Prior to TKA, the blood of 50 patients with stage III–IV knee OA and complaints of constant pain and joint dysfunction was analyzed. The control group consisted of 26 healthy individuals. Pain intensity was assessed using a visual analogue scale (VAS), a short BPI questionnaire and the WOMAC index, and the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of CPP was determined 3 and 6 months after TKA. Total RNA isolated from blood was used to determine the expression of PKM2, LDH, SDH, AMPKα, PDH, IDH, MDH and ATP synthase genes by real-time quantitative reverse transcriptase-polymerase chain reaction.Results and discussion. CPP ≥30 mm according to VAS was detected in 17 patients. Before TKA, the expression of all analyzed genes was significantly increased compared to that of the control group. However, there were no differences in clinical, pain-related and functional indicators in the analyzed group of patients with OA. Before surgery, patients who subsequently developed CPP had significantly higher expression of genes related to glycolysis (PKM2, LDH), Krebs cycle – KC (SDH) and master regulator of energy metabolism (AMPKα) than patients who were satisfied with the results of TKA. At the same time, no differences were found in the expression of PDH and other KC enzyme genes (IDH, MDH) and ATP synthase in patients with and without CPP.Conclusion. The development of CPP is associated with a higher rate of glycolysis and energy deficiency, presumably due to the higher uncoupling activity of oxidation and phosphorylation that can be observed before TKA.

Total knee and hip arthroplasty (TKA and THA respectively) is frequently used in severe structural changes in patients with osteoarthritis (OA) and rheumatoid arthritis (RA).Objective: to evaluate the dynamics of the number of TKA of THA in patients with OA and RA treated in the Department of Traumatology and Orthopedics of V.A. Nasonova Research Institute of Rheumatology.Material and methods. The analysis of 11-year period (from 2012 to 2022) of surgical activity of the Department of Traumatology and Orthopedics of V.A. Nasonova Research Institute of Rheumatology.Results and discussion. Within the mentioned period, 2955 TKA and THA were performed in 1590 patients with OA and 1365 with RA. From 2012 to 2018, the number of surgeries in patients with OA and RA was approximately the same, but since 2019 there has been a significant increase in the number of total arthroplasties (TA) in OA. The median delta (Δ) of the number of TKA and THA performed annually over 11 years was 13.5 [-17.5; 75.7] in patients with OA and 2.5 [-10.25; 25.0] in patients with RA (p=0.032).Conclusion. In the last 11 years there was no significant dynamics in the number of TKA and THA in patients with RA. At the same time, there is a statistically significant increase in the number of TA in patients with OA, which is in line with the global trend.

The article provides a description of the anthropological finding – human remains discovered in the church of St. Peter (Domashevo, Bosnia and Herzegovina, burial at the turn of the 15th and 16th centuries AD). The available morphological data most likely indicate the presence of diffuse idiopathic skeletal hyperostosis. This disease resulted in trauma to the cervical vertebrae, which altered their morphology. However, the injury did not lead to death; the person lived for a long time afterwards, as post-traumatic skeletal changes with the development of torticollis were noted.

We describe a clinical observation of a 64-year old Caucasian patient with a longstanding ankylosing spondylitis, who was admitted to the clinic for diarrhea and joint syndrome. Physical and X-ray examination showed that his musculoskeletal system disorder was represented by ankylosing spondylitis, symmetrical erosive polyarthritis of the metacarpophalangeal joints, and wrist joint ankylosis. Laboratory work-up identified that the patient was HLA-B27 positive, had high rheumatoid factor and anti-citrulline antibodies levels. At colonoscopy, there were signs of ulcerative colitis. After the differential diagnosis procedures, we were able to conclude that the patient had a combination of rheumatoid arthritis, ankylosing spondylitis, and ulcerative colitis as three independent but associated disorders. The first description of these three autoimmune diseases in one patient can be of interest for clinicians.

Relevance. Currently, the participation of immune system cells in the regulation of reparative processes is attracting more and more attention of researchers. There is an anatomical connection between the liver and spleen by means of portal vein. Thus, cytokines and other biologically active substances can enter the liver from the spleen through the portal vein, as well as cells can migrate to the liver. However, the specific mechanisms of mutual influence of the mentioned organs, including in reparative processes, remain poorly studied. The aim of our work was to study the state of spleen monocyte-macrophage population after liver resection, as well as the proliferative activity of spleen cells during liver regeneration . Materials and Methods . The model of liver regeneration after 70 % resection in mouse was reproduced in this work. The animals were taken out of the experiment after 1, 3 and 7 days. The marker of cell proliferation Ki67 was immunohistochemically detected, the state of spleen monocyte-macrophage population was evaluated by markers CD68, CD115, CD206, F4/80 by methods of immunohistochemistry and flow cytometry. Results and Discussion . The liver regeneration had a pronounced effect on the cytoarchitectonics of the spleen. In 1 day after liver resection in the spleen there was observed a decrease in the share of Ki67+cells, according to the flow cytometry data there was a decrease in the number of CD115+cells, in 3 and 7 days there was a decrease in the number of F4/80+ macrophages. Conclusion . Liver resection causes changes in the state of cell populations of the spleen as well. First of all, to the decrease in the activity of proliferative processes in it, as well as to the changes in the state of the monocyte-macrophage system. A decrease in the content of CD115+ and F4/80+ cells in the spleen was found, which indirectly indicates the migration of monocytes/macrophages after liver resection, which can also influence the course of reparative processes in the liver.

Relevance . Macrophages are the leading regulatory cell-lineage taking part in reparative processes in mammals, and the liver is no exception. The ratio of monocyte migration, proliferation and death of macrophages during liver regeneration requires further studies. The aim was to quantify the intensity of monocyte migration, cell proliferation and apoptosis of resident liver macrophages after its 70 % resection in a mouse model. Materials and Methods. We performed 70 % liver resection in sexually mature male BalbC mice. Cells of liver monocyte-macrophage system were obtained by magnetic sorting by marker F4/80. The immunophenotype of the isolated cells was further studied by cytofluorimetry, the level of proliferation and cell death, the content of cyclins and P53 was determined by western blot. Results and Discussion . It was found that after partial hepatectomy there is a marked migration of monocytes/macrophages positive for Ly6C and CD11b markers to the liver, the migration process starts already in the first day after the operation. On the same terms there is a rise in proliferative activity of macrophages, established by Ki67 marker, the peak of proliferation - 3 days after partial hepatectomy. A significant increase in the number of dying macrophages was found early after liver resection. Conclusion . The obtained data indicate that liver regeneration in mammals on the model in mice is accompanied by proliferation migration and cell death of macrophages. Taking into account the immunophenotype of macrophages, we can conclude that Ly6C+ blood monocytes migrate to the liver, and resident macrophages participate in proliferation. The obtained data confirm the universality of the course of reparative processes in mammals.

Introduction. In the structure of combat abdominal trauma during all periods of hostilities (according to ATO/JFO data), gunshot wounds dominated, accounting for 87.1%. An analysis of the distribution of those injured with gunshot wounds by the type of projectile causing the injury showed a prevalence of shrapnel injuries over bullet wounds – more than 80%. The aim of the research was to analyze the macroscopic and microscopic changes in firearm penetrating abdominal injuries with damage to the appendix. Materials and Methods. Eight appendectomies were performed due to firearm penetrating abdominal injuries with damage to the appendix. Complaints, medical history, examination data, ultrasound examination according to the FAST protocol, and radiological examinations were studied in all injured patients. To refine the diagnosis and determine the scope of surgical intervention, the WOLF videoendoscopic system was used. Histological examination of the removed appendices was performed, which were stained with hematoxylin and eosin and with the Van Gieson stain. A complex of pathomorphological studies was conducted using the Primo Star microscope (Carl Zeiss) at a magnification of ×140. Results. All injuries occurred while wearing a bulletproof vest and were characterized as blind, with 1 (12.5%) being gunshot wounds and 7 (87.5%) being shrapnel wounds. The entrance wound in firearm blind penetrating abdominal injuries with appendix damage was located in the right hypochondriac region – 4 (50%), right flank – 1 (12.5%), right inguinal region – 2 (25%), and mesogastric region – 1 (12.5%) cases. The average size of the entrance wound on the skin was 23.3±0.4×12.4±0.3 cm. All skin wounds were outside the bulletproof vest protection area. The injuries to the appendix had an average size of 15.4±1.2×9.3±0.1 cm. All removed foreign bodies were larger than 1 cm in their largest dimension. Conclusions. In most cases of firearm penetrating abdominal injuries, damage to the appendix is noted with an entrance wound predominantly on the right side. Macroscopically, in firearm blind penetrating abdominal injuries with appendix involvement, the wound on the skin is larger than on the appendix. All foreign metal bodies removed from the abdominal cavity after firearm shrapnel blind abdominal injuries with appendix involvement were of large size. Contusional injuries to the appendix tend to undergo destructive transformation, requiring surgical treatment - appendectomy. The increased frequency of appendix injuries can be explained by the widespread use of shrapnel ammunition in abdominal injuries when personal protective equipment does not provide protection for this area.

Abstract Plain bearings, renowned for their versatility and simplicity, are extensively utilized in engineering design across various industries involving moving parts. Lubrication is vital to the functioning of these bearings, yet their usage is inhibited under dynamic load conditions, or at elevated or reduced temperatures due to this dependency on lubrication. This study introduces an innovative method to significantly mitigate friction and wear in plain bearings operating without lubrication. The plain bearings were constructed from steel–bronze pairs, where the steel shafts were alloyed with bismuth oxide via short-pulse laser treatment. MnO2 was utilized as a carrier to incorporate the bismuth oxide into the surface layers of the steel. Insights from transmission electron microscopy and X-ray photoelectron spectroscopy revealed a highly non-equilibrium state of matter, unattainable through conventional engineering methods. The tribological performance of the modified steel disks was assessed via a block-on-ring sliding test, demonstrating superior wear and friction performance without lubrication, as well as an ultra-low coefficient of friction. Remarkably, the modified friction pairs remained functional after 200 km of linear sliding at a load of 250 N (12.5 MPa) and a sliding speed of 9 m/s. To substantiate the technique’s viability, we tested the performance of an internal combustion engine turbocharger fitted with a modified steel shaft. The turbocharger’s performance validated the long-term effectiveness of the steel–bronze coupling operating without lubrication at 75,000 rpm. The simplicity and resilience of this technique for modifying steel–bronze pairs offer a ground-breaking and promising approach for a wide range of applications.

Local injection therapy (LIT) is an important component of the complex treatment of musculoskeletal disorders (MSD), which is widely used in real clinical practice. Glucocorticoids, hyaluronic acid drugs (HA), autologous cell drugs, botulinum toxin type A, radioactive isotopes, etc. are used for LIT. LIT makes it possible to achieve a pronounced symptomatic effect, while in some cases, for example, repeated HA treatments in patients with osteoarthritis, the possibility of slowing the progression of the disease and reducing the need for surgical treatment is discussed.The performance of LIT requires special skills and abilities of the physician, careful compliance with the rules of asepsis and antisepsis, and instrumental visualization. LIT can be associated with serious complications and therefore must be performed according to strict indications.The Expert Council was devoted to defining the basic principles of LIT. The indications for the use of certain types of this therapies, the evidence base for its efficacy and safety, the order of application of different drugs, and the need to combine LIT with other drug and non-drug treatments of MSD were reviewed.

Abstract 12-lead electrocardiogram (ECG) recordings can be collected in any clinic and the interpretation is performed by a clinician. Modern machine learning tools may make them automatable. However, a large fraction of 12-lead ECG data is still available in printed paper or image only and comes in various formats. To digitize the data, smartphone cameras can be used. Nevertheless, this approach may introduce various artifacts and occlusions into the obtained images. Here we overcome the challenges of automating 12-lead ECG analysis using mobile-captured images and a deep neural network that is trained using a domain adversarial approach. The net achieved an average 0.91 receiver operating characteristic curve on tested images captured by a mobile device. Assessment on image from unseen 12-lead ECG formats that the network was not trained on achieved high accuracy. We further show that the network accuracy can be improved by including a small number of unlabeled samples from unknown formats in the training data. Finally, our models also achieve high accuracy using signals as input rather than images. Using a domain adaptation approach, we successfully classified cardiac conditions on images acquired by a mobile device and showed the generalizability of the classification using various unseen image formats.

Chronic shoulder pain (CSP) is a clinical syndrome associated with inflammatory and degenerative musculoskeletal changes, characterized by pain in the shoulder that persists for at least 3 months, arising or aggravated by functional activity in this area. The frequency of CSP in the modern population reaches 20–33%, it is one of the leading causes of severe suffering, disability and seeking for medical attention. The main causes of CSP are shoulder rotator impingement syndrome (subacromial impingement syndrome), calcific tendinitis, adhesive capsulitis, shoulder and acromioclavicular joint osteoarthritis. Accurate diagnosis of these diseases is necessary for the correct choice of treatment. Differential diagnosis is carried out using tests that evaluate the function of the shoulder joint and the rotator cuff muscles (Neer, Speed, Hawkins tests, etc.), as well as using instrumental methods (ultrasound, magnetic resonance tomography, X-ray). In CSP, it is necessary to exclude septic, oncological, visceral, systemic rheumatic and other diseases, as well as musculoskeletal pathology of the cervical spine, upper chest and back, which can cause pain in the shoulder region.Therapy for diseases that cause CSP should be personalized and complex, aimed at maximum pain control and restoration of function. For this purpose, non-steroidal anti-inflammatory drugs, local injection therapy with glucocorticoids, hyaluronic acid, and platelet-rich plasma are used. In some cases, muscle relaxants, antidepressants, anticonvulsants, local injections of botulinum toxin type A are indicated. Physiotherapy and medical rehabilitation methods play a fundamental role in the treatment of CSP.

Introduction. Biological grafts, including bone chips and collagen, are supposed to be promising in the treatment of bone tissue treatment. Nevertheless, manufacturing of these grafts still needs to be standardized. Aim. To optimize methodology of osteoplastic material production, based on allogenic 1 type collagen and bone chips. Material and methods. Osteoplastic material grafts were produced, using with allogeneic bone chips 180-800 µm and type 1 collagen solution in acidic acid. We studied total integrity of graft, collagen quality, morphofunctional properties of line M-22 human cells interacting with different type of osteoplastic material grafts. Results. Procedures for manufacturing the osteoplastic material did not significantly affect the quality of collagen in its composition, while lyophilized grafts had pronounced acidogenic and toxic effects in cell culture. Soaking osteoplastic material in isotonic solution for 30 min or longer increased its biocompatibility in vitro. Adhesion properties of osteoplastic material widely varied depending on collagen concentration and bone chips size. Conclusion. Osteoplastic material prepared with allogeneic bone chips of 180–800 µm and collagen solution in acidic acid had pronounced acidogenic and toxic effects in vitro that could be considerably reduced by soaking in isotonic solution. Varying the collagen concentration and the size of bone chips one could produce biocompatible osteoplastic material grafts with high and low adhesion properties.

Multiple sclerosis is a chronic progressive inflammatory autoimmune disease of the central nervous system. This disease mainly affects young females and leads to disability of the patient, which causes a significant socio-economic burden which this disease causes. Clinically, multiple sclerosis is characterized by a wide variety of neurological and neuropsychological manifestations: movement disorders, sensory disturbances and cognitive dysfunction. One of the most typical psycho-emotional disorders that occur in patients with multiple sclerosis are anxiety and depression. The article is devoted to the study of the features of these disorders in patients with multiple sclerosis. The purpose of the study is to evaluate and characterize psycho-emotional disorders in patients with relapsing-remitting multiple sclerosis. The study included 105 patients with relapsing-remitting multiple sclerosis who underwent inpatient treatment in the Department of Neurology No. 1 Municipal Institution “Dnipropetrovsk Regional Clinic Hospital named after I.I. Mechnykov" Dnipropetrovsk Regional Council". Among the patients included in the study, there were 74 women (70.5%) and 31 men (29.5%). The largest proportion of those surveyed falls on the age group from 25 to 40 years – 80 (76.2%). All participants were assessed according to the generally accepted scale for multiple sclerosis patients assessment – Expanded Disability Status Scale (EDSS). All study participants were divided into two groups – group 1 and group 2 – according to the degree of disability according to EDSS. Considering that the degree of disability according to EDSS≤3.5 is defined as mild, and most patients had just this level, they were assigned into group 1, patients with a score of 3.5

Objective: to identify risk factors for the development of the femoral head aseptic necrosis (FHAN) and osteoarthritis (OA) of the hip joint (HJ) in patients with systemic lupus erythematosus (SLE) according to a retrospective analysis.Material and methods.The retrospective study included data from the case histories of 103 patients with SLE who underwent total hip arthroplasty (HA) (unilateral in 82 patients, bilateral in 21). The total follow-up period ranged from 2 years to 21 years. Among the patients included in thestudy, the majority were women (86.4%), the ratio of women and men was 7:1. At the time of surgery, the average age of women was 36.3±13.25 years, men – 36.2±9.57 years, duration of the disease – 168.0±132.5 months. SLE activity was assessed using the SLEDAI-2K scale. All patients were taking glucocorticoids (GC). The average duration of GC treatment was 89.0±87.2 months. 71.8% of patients received immunosuppressive therapy: hydroxychloroquine – 55.3%, azathioprine – 10.7%, methotrexate – 5.8%. The functional status of hip joint was determined using the Harris scale; by the time of surgery, the average score was 45.6±13.1 points. Pain intensity was assessed using a visual analogue scale and reached an average of 70.1±16.0 mm.Results and discussion. In 58.5% of patients with SLE, the indication for HA was FHAN (Group 1) and in 41.6% – OA of HJ (Group 2). At the time of HA, the duration of the disease was longer and the age was higher in group 2 than in group 1 (p0.05).Conclusion. In SLE patients, the incidence of FHAN and HJ OA was comparable. At the time of HA, SLE patients with HJ OA were older and had a longer duration of the disease than patients with FHAN. The risk factors for FHAN were arthritis and ANF positivity at the onset of SLE.

Relevance. The large number of wounded in modern military conflicts “encourages” and in some cases requires revision and modernization of previous views, concepts and theories of medical care providing to wounded during military operations. The optimal concept for the surgical care provision transformation to wounded with soft tissues gunshot defects is to change the approach and tactics of viewpoint at soft tissues gunshot defects which should tactically and strategically rely on the principles of reconstructive and restorative surgery which corresponds to NATO countries medical protocols. Objective: to establish the characteristics of the main and additional diagnostic and treatment schemes the content and volume of surgical care for the injured with soft tissues gunshot defects in the conditions of the III and IV levels of medical care providing in the Military Medical Forces of the Ukrainian Armed Forces. Materials and methods. 342 wounded were included into the study who were treated in the health care system of the Ukrainian Armed Forces from December 2016 to December 2021. 128 of them consisted the main group and 214 - the comparison group. The third level of medical support was formed and implemented at the operational level at the expense of surgical departments (clinics) of the Military Medical Clinical Centers of the Northern and Eastern Regions, medical institutions of the Ministry of Health of Ukraine and provided for the provision of specialized medical assistance: diagnosis of injuries and necessary inpatient treatment of the wounded with the aim of their fastest return to military units or referral to the fourth level of medical care. The fourth level of medical care (highly specialized treatment and rehabilitation) was formed and implemented at the strategic level on the basis of Military Medical Clinical Centers (National, Southern, Central and Western regions Region), research institutes of the National Academy of Sciences of Ukraine and provided for provision of highly specialized medical care using high-tech equipment and highly specialized medical procedures of high complexity. Results. In general, the experience of the Ukrainian Armed Forces medical support during ATO/JFO showed the high efficiency of specialized surgical treatment of the injured with soft tissues gunshot defects in highly specialized departments of treatment and prevention institutions of the IV level using the most effective diagnostic and treatment technologies. We believe that a similar transformation of medical care provision to the wounded took place due to the fact that, in accordance with the proposed and implemented differentiated surgical tactics with a multimodal approach to wounded with soft tissues gunshot defects reconstruction, new staffs of medical companies of brigades and battalion medical posts were proposed and approved during the JFO, the positions of riflemen were introduced paramedics of departments, combat medics of platoons, senior combat medics of companies. Taking into account the results obtained it should be noted that the system of medical care providing for the transition to a higher level should include: - the possibility of qualified medical assistance providing from the II level aimed at recovery, stabilization, and in some cases saving the life of a wounded serviceman on the basis of "damage control resuscitation" which meets the NATO protocols requirements; - available in terms of time and operational situation, the use of air evacuation for the purpose of wounded with gunshot defects of soft tissues, which demonstrates an increase in the rate of preservation of 20-25% of the volume of the damaged anatomical structure; - use of modern additional technologies in the form of dynamic digital thermography and audio doppler. Conclusions. The listed positions obtained during the surgical care implementation at the III-IV levels of medical care have demonstrated that the use of additional alternative portable technologies meets the requirements and conditions of a rapidly changing theater of operations in a modern military conflict.

Castleman’s disease (angiofollicular lymphoma, giant lymph node hyperplasia, Castleman’s pseudotumor) is an understudied orphan lymphoproliferative disease with a long period of asymptomatic course and a high risk of malignancy, and variability of its clinical features can cause difficulties in diagnosis. The aim of the study. To acquaint clinicians and increase the effectiveness of early diagnosis and treatment of Castleman’s disease (CD) in children to prevent malignancy and improve prognosis. Results. The article presents a clinical case of CD in a 3.5-year-old boy with a long history of fever, stunted growth, sweating, arthralgia, anemia, high laboratory inflammatory factors, elevated IL-6. There was a complex diagnostic search except for infectious, immunodeficiency, autoimmune conditions. The diagnosis of hyaline-vascular type of CD was confirmed by immunohistochemical examination after lymph node excisional biopsy. Rapid positive dynamics was noted after radical removal of the lymph node conglomerate. At follow-up after 8 months, the patient met criteria for clinical and laboratory remission. Conclusions. Castleman’s disease should be included in the search algorithm for lymphoproliferative diseases. Determining the role of genetic mutations in interferon regulatory factor (IRF8) is of scientific interest to clarify the etiology of this disease.

Abstract Background Intratumoral heterogeneity (ITH) is a hallmark of clear cell renal cell carcinoma (ccRCC) that reflects the trajectory of evolution and influences clinical prognosis. Here, we seek to elucidate how ITH and tumor evolution during immune checkpoint inhibitor (ICI) treatment can lead to therapy resistance. Methods Here, we completed a single-arm pilot study to examine the safety and feasibility of neoadjuvant nivolumab in patients with localized RCC. Primary endpoints were safety and feasibility of neoadjuvant nivolumab. Then, we spatiotemporally profiled the genomic and immunophenotypic characteristics of 29 ccRCC patients, including pre- and post-therapy samples from 17 ICI-treated patients. Deep multi-regional whole-exome and transcriptome sequencing were performed on 29 patients at different time points before and after ICI therapy. T cell repertoire was also monitored from tissue and peripheral blood collected from a subset of patients to study T cell clonal expansion during ICI therapy. Results Angiogenesis, lymphocytic infiltration, and myeloid infiltration varied significantly across regions of the same patient, potentially confounding their utility as biomarkers of ICI response. Elevated ITH associated with a constellation of both genomic features (HLA LOH, CDKN2A/B loss) and microenvironmental features, including elevated myeloid expression, reduced peripheral T cell receptor (TCR) diversity, and putative neoantigen depletion. Hypothesizing that ITH may itself play a role in shaping ICI response, we derived a transcriptomic signature associated with neoantigen depletion that strongly associated with response to ICI and targeted therapy treatment in several independent clinical trial cohorts. Conclusions These results argue that genetic and immune heterogeneity jointly co-evolve and influence response to ICI in ccRCC. Our findings have implications for future biomarker development for ICI response across ccRCC and other solid tumors and highlight important features of tumor evolution under ICI treatment. Trial registration The study was registered on ClinicalTrial.gov (NCT02595918) on November 4, 2015.

Intratumoral heterogeneity is a defining hallmark of glioblastoma, driving drug resistance and ultimately recurrence. Many somatic drivers of microenvironmental change have been shown to affect this heterogeneity and, ultimately, the treatment response. However, little is known about how germline mutations affect the tumoral microenvironment. Here, we find that the single-nucleotide polymorphism (SNP) rs755622 in the promoter of the cytokine macrophage migration inhibitory factor (MIF) is associated with increased leukocyte infiltration in glioblastoma. Furthermore, we identified an association between rs755622 and lactotransferrin expression, which could also be used as a biomarker for immune-infiltrated tumors. These findings demonstrate that a germline SNP in the promoter region of MIF may affect the immune microenvironment and further reveal a link between lactotransferrin and immune activation.

We have developed Convacell®—a COVID-19 vaccine based on the recombinant nucleocapsid (N) protein of SARS-CoV-2. This paper details Convacell’s® combined phase I/II and IIb randomized, double-blind, interventional clinical trials. The primary endpoints were the frequency of adverse effects (AEs) and the titers of specific anti-N IgGs induced by the vaccination; secondary endpoints included the nature of the immune response. Convacell® demonstrated high safety in phase I with no severe AEs detected, 100% seroconversion by day 42 and high and sustained for 350 days anti-N IgG levels in phase II. Convacell® also demonstrated a fused cellular and humoral immune response. Phase IIb results showed significant post-vaccination increases in circulating anti-N IgG and N protein-specific IFNγ+-producing PBMC quantities among 438 volunteers. Convacell® showed same level of immunological efficacy for single and double dose vaccination regimens, including for elderly patients. The clinical studies indicate that Convacell® is safe and highly immunogenic.

The maxillary artery aneurysm occurs rarely, only a few cases were described in the foreign literature where the aneurysm were associated mainly with the past head injury. The behavior of the aneurysm is largely unknown: both spontaneous resolution and growth of the aneurysm, resulting in rupture, have been reported. We observed an aneurysm of the maxillary artery in the maxillary sinus as an intraoperative finding, with the following bleeding and embolization of the bleeding vessel. Due to the growing number of endovideoscopic operations on the axillary system, it was proposed to increase the volume of preoperative examination to prevent the intraoperative bleeding.

Introduction. Tendon grafts are widely demanded in reconstructive plastic surgery. Allogeneic tendons potentially have a number of advantages. However, the method of long-term storage of allogeneic tendons has not been optimized to date.Aim. Selection of an optimal cryoprotectant for the storage of human tendon allografts at ultra-low temperatures, which allows preserving the native tissue structure.Material and methods. We studied M. tibialis anterior tendon grafts taken from tissue donors. Endocellular/penetrating cryoprotectants (dimethyl sulfoxide, polyethylene glycol-400, glycerol) and exocellular/non-penetrating cryoprotectants (glucose solution, albumin solution) were used in the cryopreservation process. Tendon mechanical properties were evaluated using rupture and stretching-shear test, the general morphology of tendons, topography, dense and integrity of collagen fibers, preservation of cellular elements were microscopically evaluated.Results. Histological analysis showed that the safety of collagen and elastin fibers differed depending on the cryoprotectant used. At the same time, micro-fractures of collagen fibers were microscopically detected in all the experiments. In the presence of dimethyl sulfoxide, polyethylene glycol-400 and their combination the structure of collagen fibers and cells did not undergo visible changes compared to the control, whereas in all the experiments with non-penetrating cryoprotectants the topography and orientation of the fibers were clearly disturbed, deformation of many cells in the tendons was also observed.Conclusions. Cryoprotectants based on dimethyl sulfoxide, polyethylene glycol and their combinations allowed us to preserve the structural integrity of allogeneic tendons. Non-penetrating cryoprotectants did not effectively preserve the integrity of collagen fibers and cells in the tendons and cannot be recommended for cryopreservation.

Chronic postoperative pain (POP) is a serious complication of total replacement (TR) of the knee (KJ) and hip (HJ) joints.Objective: to determine the factors associated with POP in patients after TR of KJ or HJ.Patients and methods. The study group consisted of 124 patients with knee osteoarthritis or hip osteoarthritis (age 63.6±9.9 years, 63% women and 37% men) who underwent TR of KJ or HJ. POP was defined as pain ≥40 mm on a numerical rating scale persistent for ≥3 months. Its presence was assessed after 3 and 6 months by telephone survey. Comparison of patients with POP and without it was carried out for a number of factors identified before surgery.Results and discussion. The incidence of POP was 27.4%. There was no difference in the incidence of POP in patients after TR of KJ or HJ: 28.1% and 26.9% (p=0.88). POP was statistically significantly associated with parameters such as higher body mass index (BMI); the intensity of pain at rest; general assessment of impairment; WOMAC index pain, stiffness and overall; severity of symptoms of neuropathic pain (PainDETECT); signs of depression and anxiety (HADS).The risk of POP was significantly higher (p30 kg/m2 (odds ratio, OR 2.755; 95% confidence interval, CI 1.053–7.206), rest pain ≥40 mm on a visual analog scale (OR 1.349; 95% CI 0.478–3.803), PainDETECT scores ≥13 (OR 3.598; 95% CI 1.048–12.36) and HADS depression ≥8 (OR 2.193; 95% CI 0.745–6.454), presence of ≥2 sources of pain (OR 6.996; 95% CI 2.358–20.756).Conclusion. It was found that the risk of POP after TR of KJ and HJ is higher in patients with overweight, severe preoperative pain, signs of neuropathic pain and depression, as well as in the presence of several sources of pain (except for the affected joint, that was replaced surgically).

Knee osteoarthritis (kOA) is a common cause of turning for medical advice, associated with chronic pain and disability. One of the methods of OA treatment is the local administration of hyaluronic acid (HA) drugs.Objective: to evaluate the effectiveness of intra-articular (IA) administration of highly purified HA (Armaviskon Plus) in kOA.Patients and methods. The study group consisted of 58 patients (74.1% women and 25.9% men, aged 59.5±11.8 years) with kOA, experiencing moderate/severe pain (≥40 mm on a visual analogue scale, VAS). All patients received IA injection of HA Armaviskon Plus (2 ml of a 1.5% solution), 2 injections with an interval of 7 days. The effectiveness criterion was the dynamics of pain at rest and during movement (VAS 0-100 mm) and the function of the knee joint according to a numerical rating scale (NRS 0-100 points) 2 weeks, 1 and 3 months after administration of therapy.Results and discussion. During the treatment, there was a significant improvement in all indicators. The average severity of pain during movement at baseline, after 2 weeks, 1 and 3 months was 50 [40; 60], 30 [20; 40], 15 [0; 30], 20 [0; 30] mm (p

About 10–40% of patients with osteoarthritis (OA) are not satisfied with the results of total arthroplasty (TA) of large joints. At the same time, the most common complication associated with the ineffectiveness of TA is postoperative pain (PP).Objective: to identify genes whose expression in the peripheral blood before TA is associated with an increased risk of PP developing. Patients and methods. Before TA, the blood of 50 patients with late-stage knee OA was examined; the control group consisted of 26 healthy individuals. The level of pain was assessed using the visual analog scale (VAS), the BPI short questionnaire, and the WOMAC index; the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of PP was determined 3 and 6 months after TA. The levels of matrix metalloproteinase protein (MMP) 9 and tissue inhibitor of metalloproteinase (TIMP) 1 were quantified by ELISA. Total RNA isolated from blood was used to determine the expression of caspase 3, MMP9, TIMP1, cathepsins K and S, tumor necrosis factor (TNF) α, interleukin (IL) 1β, and cyclooxygenase 2 genes using a quantitative real-time reverse transcriptase polymerase chain reaction.Results and discussion. PP according to VAS ≥30 mm was noted in 17 patients. Before TA, these patients had significantly increased expression of cathepsins K and S, caspase 3, TIMP1, IL1β, and TNFα genes compared to other patients with OA. ROC analysis revealed a statistically significant relationship between the expression of these genes and the likelihood of developing pain after TA.Conclusion. High expression of genes associated with degradation of the extracellular matrix (catepsins S and K, TIMP1), inflammation (IL1β, TNFα), and apoptosis (caspase 3) can serve as an important biomarker for the development of PP in patients with knee OA. To confirm the value of preoperative gene expression testing in predicting the onset of PP, further studies involving large cohorts of patients are needed.

Urothelial cancer occupies a significant place in the routine practice of cancer treatment. Systemic antitumor treatment of patients with metastatic urothelial cancer in the first line is currently well studied, has its own standards, implemented in clinical practice. However, the problem of choosing antitumor treatment for patients with metastatic urothelial cancer in the second line remains relevant. Vinflunine is one of the treatment options for such patients. This article presents the case of successful treatment of metastatic urothelial cancer in the second line with vinflunine. A 63-year-old patient with a diagnosis of C65 Urothelial cancer of the pelvis of the left kidney T3N0M1, stage IV, bone metastases. Condition after cytoreductive left-sided nephrectomy, para-aortic lymphadenectomy from 04/16/2021. Concomitant pathology: Anemia. Diabetes mellitus type 2 Hypertonic disease. As the 1st line of treatment, 6 courses of CT were performed according to the scheme: Cisplatin + Gemcitabine. The effect was evaluated according to MSCT data of 3 zones and bone scintigraphy in accordance with Recist 1.1. The best response was obtained after the 4th cycle in August 2021 in the form of stabilization. October 2021 follow-up examination revealed progression. Since October 2021, chemotherapy of the 2nd line with Vinflunin is carried out in mono mode. All AEs are well controlled and do not require discontinuation of the drug. According to the results of the control examination, stabilization was achieved. Thereby vinflunine has been shown to be effective as a second-line treatment for platinum-resistant recurrent urothelial cancer.

Abstract The theory of scattering of ultrashort laser pulses (USP) is the basis of diffraction analysis of matter using modern USP sources. At present, the peculiarities of interaction of USP with complex structures are not well developed. In general, the research focuses on the features of the interaction of USP with simple systems, these are atoms and simple molecules. Here we present a theory of scattering of ultrashort laser pulses on molecules with a multi-atomic structure, taking into account the specifics of the interaction of USP with such a substance. The simplicity of the obtained expressions allows them to be used in diffraction analysis. As an example, the scattering spectra of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are presented. It is shown that the theory developed here is more general in the scattering theory and passes into the previously known one if we consider the duration of the USP to be sufficiently long.

Abstract Nuclear receptors (NR) are ligand-modulated transcription factors that regulate multiple cell functions and thus represent excellent drug targets. However, due to a considerable NR structural homology, NR ligands often interact with multiple receptors. Here, we describe a multiplex reporter assay (the FACTORIAL NR) that enables parallel assessment of NR ligand activity across all 48 human NRs. The assay comprises one-hybrid GAL4-NR reporter modules transiently transfected into test cells. To evaluate the reporter activity, we assessed their RNA transcripts. We used a homogeneous RNA detection approach that afforded equal detection efficacy and permitted the multiplex detection in a single-well format. For validation, we examined a panel of selective NR ligands and polypharmacological agonists and antagonists of the progestin, estrogen, PPAR, ERR, and ROR receptors. The assay produced highly reproducible NR activity profiles (r > 0.96) permitting quantitative assessment of individual NR responses. The inferred EC50 values agreed with the published data. The assay showed excellent quality ( = 0.73) and low variability ( = 7.2%). Furthermore, the assay permitted distinguishing direct and non-direct NR responses to ligands. Therefore, the FACTORIAL NR enables comprehensive evaluation of NR ligand polypharmacology.

Since the first news about the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared, a large amount of data on the variability of the virus genome have accumulated. Most of the mutations entrenched in the viral genome are aimed at improving the mechanisms of host cell penetration, altering the degree of binding to protein receptors, evading the immune system, and suppressing the antiviral immune response. Knowledge of the functional role of mutations will allow improving diagnostic methods, treatment, and vaccine prophylaxis regimens, as well as predicting the further spread and evolution of the virus. In this study, we analyzed a number of SARS-CoV-2 virus mutations in the context of viral epitope affinity for most common in Russia HLA class I and class II alleles (according to Allele Frequency Net Database). This study examined clade-forming mutations of viral clades that are classified as variants of concern according to the WHO classification. We found that some mutations reduce the number of predicted epitopes, the number of HLA alleles that bind them, or the number of both epitopes and HLA alleles simultaneously. Mutations of the viral clade B.1.1.7 (S:Y144del, S:H69-V70del, and S:A570D), mutations of the viral clade B.1.617.2 (S:T19R, S:G12D, S:F157del, and S:R158del), and mutation N:R203K related to all clades except B.1.617.2 have pronounced effects on reducing epitope affinity for HLA alleles, with some of them affecting on epitopes of all the studied strong and weak binders lengths in both HLA class I and class II.

Aim. To assess the concentrations of bacterial and eukaryotic metabolites mainly involved in indole, kynurenine, and serotonin pathways of tryptophan metabolism in a cohort of patients with obesity. Materials and methods. Using high-performance liquid chromatography with mass spectrometric detection, the concentrations of several serum metabolites, such as kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, quinolinic acid, 5-hydroxyindole-3-acetate, tryptamine, serotonin, indole-3-lactate, indole-3-acetate, indole-3- butyrate, indole-3-carboxaldehyde, indole-3-acrylate, and indole-3-propionate, were analyzed in a cohort of obese patients compared with healthy volunteers.Results. It was found that serum levels of tryptophan metabolites of microbial and eukaryotic origin were significantly increased in obese patients. Therefore, the concentration of kynurenine in the blood serum in obese patients was 2,413 ± 855 nmol / l, while in healthy volunteers of the same age group, the level of kynurenine in the blood serum was 2,122 ± 863 nmol / l. In obese patients, two acids formed due to kynurenine metabolism; the concentrations of kynurenic and quinolinic acids were increased in the blood serum. The concentration of kynurenic acid in the blood serum in obese patients was 21.1 ± 9.26 nmol / l, and in healthy patients, it was 16.8 ± 8.37 nmol / l. At the same time, the level of quinolinic acid in the blood serum in obese patients was 73.1 ± 54.4 nmol / l and in healthy volunteers – 56.8 ± 34.1 nmol / l. Normally, the level of quinolinic acid is 3.4 times higher than the concentration of kynurenic acid, and in case of obesity, there is a comparable increase in these acids in the blood serum.From indole derivatives, mainly of microbial origin, the concentrations of indole-3-lactate, indole-3-butyrate, and indole-3-acetate were significantly increased in the blood serum of obese patients. In obese patients, the serum concentration of 5-hydroxyindole-3-acetate was elevated to 74.6 ± 75.8 nmol / l (in healthy volunteers – 59.4 ± 36.6 nmol / l); indole-3-lactate – to 523 ± 251 nmol / l (in healthy volunteers – 433 ± 208 nmol / l); indole-3-acetate – to 1,633 ± 1,166 nmol / l (in healthy volunteers – 1,186 ± 826 nmol / l); and indole-3-butyrate – to 4.61 ± 3.31 nmol / l (in healthy volunteers – 3.85 ± 2.51 nmol / l).Conclusion. In case of obesity, the utilization of tryptophan was intensified by both the microbiota population and the macroorganism. It was found that obese patients had higher concentrations of kynurenine, quinolinic and kynurenic acids, indole-3-acetate, indole-3-lactate, indole-3-butyrate, and 5-hydroxyindole-3-acetate. Apparently, against the background of increased production of proinflammatory cytokines by adipocytes in obese patients, the “kynurenine switch” was activated which contributed to subsequent overproduction of tryptophan metabolites involved in the immune function of the macroorganism.

The article considers a clinical case of treatment of one of the variants of myofascial pain syndrome – piriformis syndrome without signs of sciatic nerve neuropathy. The peculiarity of the case is the comorbidity of the opioid syndrome with diabetic sensorimotor polyneuropathy and osteoporosis, which required the appointment of complex therapy. The diagnosis was confirmed by additional research methods: spondylography, MRI of the lumbosacral spine, ultrasound of the piriformis muscle, electroneuromyography. A patient management tactic was chosen based on federal clinical guidelines for the treatment of patients with nonspecific back pain. Treatment included non-medicinal and medicinal methods. In order to relieve pain, dexketoprofen was prescribed 2 ml intramuscularly per 2 ml of 0.5% lidocaine solution – 1 time а day No. 2 – under navigation by ultrasound. Subsequently, the transfer was made to oral administration of 25 mg 3 times а day for 3 days. A step-by-step scheme of prescribing dexketoprofen: its introduction into the piriformis muscle with subsequent transfer to oral administration allowed to significantly reduce the severity of pain after 5 days of treatment. The complex effect on the spasmodic piriformis muscle with the help of a tableted muscle relaxant in combination with postisometric relaxation made it possible to quickly stop the pain syndrome and prevent its chronization. The administration of the preparation of thioctic acid pursued two goals: to improve the metabolism of the spasmodic muscle and restore the energy metabolism of peripheral nerves. As a result of the use of complex, pathogenetically based therapy, a positive effect was achieved.

Objective: to evaluate the significance of clinical indicators, expression of pain syndrome genes cathepsin S and pro-inflammatory cytokines in peripheral blood for predicting the development of postoperative pain (POP) in patients with hip osteoarthritis (HOA) before total arthroplasty (TA).Material and methods. The study included 31 patients with stages III–IV of HOA (mean age 61.3±9.8 years) who underwent TA and 26 healthy volunteers (control group). Depending on the presence or absence of POP, patients were divided into two subgroups: with POP (1st subgroup, n=12) and without POP (2nd subgroup, n=19). Patients were examined before and 6 months after surgery.Prior to TA, the level of pain was determined in all patients using the visual analogue scale (VAS), as well as using the DN4 and PainDETECT neuropathic pain questionnaires. Functional status was assessed by the WOMAC index. The development of POP ≥30 mm according to VAS was assessed 6 months after TA.Total RNA was isolated from whole blood and used to evaluate gene expression for cathepsin S, interleukin 1 (IL1 ), tumor necrosis factor α (TNFα), and cyclooxygenase 2 (COX2) by quantitative real-time polymerase chain reaction. Results and discussion. Complaints of pain persisted in 12 (38.7%) patients 6 months after TA. Before surgery, the expression of cathepsin S, IL1 , TNFα, and COX2 genes was significantly higher in patients of both subgroups compared to healthy controls. In addition, in patients with POP who were not satisfied with the outcome of TA, the rates of neuropathic pain according to the DN4 questionnaire and cathepsin S gene expression were significantly higher than in other patients. At the same time, there was no significant difference in the expression of genes of pro-inflammatory cytokines in patients of the studied subgroups before TA.Conclusion. The development of POP in patients with HOA may be partially associated with its perception mechanisms disturbance, and an increase in the expression of the cathepsin S gene in the peripheral blood prior to TA can serve as its prognostic biomarker.

Post-traumatic osteoarthritis (PTOA) is an inflammatory and degenerative disease that occurs as a result of the joint structures injury. It is a common pathology, accounting for approximately 12% of all cases of osteoarthritis (OA). PTOA often occurs in people of young productive age, progresses rapidly, causing chronic pain and increasing dysfunction. Individuals undergoing joint replacement for PTOA are, on average, 10 years younger than those with primary OA. The time interval from the moment of injury to the onset of typical PTOA radiological signs varies widely – from 1 year to 15–20 years.The main injuries that cause PTOA are intra-articular fractures, anterior cruciate ligament injuries, meniscus rupture and dislocation of the patella of the knee joint, joint dislocations with damage to the ligamentous apparatus of the ankle and shoulder joints.The pathogenesis of PTOA is determined by chronic inflammation accompanied by macrophage activation, hyperproduction of cytokines, primarily interleukin (IL) 1â, chemokines and growth factors, progressive destruction of joint tissue and degenerative changes (fibrosis, neoangiogenesis, osteophytosis).Pathogenetic treatment of PTOA, which would stop the progression of the disease, has not been developed. The possibility of using inhibitors of IL1â, IL6, inhibitors of tumor necrosis factor á, glucocorticoids, hyaluronic acid, autologous cell based therapy is under study. The control of pain and inflammation in PTOA requires the prescription of traditional drugs that are widely used in the practice of managing patients with primary OA. In particular, the use of symptomatic delayed-acting agents, such as the injectable form of chondroitin sulfate, seems to be appropriate.

Arthroscopic interventions are widely used to treat the consequences of the meniscus and anterior cruciate ligament (ACL) injuries. However, the long-term consequences of these surgeries are not always favorable and not in all cases allow to avoid the development of chronic pain and posttraumatic osteoarthritis.Objective: to evaluate the incidence of persistent postoperative pain and the persistence of functional disorders in patients undergoing arthroscopic interventions on the menisci and ACL.Material and methods. The study group consisted of 147 patients (60 women and 87 men, mean age 38.8±12.5 years) who underwent arthroscopic surgery on the knee joint (KJ) in the traumatology and orthopedic department of V.A. Nasonova Research Institute of Rheumatology in 2018– 2021. The condition of patients was assessed by telephone survey and/or online questionnaire. The pain and fatigue levels were assessed on numerical rating scale (NRS, 0–10), as well as the severity of functional disorders on the Lysholm scale (LS).Results and discussion. Moderate or intense knee pain and increased fatigue (≥4 according to NRS) were noted in 11.3% and 14.7% of respondents, respectively. The state of the KJ according to LS in 35.3% of patients was assessed as excellent (95–100 points), in 29.3% – as good (84–94 points), in 21.3% – as satisfactory (65–83 points) and 14.0% – as unsatisfactory (≤64 points).Conclusion. More than 10% of patients after arthroscopic operations on the knee joint experience moderate or severe pain and fatigue, satisfactory and unsatisfactory functional results are observed in 35.4% of cases.

Knots in proteins and DNA are known to have significant effect on their equilibrium and dynamic properties as well as on their function. While knot dynamics and thermodynamics in electrically neutral and uniformly charged polymer chains are relatively well understood, proteins are generally polyampholytes, with varied charge distributions along their backbones. Here we use simulations of knotted polymer chains to show that variation in the charge distribution on a polyampholyte chain with zero net charge leads to significant variation in the resulting knot dynamics, with some charge distributions resulting in long-lived metastable knots that escape the (open-ended) chain on a timescale that is much longer than that for knots in electrically neutral chains. The knot dynamics in such systems can be described, quantitatively, using a simple one-dimensional model where the knot undergoes biased Brownian motion along a "reaction coordinate", equal to the knot size, in the presence of a potential of mean force. In this picture, long-lived knots result from charge sequences that create large electrostatic barriers to knot escape. This model allows us to predict knot lifetimes even when those times are not directly accessible by simulations.

Abstract Background Immediate loading of implant-supported full-arch rehabilitations has become routine practice when treating edentulous patients. The combination of static computer-aided implant surgery (s-CAIS) and digital prosthetic workflow could eliminate several treatment steps and facilitate prostheses delivery. The aim of this study is to evaluate the 1-year results of digitally prefabricated polymethyl methacrylate (PMMA) provisional prostheses without a cast for full-arch computer-assisted immediate loading. Materials and methods A digital pre-operative treatment planning was realized for all patients: dental implants and screw-retained abutments were selected in the planning software and two surgical templates were fabricated for each patient. The first template was mucosa or teeth-supported to drill the holes for fixating pins, while the second template was placed after raising a full-thickness flap and was supported by pins as well as soft or hard tissue distal support. Furthermore, based on the surgical planning, interim prostheses were digitally designed and milled of PMMA resin blocks with subsequent pink resin veneering. Osteotomies and implant placement were performed through the surgical guides and all implants were immediately loaded with prefabricated full-arch interim prostheses directly connected to titanium copings with a flowable resin. Results A total of 55 dental implants were placed in ten patients. In all cases, interim prostheses allowed the insertion of titanium copings without the need of access hole enlargement or adaptation. All the prostheses had 1 year of functional loading to simulate the long provisional phase. No screw loosening occurred at the first removal of the prostheses after implant osseointegration. No fracture occurred during the whole period. After 1 year, the mean marginal bone loss level was 0.37 ± 0.06 mm, while the implant survival rate was 98.18% (n=54/55), with just one implant failing but not affecting final prosthesis delivery to the patient. Conclusions Within the limitations of the present study, the authors concluded that digitally prefabricated provisional prostheses for full-arch immediate loading with s-CAIS could be a valid alternative treatment modality. Milled PMMA restorations proved to be durable enough during the long provisional phase, without prosthetic complications.

The authors have presented the review of scientific literature on producing grafts intended for surgical reconstruction of ligament ruptures. The treatment of ligament ruptures in reconstructive plastic surgery could be performed by using synthetic grafts, autologous and allogenic grafts from tissue donors. Advantages of synthetic grafts include the possibility of their regular manufacturing under sterile conditions, and providing mechanical properties, high biocompatibility. However, synthetic implants significantly increase the risk of synovitis and other complications, they can not be replaced by the native tissue, and have no ability to regeneration. Autologous grafts have ideal tissue compatibility and quick biointegration, could be harvested from different anatomical sites, but commonly the graft harvesting is followed by donor site morbidity and potential risk of injury nerves, elongates operation time, bad cosmetic results. The use of autografts may be also limited by anatomical features of the patient. Allogenic ligament biomaterial could provide wide range of grafts, but in our days there is no standardized methods for ligament graft sterilization and long storage. Wellknown sterilization methods, such as ionized radiation and chemical treatment, gave controversial results. One could conclude that estimation of ligament graft viability must include a complex study of biomechanical properties, cell and fibers integrity.

Abstract Rats are born deaf and start hearing at the end of the second postnatal week, when the ear canals open and low-intensity sounds start to evoke responses in the auditory cortex. Here, using μECoG electrode arrays and intracortical silicon probe recordings, we found that bone-conducted (BC) sounds evoked biphasic responses in the auditory cortex starting from postnatal day (P) 8. The initial phase of these responses, generated by thalamocortical input, was followed by intracortical propagation within supragranular layers. BC-evoked responses co-localized with the responses evoked by electrical stimulation of the cochlea and the deepest layers of the inferior colliculus prior to onset of low-threshold hearing (P13), as well as with the responses evoked by high-frequency (30 kHz) low-intensity (70 dB) air-conducted sounds after that. Thus, BC signals reach high-frequency processing regions of the auditory cortex well before the onset of low-threshold hearing, reflecting early integrity of the auditory system.

BackgroundSurgery is the most common treatment for localized small kidney masses (SKMs) up to 4 cm, despite a lack of evidence for improved overall survival. Nonsurgical management options are gaining recognition, as evidence supports the indolence of most SKMs. Decision aids (DAs) have been shown to improve patient comprehension of the trade-offs of treatment options and overall decision quality, and may improve consideration of all major options according to individual health priorities and preferences. ObjectiveThis pilot randomized controlled trial (RCT) primarily aims to evaluate the impact of a new web-based DA on treatment decisions for patients with SKM; that is, selection of surgical versus nonsurgical treatment options. Secondary objectives include an assessment of decision-making outcomes: decisional conflict, decision satisfaction, and an understanding of individual preferences for treatment that incorporate the trade-offs associated with surgical versus nonsurgical interventions. MethodsThree phases comprise the construction and evaluation of a new web-based DA on SKM treatment. In phase 1, this DA was developed in print format through a multidisciplinary design committee incorporating patient focus groups. Phase 2 was an observational study on patient knowledge and decision-making measures after randomization to receive the printed DA or institutional educational materials, which identified further educational needs applied to a web-based DA. Phase 3 will preliminarily evaluate the web-based DA: in a pilot RCT, 50 adults diagnosed with SKMs will receive the web-based DA or an existing web-based institutional website at urology clinics at a large academic medical center. The web-based DA applies risk communication and information about diagnosis and treatment options, elicits preferences regarding treatment options, and provides a set of options to consider with their doctor based on a decision-analytic model of benefits/harm analysis that accounts for comorbidity, age group, and tumor features. Questionnaires and treatment decision data will be gathered before and after viewing the educational material. ResultsThis phase will consist of a pilot RCT from August 2022 to January 2023 to establish feasibility and preliminarily evaluate decision outcomes. Previous study phases from 2018 to 2020 supported the feasibility of providing the printed DA in urology clinics before clinical consultation and demonstrated increased patient knowledge about the diagnosis and treatment options and greater likelihood of favoring nonsurgical treatment just before consultation. This study was funded by the National Cancer Institute. Recruitment will begin in August 2022. ConclusionsA web-based DA has been designed to address educational needs for patients making treatment decisions for SKM, accounting for comorbidities and treatment-related benefits and risks. Outcomes from the pilot trial will evaluate the potential of a web-based DA in personalizing treatment decisions and in helping patients weigh attributes of surgical versus nonsurgical treatment options for their SKMs. Trial RegistrationClinicalTrials.gov NCT05387863; https://clinicaltrials.gov/ct2/show/NCT05387863 International Registered Report Identifier (IRRID)PRR1-10.2196/41451