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The relevance of studying the impact of coronavirus infection on the development and course of autoimmune diseases is due to an increase in the incidence of COVID-19 infection, which is confirmed by reliable data from recent large-scale studies. The trigger mechanisms of autoimmune disorders, particularly those with dermatological manifestations, have been well studied. COVID-19 significantly increases not only the risk of manifestation of autoimmune diseases but also the transformation of a preexisting disorder into severe, atypical, and resistant to standard therapy forms. The article analyzes the data of patients with psoriasis treated in a day hospital from 2021 to 2023 at the affiliate of the Moscow Scientific and Practical Center of Dermatology, Venereology and Cosmetology “V.G. Korolenko Clinic” with exacerbation or onset of the disease reliably associated with a history of coronavirus infection. It is a clinically significant issue since there is a pathomorphosis of a typical pattern of exacerbations: the area of skin lesions increases, exudative and toxicoallergic components are manifested; psoriasis is torpid, which requires the development of individual algorithms for the treatment of patients with psoriasis and post-COVID syndrome, considering the mechanisms of this condition development. An essential aspect in the analysis of this sample of patients was the assessment of general somatic comorbidity, which requires a multidisciplinary approach in selecting therapy to comply with modern criteria for quality treatment, namely its maximum effectiveness and safety.

Relevance.Amonomorphic type of maculo-­papular cutaneous mastocytosis was allocated relatively recently. Inchildren and adolescents with amonomorphic type of MPCM (adult type pattern), clinical manifestations persist into adulthood and can transform into asystemic process, which determines the need for regular monitoring of this category of patients.Theaimwas to analyse the results of clinical, laboratory and instrumental examinations of an adolescent with amonomorphic type of MPCM.Materials and Methods. The study of an adolescent patient included data of laboratory examination, pathomorphological examination, ultrasound examination of the abdominal organs and cKIT gene of an adolescent with amonomorphic type of MPCM, observed at “Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology”.Resultsand Discussion.The process was represented by multiple rashes on the skin of the trunk and limbs. Darier’s sign is positive. The patient’s serum tryptase level exceeded the age norm. The late onset (atthe age of 12)of the disease, elevated tryptase levels, neurological symptoms, and the risk of anaphylaxis caused alertness regarding the development of the systemic form, therefore an ultrasound examination of the abdominal organs was performed and the presence of amutation in the cKIT gene in peripheral blood was determined.Conclusion.Clinical report of an adolescent patient in Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology was presented. Thus, the combination of clinical and laboratory data allows minimizing the number of invasive procedures in children with CM. Assessment of the tryptase level, mutation detection in the cKIT gene and ultrasound examination of abdominal organs can be useful for timely diagnosis of systemic mastocytosis, which allows to carry out the necessary correction of the disease status and drug therapy.

A cardiac examination (ECG, Echo-CG and BCA ultrasound) was carried out on 150 patients – 60 HIV-infected with various stages of the disease and 90 patients with syphilis/HIV co-infection. Cardiovascular pathology caused by HIV infection was detected in 46.6% of patients in the first group, and in 7.7% in the second group. In a comparative analysis of the effect of antiretroviral therapy (ART) among those examined, it was proven that in the absence of ART or delayed or irregular use of drugs, the proportion of patients with cardiovascular pathology is several times higher than that of people who took ART on a timely and regular basis.

The article addresses the impact of the new coronavirus infection on the occurrence of cutaneous forms of lupus erythematosus (LE). Since the beginning of the COVID-19 pandemic, there has been an increase in the incidence of cutaneous LE worldwide, the emergence of new cases, and exacerbation and aggravation of the severity of existing ones. The pathogenesis of cutaneous LE, and the role of viral infections in its occurrence, mainly COVID-19, is reviewed. The need for the SARS-CoV-2 vaccination and its potential as a possible trigger is described. It is necessary to note the importance of clinicians in diagnosing LE since it is essential for the dermatologist to know the features of its course and be able to suspect and diagnose even the rarest forms of this disease. Proper awareness and correct diagnosis determine the optimal drug therapy and patient health in the future.

Relevance. Atopic dermatitis (AD) is an inflammatory disease characterized by a chronic course with periods of remissions and exacerbations. IgE-independent atopic dermatitis is a medical and social problem of our time, since the disease manifests itself most often in childhood and is one of the most frequent forms of dermatoses among the pediatric population. The prevalence of atopic dermatitis among children is up to 20 %, among adults - 2-8 %. Recently, there has been a significant increase in atopic diseases worldwide. The aim: to study specific features of IgE-independent atopic dermatitis in children living in a metropolis. Materials and Methods. A prospective cohort study was conducted, which included 451 children aged 5 to 14 years with a diagnosis of AD who applied for outpatient care at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology for the period 2020-2021. All parents (guardians) have given voluntary informed consent to the participation of children in the study and the publication of personal data. Examination of patients included general clinical methods, assessment of the SCORAD index and laboratory allergological examination (total and 73 specific IgE in blood serum with the most common food and aeroallergens). In 103 (22.8 %) children (57 (55.3 %) boys and 46 (44.7 %) girls), the results of the allergological analysis did not confirm concomitant allergic sensitization. Atopic dermatitis in these children was defined as IgE-independent. Results and Discussion. Predictors of the development of IgE-independent AD were hereditary predisposition [odds ratio (OR) 2.42; 95 % confidence interval (CI) 1.12-5.25], artificial feeding [OR 4.04; 95 % CI 1.46-11.20], comorbidities [OR 1.42; 95 % CI 0.57-3.52], late onset [OR 1.67; 95 % CI 0.81-3.41]. According to the SCORAD index, the majority of patients (75.7 %) had a moderate degree of AD and no seasonality. Features of skin rashes corresponded to the age periods of the course of AD: erythematous-squamous forms with lichenification foci prevailed. For the first time, the features of IgE-independent atopic dermatitis in children were shown. The role of risk factors for the development of IgE-independent atopic dermatitis in children has been shown for the first time. Conclusion. IgE-independent type of AD can be diagnosed in every fifth child with AD. The study of risk factors will allow predicting the development of this type of disease.

Itchy scalp troubles many people. The causes of itching can be systemic, psychogenic, neurological, and dermatological diseases. The most common dermatological diseases associated with scalp itching are seborrheic dermatitis and psoriasis. The pathogenesis of these diseases is very different, but in both cases, skin microbiota changes may present, supporting the inflammation. Also, in both conditions, flaking and other similar clinical presentations occur. In addition to adequate therapy, the choice of care product is important. For a patient with scalp disease, the specialist should recommend shampoo and other products that can complement the basic therapy. Such products should have some features: they should help to normalize the microbiota and pH, relieve inflammation, and eliminate unpleasant symptoms, including itching. One such product is LE SANTI shampoo, which shows good clinical efficacy for several dermatological diseases.

About 187 million couples worldwide suffer from infertility, with the male factor being diagnosed in 2070% of cases. The main cause of idiopathic infertility has been recognized as the adverse effects of reactive oxygen species. On the one hand, the cellular antioxidant defense is a highly efficient multilevel system; therefore, the pharmacological targets may vary. On the other hand, antioxidant enzymes (superoxide dismutase, catalase, peroxidase) have high activity and specificity, which limits the pharmacological capabilities of direct antioxidants. Indirect methods, such as the normalization of mitochondrial function, are more promising. Mitochondria play a key role in providing energy for sperm motility (one of the main factors of male fertility). Myo-inositol (MI) derivatives involved in cell signaling regulate intracellular Ca2+ ion levels affecting mitochondrial oxidative metabolism and adenosine triphosphate production. Thus, mitochondrial antioxidants are of particular interest for therapeutic strategies. Currently, various routes and regimens of MI use in the treatment of males with oligo-astheno-teratozoospermia (OAT) are being considered in clinical practice. MI-based oral nutraceutical complexes for the treatment of male factor infertility contain both direct and indirect antioxidants. In vitro studies revealed damage to mitochondrial cristae in the sperm intermediate tract in patients with OAT. Experimental studies have demonstrated that mitochondrial structure is restored when sperm are incubated in an MI-containing medium. Clinical studies confirmed that sperm incubation in such an environment leads to increased sperm motility and viability in patients with OAT. Intravaginal administration of MI showed increased total sperm motility and an increased proportion of progressively motile sperm. It is the progressive motility that is considered the best marker for identifying quality and healthy sperm. This type of sperm is usually used for in vitro fertilization techniques. In addition, intravaginal MI administration improved the quality of cervical mucus and reduced its viscosity and crystallization. The effect of intravaginal MI on cervical mucus can be considered as an additional independent factor in increasing fertility.

One of the promising and relevant directions in the treatment of oncological diseases is currently the development of a system for the delivery of antitumor drugs based on polyanions. Therefore, the aim of this work was to study the specifics of pharmacokinetics and biodistribution of a 5-Fluorouracil polymeric complex compared with commercial 5-Fluorouracil. Materials and methods: Monomeric methacrylic acid was used to synthesize polymers; 2-phenylpropane-2-ilbenzodithioate was used for the synthesis of poly(methacrylic acid). To study the molecular-weight characteristics of poly(methacrylic acid) by gel permeation chromatography, an experimental neoplasm model was obtained by grafting PC-1 cancer cells. Blood samples were drawn from the tail vein at different points in time. The rats were sacrificed via decapitation after drawing the last pharmacokinetic blood sample. To study the biodistribution, internal organs were isolated and analyzed. The measurements were carried out by high-performance liquid chromatography. Results: Our results demonstrate that incorporation in a polymeric complex changes the pharmacokinetics and biodistribution profile of 5-FU. The polymeric complex was shown to accumulate to a higher level in the lung and spleen. Conclusion: The results obtained are the basis for further studies to verify the efficacy of the 5-Fluorouracil polymeric complex.

Background. Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex, and the exact mechanism, despite numerous studies, is still unclear. Complex genetic relationships play an important role in the pathogenesis of this skin disease. A large number of genes that are also associated with other diseases are involved in the development of psoriasis. The variety of comorbidities in patients with psoriasis often present challenges to the treatment for dermatosis. Understanding the role of certain genes in the pathogenesis of psoriasis will contribute the development of more effective targeted therapy aimed at blocking the corresponding inflammatory signaling pathways and molecules. Aim. To analyze and systematize the basic genetic and biological markers of psoriasis. Materials and methods. The study included research articles on the genetic analysis of psoriasis. The ResNet, PubMed and eLibrary databases were used. Results and discussion. Basic genetic and biological markers were identified by analysis of literature sources devoted to psoriasis. Attention is paid to the role and effects of single nucleotide polymorphisms, which make it possible to establish a clear association of a number of genes involved in the development of psoriasis. Genes with altered expression in the psoriatic process were considered separately. Conclusion. The identified biomarkers can be used in targeted biological therapy of psoriasis using biological modulators that block signaling.

Matrix metalloproteinases (MMPs) are often considered biomarkers of skin fibrosis. At the early stages of the pathological process, an elevation of their enzymatic activity causes significant changes in the composition of the extracellular matrix. MMPs secreted by immune cells facilitate their migration to the site of damage. Then, the immune cells eliminate the affected cells and biomolecules. Moreover, bidirectional changes in the activity of proteolytic enzymes, including MMPs, accompany wound healing. This study aimed to assess changes in the expression of Mmp2, Mmp3, and Mmp9 after treating mice with laser therapy using the experimental model of bleomycin-induced skin fibrosis. Using immunohistochemistry, we characterized the histological features of scarred skin. We also analyzed changes in the expression of MMPs using real-time polymerase chain reaction before and after laser irradiation. We showed that treatment of the mice with a CO2 laser partially normalized the histological features of scarred skin. We also noticed a decrease in the expression of Mmp2, Mmp3 (both p < 0.05), and Mmp9 (p = 0.065) during scar healing. The obtained results suggest that normalization of skin homeostasis requires control of MMP activity via induction of genes.

Purpose Blood pressure telemonitoring and remote counselling (BPTM) improves blood pressure (BP) control in patients with hypertension (HTN). Studies assessing the efficacy of BPTM from a value-based perspective are lacking. We investigated whether BPTM fits all principles of the value-based approach (clinical and economic effectiveness, improvement in patient-reported outcome/experience measures (PROM/PREM)). Materials and methods Two hundred and forty ambulatory patients with uncontrolled HTN were randomised in a 2: 1 manner to BPTM (n = 160, mean age 47 y.o.) and usual care (UC, n = 80; 49 y.o.) with baseline and 3-month follow-up clinic visits. BPTM employed a mobile application (for patients) and a desktop version (for clinician), which allowed communication and exchange of medical data. The main outcomes were changes in office and ambulatory systolic (S) BPs, rate of BP control. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were evaluated in economic analysis. The MOS SF-36 score was taken as a PROM, and the PEQ score was used as a PREM. Results Larger decreases in office and ambulatory SBPs (–16.8 and −8.9 mm Hg, respectively; p

Telehealth is a useful adjunct in hypertension (HTN) management. Despite obvious short-term clinical benefit, long-term social impact and cost-effectiveness have not been fully investigated. Aim. Predictive modeling of long-term clinical and social outcomes and the cost-effectiveness analysis of blood pressure (BP) telemonitoring and remote counseling (BPTM) in patients with HTN. Materials and methods. A Markov cohort-based (1000 patients in each study arm) model was developed and adopted a 10-year time horizon with 12-month time cycles. Cost and outcome data collected from the three-month study of 240 patients (160 in BPTM group and 80 controls, 48 y.o.). All patients started at a non-complicated HTN well state with a certain possibility of disease progression in a number of health states over a discrete time period. BPTM was compared with usual care in terms of 10-year healthcare costs, quality adjusted life years (QALY) using a Ministry of Health of Russian Federation perspective. Results. In the long-term run when compared with usual care BPTM was more effective in terms mortality (67 versus 91 patients lost and 9.6 versus 9.71 life years gained) and costs (cost of illness 102 508 000 RUR versus 145 237 700 RUR). Taking quality of life measures into account, the effect of BPTM was also more pronounced (8.31 versus 7.82 QALYs gained). The resultant incremental cost-utility ratio for BPTM was 275 178.98 RUR/1 QALY gained/1 patient (134 837.70 RUR/0.49 QALY/1 patient). Conclusion. According to the results of predictive modeling, implementation of BPTM into clinical practice is likely lead to reduced cardiovascular morbidity and mortality in a cost-effective way.

Abstract The study shows that whole‐exome sequencing is a promising approach to detect novel variants—and gene candidates in DSD, that, as a future direction, may improve the diagnostic gene panels for this heterogeneous disorder.

Introduction: The study objective was to determine which antibiotics are optimal in the treatment of children with complicated acute bronchitis with bronchospasm. For that, a Monte-Carlo simulation was conducted. Materials and methods: The retrospective study was performed on the antibiotic therapy data from 1604 medical records of inpatients from Nizhny Novgorod (Russian Federation) medical centers admitted with acute bronchitis with bronchospasm. The treatment programs involved cephalosporins, inhibitor-protected penicillins, and macrolides. The starter drug was selected empirically considering the possible etiology and sensitivity of the presumed pathogen to the antimicrobial agents. The input data for the model (Monte-Carlo simulation) were the costs of antibiotic therapy and the probability of the clinical outcome (recovery, or the absence of effect). The probabilities of the clinical outcome were described with β-distribution, while the costs distribution was described using gamma-distribution. Results and discussion: Most positive clinical outcomes were observed with the use of macrolides, which also provided the lowest CER (cost-efficiency ratio), and are, therefore, optimal pharmacoeconomically. During the trial, the confidence intervals were evaluated for the clinical efficiency (95% CI of the β-distribution curve). The least interval of probable clinical efficiency for the investigated nosology was found for macrolides, which indicates their high clinical efficiency. Conclusion: Monte-Carlo method visualizes the results of clinical-economical evaluation of any medical technology in one disease compared to another. That is of value for the clinical pharmacologists and health professionals selecting the drugs for healthcare facilities.

Introduction: In the recent years, much attention has been paid to the use of leukotriene receptor antagonists (LTRA) in the treatment of bronchial asthma (BA). It has been even proposed to use them as alternatives to hormone therapy. Yet, there are studies demonstrating the advantage of montelukast as similar to placebo. The objective was to create a methodology for determining the correlation of the clinical efficacy of therapy with the addition of a drug (on example, clinical efficacy of montelukast in an anti-asthmatic therapy in pediatric patients). Materials and methods: The data on prescribed regimens was retrospectively extracted from the inpatient records of 608 BA patients admitted to hospital in 2014–2015. Mathematical evaluation was based on the risk factor concept. Results and discussion: The absolute efficacies (AEs) was estimated to be 91.85% (95% CI 90.15–93.55%) in the exposed group; the attributable efficacy (AtE) was found to be 17.00% (95% CI 10.91–23.09%); the relative efficacy (RE) was found to be 1.23 (95% CI 0.21–2.24); and the population attributable efficacy (PAtE) was found to be 7.55% (95% CI 2.49–12.61%). Conclusions: The AtE, RE, and PAtE were statistically significant. The RE was found to be 1.23. However, the lower limit of its 95% CI (0.21–2.24) was less than 1, indicating that the increase in clinical efficacy was not found to be statistically significant. In the studied sample positive outcome rates were 91.85% (95% CI 90.15–93.55%) in the exposed group and 74.85% (95% CI 72.49–77.21%) in the comparator group. He presented methodology for determining the correlation of the clinical efficacy of the pharmacotherapy regimen with the addition of a drug can be successfully applied in the future.

Cancer is a leading cause of mortality globally. Despite remarkable improvements in cancer-treatment approaches, disease recurrence and progression remain major obstacles to therapy. While chemotherapy is still a first-line treatment for a variety of cancers, the focus has shifted to the development and application of new approaches to therapy. Nevertheless, the relationship between immune response, neoplastic diseases and treatment efficiency is not fully understood. Therefore, the aim of the study was to investigate the immunopharmacological effects of methacrylic acid homopolymer in an in vivo tumor model. Materials and methods: Monomeric methacrylic acid was used to synthesize polymers. Methacrylic acid was polymerized in dioxane in the presence of 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid. To study the molecular weight characteristics of PMAA by GPC, carboxyl groups were preliminarily methylated with diazomethane. An experimental cancer model was obtained by grafting RMK1 breast cancer cells. The serum levels of IL-6, IL-10, IL-17, transforming growth factor β1 (TGF-β1), and tumor necrosis factor α (TNF-α) were measured by ELISA. Results: The effect of PMAA on the serum concentrations of several cytokines was studied upon its single administration to laboratory animals in early neoplastic process. The IL-6, IL-17 and TGF-β1 concentrations were found to change significantly and reach the level observed in intact rats. The IL-10 concentration tended to normalize. Conclusion: The positive results obtained are the basis for further studies on the effect of methacrylic-acid polymers with different molecular-weight characteristics on the neoplastic process.

Cytostatic chemotherapeutics provide a classical means to treat cancer, but conventional treatments have not increased in efficacy in the past years, warranting a search for new approaches to therapy. The aim of the study was, therefore, to obtain methacrylic acid (MAA) (co)polymers and to study their immunopharmacological properties. 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CDSPA) and 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) were used as reversible chain transfer agents. Experiments were carried out in Wistar rats. The MTT assay was used to evaluate the cytotoxic effect of the polymeric systems on peritoneal macrophages. An experimental tumor model was obtained by grafting RMK-1 breast cancer cells. Serum cytokine levels of tumor-bearing rats were analyzed. The chain transfer agents employed in classical radical polymerization substantially reduced the molecular weight of the resulting polymers, but a narrow molecular weight distribution was achieved only with CDSPA and high CPDT concentrations. Toxicity was not observed when incubating peritoneal macrophages with polymeric systems. In tumor-bearing rats, the IL-10 concentration was 1.7 times higher and the IL-17 concentration was less than half that of intact rats. Polymeric systems decreased the IL-10 concentration and normalized the IL-17 concentration in tumor-bearing rats. The maximum effect was observed for a MAA homopolymer with a high molecular weight. The anion-active polymers proposed as carrier constituents are promising for further studies and designs of carrier constituents of drug derivatives.

Early social deprivation (i.e., an insufficiency or lack of parental care) has been identified as a significant adverse early experience that may affect multiple facets of child development and cause long-term outcomes in physical and mental health, cognition and behavior. Current research provides growing evidence that epigenetic reprogramming may be a mechanism modulating these effects of early adversities. This work aimed to investigate the impact of early institutionalization-the immersion in an extreme socially depriving environment in humans-on the epigenome and adaptive behavior of young children up to 4 years of age. We conducted a cross-sectional study involving two comparison groups: 29 children raised in orphanages and 29 children raised in biological families. Genome-wide DNA methylation profiles of blood cells were obtained using the Illumina MethylationEPIC array; the level of child adaptive functioning was assessed using the Vineland Adaptive Behavior Scales-II. In comparison to children raised in families, children residing in orphanages had both statistically significant deficits in multiple adaptive behavior domains and statistically significant differences in DNA methylation states. Moreover, some of these methylation states may directly modulate the behavioral deficits; according to preliminary estimates, about 7-14% of the deviation of adaptive behavior between groups of children may be determined by their difference in DNA methylation profiles. The duration of institutionalization had a significant impact on both the adaptive level and DNA methylation status of institutionalized children.