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Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. Vaccination is generally accepted as the most effective strategy for influenza prevention. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidate, evaluate its immunogenicity using the hemagglutination inhibition assay, ELISA, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidate compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with high risk of skin and systemic infections. Preventive AD therapy is based on skin barrier improvement and anti-inflammatory treatment, whereas, severe skin and systemic infections require systemic therapy. This review describes pathophysiology and possible treatment and prevention methods for AD infectious complications.

The skin is the largest organ of the human body, it creates protective barrier between the internal and external environment. Skin barrier damage may result in homeostasis imbalance, inflammation, or bacterial infection. The microbiome plays a crucial role in maintaining normal skin functioning: control of pathogenic diversity of microorganisms, stimulate immune cells, and modulate chronic dermatoses development. There are various mechanisms for restoring skin barrier function. They are associated with the microorganisms’ activity. Thus, skin restoration is an important task included in the general concept of atopic dermatitis management. One of such methods is the skin surface colonization with commensals, so significant role is assigned to the new dermatological drugs. The normalization of the microbiome in affected skin areas with cosmetic care products can significantly affect the result of skin barrier restoration.

Background. Rapp-Hodgkin syndrome is a rare genetic disease from the ectodermal dysplasia group. It manifests with damage of ectodermal structures — layer of embrional tissue that provides the development of many organs and tissues in the body, such as: skin, sweat glands, hair, teeth, and nails. Disease symptoms may range from mild to severe and include dental abnormalities, fragile, thin or no hair, abnormal nails, hypohidrosis (due to the reduced number of sweat glands), cleft lips and palate. Hidradenitis suppurativa is a chronic inflammatory disease that predominantly affects apocrine glands areas. This nosology is characterized by painful nodes, abscesses, and fistulas, prone to relapses and leading to scarring.Clinical case description. The authors present a clinical case demonstrating the combination of Rapp-Hodgkin syndrome and severe hidradenitis suppurativa in 17-year-old male patient.Conclusion. The heterogeneous clinical findings of hidradenitis suppurativa and history of rare genetic disease result in patients' admissions to various medical specialists. Thus, it leads to delayed verification of the diagnosis and incorrect treatment methods. As a result, patients have persistent cosmetic skin defects, possible complications of irrational treatment, and decreased quality of life by the time of diagnosis.

Background. Linear IgA dermatosis is a rare autoimmune bullous disease characterized by vesiculo-bullous subepidermal lesions (affecting the skin and mucous membranes) and by linear homogeneous IgA deposition in the epidermis basal membrane.Clinical case description. Clinical case of linear IgA dermatosis in children is presented. Clinical data assessment, histological examination of the skin biopsy (to determine the depth of bullous), immunofluorescent examination (to reveal IgA deposition in the epidermis basal membrane) are crucial for reliable disease diagnosis according to the studies. Altogether it helps to establish the final diagnosis and determine the patient's management. Dapsone is the first-line treatment for this disease, it has proven to be an effective and safe medication.Conclusion. This case of linear IgA dermatosis is of concern due to disease severity and its rarity in clinical practice. Differential diagnosis is rather complicated and clinically requires high-tech research methods. Only immunofluorescent examination allows to diagnose linear IgA dermatosis accurately. Lesions' regression was achieved due to systemic therapy with dapsone (1.8 mg/kg/day).

Background. Excessive colonization of the skin by various bacteria and fungi can be noted in patients with atopic dermatitis (AD), and the prevalence of secondary infection complications 30–48%. Several studies have shown that Staphylococcus aureus colonization is 60–100% in patients with AD compared to 5–30% in healthy persons from the control group. Moreover, the incidence of methicillinresistant Staphylococcus aureus (MRSA) isolates is up to 10–30% in skin cultures at AD, according to experts. Therapy of AD complicated by secondary infection is one of the crucial challenges of modern dermatology. Mupirocin can be considered as one of the most effective topical antibiotic among others used for etiotropic therapy of infectious complications in AD patients, and it has been confirmed by numerous clinical studies.Conclusion. Staphylococcus aureus is the most common trigger of AD aggravation. MRSA in AD complicated by secondary infection is difficult to manage as it becomes resistant to many types of antibiotics; however, it shows persistent sensitivity to mupirocin. Mupirocin-based (2%) external agent is the most effective, safe, and preferred therapy variant for AD complicated by secondary infection in pediatrics.

Background. Pemphigus herpetiformis is a rare atypical bullous dermatosis of autoimmune nature. It is characterized by rashes in the form of plaques with papules and vesicles at peripheral areas, or in the form of grouped papules, vesicles or tense bubbles with clinical similarity to During's herpetiformis dermatitis. Pemphigus herpetiformis diagnosis in pediatric practice is difficult due to the similarity of clinical manifestations to bullous dermatoses of other etiology, the rarity of the disease in children, and small number of scientific publications.Clinical case description. Clinical case of pemphigus herpetiformis in a child is described. All necessary diagnostic algorithms for diagnosis and therapeutic tactics for patient management are presented. Dapsone and prednisolone were used as first-line drugs during the patient's treatment. They have shown its efficacy in management of such patients.Conclusion. Differential diagnosis of pemphigus herpetiformis and other bullous dermatoses in children is presented. The results of successful drug treatment are shown.

Background. Netherton syndrome is a severe autosomal recessive disease based not only on genetically determined keratinization disorders, but also on immune system dysregulation.Clinical case description. Boy K., 9 years old, diagnosed with severe atopic dermatitis and revealed Netherton syndrome during examinations. The dupilumab was administered due to the presence of severe polysensitization and clinical signs of allergic process. Wave-like course of the disease was observed during this therapy. Patient had acute exacerbation — generalized pustular rash — at the 7th month of treatment. The therapy with secukinumab was initiated according to the foreign literature on pathogenetic treatment of Netherton syndrome with interleukin (IL) 17 inhibitor. It has shown positive dynamics. Currently patient is administered with the combined therapy of IL-17 and IL-4/13 inhibitors with significant positive effect.Conclusion. Genetically engineered biologic drugs targeting both the Th17 and Th2 have shown their efficacy in Netherton syndrome management.

Background. Hypotrichosis is a heritable form of alopecia that causes almost complete scalp hair loss in childhood. The diagnosis is typically established according to medical history and clinical picture. Genetic testing is an additional diagnostic method that allows to establish “hypotrichosis” in cases of ambiguous or subtle clinical signs of the disease, as well as to perform differential diagnosis of this condition with others commonly associated with atopic dermatitis (focal and diffuse alopecia). Clinical diagnosis of hypotrichosis in patients with severe dermatosis is challenging.Clinical case description. The girl, aged 2 years 4 months, was hospitalized with complaints on extended rash on the body with severe itching, and changes in hair thickness, quality of hair shaft, and hair loss. Severe atopic dermatitis and hypotrichosis were diagnosed. The diagnosis of atopic dermatitis was established clinically (SCORAD — 65), the diagnosis of hypotrichosis (type 6, monilethrix-like hypotrichosis) was confirmed via molecular genetic testing (nucleotide variant c.699C>T in exone 13 of the DSG4 gene (OMIM # 607892)). Patient's mother, brother, and two sisters were diagnosed with the nucleotide variant chr18:31409487C>T in heterozygous state in the DSG4 gene. Mother and brother had no clinical manifestations, while both sisters had mild scalp hair damage, as well as eyebrows and eyelashes, since birth. There were no clinical manifestations of atopic dermatitis in parents and other children in the family.Conclusion. Hypotrichosis clinical signs can be subtled, smoothed, or imitate the symptoms of other comorbid conditions, especially in patients with comorbidities or severe dermatosis. Also worth noting is that changes in certain genes can aggravate the course of atopic dermatitis. In this clinical case, mutation in the DSG4 gene leads to epidermal barrier failure by disrupting the synthesis of desmosomes transmembrane components. Thus, geneticist consultation and genetic testing (search for changes in certain genes) are crucial in such cases.

SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed. Based on our recently studied mRNA lipid nanoparticle (mRNA-LNP) platform, we have generated mRNA-LNP encoding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combination in vivo. As a result, all mRNA-LNP vaccine compositions encoding the S and N proteins induced excellent titers of RBD- and N-specific binding antibodies. The T cell responses were mainly specific CD4+ T cell lymphocytes producing IL-2 and TNF-alpha. mRNA-LNP encoding the M protein did not show a high immunogenicity. High neutralizing activity was detected in the sera of mice vaccinated with mRNA-LNP encoding S protein (alone or in combinations) against closely related strains, but was undetectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to mRNA-N in the vaccine composition enhanced the immunogenicity of mRNA-N and induced a more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancing the immune response to the N protein when they are both encoded in the mRNA-LNP vaccine.

Background. Atopic dermatitis (AD) manifests during the first year of life in majority of all cases. The early disease onset is associated with the development of comorbid atopic conditions within the «atopic march» phenomenon. The AD pathogenesis is associated with genetic predisposition, epidermal barrier dysfunction, and immune dysregulation. T2-inflammation specifically determines the entire immune cascade of inflammatory reactions, and, thus, dictates the need of early drug intervention to modify the disease course. Clinical case description. This article presents two clinical cases of severe AD in children under 6 years of age. The treatment of both cases included genetically engineered biologic drug dupilumab. Continuous therapy for 4–5 months made it possible to relieve the skin manifestations of the disease.Conclusion. AD, manifesting in infancy, is associated with high risk of developing other atopic spectrum diseases in older age. The timely onset of biological therapy allows us to affect immune dysregulation, and thereby to prevent the comorbid atopic conditions development.

Atopic dermatitis is a common chronic skin disease, its pathogenesis is associated with congenital or acquired deficiency of filaggrin protein. In recent years, extensive evidence on the causes of filaggrin deficiency has been obtained. The structure and functions of this protein are described, that opens new approaches for atopic dermatitis management.

Congenital ichthyosis is a group (almost 100 clinical variants) of rare genetic skin diseases caused by pathogenic changes in more than 50 genes. Clinical features of ichthyosis, regardless of its genotype, are dry skin, peeling, hyperkeratosis frequently accompanied with erythroderma. These patients have extremely low quality of life due to changes in appearance, discomfort due to itching and functional limitations (pain during walking, impaired motor skills and functions due to hyperkeratosis foci in functionally relevant areas), as well as impaired functions of various organs and systems in syndromic forms of disease. Patients need daily skin care and systemic medications. By now, there is no definitive treatment for ichthyosis. Diagnostic difficulties in determining the clinical forms of congenital ichthyosis are associated with their clinical heterogeneity and with similarity in external manifestations. Difficulties in differential diagnosis with other dermatoses are particularly crucial in case of syndromic forms of disease. This review presents the modern classification of ichthyoses, provides data on disease clinical and genetic variants, diagnostic algorithms, treatment methods for patients with this severe disease.

Biofilm is the dominant form of skin microbiota organization that provides adhesion and preservation of microorganisms in the skin micro-environment. It is necessary to ensure epidermal barrier function and local immunomodulation. Staphylococcus aureus becomes the major colonizer of skin lesions in case of atopic dermatitis exacerbation, and it also can form the biofilms. S. aureus growth and biofilm formation due to other microbial commensals on the skin of patients with atopic dermatitis leads to chronic output of pro-inflammatory cytokines and later to abnormalities in healthy skin microbiome. The role of microbial biofilm in human’s health makes the skin microbiota an attractive target for therapeutic intervention in various skin diseases.

Background. Psoriasis is a chronic immune-mediated disease with multifactorial nature. It often requires administration of genetically engineered biologic drugs. They have a number of features and risks that depend on various factors. The results of ustekinumab administration as a drug of choice in patients with comorbid metabolic syndrome in a child with Down syndrome, as well as a case of inefficacy of previous biologic therapy with inhibitors are considered.Clinical cases description. Two clinical cases of ustekinumab administration in children with severe psoriasis have been described. In the first case, we had to choose systemic therapy for the child suffering from Down syndrome and having complex comorbid background: obesity and steatohepatitis. The second case was interesting due to the family history of psoriasis in the patient, who received methotrexate for a long time, and then etanercept with subsequent loss of efficacy and severe disease aggravation without any pathogenetic therapy.Conclusion. Ustekinumab is the favorable genetically engineered biologic drug (according to the studies results and the clinical cases data) for children with severe psoriasis who have comorbid pathologies and who require the change in biologic agent due to its inefficacy.

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease. Its pathogenetic basis is epidermal barrier dysfunction, immune system dysregulation, as well as skin microbiome diversity decrease that occurs due to genetic predisposition. Considering these factors, the skin of patients with AD requires constant care and use of medications with active regenerative properties. The inclusion of anti-inflammatory components in the composition of modern emollients (zinc sulfate and sucralfate) is crucial for restoring the microbiome and immune mechanisms controlling the skin. This article presents data on pathogenetic applicability and clinical efficacy of emollients with anti-inflammatory compounds in patients with AD.

Background. Pemphigus vulgaris is an autoimmune bullous dermatosis. Its management generally involves lifelong administration of maintenance dose of systemic glucocorticosteroids, that leading to serious adverse effects especially in children.Clinical case description. Patient is the 16 years old boy with severe course of pemphigus vulgaris. The diagnosis was confirmed by the results of cell smear study from fresh erosions (> 50 acantholytic cells were revealed), histological examination of the skin biopsy from the lesion with the vesicle element (suprabasal vesicle was localized in the center, it included fibrin, neutrophil granulocytes, and acantholytic cells), skin biopsy from the area near the lesion (visually healthy skin), via direct immunofluorescence methods (IgG deposition was detected on keratinocytes’ surface throughout the epidermis), and enzyme-linked immunosorbent assay (desmoglein 1 IgG autoantibodies — 121 U/mL (reference value < 20 U/mL) and desmoglein 3 — > 200 U/mL (reference value < 20 U/mL)). Genetically engineered biologic drug, rituximab, and systemic glucocorticosteroid, methylprednisolone, were prescribed as first-line therapy with gradual dose reduction to permanent discontinuation in 8 months. Complete remission maintained after the completion of therapy course and discontinuation of systemic glucocorticosteroid.Conclusion. Combined therapy with systemic glucocorticosteroids and rituximab can be considered as first-line therapy in pediatric patients with pemphigus vulgaris due to relatively low risk of recurrence after rather rapid and complete drugs’ discontinuation.

UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a zinc amidase that catalyzes the second step of the biosynthesis of lipid A, which is an outer membrane essential structural component of Gram-negative bacteria. Inhibitors of this enzyme can be attributed to two main categories, non-hydroxamate and hydroxamate inhibitors, with the latter being the most effective given the chelation of Zn2+ in the active site. Compounds containing diacetylene or acetylene tails and the sulfonic head, as well as oxazoline derivatives of hydroxamic acids, are among the LpxC inhibitors with the most profound antibacterial activity. The present article describes the synthesis of novel functional derivatives of hydroxamic acids—bioisosteric to oxazoline inhibitors—containing 1,2,4- and 1,3,4-oxadiazole cores and studies of their cytotoxicity, antibacterial activity, and antibiotic potentiation. Some of the hydroxamic acids we obtained (9c, 9d, 23a, 23c, 30b, 36) showed significant potentiation in nalidixic acid, rifampicin, and kanamycin against the growth of laboratory-strain Escherichia coli MG1655. Two lead compounds (9c, 9d) significantly reduced Pseudomonas aeruginosa ATCC 27853 growth in the presence of nalidixic acid and rifampicin.

IntroductionEpidermal barrier dysfunction in children with atopic dermatitis can cause transcutaneous sensitization to allergens and allergic diseases. We evaluated the effectiveness of an early-intervention algorithm for atopic dermatitis treatment, utilizing pimecrolimus for long-term maintenance therapy, in reducing transcutaneous sensitization in infants.MethodThis was a single-center cohort observational study that enrolled children aged 1-4 months with family history of allergic diseases, moderate-to-severe atopic dermatitis, and sensitization to ≥ 1 of the investigated allergens. Patients who sought medical attention at atopic dermatitis onset (within 10 days) were group 1 “baseline therapy with topical glucocorticoids with subsequent transition to pimecrolimus as maintenance therapy”; patients who sought medical attention later were group 2 “baseline and maintenance therapy with topical glucocorticoids, without subsequent use of pimecrolimus”. Sensitization class and level of allergen-specific immunoglobulin E were determined at baseline, and 6 and 12 months of age. Atopic dermatitis severity was evaluated using the Eczema Area and Severity Index score at baseline and 6, 9 and 12 months of age.ResultsFifty-six and 52 patients were enrolled in groups 1 and 2, respectively. Compared with group 2, group 1 demonstrated a lower level of sensitization to cow's milk protein, egg white and house dust mite allergen at 6 and 12 months of age, and a more pronounced decrease in atopic dermatitis severity at 6, 9 and 12 months of age. No adverse events occurred.DiscussionThe pimecrolimus-containing algorithm was effective in treating atopic dermatitis and prophylaxis of early forms of allergic diseases in infants.Trial registrationhttps://clinicaltrials.gov/NCT04900948, retrospectively registered, 25 May 2021.

Over the past decades, the problem of bacterial resistance to most antibiotics has become a serious threat to patients’ survival. Nevertheless, antibiotics of a novel class have not been approved since the 1980s. The development of antibiotic potentiators is an appealing alternative to the challenging process of searching for new antimicrobials. Production of H2S—one of the leading defense mechanisms crucial for bacterial survival—can be influenced by the inhibition of relevant enzymes: bacterial cystathionine γ-lyase (bCSE), bacterial cystathionine β-synthase (bCBS), or 3-mercaptopyruvate sulfurtransferase (MST). The first one makes the main contribution to H2S generation. Herein, we present data on the synthesis, in silico analyses, and enzymatic and microbiological assays of novel bCSE inhibitors. Combined molecular docking and molecular dynamics analyses revealed a novel binding mode of these ligands to bCSE. Lead compound 2a manifested strong potentiating activity when applied in combination with some commonly used antibiotics against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. The compound was found to have favorable in vitro absorption, distribution, metabolism, excretion, and toxicity parameters. The high effectiveness and safety of compound 2a makes it a promising candidate for enhancing the activity of antibiotics against high-priority pathogens.

Background. There is a need to study genetically engineered biological therapy (GEBT) survivability and identify any significant risk factors for its ineffectiveness due to the increasing prevalence of psoriasis among children and the spreading GEBT administration. Such information has practical importance, it can be used to predict treatment outcomes and to develop individual therapeutic approaches. Objective. Our aim was to study biological therapy survivability and to identify risk factors for its ineffectiveness in children with moderate and severe forms of psoriasis. Methods. The study included data from 4-17 years old patients with moderate and severe forms of psoriasis vulgaris. Groups were formed according to the biological medication used. Statistical analyses were performed via SPSS Statistics. Biologic therapy survivability was determined via Kaplan-Meier method with the assessment of differences significance using log-rank test. Significant factors affecting cumulative risk growth were determined by Cox multiple regression method. Results. The study analysed data from the medical records of 105 patients. The average survivability of ustekinumab was 28.7 months, etanercept — 23.1, and adalimumab — 18.4. In the group of bio-naive patients, the survivability was higher: 30.8 months for ustekinumab and 24.4 months for ethanercept, while in the group of patients administrated previously with biological medication the survivability was 24.2 and 8.3 months, respectively. No statistically significant difference was revealed for adalimumab therapy. Significant risk factors for therapy ineffectiveness were the following: high body mass index (BMI) at the time of GEBT onset, aggravated family history, and prior use of one or several subsequent GEBT lines. Conclusion. The therapy survivability is inevitably declining over time. The best results were noted in bio-naive patients treated with ustekinumab that allows us to recommend it as the first-line drug in children with severe and moderate forms of psoriasis.

Atopic dermatitis (AD) is a disease characterized by chronic skin inflammation and epidermal barrier dysfunction leading to decrease in patients' quality of life. AD is widespread in general population including children. This article covers the disease pathophysiological mechanisms including those that depend on the endotype, as well as core principles of systemic therapy for children with moderate and severe AD. Features of targeted therapy of such patients with dupilumab (IL-4 and IL-13 inhibitor) are presented. The studies' results on dupilumab efficacy and safety in the short- and long-term are shown.

Atopic dermatitis (AtD) is multifactorial inflammatory skin disease with high prevalence in pediatric population. It is crucial to implement long-term maintenance therapy to prevent AtD exacerbations according to current clinical guidelines and expert reports. The article summarizes the results of the major studies on using pimecrolimus 1% cream. Its efficacy and safety in long-term proactive therapy of children with AtD are presented.

The spread of new coronavirus infection (COVID-19) changes specialists' approaches to patients with chronic diseases, including those with chronic dermatoses. The high risk of COVID-19 complications in patients with psoriasis is connected to the features of disease pathogenesis (such as high activity of proinflammatory cytokines) and used immunosuppressive therapy. Psoriasis affects up to 1% of children in Europe, while 10-20% of them have moderate or severe form of disease. These children may require immunosuppressive treatment, including genetically engineered biological therapy. There is only limited data on adults and children with psoriasis during the COVID-19 pandemic.

Healthy newborn skin care is challenging task. The basic principles of care should be taught to both medical staff and parents. This care is more crucial in children with atopic dermatitis who have abnormal skin acidity due to multifactorial exposure. Significant pH reduction leads to aggravation of the skin process that requires active therapeutic measures. The article presents guidelines for the first infant's skin cleaning, for conducting first and daily bathing, for using cleansing agents and daily care solutions to prevent skin acidity disorders and the development of atopic dermatitis.

The article shows the key role of IL-17 in the psoriasis pathogenesis and the opportunities of its management via monoclonal antibodies product secukinumab. The review of international randomized trials on clinical efficacy and safety of genetically engineered biologic drug secukinumab in children and adolescents with psoriasis is presented. During treatment periods of 12 to 52 weeks, secukinumab has shown high therapeutic efficacy for psoriasis severity and skin lesion areas and has improved quality of life of children and adolescents according to dynamic assessments of PASI, IGA 0/1 mod 2011 indices, CDLQI questionnaire. The safety profile of secukinumab in children is estimated as favorable and comparable to using it in adults.

Photodermatoses is a heterogeneous group of diseases resulting from abnormal skin hypersensitivity to sunlight and presented as local or generalized rashes. Specific sensitivity of children's skin to ultraviolet is often the first sign or clinical symptom of photodermatosis. Abnormal photosensitivity can be represented by diverse group of primary idiopathic conditions or photo-mediated aggravation of existing dermatosis. Number of genetic genodermatoses, metabolic disorders and connective tissue diseases is also widely known. These conditions can manifest with photosensitivity associated to other extracutaneous clinical and laboratory features. Timely diagnosis of photosensitivity in childhood allows to minimize long-term complications associated with insufficient photoprotection.

Atopic dermatitis (AtD) is multifactorial inflammatory skin disease, one of the aspects of its pathogenesis is epidermal barrier dysfunction. Early development of AtD is associated with filaggrin dysfunction. Filaggrin is a protein involved in aggregation of keratin filaments in the upper layers of epidermis and the retention of lipids and proteins between corneocytes. Frequently, filaggrin dysfunction can be accompanied with secondary infection and high risk of other allergic diseases development. This can happen due to disturbance in terminal differentiation of epidermal cells and, as consequence, malfunction of epidermal barrier. Thus, the long regular use of emollients is the basis of AtD therapy. New class of emollients (“emollents plus”) allowed us to achieve more significant treatment results in patients with AtD. These emollients reduce inflammatory process activity in the skin by replacing structural components of abnormal epidermal barrier.

Skin is the natural habitat for complex bacterial, fungal, and viral communities (ecosystems). The microbiome of such communities is always in close relationship with the host genome, and the development of these ecosystems happens under the effects of morpho-physiological and immunological characteristics of the skin (sebaceous glands concentration, humidity, and temperature) and environmental factors. Metagenomic studies have shown significant diversity in skin ecosystems. Moreover, the role of commensal microorganisms in skin immune response modulating to various agents and, thus, its correlation with skin diseases pathogenesis is no longer in doubt. New probiotic and antimicrobial agents for external treatment have been developed according to these knowledges.

Millions of people worldwide have rare genetic diseases that are caused by various mutations in DNA sequence. Classic treatments of rare genetic diseases are often ineffective, and therefore great hopes are placed on gene-editing methods. A DNA base–editing system based on nCas9 (Cas9 with a nickase activity) or dCas9 (a catalytically inactive DNA-targeting Cas9 enzyme) enables editing without double-strand breaks. These tools are constantly being improved, which increases their potential usefulness for therapies. In this review, we describe the main types of base-editing systems and their application to the treatment of monogenic diseases in experiments in vitro and in vivo. Additionally, to understand the therapeutic potential of these systems, the advantages and disadvantages of base-editing systems are examined.

Rare genetic diseases reduce quality of life and can significantly shorten the lifespan. There are few effective treatment options for these diseases, and existing therapeutic strategies often represent only supportive or palliative care. Therefore, designing genetic-engineering technologies for the treatment of genetic diseases is urgently needed. Rapid advances in genetic editing technologies based on programmable nucleases and in the engineering of gene delivery systems have made it possible to conduct several dozen successful clinical trials; however, the risk of numerous side effects caused by off-target double-strand breaks limits the use of these technologies in the clinic. Development of adenine-to-inosine (A-to-I) and cytosine-to-uracil (C-to-U) RNA-editing systems based on dCas13 enables editing at the transcriptional level without double-strand breaks in DNA. In this review, we discuss recent progress in the application of these technologies in in vitro and in vivo experiments. The main strategies for improving RNA-editing tools by increasing their efficiency and specificity are described as well. These data allow us to outline the prospects of base-editing systems for clinical application.

The issues of automation of production processes are currently not losing their relevance. Many existing devices and systems operate in manual or semi-automatic mode, which leads to known problems. The methods of connecting system elements and the choice of protocols for transmitting signals between them are quite well-established, however, due to the emergence of new devices and communication channels with improved characteristics, the issues of choosing methods and algorithms for the operation of such systems require modification. As a criterion for the quality of the constructed system, an assessment of the reliability of the system is used, provided that the specified time constraints on the performance of the main tasks are met. The elements of novelty of the presented solution are the use of domestically produced equipment at all stages of the system operation, as well as some solutions for the choice of communication channels and signal transmission protocols. Note that the main elements of novelty relate to the software implementation of the system, the description of which is beyond the scope of this article and is planned to be published in a separate work. Purpose. The aim of the work is to develop the structure of an automated control system for a stone crushing plant. Methodology. The work uses the methods of systems analysis, the theory of signal transmission and the theory of algorithms. Results. The use of the presented solution made it possible to implement a simpler and more efficient hardware and software model of the control system, which will reduce the number of failures of various subsystems of the stone crushing plant. In addition, some new features have been introduced, such as the ability to remotely control and receiving data to accounting software. Practical implications. The obtained results are advisable to be applied by production entities carrying out activities, one of the elements of which is the use of crushing plants and complexes.

Background. One of the key aspects in the development of atopic dermatitis (AtD) is epidermal barrier dysfunction leading to the penetration of pathogens and allergens through the skin with further body sensibilisation to them. Such pathological interaction can later on lead to the development of various allergic diseases in the child which not only worsen the course of atopic dermatitis itself, but also significantly reduce the quality of life of these patients. Objective. Aim of the study is to estimate the efficacy of therapeutic approaches for treatment of atopic dermatitis in reducing the transcutaneous sensibilisation risk in infants. Methods. The study included children aged 1 to 4 months with established AtD from moderate to severe forms. The severity of AtD was estimated via the EASI index. The level of specific IgE (sIgE) to food and domestic allergens was measured by the ImmunoCAP method using special reagents’ sets. The sensibilisation class was established depending on the sIgE index. Statistical analysis of the studied indexes shift and their comparison between the study groups was performed via multivariate analysis of variance (ANOVA). Results. The study included 81 patients. All patients were divided into two groups after basic AtD therapy with topical glucocorticosteroids (tGCS). Patients from study group № 1 received maintenance therapy with topical calcineurin inhibitor (TCI) (pimecrolimus 1%; PIM) for a long time, while patients from group № 2 continued to apply tGCS as proactive therapy. We have revealed that the level of sensibilisation to chicken protein and to the mixture of domestic allergens “domestic dust” was lower to the 12th month of life in group № 1 compared to group № 2 as a result of the data analysis. Children in group № 1 had faster and more significant decrease in the severity of AtD in comparison to group № 2 according to EASI index. Conclusion. Maintenance therapy including PIM is more efficient in reducing AtD severity and in prevention of transcutaneous sensibilisation in infants.

Background. Malformations in epidermal barrier in children with atopic dermatitis (AD) can cause transcutaneous sensitization with further development of allergic diseases that can worsen the AD course and significantly reduces patients’ quality of life.Objective. The aim of the study was to determine the effect of topical treatment and maintenance therapy with pimecrolimus 1% cream (PIM) and topical glucocorticosteroids (tGCS) in infants with AD on reducing the risk of developing transcutaneous sensitization (due to the levels of specific IgE to the cow milk protein over time) and on reducing the disease severity (by the EASI scale).Methods. The study included children aged from 1 to 4 months with early manifestations of moderate and severe AD. The severity of AD was estimated via the EASI scale at start of observation, then at 6, 9 and 12 months of life. The class and level of specific IgE to cow milk proteins (CMP) were determined by the ImmunoCAP method at the point of enrolment and at the ages of 6 and 12 months. Statistical analysis of studied indicators dynamics and their comparison in research groups was carried out using multifactorial dispersion analysis.Results. The study included 36 patients. All patients have received standard tGCS therapy in combination with emollients (wet wrap) for 10 days. The maintenance therapy was prescribed in postacute period. It included topical calcineurin inhibitor PIM 2 times/day for 3 months, then double application (morning/evening) 3 times/week up to the age of 1 year old (group 1). Other group had maintenance therapy — tGCS2 times/week for 3 months, and then at AD aggravation (group 2). Group 1 has shown lower level of sensitization to CMP at the age of 6 and 12 months and more significant decrease in AD severity according to EASI scale compared to group 2.Conclusion. The treatment with PIM is effective in therapy of AD and prevention of transcutaneous sensitization in infants.

Atopic dermatitis (AD) is the disease with chronic inflammation, epidermal barrier dysfunction and microbial dysbiosis. AD is widespread, including pediatric population. The article discusses the disease’s pathogenesis: skin barrier deficiency, immunological causes of chronic inflammation, characteristics of normal skin microbiome and its disorders on both affected and unaffected skin of children with AD. Main principles of systemic treatment for moderate and severe forms of disease are considered. Features of targeted therapy with dupilumab (IL 4/IL 13 inhibitor) in children with moderate and severe forms of AD are discussed. The overview of the research results on the dupilumab efficacy and safety is presented.

Vitiligo is a common skin disease characterized by idiopathic progressive skin hypomelanosis. Vitiligo is associated with several comorbid autoimmune diseases such as localized scleroderma. This article demonstrates the general development mechanism of these pathologies, as well as the key aspect of cross-effect between autoimmune diseases on the molecular level. Recently, dermatologists have noted the increasing number of patients suffering from combined pathologies. Such patients (in pediatrics) have torpid course of disease and no pathognomonic symptoms. That exaggerates the diagnostics and adequate therapy prescription. This leads to increased awareness among physicians of different specialties on possible combinations, clinical presentation and pathogenesis aspects of such conditions.

Background. The study of psoriasis biological therapy aspects in children has certain topicality due to the small number and disunity of individual observations and the lack of special registers for pediatric patients.Objective. Our aim was to study ustekinumab efficacy and safety in children with plaque (PP), erythrodermic (EP) and palmoplanar (PPP) forms of psoriasis.Methods. The analysis of ustekinumab efficacy and safety has been carrying out for 1 year. The evaluation of therapy efficacy was based on definition of improvement of PASI scores (PASI 75, PASI 90 and PASI 100) on the 16th, 28th, 40th and 52nd weeks of follow-up and children's dermatology life quality index (CDLQI). Ustekinumab therapy safety analysis was based on registration and evaluation of adverse effects. Results. The study included 67 children with PP, EP and PPP aged 12 to 18 years. PP group results: the PASI 75 response at the 52nd week of therapy was observed in 35 children (100%), PASI 90 — in 33 (94%), PASI 100 — in 30 (86%). EP group results: 10 patients (56%) have reached PASI 75 on the 16th week, while none of patients have improved to PASI 90 and PASI 100 scores. The PASI 75 response at the 52nd week of therapy was observed in 18 children (100%), PASI 90 — in 17 (94%), PASI 100 — in 7 (39%). Only 1 patient (7%) with PPP has showed the score decrease to PASI 75 on the 16th week. Adverse effects were reported in 2 patients.Conclusion. Ustekinumab is the effective and safe treatment for moderate and severe forms of PP and EP in children, and it can also be considered as one of the alternative methods for PPP treatment in pediatrics.

Psoriasis is multifactorial systemic disease characterized by excessive hyperkeratosis due to impaired keratinocytes proliferation and differentiation. This disease often manifests in childhood and it is usually associated with the development of comorbid conditions some of which are combined by the term «psoriatic march» (obesity, metabolic syndrome, etc.). The course of psoriasis and related comorbidities in children has several specific features that determine topicality of studying all the aspects of clinical diagnosis and prevention in childhood. The article summarizes recent ideas on the prevalence, pathogenesis features and early diagnosis of comorbid diseases in children with psoriasis.

Pruritus is one of the main clinical manifestations of atopic dermatitis, and it significantly reduces the quality of life of patients in childhood. Scientific images on its pathophysiological basis have now undergone significant changes. The histamine exceptional role in pruritus development was confounded, as well as data on immune system involvement in its maintenance was given. This article presents current data on differential approaches to pruritus management depending on its etiopathogenetic characteristics. The role of dermocosmetics in restoration of the skin barrier as the first stage prevention of pruritus in atopic dermatitis was considered. The results of clinical studies showing efficacy of topical agents (innovative component with anti-pruritic action — STIMU-TEX) application are presented.

Background. Nowadays, dermatoses with mixed clinical picture and resistant to classical management become more common. The presence of various genetic disorders typical for most chronic dermatoses may indicate possible combination of several nosologies.Clinical Case Description. The article presents the clinical case of multimorbid condition in 10 years old patient who has nucleotide variants in CARD14 and EXPH5 genes. Mutations in CARD14 gene are typical for patients with type 2 psoriasis and pityriasis rubra pilaris (autosomal dominant type), while mutations in EXPH5 gene are typical for patients with non-specific epidermolysis bullosa (autosomal recessive type). Mutation in the TGM1 gene that is described in patients with congenital ichthyosis (autosomal recessive type), pathogenic mutations in KRT74 gene typical for ectodermal dysplasia, hypotrichosis and uncombable hair syndrome, and mutations in the KRT86 gene typical for monilethrix were also revealed. Medical history taking and histological examination as well as clinical data evaluating are crucial for correct diagnosis. They allow to understand the absence of the such manifestations in relatives and reveal various pathological processes in the epidermis. Molecular genetic testing with new generation sequencing (NGS) helps to finally establish the diagnosis and determine the further tactics for patient management.Conclusion. Multidisciplinary approach and use of high-technology methods of examination and treatment (such as molecular genetic testing and biological therapy) are required for final diagnosis in severe forms of chronic dermatosis resistant to treatment and for decision on correct tactics for the further management of such patients.

Federation Skin lesions with development of erosive-ulcerative defects and impaired skin barrier function are common for large number of diseases. Successful epithelization of skin defects depends on the wound process, body’s compensatory functions, environmental factors and correctly selected treatment. Comprehensive treatment should include systemic and local therapy as well as current dressings. The article shows current dressings possibilities the treatment of various skin diseases, outlines all pros and cons of the major current dressings.

Atopic dermatitis (AD) is chronic recurrent inflammatory skin disease with a high prevalence and significant negative effect on patients' quality of life. AD pathogenesis is based on the complex interactions between genetic factors, immune mechanisms, state of the skin barrier and environmental effects. The climate itself is the complex of many components, such as: temperature, humidity, precipitation, wind and season. All of them play fundamental role in the natural ecosystem and human health establishment. The climate is changing rapidly, and these changes are progressing faster than ever in the last thousand years. This review shows how climate and environmental changes can affect the course of AD. The data on utilization efficiency of emollient plus for moderating of climatic conditions adverse effects on epidermal structures at patients with AD is presented.

Psoriasis is chronic inflammatory skin disease that can develop at any age. Approximately 20–30% of all patients report about first rashes before the age of 18. Psoriatic arthritis is one of psoriasis comorbid conditions. Its signs can range from mild to extremely severe destructive forms. Arthralgia, joint stiffness and swelling are the most common symptoms. Early psoriatic arthritis treatment onset allows to control joint damage which usually occurs during the first 2 years of the disease. The moderate and severe course of psoriasis and psoriatic arthritis may require systemic therapy, however, there is not much data on the efficacy and toxicity of systemic agents in the pediatric practice. This article provides the review of studies on etanercept efficacy and safety in children with psoriatic arthritis.

Atopic dermatitis (AD) is one of the most common inflammatory diseases of childhood, and it is the first one in gradual development of allergic diseases, also known as «atopic march». Sensitization establishment during the AD uncontrolled course is associated with the high risk of developing of serious allergic pathologies, increase in the severity of the disease course, and patients’ quality of life reduction. Thereby, it is crucial to achieve quick jugulation of the inflammatory process in case of severe AD with early onset of disease. This article shows modern therapeutic approaches to disease control in children.

Background. Wells syndrome (eosinophilic cellulitis) is recurrent granulomatous dermatitis with peripheral blood eosinophilia. This is extremely rare pathology, therefore, there are no reliable epidemiological data on its prevalence. Only about 200 cases were recorded worldwide and 30 of them among children according to the meta-analysis (2012). The disease is mostly sporadic, there are rare family cases, according to the results of little number of scientific publications.Clinical Case Description. The clinical case of Wells syndrome in female 4 years old patient is presented. Clinical findings included symmetrical skin lesions, nodes and large irregular edematous plaques of red-purple color with clear fluid vesicles on its surface. The disease had wavy course: rashes have recovered spontaneously over 7–10 days, new elements appeared alongside with feeling unwell, fever up to 37,8°C and abdominal pain. Similar clinical findings of rashes were observed in paternal relatives of the child.Conclusion. Differential diagnostics of Wells syndrome should be carried out with skin granulomatous diseases and hypereosinophilic syndrome that may be characterized by similar clinical findings. Verification of Wells syndrome diagnosis is complicated due to its rareness, low awareness of dermatologists and pediatricians about this pathology, as well as ignoring the need to carry out histological tests during the disease exacerbation.

В статье представлены современные данные о патогенезе вульгарных акне (ВА), особенностях клинической картины, диагностике и терапевтической тактике у детей и подростков. Приведены сведения о влиянии наиболее значимых внешних и внутренних факторов на патогенез и риск развития ВА. На основе анализа Европейских методических рекомендаций и рекомендаций Глобального альянса по лечению и диагностике ВА сформированы соответствующие диагностические и терапевтические алгоритмы ведения пациентов. Также продемонстрирована важная роль назначения эффективной терапии в виде фиксированной синергичной комбинации активных веществ, представленных топическим ретиноидом (адапален) и бензоила пероксидом.

Atopic dermatitis (AD) is one of the common multifactorial inflammatory diseases manifesting predominantly in childhood. There is significant number of cases of self-regression of the disease with aging. On the other hand, there is also another scenario ending with AD persistent course and/or development of comorbid allergic pathologies that can significantly worsen patient’s quality of life and finally lead to social maladjustment. The pathogenesis of such way includes epidermal barrier disturbance, transcutaneous sensibilisation and aberrant allergic (Th2) immune systemic response development. Main role in preventing of this pathological pathway is lying on the new class of moisturizers containing active components "emollients plus". They are considered as foundation for the therapy and prevention of the development of AD and other allergic diseases. This literature review provides relevant data on AD pathogenesis and development of comorbid allergic pathologies. This paper also covers data on the effect of emollients in restoration of the epidermal barrier and their use as preventive measures.

Abstract Background BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied. Methods Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6 cycles of therapy (every 3 weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [− 20%; 20%]. Results In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(− 8.05)-19.89%], thus, they lied within predetermined equivalence margins [− 20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n = 3; 2.65%) and comparator (n = 4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC0–504, Сmах, Тmax, T1/2. Analysis of Ctrough did not reveal any significant inter-group differences as well. Conclusions Thus, results of this study have demonstrated therapeutic equivalence of trastuzumab biosimilar BCD-022 and referent trastuzumab drug. Trial registration The trial was registered with ClinicalTrials.gov (Study Number NCT01764022 ). The date of registration was January 9, 2013.

There is crucial question on further therapeutic tactics for the management of such patients (within the severe epidemiological situation caused by the pandemic of new coronavirus SARS-CoV-2) due to widespread application of genetically engineered biologic drugs (GEBD)in management of immune mediated inflammatory diseases. This review sums up current data on the pathogenesis of COVID-19 with the development of acute respiratory distress syndrome associated with cytokine release syndrome (cytokine storm). The effects of GEBD on COVID-19 pathogenesis and their role in management of COVID-19 severe forms of are considered. This review presents the latest guidelines of international associations/consensus and observations of doctors of various specialties on the issue of interruption/continuation of GEBD therapy and with further consequence evaluation in case of interruption of biological therapy.

Pyodermas are the most frequent reason for visiting dermatologists among children. The immunity to development of pyodermas is based on skin barrier the part of which is cutaneous microbiome. The microbiome composition is unique and depends on age, localization on various body regions, environment. The change of its qualitative and quantitative composition leads to the development of purulent dermal diseases characterized by clinical diversity and severe course and development of complications (without adequate treatment). In this regard the choice of the correct therapy remains relevant. The results of studies covering the effectiveness of various topic antibacterial agents are analysed. Practical aspects of pyodermia therapy in children using local therapy are illustrated.