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Progressive pulmonary fibrosis is a major problem in respiratory medicine. Currently, there are no reliable biomarkers for early diagnosis of progressive pulmonary fibrosis, which leads to delayed diagnosis. Aim. To determine the role of serum biomarkers CA-19-9 and CA-125 and the possibilities of capillaroscopy of the nail fold in the diagnosis of progressive pulmonary fibrosis. Materials and methods. The study included 43 patients with interstitial changes in the lungs. Based on the presence/absence of signs of progression over the previous 12 months, patients were divided into 2 groups. All patients underwent forced spirometry, body plethysmography, diffusion test, CT, lung ultrasound, capillaroscopy of the nail fold, study of serum concentrations of CA-19-9 and CA-125. Results. In the group of patients with a progressive fibrotic phenotype of Interstitial lung diseases, a greater severity of capillaroscopic changes and a higher level of CA-19-9 were revealed. Correlation of these parameters with changes according to CT scan data (Warrick test) and lung ultrasound was shown. Conclusion. The data obtained demonstrate the possibilities of non-invasive diagnosis of progressive fibrosing interstitial lung diseases and require further research and prospective follow-up to assess the diagnostic and prognostic role of the studied biomarkers, as well as to determine their place in clinical practice.

Aim: The present study was conducted in an attempt to find possible direct mechanisms of action of Clostridium difficile toxins A and B (TCdA and TCdB) on contractility of isolated rat intestinal smooth muscles, as the contractive pathways affected by the toxins and responsible for motility disorders remain unclear. Materials and methods: Adult male Wistar rats were used in our experiments. Longitudinal smooth muscle (SM) preparations of proximal colon were isolated and their contractile activity was isometrically registered. The samples were mounted in tissue baths and exogenously treated with acetylcholine (ACh), serotonin (5-HT), dopamine, norepinephrine, TCdA and TCdB. The potential of TCdA and TCdB to affect the action of these mediators on SM activity was examined. Results: The experiments have shown that exciting action of ACh and 5-HT on colonic contractility is enhanced by TCdA rather than TCdB. Conversely, relaxing effect of dopamine and norepinephrine on contractile activity of colonic SM is under impact of TCdB but not TcdA. TCdA has a stronger direct effect on in vitro SM sensitivity to ACh and 5-HT than TCdB.Conclusions: TCdA and TCdB affect directly the contractile reactivity of isolated rat colon smooth muscle. TCdA has a stronger direct effect on smooth muscle sensitivity to acetylcholine and 5-HT than TCdB. Such a trend has not been established for dopamine and norepinephrine.

The COVID-19 pandemic has affected the incidence of acute respiratory infections in the modern world. Despite the growing etiological significance of viruses in the structure of infectious diseases, the importance of bacterial pathogens in the development of respiratory pathology remains. The risk of unreasonable prescription of antibacterial drugs increases. The irrational use of antibacterial drugs has affected the spread of microorganisms with high resistance to antibiotics. The article presents current knowledge on the role of the most common pathogens of community-acquired pneumonia in children, data concerning the S. pneumoniae strain with reduced sensitivity and resistance to penicillin, macrolides. Information about isolates of S. Pneumoniae with decreased susceptibility to third-generation parenteral cephalosporins (cefotaxime and ceftriaxone) have appeared. The number of β-lactamase-producing strains of H. influenzae resistant to unprotected aminopenicillins is rising. The main steps of the diagnostic process of community-acquired pneumonia approved in the clinical guidelines for community-acquired pneumonia in children in 2022, which were adopted by the Russian Ministry of Health, are considered. This document sets out clear algorithms for diagnosing and selecting antibacterial therapy in children on an outpatient basis. Algorithms for selecting initial antibacterial therapy in outpatient settings are also proposed. In most cases, S. pneumoniae is a causative agent of community-acquired pneumonia in children, which defines the selection of an initial antibacterial drug. According to the clinical guidelines, oral amoxicillin at a standard dose of 45–55 mg/kg/day given in 2–3 divided doses is such a drug for children aged 3 months and older. Particular attention is paid to amoxicillin in the form of dispersible tablets.

Abstract Intronic polymorphic TOMM40 variants increasing TOMM40 mRNA expression are strongly correlated to late onset Alzheimer’s Disease. The gene product, hTomm40, encoded in the APOE gene cluster, is a core component of TOM, the translocase that imports nascent proteins across the mitochondrial outer membrane. We used Drosophila melanogaster eyes as an in vivo model to investigate the relationship between elevated Tom40 (the Drosophila homologue of hTomm40) expression and neurodegeneration. Here we provide evidence that an overabundance of Tom40 in mitochondria invokes caspase-dependent cell death in a dose-dependent manner, leading to degeneration of the primarily neuronal eye tissue. Degeneration is contingent on the availability of co-assembling TOM components, indicating that an increase in assembled TOM is the factor that triggers apoptosis and degeneration in a neural setting. Eye death is not contingent on inner membrane translocase components, suggesting it is unlikely to be a direct consequence of impaired import. Another effect of heightened Tom40 expression is upregulation and co-association of a mitochondrial oxidative stress biomarker, DmHsp22, implicated in extension of lifespan, providing new insight into the balance between cell survival and death. Activation of regulated death pathways, culminating in eye degeneration, suggests a possible causal route from TOMM40 polymorphisms to neurodegenerative disease.

Concomitant congenital malformations are an actual problem in pediatrics. Association of tracheobronchial tree anomalies and congenital heart disease (CHD) could be the cause of the patient’s condition deterioration before and after cardiac surgery. We present a clinical case of a patient with multiple malformations with a long-term and poorly corrected broncho-obstructive syndrome, combined with pneumonia and hypoventilation. After surgery for tetralogy of Fallot at 3 months, the boy needed mechanical ventilation for a long time due to bilateral pneumonia complicated by bilateral pneumothorax. At 7 months, a respiratory infection required hospitalization in the intensive care unit. When pneumonia resolved, the boy was discharged home with continued oxygen support using an oxygen concentrator. The reason for the patient’s prolonged respiratory failure could be explained by prolonged hypoventilation due to narrowing of the left main bronchus and consecutive congenital pneumonia, repeated aspirations, and postoperative mechanical ventilation-associated pneumonia with bilateral pneumothorax. At the age of 1 year 3 months in the Department of Thoracic Surgery of St. Vladimir’s biodegradable stent in the left main bronchus was installed. The bronchus lumen was restored. The boy did not need oxygen support, and his physical and motor development indicators improved. Thus, in patients with tetrad of Fallot, a thorough assessment of the condition of the tracheobronchial tree is advisable in order to develop an appropriate treatment plan if needed. The collaboration of specialists in various fields of care for pediatric patients is the basis for a favorable prognosis in terms of the full growth and development of patients with multiple malformations.

Community-acquired pneumonia remains the leading infectious cause of death around the world. Many factors influence the prognosis and outcome of this disease. Compared with healthy individuals, patients with diabetes mellitus are at increased risk of respiratory tract infections, such as community-acquired pneumonia. Diabetes mellitus contributes to the development of pulmonary thrombotic microangiopathy, changing the functional state of the lungs. In numerous studies involving patients with diabetes mellitus, data on the state of the lungs were obtained by instrumental tests, such as spirometry, ventilation / perfusion scintigraphy, perfusion computed tomography, and diffusing capacity of the lungs for carbon monoxide. In patients with community-acquired pneumonia, diabetes mellitus causes vague clinical symptoms, leads to a severe course of the disease, and contributes to development of complications. Diagnosing the functional state of the lungs in patients with community-acquired pneumonia against the background of diabetes mellitus has not been studied.

Ketamine is shown to enhance excitatory synaptic drive in multiple brain areas, which is presumed to underlie its rapid antidepressant effects. Moreover, ketamine’s therapeutic actions are likely mediated by enhancing neuronal Ca2+ signaling. However, ketamine is a noncompetitive NMDA receptor (NMDAR) antagonist that reduces excitatory synaptic transmission and postsynaptic Ca2+ signaling. Thus, it is a puzzling question how ketamine enhances glutamatergic and Ca2+ activity in neurons to induce rapid antidepressant effects while blocking NMDARs in the hippocampus. Here, we find that ketamine treatment in cultured mouse hippocampal neurons significantly reduces Ca2+ and calcineurin activity to elevate AMPA receptor (AMPAR) subunit GluA1 phosphorylation. This phosphorylation ultimately leads to the expression of Ca2+-Permeable, GluA2-lacking, and GluA1-containing AMPARs (CP-AMPARs). The ketamine-induced expression of CP-AMPARs enhances glutamatergic activity and glutamate receptor plasticity in cultured hippocampal neurons. Moreover, when a sub-anesthetic dose of ketamine is given to mice, it increases synaptic GluA1 levels, but not GluA2, and GluA1 phosphorylation in the hippocampus within 1 hr after treatment. These changes are likely mediated by ketamine-induced reduction of calcineurin activity in the hippocampus. Using the open field and tail suspension tests, we demonstrate that a low dose of ketamine rapidly reduces anxiety-like and depression-like behaviors in both male and female mice. However, when in vivo treatment of a CP-AMPAR antagonist abolishes the ketamine’s effects on animals’ behaviors. We thus discover that ketamine at the low dose promotes the expression of CP-AMPARs via reduction of calcineurin activity, which in turn enhances synaptic strength to induce rapid antidepressant actions.

The present article focuses on a strain of ascomycete GF3 isolated from a water sample taken in the Gulf of Finland. Based on phylogenetic analysis data, the isolate was identified as Penicillium sp. GF3. The fungus GF3 demonstrates algicidal activity towards cyanobacteria (98–100%). The algicidal effect on green algae did not exceed 50%. The isolate GF3 exhibits an indirect attack mode by releasing metabolites with algicidal and/or lytic activity into the environment. Moreover, the strain Penicillium sp. GF3 is able to degrade MC-LR. After 72 h of GF3 cultivation, the MC-LR content was reduced by 34.1% and 26.7% at initial 0.1 μg/mL and 0.45 μg/mL concentrations, respectively. The high stress resistance of the GF3 to toxic MC-LR is provided by a 1.5-fold activation of catalase activity and a change in the reduced glutathione content. Additionally, during the MC-LR biotransformation, a MC-LR-GSH conjugate and linearized MC-LR were identified. The linearized MC-LR in the presence of fungi capable of degrading MCs was revealed for the first time. Using Daphnia magna as a bioindicator, it was shown that the MC-LR biotransformation led to the formation of less toxic intermediates. The toxicity of the fungal filtrate is reduced by five times compared to the abiotic control. Our findings enhance the understanding of the role that ascomycete fungi have as potential bioagents for cyanoHABs to control and detoxify water bodies.

Abstract Acute kidney injury (AKI) is associated with increased mortality in most critical settings. However, it is unclear whether its mild form (i.e. AKI stage 1) is associated with increased mortality also in non-critical settings. Here we conducted an international study in patients hospitalized with SARS-CoV-2 infection aiming 1. to estimate the incidence of AKI at each stage and its impact on mortality 2. to identify AKI risk factors at admission (susceptibility) and during hospitalization (exposures) and factors contributing to AKI-associated mortality. We included 939 patients from medical departments in Moscow (Russia) and Padua (Italy). In-hospital AKI onset was identified in 140 (14.9%) patients, mainly with stage 1 (65%). Mortality was remarkably higher in patients with AKI compared to those without AKI (55 [39.3%] vs. 34 [4.3%], respectively). Such association remained significant after adjustment for other clinical conditions at admission (relative risk [RR] 5.6; CI 3.5- 8.8) or restricting to AKI stage 1 (RR 3.2; CI 1.8–5.5) or to subjects with AKI onset preceding deterioration of clinical conditions. After hospital admission, worsening of hypoxic damage, inflammation, hyperglycemia, and coagulopathy were identified as hospital-acquired risk factors predicting AKI onset. Following AKI onset, the AKI-associated worsening of respiratory function was identified as the main contributor to AKI-induced increase in mortality risk. In conclusion, AKI is a common complication of Sars-CoV2 infection in non-intensive care settings where it markedly increases mortality risk also at stage 1. The identification of hospital-acquired risk factors and exposures might help prevention of AKI onset and of its complications.

A combination of factors, including Western European eating habits, physical inactivity and genetic predisposition, lead to a dramatic increase in adipose tissue mass. A special place is occupied by abdominal obesity, in which there is an accumulation of adipose tissue in the mesentery of the small intestine and the omentum. Developing in conditions of visceral obesity, insulin resistance, dyslipidemia and systemic inflammation are one of the key components of the pathogenesis of type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver and pancreas disease, polycystic ovary disease, some forms of cancer (breast cancer, endometrial cancer, colonic and direct intestines). At the same time, the pathogenetic role of adipose tissue is not limited to its participation in the formation of the cardiometabolic continuum and oncogenesis. The most important role of metabolically active fat in the pathogenesis of many respiratory diseases is known, including bronchial asthma, obstructive sleep apnea and pulmonary hypertension. This paper presents an overview of current data on immunological, pathophysiological and clinical features of the phenotype of the combination of respiratory diseases with overweight and obesity.

Cough is one of the most common symptoms in daily pediatric practice. Clinical presentation of cough in children may vary from a slight cough that has almost no impact on well-being and behaviour, to a strong, painful one that disrupts sleep and overall health status, which significantly worsens the child’s quality of life. Cough is a multidisciplinary problem due to a wide variety of causes, that’s why in the clinical pediatric practice there are certain difficulties in verifying the diagnosis, especially in children with prolonged cough, and in selecting the optimal treatment. The need for mucoactive therapy and the choice of a drug primarily depend on the cause and nature of the cough, the features of the development of the cough reflex in childhood, as well as the mechanisms of action of the drugs used. The main purpose of mucoactive drugs is to restore mucociliary clearance and effectively eliminate secretions from the respiratory tract, but apart from them some drugs have a few additional properties. The article presents the main causes of acute and chronic cough in children and considers the modern therapy options to treat cough. Ambroxol is one of the most commonly used mucoactive drugs to treat cough in children due to its pronounced mucolytic, expectorant, anti-inflammatory, antioxidant and immunomodulatory activity, as well as stimulation of surfactant synthesis. Ambroxol has been shown to have efficacy and favourable safety profile in numerous international and Russian studies. A wide choice of dosage forms, which provide different routes of medication administration, allows to use Ambroxol in children with acute and chronic bronchopulmonary diseases from an early age.

During COVID-19 pandemic the issue of diagnosis and rational therapy of community-acquired pneumonia in children became acute. This is caused by difficulties in verification of the diagnosis of community-acquired pneumonia in the outpatient department, peculiarities of interpretation of the respiratory system lesions. The article presents clinical cases of communityacquired pneumonia in children admitted to the pulmonology department of a pediatric hospital.Clinical case 1. 5-year-old child, medical history: acutely fell ill, on 28.11.20, had a sore throat and fever up to 39.0 C. Received Kagocel, Miramistin, Nurofen. PCR for COVID-19 on 08.12.20 was positive, on 18.12.2020, 22.12.2020, 20.01.2021 - negative. Immunoassay (ELISA) on 12.23.20: IgM - 4.47, IgG - 255.25. Lung and pleural cavity ultrasound: echo signs of sharply pronounced interstitial syndrome, massive fibrinothorax on both sides, indirect signs of bronchopleural fistulas; lung radiography: bilateral polysegmental pneumonia, bilateral hydrothorax, bilateral fibrinothorax, with no marked progression; CT scan with IV contrast: CT picture of hydrothorax on the left, hydropneumothorax on the right, pleurisy on both sides, compression atelectasis of lower lobe segments of both lungs. With no marked progression. Treatment. Thoracentesis; antibiotic therapy, antimycotics, infusion therapy, immunotherapy, partial parenteral nutrition. Against the background of the therapy, positive dynamics was obtained. Clinical examples are also given: an 8-year-old child with suspected new coronavirus infection and a 5-year-old child with bilateral polysegmental pneumonia.

Tomosynthesis is a modern effective and informative method of low-dose X-ray diagnostics, which allows obtaining a significant number of layered images with the subsequent volumetric image reconstruction. The use of tomosynthesis provides a one-time examination of a large anatomical area without loss of the image quality and diagnostics of difficult-to-visualize pathological changes that are not detected by digital radiography. The article presents an overview of the problem of improving low-dose imaging options in the radiation diagnostics, as well as the authors own data on the use of tomosynthesis for the diagnosis of community-acquired pneumonia in children.

Takayasu’s arteritis is a chronic granulomatous arteritis with predominant involvement of the aorta and its main branches. It occurs both in youth and childhood, manifests between the ages of 10 and 30 years, female patients predominate. This article presents a clinical case of Takayasu’s arteritis in a child with prolonged fever. Clinical case. A 10-year-old girl E. was hospitalized with complaints of febrile fever episodes during the last two months; weakness and back pain were also noted. Observed by an endocrinologist since 2015 with a diagnosis of Stunted growth. Delayed physical development. Diffuse changes of the thyroid gland, euthyroidism. Since 2020 has been observed with the diagnosis Constitutional immaturity. A tendency toward constipation was noted. Observed by an allergist with atopic dermatitis, food and respiratory allergies were diagnosed. By the time of hospitalization, the girl had been ill for two months. During this period, four episodes of fever with scanty catarrhal manifestations were recorded. The diagnostic search went in different directions, infectious, systemic and oncological diseases were excluded. The echographic pattern was typical and highly specific for Takayasu’s arteritis. Additional examination also revealed changes in the celiac trunk in the form of narrowing of its lumen. Clinical diagnosis «Non-specific aortoarteritis, type III, acute phase, stenotic variant, grade 1–3 activity with lesions of the right and left common carotid arteries and the celiac trunk» was made as a result of clinical, laboratory and instrumental examination. This clinical observation demonstrates the difficulty in making a diagnosis due to the variety of clinical forms and the absence of specific disease markers. It takes on average a year and a half from disease debut to clinical diagnosis of the patient. However, lack of therapy over a long period can be crucial for an adverse outcome of the disease.

The article presents a clinical example of a case of accidental diagnosis of human immunodeficiency virus in a child at the age of 1 year 10 months with an abscess in the parotid region on the left and the newly diagnosed lymphoproliferative syndrome. The expression of lymphoproliferative syndrome did not correspond to the clinical picture of the underlying disease, therefore differential diagnosis was made between such diseases as histiocytosis, haemoblastosis, primary immunodeficiency disorders, salmonellosis, yersiniosis, tuberculosis. As a result, a human immunodeficiency virus was diagnosed in a child of young age who does not have an apparently burdened history. As a result, the child was timely sent to a specialized hospital for in-depth examination and treatment.

Aim of the study. Show the possibilities of diagnosing non - tuberculous mycobacteriosis of the lungs (NTML) in the practice of the pulmonologist. Materials and methods. A survey of 90 patients with a confirmed diagnosis of non - tuberculous mycobacteriosis of the lungs (NTML) was presented. The diagnosis of pulmonary mycobacteriosis was established in accordance with the criteria proposed in 2007 by the American Thoracic Society and the American Society of Infectious Diseases (ATS/IDRS). Among the patients, 55 (61.1%) women prevailed, the average age was 51.2±15.3 years. Patients were evaluated complaints, the presence of concomitant diseases of the lungs, was carried out computed tomography of the chest high - resolution (HRCT), a culture study of sputum, in the absence of sputum or a single determination of the NTM culture in it, a study was conducted on materials of bronchoalveolar washout (ALS/BAL), or lung biopsies. Statistical processing of the research results was performed using descriptive statistics using Microsoft® Excel for Windows xp® on a personal computer. Results and conclusion. As a result of the study, it was revealed that before the diagnosis of NTML was established, 66.7% of patients were long observed for chronic lung diseases (chronic obstructive pulmonary disease, chronic bronchitis), and in 55.6% of cases (50 people) were registered with a phthisiologist about pulmonary tuberculosis. According to the CT scan of OGK, dissemination was determined in 66.7% of cases, in 48.9% - bronchiectasis, single or multiple destruction cavities - 46.7% of cases. In 72.2% of cases, non - tuberculous mycobacteria (NTM) were found in sputum, in 33.3% - in ALS and in 22.2% of NTMs were found in the surgical material. In 14.4% of cases, only surgery allowed to establish the diagnosis of mycobacteriosis.

The aim of this work was to study changes in mechanical lung properties in cases of COPD in general and in different zones depending on the body position.Materials and methods. The research was performed in 37 patients with chronic obstructive pulmonary disease (COPD) in the vertical and horizontal positions (VP and HP).Results. The analysis of integral respiration mechanics has revealed a reduction in dynamic lung compliance and an increase in total non-elastic lung resistance during expiration (TNRexp) in HP vs. VP. At the same time, despite the increase in TNRexp in HP, the total work of breathing did not increase. Unlike healthy individuals, the COPD patients were characterized by the absence of differences in regional mechanical properties in both VP and HP. There were no differences in the respiration mechanics of the left lung, and the zones of the right lung only differed in the parameters of regional non-elastic work of breathing (NWBr ) that was increasing from top downwards: the indicators of NWBr during expiration and NWBr in the lower zone were higher as opposed to those of the upper zone in VP. As for HP, NWBr during inspiration, NWBr during expiration and NWBr were higher.Conclusion. The data obtained contradict the prevailing opinion about an escalation in regional differences in ventilation and respiration mechanics under the influence of emerging focal and diffuse inflammatorysclerotic pathological changes in lungs and emphysema.

The study analyzes the expression of protein genes involved in intracellular signaling pathways associated with a profibrotic response, activation of epithelial-mesenchymal and endothelial-mesenchymal transitions, in modeling tuberculous granulomatosis and pharmaceutical effects. Material and methods. The study was performed on male BALB/c mice aged two months and weighing 18–22 g. Generalized tuberculous granulomatosis was simulated by a single intravenous (retro-orbital) injection of 0.5 mg BCG vaccine in 0.2 ml of isotonic aqueous NaCl solution (SS), after 4 months a part of mice started to receive treatment drugs, after 2 months the animals were sacrificed by decapitation (6 months after BCG vaccine administration) and their lung tissues were collected. Mice were divided into 6 groups, 5 males in each: intact, which were intravenously into the retro-orbital sinus injected with 0.2 ml SS (C); infected with BCG and receiving SS intraperitoneal injections (BS); infected with BCG and received intraperitoneal injections of isonicotinic acid hydrazide solution (INAH) (BI); infected with BCG and received intraperitoneal injections of dextrazide solution (conjugate of 40 kDa oxidized dextran and INAH) (BD); infected with BCG and received intraperitoneal or inhalation injections of solution of molecular-nanosomal pharmaceutical compositions of oxidized dextran (MNPC) (BMP and BMH, respectively). Finally, the expression of mRNA of matrix metalloproteinase 9, type III procollagen, TGF-β, and transcription factors ZEB1 and Snai1 was determined by real-time PCR in mice lung tissue. Results. The modeling of generalized tuberculous granulomatosis was found to be accompanied by the induction of epithelial-mesenchymal transition and the activation of profibrotic processes, which after 6 months was manifested in increase of the type III collagen α1-chain and TGF-β mRNA expression. Administration of traditional (INAH) and original (dextrazide, MNPC) preparations with anti-tuberculosis activity within two months has inhibitory activity of varying severity in relation to various markers of these processes.

Background. The study of morphological changes in the heart, lungs, liver on a model of chronic heart failure (doxorubicin-induced) in the experiment and on the correction background of 3-oxypyridine with hemisuccinate. Materials and methods. The experiment was conducted on white rats, divided into groups (intact, control, experimental). After the formation of the CHF model by introducing doxorubicin hydrochloride, the animals were killed, organs were removed and histological preparations were prepared. Results. A morphological study revealed a decrease in destruction and compensatory myocardial hypertrophy, the absence of intraalveolar hemorrhage in the lung tissue, a decrease in plethora of the central veins and swelling of the liver tissue. Conclusions. The results obtained indicate the effectiveness of the 3-oxypyridine hemisuccinate use in chronic heart failure. Suggested areas of application for the results are cardiology.

Acute laryngotracheitis (croup) is an acute condition that most commonly affects children of the first 6 years. Croup is caused by viral infection of the upper airway, predominantly by parainfluenza virus. Croup is characterized by the signs of subglottic stenosis, which determines croup severity. Corticosteroids are the mainstay of croup treatment due to a strong anti-inflammatory effect. Typically, duration of corticosteroid treatment in croup does not exce ed several days. Even short-course systemic corticosteroids are associated with a number of adverse effects: nausea, vomiting, behavioral changes and sleep disturbance, etc. According to Russian clinical guidelines for croup management inhaled corticosteroid budesonide is the first line therapy. Budesonide efficacy in croup has been proved in numerous clinical trials. Based on similar effectiveness of inhaled and systemic corticosteroids in croup patients, budesonide is the preferred treatment option, because it helps to minimize the risk of adverse effects.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Atopic dermatitis (AtD) is the most common inflammatory skin disease in childhood. In practical healthcare, the basic mechanism for the development of AtD in children is food allergy. However, recent studies demonstrate that disruptions of the skin barrier structure play a relevant role in the pathogenesis of AtD, contributing to xeroderma and increased skin permeability to allergens. Accordingly, AtD therapy should be targeted not only at relief of allergic reactions but also at restoration and maintenance of the skin barrier integrity. The key role here belongs to agents that restore epidermal lipid content – emollients. Among representatives of the group of treatments, the effectiveness of Stelatopia moisturizing emulsion for the treatment of atopic dermatitis in children was confirmed by clinical trials.

Objective. To evaluate the efficacy, tolerability and safety of the drug Diacerein (Artrocker) in patients with osteoarthritis (OA) of the hip joints after continuous administration for 4 months and the duration of the drug effects for 2 months. Materials and methods. The study included 30 patients with significant (by ARA criteria) OA of the hip joints of Stage 2-3 according to Kellgren-Lawrence. The average age of patients was 63.6 ± 5.8 years. Patients took Artrocker for the first 2 weeks by 50 mg (1 capsule), and then by 100 per day (2 capsules). Evaluation of the therapy effectiveness was evaluated by the WOMAC index (pain, stiffness and functional impairment), dynamics of the index in % relative to the initial visit; the health questionnaire EQ-5D; the test «get up and go», assessment of the therapy effectiveness by physician and patient overall assessment of tolerability. Results. The decrease in the intensity of pain and stiffness on the WOMAC index were noted by the end of the first month of therapy and persisted for the whole observation period (245,6 ± 64,3 and 142.5 ± 67,3 and 97.8 ± 35.6 and 64,3 ± 30,1; p = 0,000 respectively). Significant improvement of the functional status of the joints was achieved at the end of the treatment period, which remained until the end of observation (854,6 ± 306,8 and 637,2 ± of 253.7, p = 0.000). The decrease in total WOMAC index was recorded at visit 3 (1182,6 ± 834,2 358,6 and ± 322,1 p = 0,000). Statistically significant improvement of the test «get up and go» assessment of general health and quality of life according to EQ-5D were observed from the third visit to the end of the observation. Evaluation of tolerance to treatment done by a patient and a doctor did not differ from each other: the excellent tolerability was noted for 27.5% of patients, good-65,5%, and satisfactory - for 7% of patients. Only one adverse event – nausea – was noted in the study, which was the reason for the discontinuation of the drug and withdrawl of the patient from the study.

Proteus syndrome is an extremely rare genetic disorder with problematic genetic identification. It has been hypothesized that it is related to a lethal dominant somatic mutation occurring at a post-zygotic stage of embryonic development. Clinical presentation of the disease has much in common with a number of hereditary disorders and is frequently associated with malignancies. We present a clinical case of Proteus syndrome in a child aged 14 years and 11 months, in whom late diagnosis and late administration of specific treatment resulted in disease progression with the development of the end stage chronic renal disease. Only correct and early diagnosis allows for timely referral of a patient to a specialized hospital for adequate care.

Ultrasonic vocalizations (USVs) of laboratory rodents indicate animal emotional arousal and may serve as models of human disorders. We analysed spectrographically USV calls of pup and adult fat-tailed gerbils Pachyuromys duprasi during 420-s tests, including isolation, touch and handling. Based on combination of six different USV syllable contour shapes and six different note compositions, we classified 782 USV syllables of 24 pups aged 5-10 days to 18 types and 232 syllables of 7 adults to 24 types. Pups and adults shared 16 of these 26 USV types. Percentages of USV syllables with certain contour shapes differed between pups and adults. The contour shape and note composition significantly affected most acoustic variables of USV syllables in either pups or adults. The 1-note USV syllables were most common in either pups or adults. Pup USV syllables were overall longer and higher-frequency than adult ones, reminiscent of the USV ontogenetic pathway of bats and distinctive to rats and mice. We discuss that the USV syllable types of fat-tailed gerbils were generally similar in contour shapes and note compositions with USV syllable types of mice and rats, what means that software developed for automated classifying of mice ultrasound might be easily adapted or re-tuned to gerbil USV calls. However, using fat-tailed gerbils as model for biomedical research including control of USV vocalization is only possible since 6th day of pup life, because of the delayed emergence of USV calls in ontogeny of this species.

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the US with the majority of deaths due to metastatic disease. Current chemotherapeutic regimens involve highly toxic agents, which limits their utility; therefore, more effective and less toxic agents are required to see a reduction in CRC mortality. Novel fluorinated N,N'-diarylureas (FND) were developed and characterized by our group as potent activators of adenosine monophosphate-activated kinase (AMPK) that inhibit cell cycle progression. The purpose of this study was to determine the effect of a lead FND compound, FND-4b, either alone or combined with PI-103 (a dual PI3K/mTOR inhibitor) or SN-38 (active metabolite of irinotecan) on cell cycle arrest and apoptosis of CRC cell lines (both commercially-available and novel lines established from our patient population). Treatment with FND-4b for 24h resulted in a marked induction of phosphorylated AMPK expression and a concomitant reduction in markers of cell proliferation, such as cyclin D1, in all CRC cell lines. Apoptosis was also notably increased in CRC cells treated with FND-4b. Regardless of the genetic profile of the CRC cells, FND-4b treatment alone resulted in decreased cell proliferation. Moreover, the combination of FND-4b with PI-103 resulted in increased cell death in all cell lines, while the combination of FND-4b with SN-38 resulted in increased cell death in select cell lines. Our findings identify FND-4b, which activates AMPK at micromolar concentrations, as a novel and effective inhibitor of CRC growth either alone or in combination with PI-103 and SN-38.

The purpose of the study was to investigate the clinical symptoms and evolution of juvenile chronic arthritis (JCA) at different stages of it development. 39 children with duration of JCA from 6 months to 5 years in age from 2 to 18 years were examined. All patients underwent clinical examination, indicators of acute phase of inflammation (CRP, sialic acid, seromucoid, glycoproteins), rheumatoid factor, circulating immune complexes, complement, instrumental methods (X-ray and ultrasound, capillaroscopy of nail bed) were evaluated. Activity of the disease was estimated by disease activity score (DAS28). Statistically was determined the relative value (P). It was found that the disease started with monoarthritis (63,37 %). In the future, in half of the patients was formed oligoarthritis with damaging of large and medium-sized joints (68,25 %). In the majority of surveyed disease occurred against the backdrop of the minimal activity of the inflammatory process. On the stages of evolution recurrence of arthritis were observed in one third of children. If duration of the sickness is more than 5 years, it has become less frequent, than in previous years. The absence of clinical and radiographic manifestations of JCA after the abolition of medical treatment within one year, became the basis for the assumption that the disease remission, which was on the third year of the disease 25,93 %, on the fourth – 33,33 %, on the fifth – 36,36 %. The absence of radiographic signs of bone destruction, disability of patients allows interpreting JCA as a positive option of chronic juvenile idiopathic arthritis.

Several theories of oncogenesis are known at present, the most accepted of which is the mutational theory. However, none of the theories explain the whole set of phenomena associated with the initiation and development of cancer. The aim of the review was to try to develop a consistent theory of oncogenesis which generalises and supplements some of the already known concepts of the essence of malignization processes in cells with the new developments by the authors in the field of oncogenesis. It was concluded that the evolutionary aspect of oncogenesis allows to find out the causes of biochemical changes in a malignant cell as well as the nature of chromomeres and their functions in oncogenesis. Among the most important results of the proposed review are the suggestions on the role of evolutionary factors, the role of the genome instability of the malignant cells and the role of chromomeres in these cells.

Aim. To estimate of the rate of reparative processes in the lower extremity (LE) soft tissues of patients with diabetic foot (DF) syndrome in the local application of collagen-containing dressings (CCD) versus standard medical therapy. Subjects and methods. The clinical (sizes, tissue oxygenation), histological, and immunohistochemical markers of reparative processes in LE soft tissues were analyzed in patients with diabetes mellitus during the local application of collagen-containing wound dressings versus standard treatment. Forty-two patients with postrevascularization neuropathic and neuroischemic DF syndrome were examined after standard surgical wound treatment. In the perioperative period, 21 patients received local treatment using CCD and 21 patients had standard treatment. Results. In the patients using CCD, the area and depth of wound defects could be decreased by 26.4±17.2 and 30.4±25.6%, respectively (p=0.002 vs baseline). In the control group, those were 17.0±19.4 and 16.6±21.6%, respectively (p=0.002). Percutaneous oximetry assessment indicated significantly higher local microhemodynamics in the local collagen treatment group (p

Most HIV-1 tropism studies have involved non-A subtypes. Our aim was to study the prevalence of R5- and non-R5-tropic HIV-1 variants and the tropism occurrence relative to the CD4 counts, treatment experiences, transmission routes and other features of infection in Russia, where subtype A is presumably predominant. In this multicenter, single-step, cross-sectional, epidemiologic study, 943 HIV-1-infected patients were enrolled at 12 AIDS centers throughout Russia. Viral tropism was determined using a genotype method-based kit. The V3 loop sequences were analyzed using the geno2pheno resource. The tropism was successfully predicted for 823 (87.3%) patients. Frequencies of R5-tropic and non-R5-tropic viruses in successfully analyzed samples were 70.2% (578) and 29.8% (245), respectively. Co-receptor usage correlated significantly only with the treatment experiences (p = 0.018) and CD4 counts (p = 0.004). But there was no dependence of R5/non-R5 co-receptor usage frequencies on presence/absence of a therapy change (p = 0.664) or HIV infection duration (p = 0.458). According to the env sequences, 457 (83.6%) of the samples in study were subtype A and 70 (12.8%) were subtype B. This indicates a stabilizing of immune system and thus little emergence of X4 viruses. We suggest that CCR5-antagonists could be used in both naïve and experienced patients in Russia after determination of HIV tropism.

Incidence of cardiovascular events among HIV-infected patients in clinical practice has increased recently. Usually strategy of treatment in such patients differs from the conventional and requires close cooperation with experts in HIV infection. Example of successful treatment of the acute pericardial effusion in patient with stage III HIV (World Health Organizationclassification) is presented in this clinical case.