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Introduction. Soft tissue tumors account for up to 8 % of all malignant neoplasms in children. According to the international histological classification, about 150 different morphological variants of soft tissue tumors have been registered, of which 45 % are rhabdomyosarcoma (RMS). Most often, RMS occurs in early childhood – the average age of patients at the time of diagnosis is 5 years. The incidence rate of RMS is 0.9 per 100,000 children. In 25 % cases, the initial diagnosis reveals distant metastasis to the lungs, bones, bone marrow, and 8 % – leptomeningeal metastasis. More than 7 % of patients with localized parameningeal RMS develop leptomeningeal metastasis, according to the Rhabdomyosarcoma Study Group. Purpose of the study – report the incidence, prognosis of leptomeningeal metastasis and treatment outcomes in children with intracranial spread of RMS. Materials and methods. The study included 45 patients aged 1 to 17 years with a diagnosis of RMS of parameningeal localization with intracranial spread, who received special treatment from 2003 to 2020. The study included 6 (20 %) patients in whom the tumor developed in early childhood (up to 3 years). The boys predominated – 25 (55.5 %) in the study. The primary tumor spread to the orbit in 7 (15 %) cases, the skull base in 7 (15 %) cases, the middle ear in 4 (8 %) cases, the nasopharynx in 3 (6 %) cases, and the brain substance was affected in 16 (35 %). Metastases in regional lymph nodes were determined in 7 (15 %) patients. Multiple metastatic lesions of bones and bone marrow – 4 (9 %) cases, leptomeningeal metastases – in 2 (4 %). 45 (100 %) patients received drug treatment according to the protocols approved by the Academic Council of the Research Institute of Pediatric Oncology and Hematology at N. N. Blokhin National Medical Research Centerof Oncology, Ministry of Health of Russia. Radiation therapy was performed in 33 (74 %) patients, while total focal dose of 50 Gy was administered to the primary tumor. Affected lymph nodes of the neck were irradiated in 10 (23 %) patients, total focal dose is 45.0 Gy. Surgical treatment was performed in 15 (34 %) patients. Multicomponent treatment was performed in 15 (34 %) patients. Results. During the observation period from 12 months to 14 years, 21 (49 %) patients are alive. 21 (51 %) patients died from tumor progression, 1 (2 %) died from complications of special treatment. Conclusions. The treatment of this group of patients is one of the urgent problems of pediatric oncology, which is based on polychemotherapy, supplemented by intrathecal administration of anticancer drugs and craniospinal irradiation. The development of new therapies requires a multidisciplinary approach to achieve a significant improvement in the survival of children with leptomeningeal metastases RMS of parameningeal localization.

Relevance. Retinoblastoma (RB) is the most common primary intraocular tumor in children. The incidence of RB ranges from 1:14,000 to 1:20,000 newborns. To date, the survival rates of patients with RB reach almost 100 % with timely and adequate diagnosis. Among childhood oncological diseases, RB accounts for 2.3–4.5 % and 85–90 % among intraocular tumors in children. According to the volume of tumor spread, intra- and extraocular forms of the disease are distinguished. Extraocular RB is the spread of the tumor beyond the eye with invasion of the orbital tissues, as well as the possible involvement of adjacent areas, including intracranial without and with regional and/or remote metastases. The main method of treatment of children with extraocular RB is neoadjuvant chemotherapy (CT) with planning of surgical intervention and adjuvant therapy. High-dose CT (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT), it allows to increase relapse-free survival in patients without metastatic lesions of the brain and spinal cord, but with their defeat, the prognosis of survival is extremely unfavorable, the nature of the disease is recurrent with 100 % lethality.Description of the clinical case. We report a case of bilateral RB: OD – with extraocular and intracranial spread of the tumor along the optic nerve with a lesion of the chiasm and a transition to the initial parts of the visual tracts. Secondary glaucoma. OS – with intraocular tumor growth in a 3-year-old child. After neoadjuvant chemotherapy, including intrathecal, a simultaneous two-stage operation was performed in the volume of bone-plastic (temporo-orbito-zygomatic) pterionic craniotomy on the right with prechiasmal resection of the right optic nerve and enucleation of the right eye. In the postoperative period, adjuvant chemotherapy was performed, followed by HDCT with auto-HSCT. Radiation therapy has become the final stage of treatment. Brachytherapy for OS tumor and remote radiotherapy for craniospinal region, right orbit, optic nerve stump with chiasm and pituitary pedicle were successively performed. After 14 months from the beginning of treatment and 5 months after its completion, a leptomeningeal relapse of the disease was detected.Conclusion. Rare observations of RB with damage to the visual tracts do not allow us to sufficiently study the features of the course of the tumor process, as well as to develop a single effective approach to antitumor treatment. Among the causes of mortality in patients with extraocular RB, the main one is metastasis, metastasis in the brain and spinal cord.

Most bacterial genomes have a single chromosome that may be supplemented by smaller, dispensable plasmids. However, to date, approximately 10% of bacteria with completely sequenced genomes, mostly pathogens and plant symbionts, have more than one stable large replicon. Some secondary replicons are species-specific, carrying pathogenicity or symbiotic factors. Other replicons are common on at least the genus level, carry house-keeping genes, and may have a size of several million base pairs.We analyzed the abundance and sizes of large secondary replicons in different groups of bacteria and identified two patterns in the evolution of multipartite genomes. In nine genera of four families,Pseudoalteromonadaceae,Burkholderiaceae,Vibrionaceae, andBrucellaceae,we observed a positive correlation between the sizes of the chromosome and the secondary replicon with the slope in the range of 0.6–1.2. This indicates that in these genera the replicons evolve in a coordinated manner, with comparable rates of gene gain/loss, hence supporting classification of such secondary replicons as ‘chromids’. The second, more common pattern, features gene gains and losses mainly occurring in the primary replicon, yielding a stable size of the secondary replicon. Moreover, such secondary replicons are usually present in only a low fraction of the genus’ species. Hence, such replicons behave as ‘megaplasmids’. A mixed behavior was observed in symbiotic genera from theRhizobiaceaefamily (Rhizobium, Agrobacterium,Azospirillum, and Ensifer) with large, essential secondary replicons of stable size. These results may provide a general framework for understanding the evolution of genome complexity in prokaryotes.Data summaryThe datasets supporting the conclusions of this article are available athttps://github.com/zaryanichka/MultipleReplicons

Malignant tumors of parameningeal localization are various morphological neoplasms located in the nasal cavity, nasopharynx, paranasal sinuses and middle ear. As a result of tumor growth, conditions are created for the development of chronic inflammation. Studies of the microbiome of the upper respiratory tract in children with malignant tumors were practically not conducted. Objective of the research: to identify changes in the microbiome of the nasal cavity in children with malignant tumors of parameningeal localization during chemoradiotherapy. Materials and methods: the study included 29 patients with parameningeal tumors, 2–17 years old. Among the included in the study there were 18 boys (62%) and 11 girls (37%). Morphologically, the following were verified: embryonic rhabdomyosarcoma (ERMS) – 17 (58%), alveolar rhabdomyosarcoma (arms) – 3 (10%), other sarcomas – 4 (13%), nasopharyngeal cancer – 5 (17%). All patients received induction chemotherapy. Simultaneous radiotherapy (LT) and chemotherapy (CT) – in 24 (82%) cases. After completing the chemoradiotherapy stage, consolidation therapy continued in 20 (70%) patients. Results: before the start of LT (after the induction stage of chemotherapy), a variety of microflora was observed in the nasal secretions, gram-positive and gram-negative bacteria were isolated in an equal ratio. The absence of growth of microorganisms was determined in 4 (13%) cases before the start of LT. Methicillin-resistant Staphylococcus epidermidis and Staphylococcus haemolyticus were more frequently detected after LT. Colonization of the nasal cavity of Candida albicans occurred before the start of LT in 4 (13%) and persisted after irradiation in 5 (17%) patients. In the delayed period, there was an increase in the percentage of patients who ridiculed gram-negative microorganisms – Pseudomonas aeruginosa in 4 (13%) cases. After 12 months, 3 (10%) patients showed a return of nosocomial flora (S. epidermidis MRSE and S. haemolyticus MRS), a decrease in colonization of P. aeruginosa and the preservation of C. albicans. Conclusion: at different stages of chemoradiotherapy, the nasal mucosa is colonized by various microorganisms that differ in their properties and pathogenicity. The continuation of this study will clarify the clinical significance of certain types of opportunistic microorganisms in the pathogenesis of inflammatory diseases of the upper respiratory tract in children with malignant tumors.

Studies of the actions of niclosamide against tumor cells and normal human cells (human embryo kidney cells and pulmonary embryo fibroblast cells) showed higher levels of cytotoxic activity against tumor cells, including melanoma (the Mel-8, Mel-10, MS lines) and colorectal cancer (the Caco-2, COLO 320 HSR, and SW827 cells). Niclosamide was shown to have a high level of cytotoxic activity against cells with the multidrug resistance phenotype due to high levels of expression of MDR1 protein on the plasma membrane (the Mel-8 and MCF-7Adr lines). The proportion of tumor stem cells (TSC) was measured by flow cytometry as the proportion of cells forming side populations (SP). Niclosamide was found to act on TSC cells either more effectively (colorectal cancer line SW 837, (decreases in SP fraction size) or with the same effectiveness as the main population of tumor cells (SP fraction size unaltered).

Ischemic stroke (AI) is becoming an increasingly important and urgent problem in pediatrics due to the occurrence of neurological disorders that affect the quality of life and limit the social adaptation of a child. The clinical picture of ischemic stroke in pediatric practice differs from the manifestation of this pathology in adult patients. Children have special risk factors for the development of IS. In pediatric oncology, there are such factors like invasive tumor growth, the development of tumor embolism, and blood clotting disorders. Side effects of anticancer treatment occupy a special place in the development of IS. The relationship between post-radiation arteriopathies and ischemic stroke has been more studied among cancer patients who underwent neck irradiation. In children, it was found that after radiation therapy to the head and neck region and, thus, the risk of ischemic stroke in childhood increases. This review is devoted to the possible pathophysiological causes and mechanisms of stroke in children with head and neck tumors. In addition, descriptions of clinical cases of patients with ischemic stroke in the course of anticancer treatment are presented.

The second stage of the efficacy assessment of the postgraduate education of the heads of women's consultation clinics was analyzed. They underwent training at the Central Order of V.I. Lenin Institute of Advanced Training of Physicians according to the experimental cycle of the problem-target programme which was developed on the basis of the claims raised for heads of women's consultation clinics. Postgraduate students were characterized according to their length of service and the posts occupied. The second stage of the efficacy assessment of advanced education involved the analysis of the introduction of new forms and methods of work in women's consultation clinics. The analysis was carried out by means of introduction charts used at the students' places of work, special assessment criteria being applied. The study findings were grouped by the type of activity of the clinic's heads. The conclusions were very specific and indicated the necessity of improving the work of this out-patient chain of the obstetric and gynecologic service.