Modeling of a linear ion trap with driving rectangular waveforms.

We consider the operation of a digital linear ion trap with resonant radial ejection. A sequence of rectangular voltage pulses with a dipole resonance signal is applied to the trap electrodes. The periodic waveform is piecewise constant, has zero mean, and is determined by an asymmetry parameter d $$ d $$ : one value is taken on interval 0 dT $$ \left(0, dT\right) $$ and another on dT T $$ \left( dT,T\right) $$ , where T $$ T $$ is the RF period. Ion mass scanning is performed by varying the asymmetry parameter d $$ d $$ and amplitude of the negative pulse part with time. The ion oscillation frequencies and acceptance of the linear trap are calculated. The dependence of the ion mass to charge ratio m / z $$ m/z $$ on the parameter d $$ d $$ is m / z ~ d 2 $$ m/z\sim {d}^2 $$ . The maximum value is about m / z = 30 $$ m/z=30 $$  kDa for typical parameters of the linear trap: frequency 0.5 MHz, rod radius 4 mm, and negative pulse amplitude 1 kV. The dipolar excitation frequency is 0.125 MHz at which the LIT acceptance is maximal.

[Global demographic problem and active aging (literature review)].

The article presents an overview of foreign sources devoted to the problems of population aging as a significant phenomenon that has become the most important medical and socio-demographic challenge in the world. The review provides global data on this problem and shows the need for elaborating and implementing active aging strategies, optimizing opportunities for health, participation and safety in order to improve the life quality as people age. The paper employs the method of content analysis of scientific publications retrieved in PubMed database by keywords - «aging¼, «population aging¼, «demographic trend¼, «longevity¼, and «life expectancy¼. Scientific publications for the period 2018-2023, WHO and UN materials, statistical data, and popular scientific publications have been studied. The purpose of the review was to analyze trends and global nature of aging based on scientific publications and open sources, and to highlight the most promising areas of the demographic policy on the older adults. In the time of rapid demographic changes, it is extremely important to use all available opportunities that maximize healthy aging with the participation of the older adults. We should remember that aging is a natural process and it is better to accept it, both psychologically and physically, rather than ignore. Healthy aging should become and has become the main principle of life, suggesting a longer healthy life of the older adults, who, in turn, should understand how to accept and implement this principle in their lives.

[Functional and aesthetic significance of the uvula in cleft palate repair]. / Rol' yazychka v dostizhenii funktsional'nogo i esteticheskogo rezul'tata uranoplastiki.

OBJECTIVE: To investigate functional and aesthetic role of uvula in cleft palate repair. MATERIALS AND METHODS: Forty-one patients aged from 1 year 2 months to 7 years were included in this study with congenital cleft lip and/or palate. The morphological investigation of the resected hemi- uvula was done. Palatoplasty was performed in all cases. RESULTS: According to morphological results, most of the resected hemi-uvula consisted of vascularized fibrous tissue, covered with epithelium. In three groups of patients (with unilateral, bilateral and isolated cleft palate), the duration of the surgery and intraoperative blood loss did not exceed similar values for conventional methods. The volume of infusion therapy revealed a deficit of fluid intake of no more than 30%, which indicates early restoration of swallowing function. CONCLUSION: The technique of preserving one of the «hemi-uvulas¼ lead to excellent aesthetic results and increasing functionality. Resection of one of the «hemi-uvulas¼ is safe and physiological.

[Lyudmila Antoninovna Shangina as the scientist and pedagogue].

The article is devoted to scientific biography of the prominent neuroanatomist, Doctor of Medical Sciences, Professor L. A. Shangina, representative of the scientific school of Tonkov-Bushmakin. Her input into becoming of the chairs of normal anatomy of medical institutes in Irkutsk, Moscow, Kursk, Dushanbe (Tajikistan) and Smolensk and in organization of scientific community of neuromorphologists in the USSR in the middle and second half of the twentieth century is demonstrated. The special attention is paid to the results of scientific studies of L. A. Shangina and her post-graduate students of topography of nerves innervating human heart, of topography of accessory nerve (XI pair of cranial nerves), of structure of receptors of autonomic nervous system in walls of alimentary tract and urinary system.

The adjuvant effect of polymuramil, a NOD1 and NOD2 agonist, differs when immunizing mice of different inbred lines with nonstructural hepatitis C virus (Flaviviridae: Hepacivirus)proteins and is synergistically enhanced in combination with pyrogenalum, a TLR4 agonist.

INTRODUCTION: Hepatitis C is a liver disease with high chronicity, the cause of cirrhosis and hepatocarcinoma. The main obstacle to controlling hepatitis C is the lack of vaccines. The aim of the work was to compare the immunogenic activity of nonstructural recombinant proteins NS3, NS4 and NS5B of hepatitis C virus (HCV) as components of a subunit candidate vaccine and to analyze the adjuvant properties of two available commercial drugs, polymuramil and pyrogenalum. MATERIALS AND METHODS: BALB/c, DBA/2J and C57BL/6 mice were immunized with nonstructural proteins without adjuvants or with polymuramyl (NOD1 and NOD2 agonist) and pyrogenalum (TLR-4 agonist). The activity of antibodies was determined in ELISA, the cellular response - by antigen-specific lymphocyte proliferation and by production of IFN-γ in vitro. RESULTS: Recombinant proteins showed different immunogenicity. NS4 induced antibodies more efficiently than NS3 and NS5B. Significant differences were found in the immune response of three inbred lines mice: the level of IFN-γ in BALB/c and DBA/2J mice induced by NS5B protein was 30 times higher than in C57Bl/6 mice. In contrast, the induction of antibodies in BALB/c mice was lower than in C57Bl/6 and DBA/2J. Polymuramil did not increase the humoral response to NS5B and enhanced the cellular response only in C57BL/6 mice. The combined use of polymuramil with pyrogenalum significantly increased both the humoral and cellular response of mice to all recombinant HCV proteins. CONCLUSION: Different immunogenic properties and different functions of recombinant non-structural HCV proteins indicate the feasibility of their combined inclusion in subunit vaccines. It was established for the first time that immunization with HCV proteins with a complex adjuvant (polymuramyl + pyrogenalum) has a synergistic effect, significantly exceeding the effect of each of them separately.

Period-doubling bifurcation in surface radio-frequency trap: Transition to chaos through Feigenbaum scenario.

We have numerically investigated the dynamics of charged microparticles in a "five-wire" surface radio-frequency trap. The period-doubling bifurcation conditions have been shown to depend on the particle, the trap, and the alternating voltage parameters. For a comprehensive study of the dynamics chaotization through a cascade of period doubling, we have used Fourier analysis of a particle trajectory as well as the calculations of a non-trivial Lyapunov exponent map. We have demonstrated that the period-doubling bifurcation is consistent with a Feigenbaum scenario. A new approach to particle property determination can, thus, be based on observing a period-doubling bifurcation.

Endogenous Regeneration of Alveolar Bone by Decellularized Tooth Matrix.

The efficiency of bone tissue regeneration by decellularized tooth matrix, demineralized tooth matrix, and commercial xenograft Bio-Oss Spongiosa was compared on the model of a critical-size circular defect in the alveolar bone of the upper jaw of adult Wistar rats. The defect healing dynamics was assessed using histological, histomorphometrical, and immunohistochemical methods on days 30 and 60. In contrast to demineralized matrix and commercial xenograft, decellularized matrix induces the formation of the new bone tissue by day 60. Decellularized matrix can be considered as a biomaterial for cell-free tissue engineering for alveolar bone restoration in dentistry and maxillofacial surgery.

High-Q trenched aluminum coplanar resonators with an ultrasonic edge microcutting for superconducting quantum devices.

Dielectric losses are one of the key factors limiting the coherence of superconducting qubits. The impact of materials and fabrication steps on dielectric losses can be evaluated using coplanar waveguide (CPW) microwave resonators. Here, we report on superconducting CPW microwave resonators with internal quality factors systematically exceeding 5 × 106 at high powers and 2 × 106 (with the best value of 4.4 × 106) at low power. Such performance is demonstrated for 100-nm-thick aluminum resonators with 7-10.5 um center trace on high-resistivity silicon substrates commonly used in Josephson-junction based quantum circuit. We investigate internal quality factors of the resonators with both dry and wet aluminum etching, as well as deep and isotropic reactive ion etching of silicon substrate. Josephson junction compatible CPW resonators fabrication process with both airbridges and silicon substrate etching is proposed. Finally, we demonstrate the effect of airbridges' positions and extra process steps on the overall dielectric losses. The best quality factors are obtained for the wet etched aluminum resonators and isotropically removed substrate with the proposed ultrasonic metal edge microcutting.

[Difficulties in differential diagnosis of sagittal synostosis (scaphocephaly)]. / Trudnosti differentsial'noi diagnostiki sagittal'nogo sinostoza (skafotsefalii).

Craniosynostosis is characterized by congenital absence or premature closure of skull sutures. The most common form of craniosynostosis is synostosis of sagittal suture followed by scaphocephaly. There are some head deformities similar to scaphocephaly such as positional and constitutional dolichocephaly, etc. These patients have no sagittal suture synostosis. However, there are difficulties in differential diagnosis between these deformities and scaphocephaly. OBJECTIVE: To develop differential diagnostic criteria between dolichocephalic head deformities and true scaphocephaly following sagittal synostosis. MATERIAL AND METHODS: The study included 33 patients with dolichocephaly (25 (75.8%) boys and 8 (24.2%) girls) between December 2013 and August 2022. The inclusion criterion was available CT or ultrasound data confirming or excluding sagittal synostosis. Age of patients was 8.62±7.71 (1.77-36) months. We analyzed anamnestic, clinical and radiological data. Radiological data was compared with diagnostic findings in 20 patients with scaphocephaly. Both groups were comparable in age, gender and cranial index. RESULTS: We present clinical and radiological signs, as well as algorithm for differential diagnosis between scaphocephaly and dolichocephaly. CONCLUSION: There are objective difficulties in differential diagnosis between scaphocephaly following sagittal synostosis and dolichocephalic head deformities. In most cases, we cannot establish the cause of congenital forms of dolichocephaly. The most likely causes may be pre- and postnatal compressive and positional effects. Ultrasound of skull sutures is preferable for differential diagnosis between these abnormalities. Correction of dolichocephaly can be carried out according to aesthetic indications with individual cranial orthoses.

[Exosomes in the life cycle of viruses and the pathogenesis of viral infections].

Exosomes are extracellular vesicles of endosomal origin, with a bilayer membrane, 30160 nm in diameter. Exosomes are released from cells of different origins and are detected in various body fluids. They contain nucleic acids, proteins, lipids, metabolites and can transfer the contents to recipient cells. Exosome biogenesis involves cellular proteins of the Rab GTPase family and the ESCRT system, which regulate budding, vesicle transport, molecule sorting, membrane fusion, formation of multivesicular bodies and exosome secretion. Exosomes are released from cells infected with viruses and may contain viral DNA and RNA, as well as mRNA, microRNA, other types of RNA, proteins and virions. Exosomes are capable of transferring viral components into uninfected cells of various organs and tissues. This review analyzes the impact of exosomes on the life cycle of widespread viruses that cause serious human diseases: human immunodeficiency virus (HIV-1), hepatitis B virus, hepatitis C virus, SARS-CoV-2. Viruses are able to enter cells by endocytosis, use molecular and cellular pathways involving Rab and ESCRT proteins to release exosomes and spread viral infections. It has been shown that exosomes can have multidirectional effects on the pathogenesis of viral infections, suppressing or enhancing the course of diseases. Exosomes can potentially be used in noninvasive diagnostics as biomarkers of the stage of infection, and exosomes loaded with biomolecules and drugs - as therapeutic agents. Genetically modified exosomes are promising candidates for new antiviral vaccines.

Identification of Chimeric NTRK3 Genes in Papillary Thyroid Cancer Cells by Analyzing the Imbalance of the Expression of 5' and 3' mRNA Fragments.

The standard for detecting chimeric genes of neurotrophic receptor tyrosine kinases (NTRK) is next generation sequencing (NGS). However, this analysis is expensive and takes several days. As a rapid screening method for the detection of NTRK3-dependent papillary thyroid cancer, an analysis of the expression imbalance between 5' and 3' NTRK3 mRNA fragments was used (5'/3' RT-PCR). The reference method for detection of NTRK3 rearrangements was fluorescent in situ hybridization (FISH), and the most frequent rearrangements in papillary thyroid cancer were tested using reverse transcription PCR (RT-PCR). Using 5'/3' RT-PCR, 18 samples of papillary thyroid cancer carrying chimeric transcripts of NTRK3 mRNA were detected. The sensitivity of the developed technique was 88.9% and specificity was 99.3%. Thus, a fast and cost-effective method of screening samples of papillary thyroid cancer in paraffin blocks is proposed with acceptable sensitivity and specificity.

[Adjuvant effect of dispersed fullerene C60 on the immune response to constructs harboring amino acid and nucleotide sequences of hepatitis C virus nonstructural NS5B protein].

INTRODUCTION: A vaccine against hepatitis C has not yet been developed. Recombinant proteins and plasmids encoding hepatitis C virus (HCV) proteins, the components of candidate vaccines, induce a weak immune response and require the use of adjuvants. The aim of the work was to study the adjuvant action of an aqueous solution of fullerene C60 during immunization of mice with HCV recombinant protein NS5B (rNS5B) that is an RNA-dependent RNA polymerase, or with NS5B-encoding pcNS5B plasmid. MATERIALS AND METHODS: An aqueous solution of dispersed fullerene (dnC60) was obtained by ultrafiltration. C57BL/6 mice were immunized with rNS5B subcutaneously, pcNS5B intramuscularly mixed with different doses of dnC60 three times, then the humoral and cellular response to HCV was evaluated. RESULTS: Mice immunization with rNS5B in a mixture with dnC60 at doses of 250 g/mouse significantly induced humoral response: a dose-dependent increase in IgG1 antibody titers was 720 times higher than in the absence of fullerene. There was no increase in the cellular response to rNS5B when administered with dnC60. The humoral response to DNA immunization was weak in mice of all groups receiving pcNS5B. The cellular response was suppressed when the plasmid was injected in a mixture with dnC60. CONCLUSIONS: Dispersed fullerene dnC60 is a promising adjuvant for increasing the immunostimulating activity of weakly immunogenic proteins including surface and other HCV proteins, important for a protective response. Further research is needed to enhance the ability of dnC60 to boost the cellular immune response to the components of the candidate vaccine.

Differences in Transcriptomic Profiles of Brain and Thyroid Tumors with NTRK Gene Rearrangement.

For tumors with chimeric NTRK genes, entrectinib and larotrectinib can be prescribed regardless of tumor localization. We compared changes in the transcriptional activity of genes in brain tumors (BT) and thyroid cancer (TC) with rearrangement (NTRK+) and without rearrangement (NTRK-) of the NTRK genes using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We revealed an increase in the transcription of the JUN gene in NTRK+ samples in comparison with NTRK- samples: by 1.6 times for BT (p=0.239) and by 2.5 times for TC (p=0.003). The transcription of eight HOX genes in NTRK+ BT samples was also increased (by 85-725 times, p<0.05) in comparison with NTRK-. In NTRK+ TC samples, the level of miR-31 and miR-542 was statistically significantly higher (by 3 and 2.5 times, respectively) than in NTRK-samples. For the NTRK+ BT samples, the levels of miR-10b, miR-182, and miR-21 more than 5-fold surpassed the corresponding values in NTRK-samples (p<0.05). These findings reflect differences in activation of gene transcription resulting from NTRK gene rearrangement in BT and TC.

Histological Variants of Papillary Thyroid Cancer in Relation to Clinical and Morphological Parameters and Prognosis.

The correlation of histological features of papillary thyroid cancer with clinical and morphological prognostic factors and cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center (25 cases with lethal outcome and 64 follow-up controls). Significant variability was revealed in the histological structure of papillary thyroid cancer with the prevalence of classic (62%) and less frequent follicular (19%), tall cell (8%), and solid (7%) variants. In comparison with the classic variant, the solid variant was more often associated with male sex and large tumor size; follicular and tall cell variant was associated with more frequent metastases to regional lymph nodes; follicular and solid variants were associated with an increased proportion of cases with disease stages III-IV. The main differences reflecting the effect of histological factor on the disease outcome were associated with the solid variant of papillary thyroid cancer that was detected in 21% of lethal cases and only in 2% of control subjects. The detection of this variant can be of importance as an additional prognostic factor of the postoperative survival in papillary thyroid cancer.

А rare case of primary malignant melanoma of the female urethra.

Primary malignant melanoma of the female urethra is an extremely rare disease. Its frequency is only 0.2% of all malignant melanomas. This type of carcinoma is associated with a poor prognosis and short survival due to the early occurrence of metastases and delayed diagnosis. We present a patient with primary malignant melanoma invading the distal urethra, part of the labia minora, and sections of the anterior vaginal wall, where 15 months of overall survival were achieved against the background of the complex treatment.

Analysis of the Morphology of Monocytes and Lymphocytes from COVID-19 Patients Using Low-Voltage Scanning Electronic Microscopy.

Severe course of COVID-19 is largely determined by hyperactivation of the immune system, or cytokine storm, in which immune cells (lymphocytes, monocytes, etc.) play a major role. Using low-voltage scanning electron microscopy, we studied the morphology of lymphocytes and monocytes during cytokine storm. Monocytes and lymphocytes were isolated by fluorescence sorting from the blood of healthy volunteers (n=6) and patients with COVID-19 (n=5) during cytokine storm (IL-6>23 ng/ml, smear positive for SARS-CoV-2). For each patient, 11-32 individual cells were analyzed at magnification of 18-32,000 times. Measurements showed that monocyte size was increased during cytokine storm (p=0.0001).

[ANALYSIS OF THE STAFFING OF MEDICAL ORGANIZATIONS SUBORDINATE TO THE DEPARTMENT OF HEALTH OF THE CITY OF MOSCOW IN 2021].

An analysis was made of the structure and number of medical workers (doctors and paramedical personnel) of the Moscow healthcare system for the period 2017-2021. The analysis showed that the number of medical full-time positions over the same period increased by 13.6%, and regular positions of nursing staff by 8.9%. The provision of the population (per 10 thousand population) with doctors increased by 13.0% from 35.6 in 2017 to 40.2 in 2021. The provision of the population with nurses decreased by 2.4% from 58.4 in 2017 to 57.0 in 2021. Among medical workers, the number of individual doctors, over the same period, increased by 15.5%, and the number of individuals of paramedical personnel decreased by 3.4%. The staffing of medical rates (by positions), in general, decreased by 2.4% from 82.5 in 2017 to 80.5 in 2021, and the rates of nursing staff decreased by 9.7% from 87.4% in 2017 to 79.0% in 2021. The part-time ratio was 1.1 for medical positions and for positions of paramedical personnel. Issues related to low staffing and the coefficient of part-time employment for individual medical positions and positions of paramedical personnel require further resolution.

[Interactomics of CXXC proteins involved in epigenetic regulation of gene expression]. / Interaktomika CXXC-belkov, uchastvuiushchikh v épigeneticheskoi reguliatsii gennoi ékspressii.

Regulation of gene expression is an extremely complex and multicomponent biological phenomenon. Proteins containing the CXXC-domain "zinc fingers" (CXXC-proteins) are master regulators of expression of many genes and have conserved functions of methylation of DNA bases and histone proteins. CXXC proteins function as a part of multiprotein complexes, which indicates the fundamental importance of studying post-translational regulation through modulation of the protein-protein interaction spectrum (PPI) in both normal and pathological conditions. In this paper we discuss general aspects of the involvement of CXXC proteins and their protein partners in neoplastic processes, both from the literature data and our own studies. Special attention is paid to recent data on the particular interactomics of the CFP1 protein encoded by the CXXC1 gene located on the human chromosome 18. CFP1 is devoid of enzymatic activity and implements epigenetic regulation of expression through binding to chromatin and a certain spectrum of PPIs.

Physiological Media in Studies of Cell Metabolism.

Changes in cell metabolism accompany the development of a wide spectrum of pathologies including cancer, autoimmune, and inflammatory diseases. Therefore, usage of inhibitors of metabolic enzymes are considered a promising strategy for the development of therapeutic agents. However, the investigation of cellular metabolism is hampered by the significant impact of culture media, which interfere with many cellular processes, thus making cellular models irrelevant. There are numerous reports that show that the results from in vitro systems are not reproduced in in vivo models and patients. Over the last decade a novel approach has emerged, which consists of adaptation of the culture medium composition to that closer to the composition of blood plasma. In 2017‒2019, two plasma-like media were proposed, Plasmax and HPLM. In the review, we have summarized the drawbacks of common media and have analyzed changes in the metabolism of cells cultivated in common and plasma-like media in normal and pathological conditions.

Mechanisms of Survival of Cytomegalovirus-Infected Tumor Cells.

Human cytomegalovirus (HCMV) DNA and proteins are often detected in malignant tumors, warranting studies of the role that HCMV plays in carcinogenesis and tumor progression. HCMV proteins were shown to regulate the key processes involved in tumorigenesis. While HCMV as an oncogenic factor just came into focus, its ability to promote tumor progression is generally recognized. The review discusses the viral factors and cell molecular pathways that affect the resistance of cancer cells to therapy. CMV inhibits apoptosis of tumor cells, that not only promotes tumor progression, but also reduces the sensitivity of cells to antitumor therapy. Autophagy was found to facilitate either cell survival or cell death in different tumor cells. In leukemia cells, HCMV induces a "protective" autophagy that suppresses apoptosis. Viral factors that mediate drug resistance and their interactions with key cell death pathways are necessary to further investigate in order to develop agents that can restore the tumor sensitivity to anticancer drugs.