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Abstract Neurodevelopmental disorders are thought to arise from intrinsic brain abnormalities. Alternatively, they may arise from disrupted crosstalk among tissues. Here we show the local reduction of two vestibulo-cerebellar lobules, the paraflocculus and flocculus, in mouse models and humans with 22q11.2 deletion syndrome (22q11DS). In mice, this paraflocculus/flocculus dysplasia is associated with haploinsufficiency of the Tbx1 gene. Tbx1 haploinsufficiency also leads to impaired cerebellar synaptic plasticity and motor learning. However, neural cell compositions and neurogenesis are not altered in the dysplastic paraflocculus/flocculus. Interestingly, 22q11DS and Tbx1 +/– mice have malformations of the subarcuate fossa, a part of the petrous temporal bone, which encapsulates the paraflocculus/flocculus. Single-nuclei RNA sequencing reveals that Tbx1 haploinsufficiency leads to precocious differentiation of chondrocytes to osteoblasts in the petrous temporal bone autonomous to paraflocculus/flocculus cell populations. These findings suggest a previously unrecognized pathogenic structure/function relation in 22q11DS in which local skeletal deformity and cerebellar dysplasia result in behavioral deficiencies.

INTRODUCTION. Severe pain syndrome is a significant complication of the postoperative period. Despite the prevalence of laparoscopic surgical interventions for colorectal cancer, there is still a lack of commonly agreed strategies to provide the most effective perioperative analgesia in such patients. Multimodal analgesia is a modern method of anesthesia that affects multiple components of the pathogenesis of pain syndrome. Proposed as a gold standard for open colorectal surgeries, thoracic epidural anesthesia as a component of multimodal analgesia does not show the same beneficial results in laparoscopic colorectal intervention.The OBJECTIVE was to compare different techniques of local anesthesia and to identify the most perspective method of local anesthesia as a part of a multimodal analgesia in terms of effectiveness and affordability in daily practice.METHODS AND MATERIALS. A review of the current scientific literature was conducted in order to search and assess the usability of different local anesthesia techniques.CONCLUSION. Infiltration of a local anesthetic solution into the trocar wound area is the most uncomplicated and affordable method of anesthesia, comparable in efficacy with other methods of locoregional anesthesia, which can potentially be a promising component of multimodal analgesia in colorectal oncosurgery.

Subject and Purpose. The improvement of the atmosphere brightness temperature measuring method at frequencies of about 100 GHz is considered. The possibilities of the atmospheric carbon monoxide (CO) remote sensing instrument, developed at Institute of Radio Astronomy of the National Academy of Sciences of Ukraine were analyzed. They show that the functional of this instrument can be significantly expanded. It can provide more operational information about the troposphere, useful for aeronomy and radio astronomy. The purpose of this work is to improve the atmosphere brightness temperature measuring method in relation to the existing instrument. We determine the possibility of the spectroradiometer broadband channel to measure the sky brightness temperature. Methods and Methodology. A detailed analysis of the existing installation for monitoring atmospheric CO was carried out and the measurement method was improved. It is shown that the broadband channel of this instrument, created as a service, can be used to measure atmosphere brightness temperature. Such measurement will allow creating a database of the zenith brightness temperature of the sky at frequencies of about 100 GHz. Results. It is possible to create the base data of the brightness temperature of the sky at frequencies about 100 GHz. In order to do this, it is necessary to make only some modifications of the instrument. The main thing is to make changes to the data capture file of the broadband channel and create a program to convert the data obtained from the instrument into brightness temperature values according to the specified formulas. All necessary formulas for presenting observational results in the form of brightness temperatures are given. Conclusions. It has been proven that there is a possibility to create the base date of the troposphere brightness temperature over Kharkiv (Ukraine) at the frequencies of the short-wave part of the mm range. The high stability of the radiometric part of the installation allows determining the brightness temperature of the sky with an accuracy that is sufficient for aeronomical, radioastronomical and radiophysical studies. On the basis of analytical calculations and experimental data, the necessary modifications for creating such a base data are defined.

Subject and Purpose. The current research projects in astrophysics are in need of high-sensitivity scientific instruments. The accuracy and sensitivity of observations can be enhanced through the use of large radio telescopes and other radio frequency systems, as well as via application of diagnostic instruments intended for exploring the radio propagation conditions along the signal paths. The paths traverse all of the Earth’s outer structural shells, from the atmosphere to remote layers of the magnetosphere. The present work is aimed at developing a highly sensitive off-set radiometer, operable in the frequency range of 20…25 GHz (1.35 cm waveband) and capable of monitoring the atmosphere above large centimeter-wavelength radio astronomical instruments, such as the recently developed radio telescope RT-32. The instruments like that should help making account of the integrated tropospheric absorption of the signals arriving from space radio sources and artificial objects in the near space. Methods and Methodology. The modern software that is used for simulating operation of microwave circuits, and the high quality models of microwave units available on the market, allow analyzing various circuit options, thus enabling a full-fledged development of such devices. As long as the intended implementations of the radiometer suggest the use of exclusively standard, commercially available and preferably off-the-shelf components, the development was based on analyzing the parameters and layout of such units. Results. An ultra-high sensitivity, broadband radiometer for the 1.35 cm range has been developed, which is intended for measuring integrated tropospheric absorption of the relevant radio waves. The calculated noise factor of the instrument is 2.3 dB. The extended bandwidth and high stability of the radiometer elements will provide for a sufficient sensitivity of the instrument as operated in conjunction with the receive system of the RT-32 radio telescope. Conclusions. The high-sensitivity, broadband radiometer that has been developed will provide for a much greater operative accuracy of radio astronomical and radio physical research projects. The radiometer, which has potential for further modernization, has been designed for use with the multi-band, high-tech radio telescope RT-32 in the interests of radio astronomy and space science, in particular for monitoring and forecasting the state of atmospheric and space weather systems.

Background. One of the most common methods of breast reconstruction after mastectomy for malignant tumors is reconstruction using an endoprosthesis. However, this technique is associated with the risk of developing periprosthetic complications. The classic solution to this problem is to remove the endoprosthesis, achieve complete remission of the infectious process and repeat the cycle of reconstructive measures. In this work we present a new approach to the treatment of periprosthetic complications.Aim. To evaluate the effectiveness of the controlled negative pressure system (CNP) in the treatment of periprosthetic breast complications.Materials and methods. From 2019 to 2023, the study included 23 patients who underwent combined/complex treatment for breast cancer, including reconstructive plastic surgery with the installation of endoprostheses, and 1 patient who underwent aesthetic surgery was included. All patients experienced various complications after the reconstructive stage: protrusion of the endoprosthesis, ischemia of the flap and/or local inflammation. To relieve the complications that arose, treatment was carried out using a flushing system and a CNP.Results. The duration of therapy with the sequential installation of a flushing system followed by replacement with a СNP averaged 15 days. In 7 cases out of 24, it was not possible to preserve or reinstall endoprostheses due to thinning of the musculocutaneous flap, resistance of the microflora to the treatment, or relapse of the infectious process. In 17 cases, no complications were recorded after re-installation of endoprostheses for 2 years. As a result of the work, in most cases, within one hospitalization, it was possible to preserve the skin sheath, achieve complete regression of complications and perform repeated reconstructive interventionConclusion. In most cases, the use of a CNP allows you to save the bed for the full installation of a new endoprosthesis. To do this, a number of conditions must be met: absence of microflora growth; presence of granulation after treatment; full thickness and integrity of the musculocutaneous flap. Systemic treatment and a history of radiation therapy are not a contraindication to retaining endoprostheses.

Subject and Purpose. A new method for detecting narrow band interferences is discussed, with the use of an example record of Jovian Io-C decametric radio storm as obtained with the UTR-2 array on April 10, 2020. We aimed at developing an efficient and simple algorithm based on a detailed analysis of the effect the radio interference environment and the frequency response of the telescope may have on the efficiency of the interference mitigation procedure. Methods and Methodology. The ‘orthogonal detection’ method proposed for identifying linear interference patterns in dynamic spectra of powerful radio sources has been adapted for application to narrow band interferences of various spectral widths and variable brightness, which often happen to be located close to (or intersect with) the signal of interest. In order to minimize the impact of the telescope’s frequency response, a discretized frequency-scanning technique is used, which permits a steady approximation of the averaged spectrum by low order polynomials, as well as removal of the frequency trend which hinders distinguishing between the low-level interference signals and those coming from the source. Results. An efficient approach to the problem of detecting long lasting, narrowband interference's in dynamical spectra (conditionally stationary interferences) is proposed. The algorithm has been tested on the example of a powerful storm of Jovian radio emission. The proposed technique can be especially useful in situations where the signal of interest overlaps with the interference in the time-frequency domain. Conclusions. The new approach to the problem of interference mitigation, based on the development of combined algorithms of signal separation in the time-frequency domain, has been shown to offer an effective method of signal processing. In contrast to the previously used methods based on calculation of statistical moments for amplitudes, the new approach allows avoiding use of the same statistical indicators for both interference detection and subsequent steps of data analysis intended for building physical models and interpreting the observational data.

This paper is an attempt of paying tribute to the memory of Leonid Mykolayovych Lytvynenko (LML), an outstanding Ukrainian scientist, Full Member of the National Academy of Sciences who worked most fruitfully in the fields of radio science and radio astronomy. Starting of 1985, Dr. Lytvynenko was, over a 30-plus years period, at the head of the Institute of Radio Astronomy, Acad. Sci. of the Ukrainian SSR (currently the National Academy of Sciences of Ukraine) that had been established owing to his vigorous and direct participation in the process. In 1996 LML promoted foundation of a new scientific journal, namely the "Radio Physics and Radio Astronomy", which he devotedly served for, in the Editor-in-Chief capacity, during the 25 years that followed. Dr. L. Lytvynenko was one of the brightest representatives of the school of theoretical radio physics that had developed within the O. Usikov Institute for Radio Physics and Electronics in Kharkiv and further flourished within the Institute of Radio Astronomy. He is known as the founder of a new branch of radio science, specifically theory of electromagnetic wave diffraction and propagation through composite and multilayered periodic structures.

The object of this study was to study the energy consumption of the on-board computer of the CubeSat nanosatellite. The subject of this study is the on-board computer energy consumption model and its energy efficiency optimization method. The purpose of this work was to develop a model of an on-board computer’s energy consumption and a method of optimizing its energy efficiency, followed by an experimental verification of the effectiveness of this method. Task: justify the feasibility of finding new methods for optimizing the energy efficiency of the on-board computer of the CubeSat nanosatellite; prepare for the experiment, namely, develop a model of the on-board computer's energy consumption and a method of optimizing its energy efficiency, develop an experiment plan, and conduct measurement methodology; conduct experimental research and present the main results of the experiment; provide a meaningful interpretation of the obtained experimental results; generalize the conclusions, formulate the advantages and disadvantages of this work, and propose directions for further research. Conclusions. The power consumption of the on-board computers of nanosatellites must be reduced by hardware and software means. This study examines the effectiveness of known energy-saving methods for the authors' "Falco SBC 1.0" computing platform. These methods include dynamic frequency scaling (DFS), the race-to-dark (RTD) algorithm, and the combined algorithm, which proved to be the most effective. The results were idealized because they did not consider OS overhead. The proposed methodology can be used to evaluate other platforms. The following studies will consider the following areas: energy consumption in various processor energy-saving modes, overhead costs of multi-threaded real-time operating systems, and power management of non-processor components. Solving these problems remains an important area of scientific research.

INTRODUCTION. In the Russian Federation, among all malignant diseases in the male population, gastric cancer ranks the 4th, in women – 5th place, and in terms of mortality in both sexes from malignant diseases – 2nd place. During surgical treatment of patients with gastric cancer, anemia is detected in more than 1/4 of patients, who significantly worsens the prognosis due to postoperative complications. Timely correction of anemia can reduce the risk of complications during surgical treatment and improve the course of the postoperative period.OBJECTIVE is to evaluate the effectiveness of correction of anemia in the preoperative period and the results of radical surgical treatment in patients with gastric cancerMETHODS AND MATERIALS. The article presents the analysis of medical records of 30 patients aged 56–75 years with a diagnosis of gastric cancer complicated by anemia (hemoglobin level < 80 g/l). All patients in the preoperative period for the correction of anemia were prescribed iron (III) hydroxide oligoisomaltose intravenously at the dose of 20 mg/kg 21 days before surgery, due to the detection of iron deficiency in them.RESULTS. The target blood hemoglobin level was more than 95 g/l. In the absence of the desired effect, erythrocyte transfusion was performed. The use of iron preparations made it possible to correct anemia in 14 (46.7 %) patients without resorting to transfusions, in 16 (53.3 %) patients, it was required to additionally transfuse 1 dose of erythrocytes, while earlier in the preoperative anemia was corrected using transfusions of 2–3 doses of erythrocytes. All patients underwent radical surgery with D2 lymph node dissection. Operations were accompanied by blood loss of 201.0±94.4 ml (120–475 ml). It was revealed that radical surgeries for gastric cancer in patients who received anemia correction in the preoperative period are accompanied by a low number of purulent-inflammatory (in 27.3 % of patients) and cardiovascular complications (in 20 % of patients).CONCLUSION. Correction of anemia is a mandatory part of therapy in the preoperative period and allows to perform a full range of radical surgical intervention, improve the safety of surgical treatment and improve the course of the postoperative period.

Summary: Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids. Single-nucleus RNA sequencing revealed that >80% of cells in thalamic organoids were glutamatergic neurons. When fused to form thalamocortical assembloids, thalamic and cortical organoids formed reciprocal long-range axonal projections and reciprocal synapses detectable by light and electron microscopy, respectively. Using whole-cell patch-clamp electrophysiology and two-photon imaging, we characterized glutamatergic synaptic transmission. Thalamocortical and corticothalamic synapses displayed short-term plasticity analogous to that in animal models. LTP and LTD were reliably induced at both synapses; however, their mechanisms differed from those previously described in rodents. Thus, thalamocortical assembloids provide a model system for exploring synaptic plasticity in human circuits.

Approaches to the diagnosis and treatment of abnormal uterine bleeding (AUB) are constantly updated due to the new results of clinical studies and in the process of revising international clinical guidelines. These updates need to be implemented in clinical practice. Therefore, on October 20, 2023, the II Ukrainian Forum of experts on AUB was held, the key provisions of which are outlined in this resolution. A new multi-level three-component classification system «HyPO-P + GAIN-FIT-PIE» developed by the International Federation of Gynecology and Obstetrics (FIGO) in 2022 was presented at the Forum. FIGO experts anatomically grouped the causes of ovulation disorders into 4 groups: I – hypothalamic, II – pituitary, III – ovarian, IV – polycystic ovary syndrome (first level HyPO-P). Also, this classification system includes the second level GAIN-FIT-PIE (genetic, autoimmune, iatrogenic, neoplastic; functional, infectious, inflammatory, traumatic, vascular; physiological, idiopathic, endocrine) and the third level with examples of specific conditions within the subgroups of the second level. Correct classification of ovulation disorders is important for the AUB diagnosis and management, since ovulation disorders are associated with disorders of the menstrual cycle characteristics, which leads to the development of functional AUB. In order to optimize the treatment of patients with AUB, the experts of the Forum developed an algorithm for the AUB management taking into account the individual approach and characteristics of the patient, which is based on the current FIGO classifications – PALM-COEIN (2018) and HyPO-P + GAIN-FIT-PIE (2022). According to this algorithm, patient management tactics depend on the type of disorders (structural, functional), the patient’s reproductive stage (adolescence, active reproductive age, perimenopause) and the need for contraception. Hormonal drugs (combined oral contraceptives and progestogens) are main direction of pharmacotherapy of functional AUB. The high efficiency of dydrogesterone among the progestogens has been proven, starting from the first cycle of therapy.

Objective of the study: to optimize non-hormonal therapy of menopausal syndrome in perimenopausal women. Materials and methods. 60 female patients aged 40–55 years with mild climacteric disorders were examined. Group I included 30 women who received a psychological consultation with recommendations on lifestyle and dietary correction, group II included 30 women who received Ayurvedic herbal drug Zintago 10 ml three times a day for three months a psychological consultation with recommendations on lifestyle and dietary correction. Patients were tested before treatment and 1 and 3 months after therapy according to the following scales: Spielberger-Hanin, PSM-25, MRS, and according to the SF-36 scale before treatment and 3 months after. Results. 1 (31.4 ± 1.9 points) and 3 (27.8 ± 2.3 points) months after treatment in the II group there was a significant (p < 0.05) decrease in the indicator of personal anxiety according to the Spielberger scale in comparison with the initial level. There was a decrease in the index of situational anxiety from 36.4 ± 1.9 points before treatment to 26.2 ± 1.7 points (p < 0.05) in group II after 3 months of therapy. There were no significant clinical results in group I. According to the PSM-25 scale, a clinically significant effect was in both groups after 3 months of treatment, but in group II it was achieved faster, after only one month – from 154.7 ± 9.6 to 122.6 ± 8.3 points (p < 0.05). According to the SF-36 scale, a significant improvement in the quality of life in group I after 3 months of therapy was only in the indicators of social functioning (from 54.6 ± 7.1 points before treatment to 73.8 ± 5.8 after 3 months of therapy, p

On November 23, 2023, the V International Forum of Experts on Menopausal Hormone Therapy (MHT) was held. The Expert Council’s working group included leading experts in the field of endocrine gynaecology and related areas from Azerbaijan, Armenia, Georgia, Kazakhstan, Moldova, Uzbekistan, and Ukraine. The Forum experts noted the importance of dialogue and understanding between doctor and patient, the need for interdisciplinary integration between doctors of those specialties that deal with women’s health issues. Close cooperation with related specialists who provide care to women is necessary, as they are often the ones who encounter the first manifestations of menopause in patients and can therefore refer them to an obstetrician-gynaecologist in a timely manner. The experts reviewed the issue of cardiovascular risk and MHT and determined the following benefit/risk ratio for the cardiovascular effects of MHT: • MHT is not recommended for women at high cardiovascular risk or with previous cardiovascular disease; • MHT may reduce the risk of CVD-related all-cause death in women < 60 years of age and with menopause of up to 10 years; • timely initiation of MHT (in women under 60 years of age or within 10 years of menopause) has the greatest cardiovascular health benefits. The forum updated the Algorithm for prescribing MHT in premature and early menopause and addressed the management of women with polycystic ovary syndrome in menopause. Since the majority of women with this syndrome are overweight and obese, they should use the most metabolically neutral drugs, i.e. those containing didrogesterone or progesterone, for MHT. MHT with didrogesterone has a favourable safety profile in relation to the most common risks of MHT: does not increase the risk of breast cancer and venous thromboembolism, has a favourable safety profile with respect to the endometrium, and does not affect metabolism.

The human gut microbiome is a complex biological system whose functions and metabolic processes are the result of multiple interactions between microbial groups. Within these groups and between them, specific relationships are formed that allow duplicating and reserving individual functions, systematically managing their implementation and, in general, ensuring the reliable functioning of the entire microbiome, including in the interests of the host macroorganism. The functional and metabolic microbial nucleus plays a crucial role in the functioning of microbiocenosis as a whole system. Due to its natural properties, the modern probiotic Lactobacillus paracasei DG performs the function of a conductor of the microbiocenosis of the gastrointestinal tract, regulating the metabolic activity of the intestinal normoflora, realizing immunotropic effects due to the production of exopolysaccharides, including previously unknown exopolysaccharides b, maintaining the integrity of the intestinal epithelial barrier, exerting antiviral action, exerting distant effects against microbiocenoses of other ecological niches.

Subject and Purpose. The writers aim at developing and testing a new method of interference mitigation, proceeding from the example of radio emissions from Jupiter. Its effectiveness is compared with the results of other workers, equally relating to the case of a significant overlapping, within the time-frequency window under analysis, of the areas occupied by the useful signal and the interference. Methods and Methodology. The analysis has revealed several fundamental limitations associated with the use of standard statistical methods for identifying sources of interference. A new approach is proposed that allows separating useful signals from interference in the time-frequency plane. It is based on the idea of transferring the statistical analysis from the space of signal amplitudes to such of linear patterns which are formed by maximal readings while the spectrograms are being scanned in time, frequency or otherwise. Results. Methods of statistical data processing have been suggested which allow analysis of signals of a variety of power levels against the background of interference of comparable intensity. This enables a detailed analysis of the time-frequency patterns demonstrated by signals with a broad range of parameter variations. The algorithms developed demonstrate stability against changes in the interference background conditions that may be caused either by human activity or by natural factors, such as, e.g. ionospheric perturbations, changes in the fronted frequency response of a receiver resulting from a changed antenna beam orientation, or else from Faraday’s polarization plane rotation in the radio emission being received. Conclusions. The necessity of creating new interference mitigation techniques is stipulated both by worsening of the general level of interference at radio frequencies, and by the growth of complexity in the sporadically emerging time-frequency patterns that result from the improved time and frequency resolutions in the course of signal reception. A significant progress has been achieved, owing exclusively to the fundamental modifications of the signal processing algorithms that are based on varying the direction of analysis in the time-frequency plane. Conclusions. The necessity of creating new interference mitigation techniques is stipulated both by worsening of the general level of interference at radio frequencies, and by the growth of complexity in the sporadically emerging time-frequency patterns that result from the improved time and frequency resolutions in the course of signal reception. A significant progress has been achieved, owing exclusively to the fundamental modifications of the signal processing algorithms that are based on varying the direction of analysis in the time-frequency plane.

This article delves into the profound impact of postmodernism on the trajectory and evolution of future public administration. The 20th century witnessed radical changes in worldview, marking the transition from modernity to postmodernity. The basic principles of postmodernism, encompassing deconstruction, fragmentation, future shock, and cultural relativism, have instigated a paradigm shift challenging traditional administrative frameworks (M. Foucault, J.-F. Lyotard, A. Toffler, etc.). The article explores how these postmodern tenets influence administrative practices, power structures, and the very nature of governance. Postmodernity is characterized by a unique attitude towards truth, acknowledging its relativity, and by decentration, the absence of a single center, replaced by multipolarity and globalization. “Post-truth” replaces truth, posing new challenges to the future of public administration. The public administration of the future will be shaped by existing trends, including Public-Private Partnerships (PPP), Non-Governmental Organizations (NGOs), Corporate Social Responsibility (CSR), etc. It will also depend on modern technologies such as artificial intelligence, blockchain, data analysis, and data-driven decision-making, as underscored by the need for digitalization in response to the pandemic (according to EIB). However, alongside advantages, there are also challenges, such as issues of liability in the use of AI for future public administration. These risks can be mitigated through collaborative and participatory governance models, adaptive leadership, an emphasis on inclusivity, diversity, and social equity, addressing environmental concerns, advanced training courses, and other strategic measures.

Four new glycosides of polyhydroxysteroids, ceramasterosides A, B, D, and E (1–4), and two previously known compounds, ceramasteroside C1 (5) and attenuatoside B-I (6), were isolated from an extract of a deep-sea sea star species, the orange cookie star Ceramaster patagonicus. The structures of 1–4 were elucidated by the extensive NMR and ESIMS methods. Steroid monoglycosides 1 and 2 had a common 3β,6α,8,15β,16β-pentahydroxysteroid nucleus and a C–29 oxidized stigmastane side chain and differed from each other only in monosaccharide residues. Ceramasteroside A (1) contained 3-O-methyl-4-O-sulfated β-D-xylopyranose, while ceramasteroside B (2) had 3-O-methyl-4-O-sulfated β-D-glucopyranose, recorded from starfish-derived steroid glycosides for the first time. Their biological activity was studied using a model of lipopolysaccharide-induced (LPS) inflammation in a SIM-A9 murine microglial cell line. During the LPS-induced activation of microglial cells, 1, 3, and 5, at a non-toxic concentration of 1 µM, showed the highest efficiency in reducing the production of intracellular NO, while 4 proved to be most efficient in reducing the extracellular nitrite production. All the test compounds reduced the LPS-induced malondialdehyde (MDA) production. The in vitro experiments have demonstrated, for the first time, the antioxidant activity of the compounds under study.

Introduction. The absence of specific clinical symptoms in the early stages of colorectal cancer development leads to the fact that a quarter of patients who seek help for the first time have a metastatic stage of the disease. For the timely detection of pre-tumor disorders or hidden foci of malignancy, the possibilities of modern molecular biological technologies are being actively studied today.Aim. To develop a method for diagnosing tumor diseases of the colon based on molecular genetic analysis of morphologically unchanged intestinal epithelium distant from the focus of the tumor lesion.Materials and methods. We examined the matrix RNA (mRNA) expression profile of 63 candidate genes potentially associated with the pathogenesis of neoplastic changes in rectal mucosal samples. Samples were obtained during prophylactic and/or diagnostic video colonoscopy of 122 patients, 41 of whom had no history of breast cancer (“Normal”), 32 patients were diagnosed with breast cancer polyps (“Polyposis”) and 49 patients were diagnosed with breast cancer (“colorectal cancer”). mRNA expression was assessed by reverse transcription polymerase chain reaction.Results. Using the discriminant analysis method, it was established that the cellular material of scrapings from the rectum in the “colorectal cancer” group reliably, with a classification accuracy above 96 %, differs in expression phenotype from the “Normal” and “Polyposis” groups.Conclusion. The data obtained are a prerequisite for the development of a minimally invasive diagnostic method that can be used as part of an outpatient examination to assess the risk of colon tumor disease.

Background: Differences in the embryonic development of the colonic mucosa determine the physiological embryonic-anatomical asymmetry of its structure and can manifest themselves via different molecular phenotypes (expression profiles) of the colon segments. These molecular characteristics are hypothesized to determine differences in the carcinogenesis mechanisms and influence the prognosis of right- or left-sided colorectal cancer (CRC). Studies of the tumors molecular phenotypes depending on their localization may be of interest for assessment of the prognosis and choice of treatment for CRC. Aim: To perform comparative analysis of molecular phenotypes of the normal colonic mucosa and adenocarcinoma CRC tissues depending on the natural embryonic anatomic asymmetry of the colon. Materials and methods: We performed a retrospective study of molecular phenotypes (mRNA expression of 61 genes) from different embryonic-anatomical parts of healthy colon and CRC. The normal group included 254 samples of mucosa from three different parts of the colon from 74 healthy donors who had no cancer and no organic abnormalities of the colon, including 90 samples from the right colon, 116 from the left colon, and 48 from the rectum. The CRC group consisted of 154 samples of localized stage T1–4N0–2M0 adenocarcinoma from 154 patients who had not received neoadjuvant radio- and chemotherapy, including 40 samples from the right colon, 54 from the left colon, and 60 from the rectum. The relative mRNA abundance of 61 genes was assessed by reverse-transcriptase polymerase chain reaction. In both groups, the resulting expression phenotypes were compared between the anatomical parts of the colon. Statistical management of the data included the discriminant analysis with stepwise inclusion of variables. Results: Based on the assessment of the mRNA level of the studied genes, a discriminant model was built that allows for classification of the normal group samples according to their anatomic origin in the colon with an accuracy of 95.8%. The most significant (p 0.05) for classification are the following 19 genes: CCND1, SCUBE2, TERT, BAG1, NDRG, IL1b, IL2Ra, IL7, ESR1, TGFb, IGF1, MMP9, MMP11, PAPPA, CD45, CD69, TLR2, TLR4, LIFR. The discriminant model built for the CRC group included 27 genes and made it possible to differentiate samples from three parts of colon with an accuracy of 75.2%. A statistically significant (p 0.05) contribution to the samples differentiation by the discriminant model was made by the COX-2, BIRC5, LIFR, TPA, IL1b, MMP11, MMP7, and P16INK4A genes. When combining samples from the two groups into one model in accordance with their embryonic-anatomical origin, there was a clear separation of tumor tissue samples and healthy colonic mucosa in the discriminant function space. Conclusion: The analysis of CRC gene expression profiles using the discriminant model showed that genetic changes in the colonic mucosa in CRC flatten the molecular phenotypic boundaries of the embryonic-anatomical parts. These changes are specific to CRC, forming a particular “pathological” molecular phenotype.

Endometriosis affects 10% of all women of reproductive age, i.e. 190 million patients. Ukraine currently does not gather statistics on the incidence of endometriosis, but, at a rough estimate, this number is approximately 280 thousand women and the real number may be higher. Endometriosis has known significant social, medical and economic impact. Therefore, Ukrainian leading specialists in obstetrics and gynecology focus on new treatments for endometriosis, given current scientific data and the needs of patients. The given resolution and algorithms for treatment for endometriosis are the common stand of leading specialists in gynecology in our country and were developed on the basis of modern domestic and foreign data and current clinical guidelines. This resolution aims to improve clinical approaches to the routine practice of treatment for endometriosis. The constant increase in the incidence of endometriosis and its management characteristics allows to conduct an extensive study of the effectiveness and safety profile of various progestogens. In recent years, a number of further evidence have appeared regarding dydrogesterone treatment for endometriosis. New data on the effectiveness of dydrogesterone offer another hormone-based treatment for endometriosis, which is extremely important given the need for long-term and individualized treatment for endometriosis. The Europ ean Society of Human Reproduction and Embryology (ESHRE) states that the degree of pain relief in endometriosis is the same for all hormone-based treatments, but the safety and tolerability profiles of different medicinal products differ, which must be considered. According to the obtained data on the effectiveness and metabolic safety profile of various progestogens and during the discussion, algorithms for dydrogesterone-based treatment for endometriosis were proposed.

Original citation: J Clin Invest. 2023;133(14):e160309. https://doi.org/10.1172/JCI160309. Citation for this erratum: J Clin Invest. 2024;134(8):e181331. https://doi.org/10.1172/JCI181331. During the preparation of this manuscript, a text error was introduced during copyediting by [...]

Summary: Meaningful auditory memories are formed in adults when acoustic information is delivered to the auditory cortex during heightened states of attention, vigilance, or alertness, as mediated by neuromodulatory circuits. Here, we identify that, in awake mice, acoustic stimulation triggers auditory thalamocortical projections to release adenosine, which prevents cortical plasticity (i.e., selective expansion of neural representation of behaviorally relevant acoustic stimuli) and perceptual learning (i.e., experience-dependent improvement in frequency discrimination ability). This sound-evoked adenosine release (SEAR) becomes reduced within seconds when acoustic stimuli are tightly paired with the activation of neuromodulatory (cholinergic or dopaminergic) circuits or periods of attentive wakefulness. If thalamic adenosine production is enhanced, then SEAR elevates further, the neuromodulatory circuits are unable to sufficiently reduce SEAR, and associative cortical plasticity and perceptual learning are blocked. This suggests that transient low-adenosine periods triggered by neuromodulatory circuits permit associative cortical plasticity and auditory perceptual learning in adults to occur.

With the successes achieved in the treatment of gastric cancer, the problem of combined neoadjuvant therapy for stenosing tumors remains unresolved. To find the optimal method of treatment, we carried out the analysis of modern domestic and foreign literature. The standard methods are the implantation of a self- expandable stent, argon-plasma coagulation, the implantation of a nasointestinal feeding tube, the formation of gastroenteroanastomoses, gastro/enterostomy. However, there is no evidence base about the effectiveness and safety of the above methods when applying them as part of the combined treatment of potentially operable gastric cancer. The method of endoscopic photodynamic therapy seems promising.

Introduction. Perioperative FLOT chemotherapy has improved prognosis in patients with locally advanced resectable gastric cancer (GC). However, in 80 % of cases, the tumor is resistant to the therapy, resulting in unnecessary toxicity and delayed surgical treatment.Aim. Evaluation of clinico-morphological patterns of microsatellite instability, HER2 gene amplification, changes in gene copy number and their relationship with the response to perioperative FLOT chemotherapy in patients with locally advanced resectable GC.Materials and methods. The retrospective study included 185 patients. All tumor samples were assessed for HER2 and microsatellite instability status. Among all cases there were 45 patients with locally advanced T2–4N1–2 M0 GC, who underwent a total or subtotal gastrectomy with D2 lymphadenectomy and perioperative chemotherapy with FLOT. Microsatellite instability detection was performed using fragment analysis, HER2 gene amplification testing – fluorescent in situ hybridization. Also 19 patients were tested for copy number changes of the FGFR1, FGFR2, KRAS, MET, EGFR, CCND1, MYC genes using Multiplex ligation-dependent probe amplification. The endpoints were progression-free survival and objective response rate.Results. Microsatellite instability was detected in 4.8 % (9/185) of GC cases. Microsatellite instability was associated with advanced age (p = 0.005), low grade of differentiation (p = 0.011), presence of tumor-infiltrating lymphocytes (p = 0.0004), and high preoperative CA 72–4 levels (p = 0.025). Prevalence of HER2 amplification was 7.5 % (14/185). It was associated with low grade of differentiation (p = 0.048) and metastasis in regional lymph nodes (p = 0.037). PFS in patients with HER2-positive (HER2 – human epidermal growth factor receptor 2) GC treated with perioperative FLOT chemotherapy (4/45) was significantly lower than in patients with HER2-negative GC: the median was 156 and 317 days, respectively (hazard ratio 0.49; 95 % confidence interval 0.16–1.47; p = 0.0006). There was no correlation between the presence of the alteration and ORR (p = 1.0). Progression-free survival in GC patients with KRAS amplification (3/19) was significantly lower comparing with patients without it: the median was 98 and 327 days, respectively (hazard ratio 0.29; 95 % confidence interval 0.07–1.19; p 0.05).Conclusion. The presence of HER2 and KRAS amplification have been shown as promising predictive markers of the treatment failure in patients treated with perioperative FLOT chemotherapy for locally advanced resectable GC.

Background: Drosophila melanogaster provides a powerful platform to study the physiology and genetics of aging, i.e., the mechanisms underpinnings healthy aging, age-associated disorders, and acceleration of the aging process under adverse environmental conditions. Here, we tested the responses of daily rhythms to age-accelerated factors in two wild-type laboratory-adapted strains, Canton-S and Harwich. Methods: On the example of the 24 h patterns of locomotor activity and sleep, we documented the responses of these two strains to such factors as aging, high temperature, carbohydrate diet, and diet with different doses of caffeine-benzoate sodium. Results: The strains demonstrated differential responses to these factors. Moreover, compared to Canton-S, Harwich showed a reduced locomotor activity, larger amount of sleep, faster rate of development, smaller body weight, lower concentrations of main sugars, lower fecundity, and shorter lifespan. Conclusions: It might be recommended to use at least two strains, one with a relatively fast and another with a relatively slow aging process, for the experimental elaboration of relationships between genes, environment, behavior, physiology, and health.

Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics, remains relevant. The aim of this study is to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae as a personalized functional food product (PFFP) in the complex therapy of colorectal cancer (CRC) in the early postoperative period. A total of 36 patients diagnosed with CRC were enrolled in the study. Study group A comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group C included 12 CRC patients without autoprobiotic therapy. Prior to surgery and between days 14 and 16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complaints analysis, examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), and analysis of interleukins in the serum. Results: The use of autoprobiotics led to a decrease in dyspeptic complaints after surgery. It was also associated with the absence of postoperative complications, did not cause any side effects, and led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra and Fusobacterium nucleatum, and a decrease in the quantitative content of Clostridium perfringens and Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The introduction of autoprobiotics in the postoperative period is a highly effective and safe approach in the complex treatment of CRC. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine, and neural systems.

New imidazolidine-2,4,5-triones with norabietic, nordehydroabietic, and adamantane substituents were synthesized by reacting oxalyl chloride and the corresponding ureas, providing good yields. Bioisosteric replacement of the ureide group with a parabanic acid fragment made it possible to increase the solubility of compounds and conduct biological studies. The compounds inhibit the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 in submicromolar concentrations. Cytotoxic concentrations were also studied on the glioblastoma cell line SNB19.

Objective: to evaluate the clinical tolerability, effectiveness and stability of the therapeutic result when using different regimens for the treatment of recurrent bacterial vaginosis (BV) in women of reproductive age. Materials and methods. 105 women of reproductive age with diagnosed recurrent symptomatic BV participated in the study. The participants were randomized into three comparable groups of 35 women each. A ten-day primary decontamination of the vaginal tract was carried out in all groups: intravaginal administration of the drug Tergynan for group 1 and Femiril suppositories in groups 2 and 3. After the initial treatment patients of group 3 received the vaginal probiotic suppositories Alactel Femi for 15 days, after that they used it twice a week No. 10. The effectiveness of BV therapy was evaluated immediately after the antibacterial course and after a 6-month follow-up period based on the results of clinical examination and determination of vaginal pH. Results. Subjective and objective signs of bacterial infection were not detected in all participants after the course of vaginal decontamination. The pH of vaginal secretion was within the normal range and did not differ statistically between the groups. After 6 month, according to the results of a gynecological examination and pH test, one recurrence of BV was confirmed in group 1 and 2. The patients of group 3 had no complaints about manifestations of reinfection, which, in combination with the data of pH-metry, allowed confirming the absence of BV recurrences in them. Additional use of a probiotic in a complex with lactic acid in group 3 was associated with a stable normalization of the acid-alkaline balance of the vaginal secretion: 4.43 ± 0.12 and 4.39 ± 0.14 in groups 1 and 2, respectively, against 4.02 ± 0 ,12 in the 3rd group (p < 0.05). Conclusions. Obtained results indicate a more stable anti-relapse effectiveness and safety of the local use of Femiril, followed by the restoration of the physiological parameters of the vaginal biotope with a complex of probiotics and lactic acid in the Alactel femi. The effectiveness of this approach consists in combining the antibacterial effect of phytoextracts with the successive restoration of vaginal immunity and metabolism through persistent colonization of the mucous membrane with living lactobacilli of eubiotic origin.

Background: Activity plays a very important role in keeping bodies strong and healthy, slowing senescence, and decreasing morbidity and mortality. Drosophila models of evolution under various selective pressures can be used to examine whether increased activity and decreased sleep duration are associated with the adaptation of this nonhuman species to longer or harder lives. Methods: For several years, descendants of wild flies were reared in a laboratory without and with selection pressure. To maintain the “salt” and “starch” strains, flies from the wild population (called “control”) were reared on two adverse food substrates. The “long-lived” strain was maintained through artificial selection for late reproduction. The 24 h patterns of locomotor activity and sleep in flies from the selected and unselected strains (902 flies in total) were studied in constant darkness for at least, 5 days. Results: Compared to the control flies, flies from the selected strains demonstrated enhanced locomotor activity and reduced sleep duration. The most profound increase in locomotor activity was observed in flies from the starch (short-lived) strain. Additionally, the selection changed the 24 h patterns of locomotor activity and sleep. For instance, the morning and evening peaks of locomotor activity were advanced and delayed, respectively, in flies from the long-lived strain. Conclusion: Flies become more active and sleep less in response to various selection pressures. These beneficial changes in trait values might be relevant to trade-offs among fitness-related traits, such as body weight, fecundity, and longevity.

This work is devoted to the problem of infrared monitoring of the metal temperature of the surface of superheater pipes. Monitoring is implemented on the basis of a thermal imager cameras that performs contactless monitoring of the surface temperature of the pipes of the wall superheater. The results of modeling the temperature distribution along the pipe of a wall-mounted superheater in the presence of contamination and without are presented. The calculation of the number of thermal imager cameras required for infrared monitoring is performed. The developed design solutions for the installation site of thermal imager cameras on a TP-82 type boiler have been confirmed experimentally.

Abstract Background Lake Baikal, the world’s deepest freshwater lake, contains important numbers of Candidatus Patescibacteria (formerly CPR) in its deepest reaches. However, previously obtained CPR metagenome-assembled genomes recruited very poorly indicating the potential of other groups being present. Here, we have applied for the first time a long-read (PacBio CCS) metagenomic approach to analyze in depth the Ca. Patescibacteria living in the bathypelagic water column of Lake Baikal at 1600 m. Results The retrieval of nearly complete 16S rRNA genes before assembly has allowed us to detect the presence of a novel and a likely endemic group of Ca. Patescibacteria inhabiting bathypelagic Lake Baikal. This novel group seems to possess extremely high intra-clade diversity, precluding complete genomes' assembly. However, read binning and scaffolding indicate that these microbes are similar to other Ca. Patescibacteria (i.e. parasites or symbionts), although they seem to carry more anabolic pathways, likely reflecting the extremely oligotrophic habitat they inhabit. The novel bins have not been found anywhere, but one of the groups appears in small amounts in an oligotrophic and deep alpine Lake Thun. We propose this novel group be named Baikalibacteria. Conclusion The recovery of 16S rRNA genes via long-read metagenomics plus the use of long-read binning to uncover highly diverse “hidden” groups of prokaryotes are key strategies to move forward in ecogenomic microbiology. The novel group possesses enormous intraclade diversity akin to what happens with Ca. Patescibacteria at the interclade level, which is remarkable in an environment that has changed little in the last 25 million years.

Clostridium difficile was reclassified in 2016 under a new name of Clostridioides difficile. In 2021 to 2022, some changes were implemented into the main clinical guidelines on the diagnosis and treatment of infections caused by this pathogen. A two-step algorithm based on identification of C. difficile and then its toxins is still recommended for the diagnosis. The treatment regimens for the first episode and relapses of C. difficile-associated infection are based on metronidazole, vancomycin and fidaxomycin. Additional effectiveness of therapy has been associated with the use of microbiocenosis-oriented technologies aimed at restoration of the colon microbiota. In the Russian Federation, all widely applied diagnostic methods are available and all recommended antimicrobials, except fidaxomycin, as well as bezlotoxumab and fecal microbiota transplantation.