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Introduction. Surgical intervention remains the main method for treatment of the oral mucosa cancer. The generally accepted standard of the resection boundary that provides optimal local control is 5 mm. Adequate boundaries of indentation and choice of the reconstruction method are important issues facing specialists in head and neck tumors. Aim. To evaluate parameters of the resection edge in the surgical treatment of malignant neoplasms of the oral mucosa depending on the method of eliminating of the post-resection defect and its effect on the frequency of local relapse. Materials and methods. A retrospective analysis included 168 primary patients (50 % men and 50 % women) who received surgical treatment in the head and neck tumor department of the Republican Clinical Oncology Dispensary of the ministry of Health of the Republic of Bashkortostan (ufa) from 2019 to 2023. The median age of patients was 63 years (interquartile range (IQR) 55–69 years). most often, the primary tumor was located in the tongue – in 59.5 % (100/168) of cases. According to the method of post-resection defect removal, the patients were divided into 3 groups. In group 1, reconstruction was performed with local tissues (n = 71), in group 2 – with pedicle flaps (n = 41), and in group 3 – with revascularized flaps (n = 56). The median follow-up period was 18 months (IQR 8–28 months). Results. Resection boundaries in group 1 were 7.0 mm (IQR 5.0–12.5 mm), in group 2 – 6.5 mm (IQR 5–13 mm), and in group 3 – 12.5 mm (IQR 7.5–15.0 mm). The overall frequency of near/positive resection boundaries was 14.8 % (25/168). In group 1, it was 15.5 % (11/71), in group 2 – 19.5 % (8/41), in group 3 – 10.7 % (6/56). According to the analysis, relapse of the disease after radical treatment was noted in 32 % (55/168) of patients, of which 14.8 % (25/168) had a local relapse, 12.5 % (21/168) had a regional relapse, and 5.4 % (9/168) developed distant metastases. The frequency of local relapse in group 1 was 18.3 % (13/71), in group 2 – 23.8 % (10/41), in group 3 – 5.5 % (3/56). According to the analysis data, statistically significant differences in the boundary of indentation in the groups were revealed depending on the reconstruction method (p = 0.005). Conclusion. Based on the results of the present retrospective analysis, the choice of reconstruction method affects the resection boundary in real clinical practice. Limitations in the surgical indentation that surgeon faces when choosing a method for eliminating a post-resection defect are demonstrated.

Introduction. Th e growing incidence of oropharyngeal cancer is driven by an increase in frequency of HPV-associated oropharyngeal cancer. Th e morbidity pattern of oropharyngeal cancer is area-specific.Aim. To analyze the oropharyngeal cancer diagnosis and treatment in the Republic of Bashkortostan for 2020.Materials and methods. Th e authors carried out a 2020 retrospective analysis of the diagnosis and treatment results of patients with oropharyngeal cancer. 79 patients were identified with this diagnosis. 84.8% (67/79) among them were males and 15.2% females (12/79). Th e mean age of the patients was 59.1 years. Th e site of primary tumor was on the oropharynx lateral wall in 37.8% cases (30/79), in the tongue root area — 24.1% (19/79), in the tonsils area — 17.7% (14/79), on the soft palate — 16.5% (13/79), on the oropharynx posterior wall — 3.8% (3/79).Results. Examination of tumor morphological types revealed squamous cell carcinoma (SCC) with various degrees of differentiation in 92.4% cases (73/79), adenocarcinoma of minor salivary gland — in 6.3% (5/79) and sarcoma in 1.2% (1/79). 57.5% of 73 patients with SCC (42/73) underwent protein (p16) immunohistochemistry, while 42.5% of the patients (31/73) did not. According to a surrogate marker for HPV, the following results were obtained for 42 patients: p16-positive in 23.8% cases (10/42), p16-negative in 76.2% (32/42). Stage distribution according to TNM-7: stage I — 11.4% (9/79), stage II — 17.7% (14/79), stage III — 36.7% (29/79), stage IV — 46.8% (37/79). Stage distribution according to TNM-8 (patients who underwent p16 immunohistochemistry): stage I — 11.9% (5/42), stage II — 23.8% (10/42), stage III — 19% (8/42), stage IV — 45.2% (19/42). In 2020, 72% of patients (57/79) received definitive treatment, 10.1% (8/79) — palliative care, 15.2% (12/79) — supportive care, and 2.5% (2/79) refused medical treatment.Discussion. Th e various types of radiation therapy were used as the main defi nitive treatment for patients with oropharyngeal cancer in 69.2% cases (45/65). Only 18.5% of patients (12/65) underwent surgery, 58.3% of which (7/12) received post-surgery radiation therapy.Conclusion. 57.5% of patients (42/73) were detected with HPV status, 23.8% (10/42) revealed surrogate markers for HPV association. 69.2% of patients (45/65) received radiation therapy as the definitive treatment. 18.5% of patients (12/65) underwent surgery, 58.3% of which (7/12) received postsurgery radiation therapy.

Introduction. Basal cell carcinoma is the most common type of non-melanocytic malignant tumors of the skin. The main treatment methods for this pathology are local methods such as surgery and radiation. In rare cases, basal cell carcinoma can become locally advanced and / or metastatic.Aim. To demonstrate the possibility of reconstructive surgery for large defects after removal of locally advanced tumors of the face and describe a rare case of basal cell carcinoma metastasis into the regional lymph nodes.Clinical case. The article presents a clinical case of treatment of basal cell skin cancer with metastases into the regional lymph nodes. According to the patient, tumor on the skin of the left cheekbone area first appeared in 2007. The patient did not seek medical help. In 2017, the tumor was resected at the local medical facility. In 2018, the patient noted repeat tumor growth. In November of 2021, when the patient first consulted at the Republican Clinical Oncological Dispensary of the ministry of Health of the Bashkortostan Republic, the tumor was 7 × 5 cm. Invasion depth was up to 1.5 cm, infiltration into the temporal and mastication muscles and destruction of the zygomatic bone were observed. On 18.11.2021 at Republican Clinical Oncological Dispensary of the ministry of Health of the Bashkortostan Republic, wide resection of the skin tumor with resection of the zygomatic arch, parotidectomy on the left with defect removal using anterolateral thigh flap was performed. per histological examination, basal cell carcinoma with lymphovascular and perineural invasion and advancement into the masticator muscle and zygomatic bone was diagnosed, as well as carcinoma metastases in 2 lymph nodes with advancement beyond the capsule.Conclusion. Implementation of revascularization flaps significantly widens choices for surgical treatment of this patient group in a regional oncological dispensary and gives satisfactory esthetic results due to removal of large defects after surgical intervention.

The study objective is to evaluate the possibility of determining the signaling lymph node (SLN) in oral cancer (T1–2N0M0) with lymphoscintigraphic method.Materials and methods. In 2016–2018, SLNs were determined for 23 patients with oral cancer (cT1–2N0M0): for 15 patients with cancer of the tongue, for 8 patients with cancer of the floor of the mouth cavity. SLNs were determined by radiolymphoscintigraphic method by peritumoral administration of Tehnefit radiopharmaceutical in a dose of 40 to 80 MBq, depending on the timing of the signal lymph node biopsy. Visualization of the signaling lymph node was carried out by planar scintigraphy and single-photon emission computed tomography combined with x-ray computed tomography. Intraoperative SLN was detected using intraoperative radiometry using a gamma probe.Results. In cancer of the floor of the mouth, SLNs were identified only in 2 (25 %) of 8 cases. In cancer of the language, SLN were identified in 14 (93.3 %) of 15 cases. In total, SLNs were diagnosed with cancer in 17 patients. In 4 (26.7 %) of 15 patients, cancer metastases in SLNs were identified. False negative results were obtained in 6.7 % of cases.Conclusion. A biopsy of the SLN by the lymphoscintigraphic method has a high diagnostic value for staging the early stages of cancer of the tongue.

The problem of tuberculosis in penitentiary institutions is still relevant today. While the number of prisoners reduced by 3.7% in 2015 compared to 2014, TB incidence among persons entering preliminary detention units remains the same. However, in prisons incidence of tuberculosis and mortality has declined by 10% and 35.2%, respectively, over the same period. In order to optimize approaches to the prevention of tuberculosis in penitentiary institutions, we examined the prevalence of Mycobacterium tuberculosis infection and the incidence of mental stress among inmates on their admission to an Altai territory detention unit. Based on the study results, we suggest measures for TB prevention in prisons.

The focus of this article is the problem of choice of methodological tools for research conducted in the field of system of internal financial control of companies. The authors reveal the limitations of the dominant methodology for a systematic approach here, and as an alternative to propose to use the methodology of the system analysis. This assesses the theoretical and practical consequences caused by the use of system analysis methodology.

In the millennium that is coming to an end, the world has approached a certain cardinal line. The dominant civilization has reached the peak of power, becoming global, but it is not experiencing a real catastrophe. The Christian culture, the living source of this "supercivilization", consistently gives way to new realities, other forms of organization of consciousness, although

Recent discoveries related to the habitability and astrobiological relevance of the outer Solar System have expanded our understanding of where and how life may have originated. As a result, the Icy Worlds of the outer Solar System have become among the highest priority targets for future spacecraft missions dedicated to astrobiology-focused and/or direct life detection objectives. This, in turn, has led to a renewed interest in planetary protection concerns and policies for the exploration of these worlds and has been a topic of discussion within the COSPAR (Committee on Space Research) Panel on Planetary Protection. This paper summarizes the results of those discussions, reviewing the current knowledge and the history of planetary protection considerations for Icy Worlds as well as suggesting ways forward. Based on those discussions, we therefore suggest to (1) Establish a new definition for Icy Worlds for Planetary Protection that captures the outer Solar System moons and dwarf planets like Pluto, but excludes more primitive bodies such as comets, centaurs, and asteroids: Icy Worlds in our Solar System are defined as all bodies with an outermost layer that is believed to be greater than 50 % water ice by volume and have enough mass to assume a nearly round shape. (2) Establish indices for the lower limits of Earth life with regards to water activity (LLAw) and temperature (LLT) and apply them into all areas of the COSPAR Planetary Protection Policy. These values are currently set at 0.5 and -28 °C and were originally established for defining Mars Special Regions; (3) Establish LLT as a parameter to assign categorization for Icy Worlds missions. The suggested categorization will have a 1000-year period of biological exploration, to be applied to all Icy Worlds and not just Europa and Enceladus as is currently the case. (4) Have all missions consider the possibility of impact. Transient thermal anomalies caused by impact would be acceptable so long as there is less than 10 -4 probability of a single microbe reaching deeper environments where temperature is >LLT in the period of biological exploration. (5) Restructure or remove Category II* from the policy as it becomes largely redundant with this new approach, (6) Establish that any sample return from an Icy World should be Category V restricted Earth return., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

X-ray structures of two enzymes in the sterol/isoprenoid biosynthesis pathway have been determined in a structural genomics pilot study. Mevalonate-5-diphosphate decarboxylase (MDD) is a single-domain alpha/beta protein that catalyzes the last of three sequential ATP-dependent reactions which convert mevalonate to isopentenyl diphosphate. Isopentenyl disphosphate isomerase (IDI) is an alpha/beta metalloenzyme that catalyzes interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, which condense in the next step toward synthesis of sterols and a host of natural products. Homology modeling of related proteins and comparisons of the MDD and IDI structures with two other experimentally determined structures have shown that MDD is a member of the GHMP superfamily of small-molecule kinases and IDI is similar to the nudix hydrolases, which act on nucleotide diphosphatecontaining substrates. Structural models were produced for 379 proteins, encompassing a substantial fraction of both protein superfamilies. All three enzymes responsible for synthesis of isopentenyl diphosphate from mevalonate (mevalonate kinase, phosphomevalonate kinase, and MDD) share the same fold, catalyze phosphorylation of chemically similar substrates (MDD decarboxylation involves phosphorylation of mevalonate diphosphate), and seem to have evolved from a common ancestor. These structures and the structural models derived from them provide a framework for interpreting biochemical function and evolutionary relationships.

We report on a series of alkyl- and alkoxy-substituted 1,4-dihydroquinoxaline-2,3-diones (QXs), prepared as a continuation of our structure-activity relationship (SAR) study of QXs as antagonists for the glycine site of the N-methyl-D-aspartate (NMDA) receptor. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [3H]-5,7-dichlorokynurenic acid ([3H]DCKA) in rat brain cortical membranes. In general, methyl is a good replacement for chloro or bromo in the 6-position, and alkoxy-substituted QXs have lower potencies than alkyl- or halogen-substituted QXs. Ethyl-substituted QXs are generally less potent than methyl-substituted QXs, especially in the 6-position of 5,6,7-trisubstituted QXs. Fusion of a ring system at the 6,7-positions results in QXs with low potency. Several methyl-substituted QXs are potent glycine site antagonists that have surprisingly high in vivo activity in the maximal electroshock (MES) test in mice. Among these, 7-chloro-6-methyl-5-nitro QX (14g) (IC50 = 5 nM) and 7-bromo-6-methyl-5-nitro QX (14f) (IC50 = 9 nM) are comparable in potency to 6,7-dichloro-5-nitro QX (2) (ACEA 1021) as glycine site antagonists. QX 14g has an ED50 value of 1.2 mg/kg iv in the mouse MES assay. Interestingly, alkyl QXs with log P values of 0.5 or less tend to be more bioavailable than QXs with higher log P values. QX 14g has 440-fold selectivity for NMDA vs alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as determined electrophysiologically under steady-state conditions in oocytes expressing rat cerebral cortex poly(A)+ RNA. Overall, 14g was found to have the best combination of in vitro and in vivo potency of all the compounds tested in this and previous studies on the QX series.

Inositol 1,4,5-trisphosphate (InsP3) acts on intracellular receptors to cause liberation of Ca2+ ions into the cytosol as repetitive spikes and propagating waves. We studied the processes underlying this regenerative release of Ca2+ by monitoring with high resolution the kinetics of Ca2+ flux evoked in Xenopus oocytes by flash photolysis of caged InsP3. Confocal microfluorimetry was used to monitor intracellular free [Ca2+] from femtoliter volumes within the cell, and the underlying Ca2+ flux was then derived from the rate of increase of the fluorescence signals. A threshold amount of InsP3 had to be photoreleased to evoke any appreciable Ca2+ signal, and the amount of liberated Ca2+ then increased only approximately fourfold with maximal stimulation, whereas the peak rate of increase of Ca2+ varied over a range of nearly 20-fold, reaching a maximum of approximately 150 microMs-1. Ca2+ flux increased as a first-order function of [InsP3]. Indicating a lack of cooperativity in channel opening, and was half-maximal with stimuli approximately 10 times threshold. After a brief photolysis flash, Ca2+ efflux began after a quiescent latent period that shortened from several hundred milliseconds with near-threshold stimuli to 25 ms with maximal flashes. This delay could not be explained by an initial "foot" of Ca2+ increasing toward a threshold at which regenerative release was triggered, and the onset of release seemed too abrupt to be accounted for by multiple sequential steps involved in channel opening. Ca2+ efflux increased to a maximum after the latent period in a time that reduced from > 100 ms to approximately 8 ms with increasing [InsP3] and subsequently declined along a two-exponential time course: a rapid fall with a time constant shortening from > 100 ms to approximately 25 ms with increasing [InsP3], followed by a much smaller fail persisting for several seconds. The results are discussed in terms of a model in which InsP3 receptors must undergo a slow transition after binding InsP3 before they can be activated by cytosolic Ca2+ acting as a co-agonist. Positive feedback by liberated Ca2+ ions then leads to a rapid increase in efflux to a maximal rate set by the proportion of receptors binding InsP3. Subsequently, Ca2+ efflux terminates because of a slower inhibitory action of cytosolic Ca2+ on gating of InsP3 receptor-channels.

A series of mono-, di-, tri-, and tetrasubstituted 1,4-dihydroquinoxaline-2,3-diones (QXs) were synthesized and evaluated as antagonists at N-methyl-D-aspartate (NMDA)/glycine sites and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-preferring non-NMDA receptors. Antagonist potencies were measured by electrical assays in Xenopus oocytes expressing rat whole brain poly(A)+ RNA. Trisubstituted QXs 17a (ACEA 1021), 17b (ACEA 1031), 24a, and 27, containing a nitro group in the 5 position and halogen in the 6 and 7 positions, displayed high potency (Kb approximately 6-8 nM) at the glycine site, moderate potency at non-NMDA receptors (Kb = 0.9-1.5 microM), and the highest (120-250-fold) selectivity in favor of glycine site antagonism over non-NMDA receptors. Tetrasubstituted QXs 17d,e were more than 100-fold weaker glycine site antagonists than the corresponding trisubstituted QXs with F being better tolerated than Cl as a substituent at the 8 position. Di- and monosubstituted QXs showed progressively weaker antagonism compared to trisubstituted analogues. For example, removal of the 5-nitro group of 17a results in a approximately 100-fold decrease in potency (10a,b,z), while removal of both halogens from 17a results in a approximately 3000-fold decrease in potency (10v). In terms of steady-state inhibition, most QX substitution patterns favor antagonism at NMDA/glycine sites over antagonism at non-NMDA receptors. Among the QXs tested, only 17i was slightly selective for non-NMDA receptors.

1. Calcium liberation induced in Xenopus oocytes by flash photorelease of inositol 1,4,5-trisphosphate (InsP3) from a caged precursor was monitored by confocal microfluorimetry. The object was to determine whether inhibition of Ca2+ release seen with paired flashes arose as a direct consequence of elevated cytosolic free [Ca2+]. 2. Responses evoked by just-suprathreshold test flashes were not inhibited by subthreshold conditioning flashes, but were strongly suppressed when conditioning flashes were raised above threshold. 3. Inhibition at first increased progressively as the inter-flash interval was lengthened to about 2 s and thereafter declined, with a half-recovery at about 4 s. 4. Intracellular injections of Ca2+ caused relatively slight inhibition of InsP3-evoked signals, even when cytosolic free [Ca2+] was elevated to levels similar to those at which strong inhibition was seen in paired-flash experiments. 5. Recovery from inhibition was not appreciably slowed when Ca2+ was injected to raise the free Ca2+ level between paired flashes. 6. We conclude that inhibition of InsP3-evoked Ca2+ liberation is not directly proportional to cytosolic free Ca2+ level and that recovery from inhibition in paired-pulse experiments involves factors other than the decline of cytosolic [Ca2+] following a conditioning response.

1. The effects of ethanol and other alcohols on inositol 1,4,5-trisphosphate (InsP3) signalling were studied in Xenopus oocytes by the use of flash photolysis of caged InsP3. Calcium liberation induced by InsP3 was monitored by voltage-clamp recording of Ca(2+)-activated membrane currents, and by fluorescence of the Ca2+ indicator Fluo-3. 2. Membrane current and fluorescence Ca2+ signals evoked by light flashes giving small responses were initially potentiated by bath application of ethanol (80-400 mM). However, the responses subsequently declined while ethanol was present and were strongly reduced or suppressed when it was removed. 3. These effects did not arise artifactually from changes in photolysis of caged InsP3, as similar results were seen with responses evoked by intracellular injections of InsP3. Also, the effects on the membrane current did not arise primarily through actions on the Ca(2+)-dependent Cl- channels, since currents evoked by intracellular injections of Ca2+ were little changed by ethanol. 4. Ethanol reduced the threshold level of InsP3 required to cause Ca2+ liberation. Thus, potentiation was most prominent with small responses evoked by brief light flashes, whereas the predominant effect on larger responses was inhibitory. 5. The facilitatory and inhibitory actions of ethanol persisted after removing extracellular Ca2+. 6. Intracellular injections of ethanol produced an initial inhibition of InsP3 responses, followed, in some oocytes, by a potentiation. 7. Methanol had little effect on InsP3 responses, whereas butanol and other long-chain alcohols produced strong inhibition, but little or no potentiation. 8. We conclude that extracellular application of ethanol produces a rapid potentiation of InsP3-mediated Ca2+ liberation, and a more slowly developing inhibition. The potentiation may arise through stimulation of InsP3 formation at the plasma membrane, whereas the inhibition occurs more deeply in the cell. Both actions were evident at relatively low concentrations (a few tens of millimoles per litre), and might thus be important in the behavioural effects of ethanol intoxication.

The localization of two cloned D. melanogaster DNA fragments in polytene chromosomes was determined by means of in situ hybridization. These different fragments (Dm 225 and Dm 234B) are present in the genome in hundreds copies and contain genes whose transcription yields two different classes in abundant mRNA (Ilyin et al., 1976, 1977; Tchurikov et al., 1978). About 20--30 sites of these genes are demonstrable in the polytene chromosomes of a given stock. There are small but significant variations in the number and localization of these sites among individuals of the same stock. On the other hand, different stocks of D. melanogaster have an utterly different distribution of revealed hybridization sites in the polytene chromosomes. The location of both fragments (Dm 225 and Dm 234) was found to be virtually identical within any given stock of D. melanogaster. 69 sites for localization of Dm 225 or Dm 234 genes were detected in the chromosomes of 11 individuals studied. At least 50 (and up to 62) of them coincide with intercalary heterochromatin regions which are known to be characterized by ectopic pairing, late replication and the presence of "weak spots" in the chromosome. The ability of Dm225 and Dm 234 to code for the "abundant" classes of messenger RNA (Ilyin et al., 1976) and the fact that their location may coincide with the histone and ribosomal genes suggest that intercalary heterochromatin regions are "nests" containing various types of actively transcribable tandem-repeated genes coding for common "household" cell functions.