[Organization of maxillofacial and dental care for the wounded of the Voronezh front (July 1942 - July 1943)]. / Organizatsiya chelyustno-litsevoi i stomatologicheskoi pomoshchi ranenym Voronezhskogo fronta (iyul' 1942 g. ­ iyul' 1943 g.).

The article is devoted to the history of the formation of the system of assistance to maxillofacial wounded soldiers of the Voronezh Front during the battles for Voronezh in 1942-1943. The difficulties and achievements in the implementation of phased assistance to the wounded in the face, as well as the improvement of the organizational structure of surgical and dental care for soldiers and officers of the front are reflected.

Selected trends in head and neck cancer epidemiology in Slovakia - an international comparison.

BACKGROUND: Head-and-neck malignant neoplasms (diagnosis group C00-C14, according to ICD-10) form a heterogeneous group of diseases with close anatomical localization. The incidence is twice to three times higher in men than in women and is increasing worldwide. OBJECTIVE: The aim of our analysis was to estimate changes of incidence and mortality rates of head-and-neck malignancies associated with anatomical topographic regions over the time as well as to compare these indicators in different selected countries of the world. Secondary endpoints included the assessment of patients' age distribution, clinical stages of newly diagnosed cases, and point prevalence of the disease in the Slovak Republic (SR). MATERIAL AND METHODS: The data base for the calculations was obtained from national databases and outputs of the National Cancer Registry (NCR) of the SR (with summary data available from the National Epidemiological Portal of Malignant Tumors, which analyzed data from 1984-2003 and was available until 2009, the remaining data were obtained from annual analyses of the NCR of the SR and the National Centre for Health Information (NCZI)), from the Statistical Office of the SR, and from the IARC WHO global database outputs on incidence, mortality, prevalence and survival of the patients. Incidence and mortality data in the SR were available up to 2012 (including) and up to 2021 (including), respectively. A log-linear joinpoint regression model was used to analyze the development of incidence and mortality rates over time by using Joinpoint Regression Program software. To achieve maximum precision in the estimated total surviving population of patients with head and neck malignant neoplasms, a model was developed to calculate the point (overall) prevalence based on absolute numbers of long-term registered national counts of newly diagnosed patients, mortality from the disease, overall mortality, and survival probability. The representation of clinical stages of head and neck carcinoma in the SR was compiled from available national data (2000-2012) and from predictions and does not consider changes in TNM classifications over the time. RESULTS: The age-adjusted (to the world standard population, ASR-W) incidence rate and the age-adjusted (ASR-W) mortality rate of head-and-neck malignant tumors in the SR have shown a significantly decreasing tendency in men since 1990; however, in women both of these indicators have shown a significant increasing tendency, especially the significantly growing incidence since 2004. In 2012, the overall age-adjusted incidence and mortality rate of head-and-neck cancers in the SR were significantly higher in males (ASR-W incidence 22.6/100,000 and ASR-W mortality 15.26/100,000) compared to females (ASR-W incidence 4.21/100,000 and ASR-W mortality 1.52/100,000). More than 75% of newly diagnosed cases are already in advanced and metastatic clinical stages, which is the most unfavourable survival factor. The absolute prevalence of these patients in the SR was estimated to be N = 9,395 in the year 2021. CONCLUSION: It is necessary to get a current and well evaluated epidemiological overviews to be able to plan preventive and intervention programs in oncology.

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MicroRNAs epigenetically regulate physiological and pathological processes. Previously, we found that miR-204-5p is expressed at low levels in melanoma cells, and an increase in its level leads to a change in proliferation, migration, and invasion of these cancer cells. Now, using bioinformatics analysis, it has been shown that the target of miR-204-5p is FOXC1 transcription factor, which is implicated in carcinogenesis. Using the luciferase reporter assay, it was found that miR-204-5p suppresses expression of the FOXC1 gene by binding to its 3' non-coding region. Transfection of small interfering RNA (siRNA) targeting FOXC1 into melanoma cells caused a decrease in miR-204-5p levels, which is consistent with the generally accepted concept of feedback regulation of miRNA expression by target genes. According to the results of the MTT test and fluorescence microscopy, the proliferation level of melanoma cells under the influence of siRNA to FOXC1 decreased 72 h after transfection. Changes in the ratio of cells by cell cycle phase were analyzed using flow cytometry. Regulatory relationships between FOXC1 and miR-204-5p, and an inhibitory effect of FOXC1 knockdown on melanoma cell proliferation were revealed. Based on the results, it can be assumed that miR-204-5p regulates proliferation of melanoma cells by affecting FOXC1 expression.

[Correlation of the genetic profile and features of the rehabilitation after ischemic stroke]. / Korreliatsiia geneticheskogo profilia i osobennostei reabilitatsii posle ishemicheskogo insul'ta.

AIM: To examine an effect of polymorphisms of lipid peroxidation system genes on the risk of ischemic stroke as well as the prognosis of disease outcome after rehabilitation measures. MATERIAL AND METHODS: Seven hundred and forty-six patients with ischemic stroke and 500 patients of the control group were genotyped for 6 polymorphisms of lipid peroxidation system genes: HIF1a C1772T, ApoE Σ2/Σ3/Σ4, MnSOD C47T, GPX-1 C599T, BDNF G196T, p22phox C242T. RESULTS AND CONCLUSION: The HIF1a C1772T polymorphism was a significant risk factor for the development of ischemic stroke with the odds ratio 1.702 (p<0.05). For GPX-1 C599T and BDNF G196T polymorphisms, a trend towards a higher frequency of heterozygous genotypes was shown in patients with the negative dynamics of neurological status. The results suggest the influence of genetic variants not only on the risk of stroke but also on treatment and rehabilitation outcomes.

Coelenterazine-dependent luciferases.

Bioluminescence is a widespread natural phenomenon. Luminous organisms are found among bacteria, fungi, protozoa, coelenterates, worms, molluscs, insects, and fish. Studies on bioluminescent systems of various organisms have revealed an interesting feature - the mechanisms underlying visible light emission are considerably different in representatives of different taxa despite the same final result of this biochemical process. Among the several substrates of bioluminescent reactions identified in marine luminous organisms, the most commonly used are imidazopyrazinone derivatives such as coelenterazine and Cypridina luciferin. Although the substrate used is the same, bioluminescent proteins that catalyze light emitting reactions in taxonomically remote luminous organisms do not show similarity either in amino acid sequences or in spatial structures. In this review, we consider luciferases of various luminous organisms that use coelenterazine or Cypridina luciferin as a substrate, as well as modifications of these proteins that improve their physicochemical and bioluminescent properties and therefore their applicability in bioluminescence imaging in vivo.

THE ANALYSIS OF MAJOR RISK FACTORS OF CARDIOVASCULAR DISEASES AMONG INHABITANTS OF THE NORTH REGION.

Last years the problem of organism's adaptation to severe climate-environmental conditions of the Far North has been intensively developed. The Republic of Sakha (Yakutia) is the most northern republic of the Russian Federation. People have created a unique way of life, language, original culture on this cold part of the earth and have carried centuries later. This unique experience has been saved up throughout many centuries and generated in natural environment of habitation and passed from generation to generation. Last years the changes of living conditions of indigenous population, urbanization and globalisation, deterioration of ecological conditions exhausted reserve possibilities of organism. Among the indigenous population health change has menacing character, especially among the children's population. The analysis of major risk factors of the development of cardiovascular diseases among the indigenous population of the north has been carried out in this research.

Relaxed functional constraints on triplicate α-globin gene in the bank vole suggest a different evolutionary history from other rodents.

Gene duplication plays an important role in the origin of evolutionary novelties, but the mechanisms responsible for the retention and functional divergence of the duplicated copy are not fully understood. The α-globin genes provide an example of a gene family with different numbers of gene duplicates among rodents. Whereas Rattus and Peromyscus each have three adult α-globin genes (HBA-T1, HBA-T2 and HBA-T3), Mus has only two copies. High rates of amino acid evolution in the independently derived HBA-T3 genes of Peromyscus and Rattus have been attributed to positive selection. Using RACE PCR, reverse transcription-PCR (RT-PCR) and RNA-seq, we show that another rodent, the bank vole Clethrionomys glareolus, possesses three transcriptionally active α-globin genes. The bank vole HBA-T3 gene is distinguished from each HBA-T1 and HBA-T2 by 20 amino acids and is transcribed 23- and 4-fold lower than HBA-T1 and HBA-T2, respectively. Polypeptides corresponding to all three genes are detected by electrophoresis, demonstrating that the translated products of HBA-T3 are present in adult erythrocytes. Patterns of codon substitution and the presence of low-frequency null alleles suggest a postduplication relaxation of purifying selection on bank vole HBA-T3.

A comparison of measured and calculated free 25(OH) vitamin D levels in clinical populations.

OBJECTIVE: Our goal was to compare direct quantitation of circulating free 25-hydroxyvitamin D (25(OH)D)levels to calculated free 25(OH)D levels and their relationships to intact PTH (iPTH), a biomarker of 25(OH)D effect, in humans with a range of clinical conditions. PATIENTS AND METHODS: Serum samples and clinical data were collected from 155 people: 111 without cirrhosis or pregnancy (comparison group), 24 cirrhotic patients with albumin <2.9 g/dL, and 20 pregnant women (second and third trimester). Total 25(OH)D (LC/MS/MS), free 25(OH)D (immunoassay), vitamin D binding protein (DBP) (immunoassay), albumin, and iPTH (immunoassay) were measured. RESULTS: Total 25(OH)D, DBP, and albumin were lowest in patients with cirrhosis, but measured free 25(OH)D was highest in this group (P < .001). DBP was highest in pregnant women (P < .001), but measured free 25(OH)D did not differ from the comparison group. Calculated free 25(OH)D was positively correlated with measured free 25(OH)D (P < .0001) but explained only 13% of the variability with calculated values higher than measured. African Americans had lower DBP than other ethnic populations within all clinical groups (P < .03), and differences between measured and calculated free 25(OH)D were greatest in African Americans (P < .001). Measured free 25(OH)D was correlated with total 25(OH)D (P < .0001; r(2) = 0.51), but calculated free 25(OH)D was not. Similarly, both measured free 25(OH)D (P < .02) and total 25(OH)D (P < .05) were correlated with iPTH, but calculated free 25(OH)D was not. CONCLUSIONS: Calculated free 25(OH)D levels varied considerably from direct measurements of free 25(OH)D with discrepancies greatest in the data for African Americans. Differences in DBP binding affinity likely contributed to estimation errors between the races. Directly measured free 25(OH)D concentrations were related to iPTH, but calculated estimates were not. Current algorithms to calculate free 25(OH)D may not be accurate. Further evaluation of directly measured free 25(OH)D levels to determine its role in research and clinical management of patients is needed.

Association of CYP2C9*2 with bosentan-induced liver injury.

Bosentan (Tracleer) is an endothelin receptor antagonist prescribed for the treatment of pulmonary arterial hypertension (PAH). Its use is limited by drug-induced liver injury (DILI). To identify genetic markers of DILI, association analyses were performed on 56 Caucasian PAH patients receiving bosentan. Twelve functional polymorphisms in five genes (ABCB11, ABCC2, CYP2C9, SLCO1B1, and SLCO1B3) implicated in bosentan pharmacokinetics were tested for associations with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and DILI. After adjusting for body mass index, CYP2C9*2 was the only polymorphism associated with ALT, AST, and DILI (ß = 2.16, P = 0.024; ß = 1.92, P = 0.016; odds ratio 95% CI = 2.29-∞, P = 0.003, respectively). Bosentan metabolism by CYP2C9*2 in vitro was significantly reduced compared with CYP2C9*1 and was comparable to that by CYP2C9*3. These results suggest that CYP2C9*2 is a potential genetic marker for prediction of bosentan-induced liver injury and warrants investigation for the optimization of bosentan treatment.

Functional characterization of ABCC2 promoter polymorphisms and allele-specific expression.

Multidrug resistance protein 2 (MRP2, ABCC2) is an efflux membrane transporter highly expressed in liver, kidney and intestine with important physiological and pharmacological roles. The goal of this study was to investigate the functional significance of promoter region polymorphisms in ABCC2 and potential allele-specific expression. Twelve polymorphisms in the 1.6 kb region upstream of the translation start site were identified by resequencing 247 DNA samples from ethnically diverse individuals. Luciferase reporter gene assays showed that ABCC2 -24C>T both alone and as part of a common haplotype (-24C>T/-1019A>G/-1549G>A) increased promoter function 35% compared with the reference sequence (P<0.0001). No other common variants or haplotypes affected ABCC2 promoter activity. Allele-specific expression was also investigated as a mechanism to explain reported associations of the synonymous ABCC2 3972C>T variant with pharmacokinetic phenotypes. In Caucasian liver samples (n=41) heterozygous for the 3972C>T polymorphism, the 3972C allele was preferentially transcribed relative to the 3972T allele (P<0.0001). This allelic imbalance was particularly apparent in samples with haplotypes containing two or three promoter/untranslated region variants (-1549G>A, -1019A>G and -24C>T). The observed allelic imbalance was not associated with hepatic or renal ABCC2 mRNA expression. Additional mechanisms will need to be explored to account for the interindividual variation in ABCC2 expression and MRP2 function.

Discovery of regulatory elements in human ATP-binding cassette transporters through expression quantitative trait mapping.

ATP-binding cassette (ABC) membrane transporters determine the disposition of many drugs, metabolites and endogenous compounds. Coding region variation in ABC transporters is the cause of many genetic disorders, but much less is known about the genetic basis and functional outcome of ABC transporter expression level variation. We used genotype and mRNA transcript level data from human lymphoblastoid cell lines to assess population and gender differences in ABC transporter expression, and to guide the discovery of genomic regions involved in transcriptional regulation. Nineteen of 49 ABC genes were differentially expressed between individuals of African, Asian and European descent, suggesting an important influence of race on expression level of ABC transporters. Twenty-four significant associations were found between transporter transcript levels and proximally located genetic variants. Several of the associations were experimentally validated in reporter assays. Through influencing ABC expression levels, these single-nucleotide polymorphisms may affect disease susceptibility and response to drugs.

Ca(2+)-triggered coelenterazine-binding protein from Renilla as an enzyme-dependent label for binding assay.

The recombinant Ca(2+)-triggered coelenterazine-binding protein (CBP) from Renilla muelleri was investigated as a biospecifically labeled molecule for in vitro assay applications. The protein was shown to be stable in solutions in the frozen state, as well as stable under heating and to chemical modifications. Conjugates with biotin, oligonucleotide, and proteins were obtained and applied as biospecific molecules in a solid-phase microassay. CBP detection was performed with intact (no modifications were made) Renilla luciferase in the presence of calcium, and the detection limit was found to be 75 amol. Model experiments indicate that this approach shows much promise, especially with regard to the development of multianalytical systems.

[Secondary abdominal pregnancy in 19 w.g.--diagnosis and therapy].

Preserving of tubal pregnancy after first trimester is rare and very often ends fatal. Nevertheless new methods of diagnosis and therapy of ectopic pregnancy, in industrial countries it remains on first place as reason for mother mortality in first three months of pregnancy and represents 10% of all mother mortality.

[Peculiarities of maternal mortality in the University Hospital of Pleven for period 1977-2001].

The authors report retrospective investigation of causes for maternal mortality in the Department of Obstetric and Gynecology in Hospital in Pleven for the period 1977-2001 and comparison between indexes for a different period of time. Objects of investigation were patient histories necropsy report and forensic expertise. Vital births were 73922 for a period of 25 years in Pleven. Dead pregnant and maternity were 45 and the rate of maternal mortality was 60,07/per 100 000 vital births. Causes of maternal mortality were divided in immediate 40 cases (88,88%) and indirect--5 cases (11,11%). The hemorrhage was the most common cause of maternal mortality--18 cases (45%). The authors mention that the absolute number of maternal losses is comparatively constant but the rate of maternal mortality in creases because of tendency of decrease of birthrate and concentration of pathology in Department of Obstetric and Gynecology in Pleven.

Bioluminescent signal system: bioluminescence immunoassay of pathogenic organisms.

The Ca(2+)-regulated photoprotein obelin has been examined as a label for bioluminescence immunoassay of infective agents. The hepatitis B virus (HbsAg) and the bacteria Escherichia coli and Shigella sonnei lipopolysaccharide (LPS) were chosen as model antigens. Chemically synthesized obelin-corresponding antibody conjugates were used in a solid-phase microplate immunoassay. The sensitivities achieved by the assay were 0.25 ng/mL for S. sonnei LPS and 0.375 ng/mL for HbsAg. A novel, filter-based immunoassay to determine bacterial admixtures in the environment was proposed. The NanoCeram filters were effectively applied to 'trap' and pre-concentrate pathogens from samples under study for the purposes of further detection and measurement of the absorbed material by bioluminescence immunoassay.

[Rear cases of tubal pregnancy during second trimester--diagnostic and therapeutic problems].

The lack of space abilities predetermine the fate of tubal pregnancy. Very often it disturbs in first few weeks. Preserving the tubal pregnancy after first trimester is very rear and often ends fatal. During 1970 in France the extrauterine pregnancy is met once on every 100 births. Now it is 2% from all births. In our country the relative part of ectopic pregnancy for last 20 years has grown twice. The authors represent two cases of tubal pregnancy, developed until second trimester, one of them ended fatal. The difficulties during diagnosing, characteristics of clinic and therapeutic problems are shown. Analysis are made on tendency of growing frequency of ectopic pregnancy, nevertheless modern diagnostic methods and also its role for maternal mortality.

[Terminated pregnancy following prenatal diagnosis of congenital anomalies--a part of register of congenital anomalies].

UNLABELLED: The most of European registries of congenital anomalies (CA) collected information of CA in livebirths, stillbirths and terminated pregnancies following prenatal/ultrasound diagnosis. OBJECTIVES: to assess terminated pregnancies after prenatal/ ultrasound diagnosis of CA as a part of register of CA performed in University Hospital-Pleven. Among 21 202 births monitored during the study period (1996-2005), 679 CA were detected. The total prevalence of CA was 32/ 1000 births. The outcome of pregnancy for all cases of selected CA by register was 620 livebirths (91.3%), 36 stillbirths (5.3%), 23 terminated pregnancies (TP) (3.4%). The percentage of pregnancy termination was higher in the case of isolated anomalies, mainly lethal and CA associated with a low survival rate (61%), than with multiple ones. The most common CA detected after prenatal/ ultrasound diagnosis were neural tube defects (NTD) - the main reason for TP (52% of cases). The low proportion of these CA in TP (1/3) compared to their proportion in livebirths (50%) demonstrated an insufficiency of prenatal diagnosis of NTD as a part of register of CA performed in University Hospital-Pleven. Prenatal diagnosis of CA allows an early genetic counseling of mother presenting information on neonatal prognosis and recurrence risk for subsequent pregnancies. It helps family to take an adequate decision for termination of pregnancy with bad prognosis about heavy fetal CA.

[Calcium-regulated photoproteins of marine coelenterates].

Ca(2+)-regulated photoproteins are bioluminescent proteins responsible for bioluminescence of marine coelenterates. The photoprotein molecule is a stable enzyme-substrate complex consisting of a single polypeptide chain and an oxygen "pre-activated" substrate, 2-hydroperoxycoelenterazine, which is tightly but non-covalently bound with a protein. The bioluminescence is triggered by calcium ions and originates from an oxidative decarboxylation of a protein bound substrate. The review provides current data on the photoproteins structure, the mechanism of bioluminescent reaction, the function of some amino acid residues of an active site in the catalysis and the formation of the emitter, as well as on applications of these proteins in a bioluminescent analysis.