[Indicators of oral fluid and their correction by means of hygiene in elderly people with general somatic diseases.]

The results of the study of oral fluid in older persons with somatic pathology, which was followed for 1 month, are presented. The acid-base state of the oral fluid was evaluated, and the viscosity of the oral fluid was determined. According to the results of the study of oral fluid and its correction by means of hygiene in older persons with somatic diseases, the dynamics of the indicators of the acid-base state of the oral fluid, its shift to the alkaline side and the positive dynamics of the effect of the viscosity of the oral fluid were noted. To ensure that the risk of adverse effects from changes in the state of the oral fluid is reduced, a joint approach involving all health professionals is needed, taking into account the determinants of health and ensuring the development of effective methods for the prevention of dental diseases in older persons.

[Study of the functional state of the periodontium in older persons and its correction by means of oral hygiene.]

The study involved 258 older persons with generalized chronic periodontitis, who were monitored for a month. For an in-depth study of the properties and effectiveness of toothpastes recommended for older and elderly people with preventive anti-inflammatory purpose, tests were conducted to determine the true characteristics and properties of the studied pastes. Periodontal indices PMA and PI were used to study the anti-inflammatory effect of toothpastes. The most pronounced anti-inflammatory effect was revealed in the samples, the active components of which were oat extract, thymol, anise and essential oils of tea tree, as well as eucalyptus. Proper selection of means of individual oral hygiene and the development of «Individual hygienic program of prevention of chronic generalized periodontitis in older and elderly people¼ can reduce the phenomenon of inflammation in the periodontium, the development of mediators of inflammation and improve dental health of older and elderly people.

[Effectiveness and safety of drug combination therapy in patients with advanced primary open-angle glaucoma]. / Effektivnost' i bezopasnost' kombinirovannoi terapii pervichnoi otkrytougol'noi glaukomy.

PURPOSE: To study the hypotensive effectiveness and safety of Bimoptic Plus (bimatoprost 0.03% + timolol 0.5%) in patients with developed primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study included 30 patients aged 57 to 72 years (45 eyes). The 1st group included 15 patients (24 eyes) who were first diagnosed with developed glaucoma with moderately elevated and high intraocular pressure (IOP) and prescribed the drug as starting therapy. Patients of the 2nd group (15 patients, 21 eyes) were prescribed Bimoptic Plus with insufficient effectiveness of monotherapy with prostaglandin analogues. The follow-up period was 6 months. RESULTS: The study was completed by 26 patients (41 eyes). Three patients (10%) has stopped using Bimoptic Plus due to side effects, one (3.3%) - due to insufficient hypotensive effect. In the 1st group, the maximum IOP decrease was recorded at the 1st month of the study and amounted to 8.34±1.47 mm Hg (32.2%) compared to baseline, while after 2 weeks, 3 and 6 months it decreased to 8.1±1.52 mm Hg (31.3%), 7.93±1.35 mm Hg (30.6%) and 7.9±1.42 mm Hg (30.5%), respectively. In patients of the 2nd group, additional IOP decrease after 2 weeks, 1, 3, and 6 months from the start of therapy was 4.68±1.24 mm Hg (20.5%), 4.94±1.18 mm Hg (21.7%), 4.55±1.23 mm Hg (20%), 4.5±1.26 mm Hg (19.7%), respectively. CONCLUSION: Bimoptic Plus effectively reduces the IOP level and has the least amount adverse reactions. It can be recommended for wide use in the treatment of patients with POAG.

Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer.

BACKGROUND: Argonaute-2 (Ago2) is an essential component of microRNA biogenesis implicated in tumourigenesis. However Ago2 expression and localisation in breast cancer remains undetermined. The aim was to define Ago2 expression (mRNA and protein) and localisation in breast cancer, and investigate associations with clinicopathological details. METHODS: Ago2 protein was stained in breast cancer cell lines and tissue microarrays (TMAs), with intensity and localization assessed. Staining intensity was correlated with clinicopathological details. Using independent databases, Ago2 mRNA expression and gene alterations in breast cancer were investigated. RESULTS: In the breast cancer TMAs, 4 distinct staining intensities were observed (Negative, Weak, Moderate, Strong), with 64.2% of samples stained weak or negatively for Ago2 protein. An association was found between strong Ago2 staining and, the Her2 positive or basal subtypes, and between Ago2 intensity and receptor status (Estrogen or Progesterone). In tumours Ago2 mRNA expression correlated with reduced relapse free survival. Conversely, Ago2 mRNA was expressed significantly lower in SK-BR-3 (HER2 positive) and BT-20 (Basal/Triple negative) cell lines. Interestingly, high levels of Ago2 gene amplification (10-27%) were observed in breast cancer across multiple patient datasets. Importantly, knowledge of Ago2 expression improves predictions of breast cancer subtype by 20%, ER status by 15.7% and PR status by 17.5%. CONCLUSIONS: Quantification of Ago2 improves the stratification of breast cancer and suggests a differential role for Ago2 in breast cancer subtypes, based on levels and cellular localisation. Further investigation of the mechanisms affecting Ago2 dysregulation will reveal insights into the molecular differences underpinning breast cancer subtypes.

Quantifying Tip60 (Kat5) stratifies breast cancer.

Breast cancer is stratified into four distinct clinical subtypes, using three key biomarkers (Her2/Neu gene status, Estrogen and Progesterone receptor status). However, each subtype is a heterogeneous group, displaying significant variation in survival rates and treatment response. New biomarkers are required to provide more precise stratification of breast cancer cohorts to inform personalised treatment options/predict outcomes. Tip60 is a member of the MYST sub-family of histone acetyltransferases (HATs), and is directly involved in genome maintenance, gene regulation and DNA damage response/repair pathways (key chemotherapeutic influencing mechanisms). We aimed to determine if quantifying Tip60 staining patterns improved breast cancer stratification. We defined Tip60 protein in vivo, quantifying location (cytoplasmic, nuclear), percent of cells and staining intensity in a breast cancer tissue microarray (n = 337). A significant association of specific Tip60 staining patterns with breast cancer subtype, ER or PR status and Tumour grade was found. Importantly, low Tip60 mRNA expression correlated with poor overall survival and relapse free survival. We found Tip60 is a biomarker able to stratify breast cancer patients, and low Tip60 expression is a significant risk factor indicating a higher chance of disease reoccurrence. This work highlights Tip60 regulation as a key factor influencing the development of breast cancer.

[The detection of antibodies to HCV F protein with immune enzyme analysis using synthetic peptide.]

Alternative reading frame encoding a single protein known as protein F or core + 1 / ARFP is located in the core region of the hepatitis C virus (HCV) genome. The presence of antibodies to the F protein of HCV in the serum of patients with chronic hepatitis C indicates the expression of this protein in vivo. In this study, to determine antibodies to the F protein of HCV in serum samples the methodology of the enzyme immunoassay (ELISA) was developed using the synthetic peptide F10 corresponding to the antigenic determinant of the F protein of the HCV subtype 1b. The immunogenicity and immunochemical specificity of synthetic F10 peptide has been demonstrated in laboratory animals (mice).

Spatial distribution of disease-associated variants in three-dimensional structures of protein complexes.

Next-generation sequencing enables simultaneous analysis of hundreds of human genomes associated with a particular phenotype, for example, a disease. These genomes naturally contain a lot of sequence variation that ranges from single-nucleotide variants (SNVs) to large-scale structural rearrangements. In order to establish a functional connection between genotype and disease-associated phenotypes, one needs to distinguish disease drivers from neutral passenger variants. Functional annotation based on experimental assays is feasible only for a limited number of candidate mutations. Thus alternative computational tools are needed. A possible approach to annotating mutations functionally is to consider their spatial location relative to functionally relevant sites in three-dimensional (3D) structures of the harboring proteins. This is impeded by the lack of available protein 3D structures. Complementing experimentally resolved structures with reliable computational models is an attractive alternative. We developed a structure-based approach to characterizing comprehensive sets of non-synonymous single-nucleotide variants (nsSNVs): associated with cancer, non-cancer diseases and putatively functionally neutral. We searched experimentally resolved protein 3D structures for potential homology-modeling templates for proteins harboring corresponding mutations. We found such templates for all proteins with disease-associated nsSNVs, and 51 and 66% of proteins carrying common polymorphisms and annotated benign variants. Many mutations caused by nsSNVs can be found in protein-protein, protein-nucleic acid or protein-ligand complexes. Correction for the number of available templates per protein reveals that protein-protein interaction interfaces are not enriched in either cancer nsSNVs, or nsSNVs associated with non-cancer diseases. Whereas cancer-associated mutations are enriched in DNA-binding proteins, they are rarely located directly in DNA-interacting interfaces. In contrast, mutations associated with non-cancer diseases are in general rare in DNA-binding proteins, but enriched in DNA-interacting interfaces in these proteins. All disease-associated nsSNVs are overrepresented in ligand-binding pockets, and nsSNVs associated with non-cancer diseases are additionally enriched in protein core, where they probably affect overall protein stability.

Trends in breast reconstruction practices in a specialized breast tertiary referral centre.

BACKGROUND: Breast reconstruction is an important component of multidisciplinary breast cancer management. The practice of breast reconstruction after mastectomy has evolved significantly in the past decade as a result of both increasing mastectomy rates and advances in reconstructive strategy. These changes have significantly influenced the contemporary surgical management of breast cancer. The aim of this study was to examine trends in breast reconstruction after mastectomy in an Irish population. METHODS: Data were reviewed from a database of all patients who had mastectomy with or without breast reconstruction at Galway University Hospital, a tertiary breast cancer referral centre, between 2004 and 2014. Trends in breast reconstruction after mastectomy were explored with respect to patient demographics, clinicopathological features, and neoadjuvant and adjuvant therapy. RESULTS: Of 1303 patients who underwent mastectomy during interval studied, 706 (54.2 per cent) had breast reconstruction after mastectomy. In 629 patients (89·1 per cent), breast reconstruction was performed in the immediate setting. Reconstruction rates increased over time from 20·5 per cent in 2004 to 44·7 per cent in 2014. Reconstruction was more commonly performed in younger patients and those with benign, in situ and early-stage disease. A negative relationship between radiotherapy and reconstruction was observed. A pedicled flap with or without an implant was the most commonly used reconstructive approach in patients receiving radiotherapy. CONCLUSION: Breast reconstruction after mastectomy has become the standard of care in the surgical treatment of breast cancer. Recent trends show a transition favouring implant-based approaches.

[VIRAL HEPATITIS C: EVOLUTION OF THE EPIDEMIOLOGIC PROCESS, EVOLUTION OF THE VIRUS].

Periodization of the evolution of epidemic process of hepatitis C is given based on the results of phylodynamic, phylogeographic, historic and demographic studies: invasion of the virus into European and North-American population in 1700-1850; primary activation of the epidemic process in the years of the World War 1; expansive giowth of prevalence in 40--60s of the 20th century due to mass parenteral interventions; new rise due to heroine drug abuse in 60--80s of the 20th century; manifold reduction of incidence of acute hepatitis C in industrial countries for the last 10-15 years as a result of general medical measures of prevention of hemocontact infec-tions. A problem of possibility of hepatitis C management and necessity of evaluation of effectiveness of existing prophylaxis measures involving quantitative analytical methods of epidemiology is discussed. Data from phylogenetic studies on stages of hepatitis C virus evolution (HCV) are provided: division of its root genetic lineage with homologous hepaciviruses of animals 985--2013 years ago; division of HCV into genotypes 500--2000 years ago; division of genotypes into subtypes 70--300 years ago. Contribution of mutations and genetic recombinations into HCV evolution is discussed. Genotyping is stated as an inefficient approach for determination of pathogenicity determinants, immune evasion, non-responsiveness to therapy, as well as search for predictors of infection outcome. A necessity of genomic approach for these aims is justified, as well as for risk monitoring, ensuing from continuing evolution and biodiversity of HCV and other hepaciviruses.

Present state of the Aral Sea: diverging physical and biological characteristics of the residual basins.

Latest data on the hydrophysical and biological state of the residual basins of the Aral Sea are presented and compared. Direct, quasi-simultaneous observations were carried out in the central part of the Western Large Aral Sea, the northern extremity of the Large Aral known as Chernyshev Bay, Lake Tshchebas, and the Small Aral Sea in October 2014. The Large Aral Sea and Lake Tshchebas transformed into hyperhaline water bodies with highly special taxocene structure. The Small Aral Sea was a relatively diverse brackish ecosystem, which was rather similar to the pre-desiccation environment. The Small Aral Sea and Lake Tshchebas exhibited a fully-mixed vertical structure, whereas the Western Large Aral Sea was strongly stratified. Our data show that during desiccation, different parts of the Aral Sea experienced different environmental conditions, resulting in qualitative and quantitative differences in the physical and biological regimes among the different residual basins.

[Genome organization and life cycle of the hepatitis c virus].

The review summarizes the current data about the hepatitis C viral genome and polyprotein organization. The functional role of the structural and non-structural viral proteins including their interaction with cellular regulatory proteins and cell structural elements is discussed. Specific peculiarities of the life cycle of the hepatitis C virus important for the understanding of the viral hepatitis C pathogenesis are summarized.

[Phylodynamic of HCV Populations].

Hepatitis C virus is an actual public health problem worldwide since its discovering in 1989. It is explained not only by the wide spreading and frequent adverse outcomes of disease, the lack of effective preventive vaccine, but also by the high genetic variability of the virus. The current review summarizes the results of phylodynamic and phylogeographic studies of different HCV populations that allowed to characterize epidemic processes, to analyze the divergence of HCV into genotypes and subtypes, and to determine the geographic origin of the current HCV epidemic variants.

[Possibilities for the improvement of the quality of knowledge and their evaluation in the course of studying clinical medicine].

The authors consider objective and subjective factors exerting negative influence on the quality of knowledge of physicians. The generally accepted methods for its evaluation (testing and rating-systems) have limitations. Testing reflects the level of knowledge with respect to the mode of thinking of its designer while rating mostly characterizes diligence of the trainee. It is proposed to improve the quality of knowledge by teaching the theory of diagnostics and to evaluate the amount of knowledge from the contents of the descriptive part of the medical history. The quality of knowledge can be assessed based on the contents of professional comments on the clinical picture described in the model case history.

[Age peculiarities of the sebaceous glands in the temporal area of the scalp skin in men].

The changes of the sebaceous gland number, size and sebocyte proliferative activity were studied in the temporal area of the scalp skin in the male individuals aged 10 to 70 years (n=77, autopsy material). The minimal number of the sebaceous glands was observed in children. This index rapidly increased thereafter, reaching a peak at 20 years, then gradually decreased. These parameters correlated with the sebaceous gland size, sebocyte proliferative activity and total blood testosterone level. In older men the size of the sebaceous glands was increased.

[Efficacy of vitamin mineral complex "Focus forte" in combined treatment of primary open-angle glaucoma and age-related macular degeneration].

The efficacy of Focus forte is proved in patients with primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) in terms of improvement of functional retinal activity, oxygenation, metabolism normalization as well as morphometric retinal and optic nerve indices. Principles of evidence based pharmacotherapy in this study allow advising Focus forte in the treatment of patients with POAG and AMD.

[The natural triterpenoid miliacin prevents methotrexate-induced oxidative stress and normalizes the expression of genes encoding the cytochrome P-450 2E1 isoform and glutathione reductase in the liver].

We studied the role of the natural triterpenoid miliacin (3-3-methoxy-Al8-oleanene) in the regulation of oxidative stress in the liver of (CBAxC57B1(6))F1 mice exposed to methotrexate. Miliacin attenuated methotrexate-induced lipid peroxidation as determined by an attenuation of thiobarbituric acid-reacting products in the liver. Furthermore, miliacin normalized the expression of genes encoding the 2e1 isoform of cytochrome P-450 and glutathione reductase that were dramatically dysregulated by methotrexate. These results established the role of miliacin in modulation of redox genes, thereby providing evidence for a new mechanism of organ protection by this triterpenoid.

[Low-manifest infections in children and adolescents with consequences of perinatal damage of nervous system].

AIM: Study the specter of low-manifest infections (LMI) and their role in children and adolescents with diseases of central nervous system (CNS) against the background of consequences of perinatal damage of nervous system (PDNS). MATERIALS AND METHODS: Infectologic and neurologic examinations were carried out in 42 patients with consequences of PDNS (17 girls and 25 boys, 3 - 15 years). Detection of LMI resulted in etiotropic therapy with evaluation of clinical and laboratory data in dynamics. RESULTS: In 93% (39/42) of patients causative agents of LMI were diagnosed in various combinations and in various biological materials. Among those: Chlamydia spp.--in 71% of patients, Mycoplasma spp.--in 31%, Ureaplasma urealyticum--in 14% (in total the listed microorganisms were diagnosed in 83% of patients); Herpesviridae family viruses--in 75% (HHV-6--in 67%, VEB--in 36%, CMV--in 11%, HSV-1,2--in 11%). Combination of Chlamydia spp. with HHV-6 (R tetr = +0.61) and with VEB (R tet = +0.74) (P < 0.05) was detected. None of the patients had typical signs of encephalitis clinically or based on MRT. MRT signs of gliosis-atrophic changes in the CNS were detected in all the patients. Reduction of a number of psycho-neurologic and neurologic syndromes was noted in all the patients during LMI therapy. CONCLUSION: Most of the patients with consequences of PDNS had low-intensity inflammatory-degenerative process in the CNS determined by LMI, first of all by Chlamydia spp. as well as Mycoplasma spp.

[The development of secondary immunodeficiency in body when exposed to the effect of xenobiotics with immunosuppressive activity].

The State Education Institution of Higher professional education "The Orenburg State Medical Academy of Federal Agency in Public Health and Social Development". In the experiment on mice (CBA x C57Bl6) F1 and Wistar rats is shown the protective effect of triterpenoid plant--miliatsina (3-beta-methoxy-delta18-oleanena) in relation to the humoral immune response and clearance macrophage function hepatic xenobiotic conditions of use--methotrexate. The results define the term as used miliatsina immunoprotector with adverse effects on the body of environmental and industrial chemical factors that form the secondary immunodeficiency.

[Low-manifest infections with CNS damage in patients in prolonged unconscious state of non-inflammatory etiology].

AIM: Study of specter of low-manifest infections (LMI) with central nervous system (CNS) damage and their role in patients in prolonged unconscious state (PUS) of noninflammatory etiology. MATERIALS AND METHODS: 32 patients (23 male, 9 female; age 14-58) in PUS of various etiology were examined. The main group (18 patients) received therapy against all infectious diseases including LMI; control group (14 patients)--only against common and nosocomial microflora. Patients were immunologically, infectologically and neurologically examined in dynamic. The data obtained were treated by using STATISTICA for Windows (version 5.5). RESULTS: Significant differences in immune and infectologic status depending on the nature of primary CNS damage were not detected. Immunodeficiency was detected in all patients; 94% of patients had increased non-specific IgM and IgE. Among LMI agents Chlamydia spp. were predominant. Cultural and/or PCR methods detected this microorganism during the primary examination in cerebrospinal fluid samples in 56% patients and in blood samples in 56%; during the second diagnostics or autopsy--only in 13 and 25%, respectively. Detection of Bacteroides fragilis, Human Herpes Virus (HHV-6), Virus Epstein Barr (VEB), Cytomegalovirus (CMV) in cerebrospinal fluid, blood and on mucous membranes of nasopharynx and conjunctiva was grouped more frequently with the presence of Chlamydia spp. in the CNS (p < 0.05) than with other LMI agents. Sanation of CNS from LMI was significantly accompanied by regeneration of communicative activity in comparison with the control group. CONCLUSION: In patients with PUS high frequency of CNS infection by various LMI agents and primarily Chlamydia spp. should be considered. Sanation from LMI can become a "window" for effective neuro-regenerative treatment.