[Enzyme immunoassay system for serological diagnosis of hemorrhagic fever with renal syndrome based on inactivated purified Puumala virus (Hantaviridae: Orthohantavirus)].

INTRODUCTION: Hemorrhagic fever with renal syndrome (HFRS) is the most common zoonotic human viral disease in the Russian Federation. More than 98% of the HFRS cases are caused by Puumala orthohantavirus (PUU). Effective serological tests are required for laboratory diagnosis of HFRS. OBJECTIVE: Construction of an enzyme immunoassay (ELISA) test system for detection of specific antibodies using standard antigen in the form of highly purified inactivated PUU virus as immunosorbent. MATERIALS AND METHODS: Preparation of PUU virus antigen, designing the ELISA for detection of specific antibodies, developing parameters of the ELISA system, parallel titration of HFRS patients sera by fluorescent antibody technique (FAT) and the new ELISA. RESULTS AND DISCUSSION: For the first time, ELISA based on purified inactivated PUU virus as standard antigen directly absorbed onto immunoplate was developed. Parallel titration of 50 samples from HFRS patients blood sera using FAT and the developed ELISA showed high sensitivity and specificity of this ELISA, with 100% concordance of testing results and significant level of correlation between the titers of specific antibodies in the two assays. CONCLUSION: The ELISA based on purified inactivated PUU virus as an immunosorbent can be effectively used for HFRS serological diagnosis and for mass seroepidemiological studies.

[Full and D-Box-Deficient PTTG1 Isoforms: Effects on Cell Proliferation].

Human securin (PTTG1) is a protooncogene whose expression is elevated in many types of malignant cells. We previously discovered a minor short isoform of securin lacking exons 3 and 4. The missing exons encode the main recognition site (D-box) of the anaphase-promoting complex (APC/C). We show that these two PTTG1 isoforms have different effects on transcription. Here, we have studied the effects of overexpression and selective knockdown of the short and complete securin isoforms on cell proliferation using the xCELLigence system. Notably, selective knockdown of the short isoform mRNA led to a dramatic decrease in cell growth, while overexpression of both isoforms accelerated cell growth. To search for genes with alternative isoforms similar to securin, we analyzed the GENCODE database and found that 54 of 128 genes with a PTTG1-like set of APC/C recognition sites have known isoforms without the D-box. Overall, the data obtained indicate the existence of a new class of alternative isoforms and reinstates the importance of minor isoforms.

[Evaluation of the clinical effectiveness of the use of a navigational surgical template in the vestibuloplasty protocol in patients with periodontal diseases]. / Otsenka klinicheskoi effektivnosti primeneniya navigatsionnogo khirurgicheskogo shablona v protokole vestibuloplastiki u patsientov s boleznyami parodonta.

THE AIM OF THE STUDY: Was to evaluate the clinical effectiveness of the use of a navigational surgical template in the vestibuloplasty protocol in patients with periodontal diseases. MATERIALS AND METHODS: There were 48 people selected to participate in the study and randomly divided into 2 equal groups. The patients of the main group underwent vestibuloplasty procedure using a free gingival graft modeled using the developed protocol and a navigational surgical template. Patients in the control group underwent a similar operation using classical technology. The study assessed postoperative pain, the index of early wound healing, Doppler fluometry of the transplanted flap and flap morphometric measurements. RESULTS: The results of all conducted studies confirmed the effectiveness of the developed clinical protocol. CONCLUSION: According to objective and subjective assessments, the use of a surgical navigation template can reduce the time and invasiveness of vestibuloplasty surgery, make it more comfortable for the patient and get a more predictable clinical result.

[Real-time PCR assay development for the control of vaccine against hemorrhagic fever with renal syndrome].

INTRODUCTION: Hemorrhagic fever with renal syndrome (HFRS) holds a leading place among natural focal human diseases in Russian Federation. There is no etiotropic therapy for the disease now. The vaccine prophylaxis is the most effective method to control this infection. The main criteria for inactivated vaccines evaluation are its immunogenicity and specific activity.The study purposes were to develop a sensitive and specific real-time PCR method for viral RNA quantification in the inactivated vaccine and to study the correlation between the viral RNA amount and vaccine immunogenicity. MATERIAL AND METHODS: L-segment fragments of the Puumala, Hantaan, and Sochi vaccine strains were selected as diagnostic targets for oligonucleotides and fluorescent probes. The immunogenicity of experimental vaccines was determined by the induction of neutralizing antibodies in BALB/c mice. RESULTS: A highly specific, sensitive and reproducible real-time PCR method has been developed. The analytical sensitivity was 1.24 ± 1.5 x 102 copies/ml for Puumala virus; 1.16 ± 1.4 * 102 copies/ml for Hantaan; 1.32 ± 1.8 * 102 copies/ ml for Sochi, with a virus content of 1.5 ± 0.5 lg FFU/ml; 1.8 ± 0.5 lg FFU/ml and 2.2 ± 0.5 lg FFU/ml, respectively. The viral RNA amount in experimental vaccine preparations inactivated with ß-propiolactone was proportional to the neutralizing antibodies titer observed in mice following the immunization. DISCUSSION: It was found that different virus inactivators differently affects the detected viral RNA amount, but not the vaccine immunogenicity, which indicates the same degree of the immunogenic proteins damage. The direct relationship between the viral RNA copy number and vaccine immunogenicity makes it possible to use this criterion for vaccine dosage preparation. CONCLUSION: The developed method for viral RNA quantification is a promising tool for the specific activity control of the HFRS vaccine.

[The role of comprehensive geriatric assessment in the treatment of cancer patients in elderly and senile age.]

Modern approaches to the organization of diagnosis and treatment of elderly and senile patients with malignant tumors allow to maintain the necessary level of health, improve the quality of life and increase life expectancy. Assessment of geriatric status in Oncology allows: to predict complications during the complex treatment, including drug treatment; to modify treatment to reduce the risk factors of adverse outcomes; to select patients for specialized treatment using standard schemes. So, timely assessment of geriatric syndromes and their correction can expand the indications for specialized treatment of elderly and senile patients.

[Hemorrhagic fever with renal syndrome group outbreak caused by Sochi virus.]

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) occupies a leading place among natural focal human diseases in the Russian Federation. Sporadic incidence of HFRS-Sochi has been annually recorded in the Krasnodar Territory since 2000. The group outbreak of the HFRS-Sochi was first registered in Gelendzhik in the fall of 2013. METHODS: Serological methods were used: indirect immunofluorescence, enzyme immunoassay, FRNT in Vero cells, and methods for the viral RNA detection: PCR and RT-PCR. RESULTS: Data of clinical, epidemiological, immunological and molecular studies of 3 out of 4 cases in HFRS-Sochi outbreak are presented. Severity of the disease correlated with early gastrointestinal disorders appearance. Patient MA gastrointestinal disorders were joined on day 3 of a fever. Clinical and laboratory studies revealed signs of kidneys, liver, pancreas damage, bilateral hydrothorax, bilateral polysegmental pneumonia and polyneuropathy. As a result of long-term treatment, the patient recovered. Patient AA had gastrointestinal disturbances the next day after fever onset. The patient was not saved, despite early hospitalization. Hantavirus antigen and RNA were detected in the lung tissues 2 out of 10 Black-Sea field mice captured in the affected area, as well as in the organs of deceased patient. The most severe clinical course of the disease in close relatives, son and father, with a fatal outcome in the latter case may be the result of genetic features. The severity and outcome of the disease was not depend on day of hospitalization and correlated with the early manifestations of gastrointestinal disorders. CONCLUSIONS: Presented data confirm high virulence and pantropism of the Sochi virus, as well as the epidemiological role of Black-Sea field mouse (Apodemus ponticus) as the host of the Sochi virus and the source of human infection.

[Optimization of cognitive rehabilitation of elderly patient with motor disorders on the basis of modern digital technologies.]

The problem of cognitive dysfunction in modern gerontological aid goes to the leading positions, complicating treatment and rehabilitation of concomitant motor disorders. The current trend in recent years is the search and development of models of cognitive rehabilitation of elderly patients on the basis of digital technology with the ability to transfer the effect on the motor and mental sphere. The literature sources of the last 5-7 years describe dozens of methods of cognitive rehabilitation, including on the basis of computer games, which demonstrate the importance of these techniques not only in improving the cognitive abilities of patients, but also in Preservation of social adaptation and daily functioning. At the same time negligible attention is paid to the problem of application of digital technologies in rehabilitation of cognitive disorders in patients with motor disorders and possible transfer of effect between spheres. This study shows the application of the algorithm of action with the participation of electronic devices as cognitive rehabilitation with compensatory mechanism in comorbid patients with motor and moderate cognitive impairment.

[PROTECTIVE PROPERTIES OF DRUGS OF PLANT ORIGION IN ACUTE EMOTIONAL AND PAINFUL STRESS IN RATS].

The aim of the investigation was to study the protective properties of the herbal preparation - biotrite and tranquilizer diazepam under the modeling of emotional and painful stress in rats. Materials and methods. The experiment was conducted on 24 white male rats of 5 months of age. Animals (6 rats in the group) were kept on the standard diet of the vivarium: 1st group was intact; rats of the 2nd, 3rd and 4th groups were reproduced acute painful emotional stress for 3 hours. 60 minutes before the stress, rats received per os: the 2nd group - water, the 3rd group - diazepam in a dose of 1.25 mg / kg body weight of rats; 4th group - a preparation of biotrite in a dose of 50 mg / kg. Results and conclusion. The conducted studies demonstrated significant adaptive properties of the biotrite preparation, and the degree of their manifestations was higher than the stress-protective effects of diazepam.

[All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults]. / Vserossiiskii konsensus po diagnostike i lecheniyu tseliakii u detei i vzroslykh.

The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

[TROPHOLOGY ASPECTS OF NOOCPHEROGENESIS. On the 90th anniversary of A M Ugolev].

This paper presents an analytical review of A. Ugolev's scientific heritage (the theory of adequate nutrition, all-purpose functional blocks, the unity of natural and artificial technologies, the discovery of membrane digestion, new doctrine--trophology) to explain trophological aspects of noospherogenesis. The authors have presented their specific views for the development of these ideas; the theory of therapeutic infections, the holistic theory of nutrition, the endoecological deficiency syndrome, the activation of all-purpose functional blocks, evasion receptors, new principles of treatment with the effects on microbiota, combining the essence of the diseases and their treatment.

[Comparative analysis of different methods of geroprotective].

In the monitoring process 110 representatives of different age groups held a comparative analysis of the efficacy and safety of several geroprotective techniques, including the use of dry carbon dioxide baths, hyperbaric oxygen therapy, therapeutic massage and receiving Oligopeptide preparations containing complexes lysyl-glutamyl-asparagin and glutamyl-asparagin-arginine (Vezugen and Pinealon). The most pronounced positive impact on indicators of biological age were detected during the combined use of these two Oligopeptide complexes. The most safe from the point of view of influence on a number of biochemical, immunological parameters, clinical condition of the patients were therapeutic massage and Oligopeptide drugs. The use of dry carbon dioxide baths and hyperbaric oxygenation with an undoubtedly positive influence on the indices of biological age has a number of limitations and contraindications regarding its security.

NUTRITIONAL FACTORS OF ANEMIA IN ULCERATIVE COLITIS PATIENTS.

The study aim was to assess the relationship between nutritional markers decrease and hemoglobin level in ulcerative colitis (UC) patients. METHODS: The cross-sectional retrospective analysis was performed. Data from medical records of 103 ulcerative colitis patients was included to analysis. Demographic characteristics, disease behavior, gut involvement extension, hemoglobin and total serum protein levels were collected. Body mass index (BMi) and fat-free mass index mass were collected retrospec- tively from bloimpedance analysis data. A multiple linear regression analysis was performed to study the relationship be- tween nutrition status parameters and hemoglobin level adjusted for demographic and diseaseTassociated characteristics. RESULTS: Prevalence of anemia in the sample was 37.9%. In adjusted multiple linear regression model total serum protein level and fat-free mass index were directly associated with the hemoglobin level: standardized ß 0.369 (p = 0.010) and standardized ß = 0.509 (p <0.001) respectively. CONCLUSIONS: We assume undernutrition is one of causative agents of anemia in UC patients. It is likely the anemia treat- ment in UC patient with undernutrition must be performed with nutritional support.

METABOLIC DYSBIOSIS OF THE GUT MICROBIOTA AND ITS BIOMARKERS.

Existing methods of clustering of gut microbiota (enterotypes, clusters, gradients), as well as the term 'phylogenetic core' do not reflect its functional activity. The authors propose to describe the key microbiora using term 'phylometabolic core of intestinal microbioca which more accurately reflects the functional importance of metabolically active microbiota. Phylometabolic core includes functional groups of microorganisms that perform similar metabolic functions: butyrate-producing bacteria, propionate-producing bacteria, acetate-produc- ing bacteria (acerogens), hydrogenosrophic microorganisms (reductive acetogens, sulfate-reducing bacteria, methanogens), lactate-producing and lactate-utilizing bacteria, bacteria involved in bile acids metabolism, bacteria that metabolize proteins and amino acids, vitamin-producing microorganisms, oxalate-degrading bacteria and others. The hypothesis that disturbance of microbial metabolism is the root of many human diseases is discussed. The microbial dysmexabo- lism leads to the metabolic dysbiosis (a particular form of dysbiosis) that is primarily characterized by metabolic abnormalities (e.g. serum, urinary, fetal or exhaled air). Metabolic dysbiosis is not necessarily accompanied by appreciable quantitative and/or qualitative changes in microbiora composition that called taxonomic dysbiosis. Since in the metabolic dysbiosis metabolic pathways can be switched only, it means the need for completely different approaches to its assessment using metabolomics (metabolic fingerprinting, metabolic profiling, meta-metabolomics). Metabolites concentrations in colon (feces, biopsy samples), blood (serum, plasma), urine or exhaled air, as well as metabolic profiles of examined substrates can serve as biomarkers. The main clinical variants of metabolic dysbiosis are due to the disturbances in microbial synthesis of short-chain fatty acids (primarily butyrate and propionate) and due to increasing bacterial production of hydrogen sulfide, ammonia and secondary bile acids (particularly deoxycholic acid). These kinds of metabolic dysbiosis can eventually lead to inflammatory bowel disease (IBD) or colorectal cancer (CRC). The metabolic dysbiosis due to bacterial choline dysmetabolism followed by overproduction of trimethylamine (TMA), arherogenic precursor of trimethylamine N-oxide (TMAO), is associated with atherogenesis and increased risk of cardiovascular disease. Dysmetabolism of aromatic amino acids leads to changes in the microbial production of phenylalanine and tyrosine derivatives (phenyl carboxylic acid, p-cresol) and tryptophan indole derivatives (indole carboxylic acid, indole) and contributes to pathogenesis in lBS. IBD, CRC, chronic liver and kidney diseases, cardiovascular diseases, autism and schizophrenia. Metabiotics, a new class of therapeutic agents, e.g. based on microbial metabolites, can correct metabolic dysbiosis, prevent diet- and microbiota-relared diseases and increase the effectiveness of treatment.

FUNCTIONAL FOODS ARE CRITICAL COMPONENTS OF TREATMENT OF METABOLIC DISORDERS IN CELIAC DISEASE.

AIM: To evaluate the effectiveness of Native-complex functional food to correct nutritional disorders and to normalize gastrointestinal motor activity in celiac disease (CD). METHODS: 20 CD patients with constipation and metabolic disorders were included in the study (age 31.8?9.5 years, male to female ratio 1:5.3). The diagnosis of CD was confirmed by clinical and anamnestic data, endoscopy, histopathology of duodenal biopsy specimens, HLA-DQ2 and HLA-DQS typing. All patients received Native-complex Fucus jelly (Kelp jelly) within 2 months. RESULTS: At the beginning of the study45% of patients had stools corresponding to the Bristol Stool Form ScaleType 1,40% of patients had Type 2 stools and 15% of patient had Type 3 stools. 15 patients (75%) showed a decrease in fat mass and 13 patients (65%) showed a decrease in fat-free mass indicated by bloimpedance measurement. All patients had low values of total bacterial counts and increased abundance of pathobionts including fungi and viruses in fecal microbiota. Supple- mentary nutrition significantly improved symptoms, intestinal circadian rhythms and stool consistency in CD patients. At the end of the study 70% of patients had daily bowel movements, 30% of patients had stools every other day. The average stool frequency was 5,95 ? 1,80 per week. 80% of patients had Type 4 or Type 5 stools,20% of patients had Type 3 stools according to the Bristol Scale. Supplementary nutrition significantly improved gut microbiota profile. CONCLUSION: Long-term gluten-free diet in celiac disease leads to a decrease in dietary fiber and polysaccharides consumption and promotes intestinal dysbiosis. Functional foods improve symptoms; stool consistency and gut microbiota profile in adult celiac patients on gluten-free diet.

THE PSYCHO-PHYSIOLOGICAL STATUS IN CELIAC DISEASE.

Based on the results of a comprehensive study of 35 people aged from 19 to 52 years, among them 20 women and 15 men with celiac disease features of their physiological status were studied, reflecting the severity of the disease and quality of life. The diagnosis was based on the clinical and anamnestic data, endoscopy, histomorphological, immunological and genetic exams. Psychophysiological analysis showed that in celiac disease is characterized by the formation reactions with anxiety, anxiety-phobic, neurotic, affective, and hypochondriacal symptoms. The results of the study emphasized the importance of adaptive physiological capacity of the body to build tolerance to the development of psycho-vegetative, hypochondriacaldepressive and other disorders.

[The first results of assessment of clinical efficacy of melatonin and metformin in patients with disseminated skin melanoma receiving dacarbazine as first-line systemic therapy].

The aim of the study was to assess efficacy and safety of combined therapy with dacarbazine and melatonin or metformin in comparison with dacarbazine alone in the 1st line of therapy of cutaneous melanoma. Thirty-six patients with disseminated melanoma, therapy naïve, were included between March 2014 and December 2015. Patients received DTIC 1000 mg/m2 in day 1 of 28-day cycle either as monotherapy (group 1) or in combination with melatonin 3 mg PO daily (group 2) or metformin 850 mg 2 times a day PO daily (group 3). Thirty-four patients were randomized (15-in group 1, 8 - in group 2, 13 - in group 3) and received 119 cycles of therapy. Response rate was 11% in groups 1 and 2, and 8,3% - in group 3 (p=0,57). Median time to progression was 52, 79 and 63 days, respectively in the 1st, 2nd and 3rd group (р=0,468). Two patients from the 2nd and 3rd group showed delayed response to therapy. No adverse events of grade 3-4 were seen. Thus, DTIC with melatonin or metformin was well tolerated. No meaningful increase of adverse event incidence was seen. No benefit of either combination was shown in this interim analysis. Delayed responses in melatonin and metformin combination groups were registered. This suggests immunologic effect of both drugs and warrants further study.

[EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION].

We've estimated the cellular and metabolic part of geroprophylactic effects of short synthetic tripeptides vesugen and pinealon for correction of the biological age. 32 people (18 men, 12 women) aged 41-83 years with polymorbidity and the organic brain syndrome in remission participated in the study. The preparations of "Pinealon" and "Vesugen" have had the significant anabolic effect. They have improved the activity of the Central nervous system and other vital organs, which slows the rate of aging by biological age indicators. Vesugen has demonstrated more visible geroprophylactic effect than Pinealon. At the same time we've found the prooxidant activity through chemiluminescence. Decrease of markers CD34+ positive hematopoietic polypotent cells in blood has shown significant inhibition of hemopoiesis. Apparently, the cells have not been involved in the adaptive reactions. Pinealon and Vesugen haven't affected the degree of chromatin condensation, so they are safe on nuclear genetic level. This property should be studied in future. In geriatric practice, we recommend to apply the peptides Pinealon and Vesugen as geroprotectors anabolic neuroprotective and no antioxidant type for reducing the rate of aging in patients with the organic brain syndrome vascular and/or traumatic genesis.

[Connective tissue dysplasia in patients with celiac desease as a problem of violation of adaptation reserve islands of the body].

Clinically significant dysplasia of connective tissue in patients with celiac disease is often responsible for various visceral disorders. Different disturbances of motor and evacuation functions are often determined in this patients (gastroesophageal reflux, duodenogastral reflux, spastic and hyperkinetic dyskinesia). The clinical course of the celiac disease, associated with connective tissue dysplasia, is characterized by asthenovegetative syndrome, reduced tolerance to physical activity, general weakness, fatigue and emotional instability. These data should be considered in choosing a treatment.

[Impact of bariatric surgery on vitamin metabolisms in obese patients].

AIM: To investigate the impact of bariatric surgery (BS) on the level of vitamins in obese patients. SUBJECTS AND METHODS: One hundred obese patients (78 women and 22 men) aged 19 to 61 years were examined. Controlled gastric banding (CGB) was carried out in 20 patients (mean body mass index (BMI), 41.3 ± 8.2 kg/m2); gastric sleeve resection (GSR) in 40 patients, and gastric shunting (GS) in 40 (the mean BMI in these groups were 41.1 ± 17.8 and 45.9 ± 6.2 kg/m2, respectively). A control group consisted of 10 apparently healthy individuals (BMI, 24.9 ± 3.2 kg/m2). An enzyme immunoassay was used to determine the serum concentrations of vitamins B1, B2, B5, B6, B9, B12, C, and D, niacin, biotin, and retinol-binding protein (RBP) before and 1 year after surgery. RESULTS: All the three groups showed a considerable decrease in the levels of vitamins C, B5, B6, and D, and RBP both prior to and following BS. More than 50% of the patients who had undergone GSR had also a lower baseline niacin level. A year after CGB, GSR, and GS, the number of patents with deficiency of these vitamins remained the same or increased. The majority of patients with the same level of vitamin B2, niacin, and folic acid (FA) were observed to have its decrease a year postsurgery. The concentration of the other test vitamins was also reduced a year after all operations; however, it remained within the normal range. GS had no substantial impact on the concentrations of FA, vitamins B2, B12, B1, and biotin. The lower serum vitamin levels were not accompanied by clinical symptoms in most patients following BS. CONCLUSION: In 80% of the patients with obesity, the levels of vitamins C, B6, and D were decreased to a variable degree. After BS, there was a rise in the number of patients with low serum vitamin C, D, B6, B5, niacin, FA, and RBP concentrations, at the same time the number of patients with FA deficiency increased by more than twice. BS did not significantly affect the metabolism of vitamins B1 B2 B12, and biotin.