[Surgical treatment and prognostic factors in perihilar tumors]. / Khirurgicheskoe lechenie i faktory prognoza pri perikhilyarnoi opukholi.

OBJECTIVE: To study the results of surgical treatment in patients with perihilar tumors. MATERIAL AND METHODS: We analyzed 98 patients with perihilar tumors who underwent surgery. RESULTS: We prefer percutaneous transhepatic biliary drainage (n=58) for jaundice. Retrograde interventions were performed in 18 cases (20.5%), complications grade III-IV were more common (p=0.037) in the last group. Postoperative mortality was 12%. Complications developed in 81 patients (82.7%), grade ≥3 - in 39 (39.8%) cases. Portal vein resection (n=26) increased the incidence of complications grade ≥III (p=0.035) and portal vein thrombosis (p=0.0001). Chemotherapy after surgery was performed in 47 patients (48.0%), photodynamic therapy - in 7 (7.1%) patients. A 5-year overall survival was 28.1%, the median survival - 29 months. R2 resection and/or M1 stage (n=12) significantly worsened the prognosis and overall survival (16.5 vs. 31 months, p=0.0055). Lymph node (LN) lesion, microscopic status (R0 vs. R1) of resection margin, technique of decompression and isolated resection of extrahepatic bile ducts did not affect the prognosis, and we combined appropriate patients (n=72) for analysis. SI resection and excision of ≥6 lymph nodes were independent positive factors for disease-free survival (p=0.042 and p=0.007, respectively). Blood transfusion and high preoperative neutrophil-lymphocyte index (NLI ≥2.15) worsened overall (p=0.009 and p=0.002, respectively) and disease-free survival (p=0.002 and 0.007, respectively). The absence of adjuvant therapy worsened disease-free survival alone (p=0.024). CONCLUSION: SI liver resection, adequate lymph node dissection and adjuvant therapy should be used for perihilar tumors. Isolated resection of extrahepatic bile ducts is permissible in some cases. Blood transfusion and NLI ≥2.15 are independent negative prognostic factors.

[Effective Viral Delivery of Genetic Constructs to Neuronal Culture for Modeling and Gene Therapy of GNAO1 Encephalopathy].

GNAO1 encephalopathy is an orphan genetic disease associated with early infantile epilepsy, impaired motor control, and severe developmental delay. The disorder is caused by mutations in the GNAO1 gene, leading to dysfunction of the encoded protein Gao1. There is no cure for this disease, and symptomatic therapy is ineffective. Phenotypic heterogeneity highlights the need for a personalized approach for treating patients with a specific clinical variant of GNAO1 and requires the study of the disease mechanism in animal and cell models. Towards this aim, we developed an approach for modeling GNAO1 encephalopathy and testing gene therapy drugs in primary neurons derived from healthy mice. We optimized the delivery of transgenes to Gαo1-expressing neurons using recombinant adeno-associated viruses (rAAV). We assessed the tropism of five neurotropic AAV serotypes (1, 2, 6, 9, DJ) for Gαo1-positive neurons from the whole mouse brain. The DJ serotype showed the highest potential as a reporter delivery vehicle, infecting up to 66% of Gαo1-expressing cells without overt cytotoxicity. We demonstrated that AAV-DJ also provides efficient delivery and expression of genetic constructs encoding normal and mutant Gαo1, as well as short hairpin RNA (shRNA) to suppress endogenous Gnao1 in murine neurons. Our results will further simplify the study of the pathological mechanism for clinical variants of GNAO1, as well as optimize the testing of gene therapy approaches for GNAO1 encephalopathy in cell models.

ENZYMATIC ACTIVITY IN MICROSOMES, LIPID PEROXIDATION OF MICE HEPATOCYTES UNDER THE SODIUM FLUORIDE.

Fluorine is one of the most widespread and necessary microelements for the body of animals and humans, which is necessary in a clearly limited amount. Different concentrations of fluorine can affect the state of lipid peroxidation, as well as the functional state of the microsomes of liver hepatocytes. The studies were carried out on mature Wistar rats weighing 180-220 g. Animals were inoculated with an aqueous solution of sodium fluoride once a day for 60 days at doses of 1/10, 1/100 and 1/1000 DL50, which was 20 mg/kg, 2 mg/kg and 0,2 mg/kg body weight. Control rats received drinking water. Each group consisted of 10 animals, the studies of indicators were carried out on days 10, 20, 30, 50 and 60. The induction of free radical processes by sodium fluoride was confirmed using a chemiluminescent reaction of blood serum, the amount of diene conjugates in rat liver tissue homogenates was assessed spectrophotometrically, the content of TBA reactants in rat liver tissue homogenates was determined by the reaction of malondialdehyde and thiobarbituric acid (TBA). The level of chiff bases was determined with a spectrofluorometer, subcellular fractions of the liver were isolated by the method of differentiated centrifugation. An increase in the level of the indicator at a dose of 1/10 and 1/100 DL50 of the intensity of lemiluminescence on the 30th day and its decrease on the 60th day was established.Increase in the activity of NAD (P) H-cytochrome c reductase in the microsomal fraction of the liver at the beginning of the study and a gradual decrease on the 50th and 60th days when using both dosages. The same dynamics was observed for NADH-cytochrome c reductase. With respect to diene conjugates of TBA-reactants and chiff bases, a tendency to increase was observed at all periods of the experiment. Indicators of cytochrome P-450 cytochrome b5 were increased up to 30 days and gradually decreased by 60 days. Long-term administration of sodium fluoride can cause the formation of toxic products and a decrease in the activity of enzymes of the microsomal membrane of hepatocytes.

INVESTIGATION OF BONE MINERALIZATION IN PATIENTS WITH CORONARY HEART DISEASE COMPLICATED BY CHRONIC HEART FAILURE, STAGE II-A.

The majority of the studies have shown that individuals with cardiovascular diseases have a higher risk of experiencing bone loss and thus greater predisposition to risk of fracture. On the other hand there is growing evidence that individuals with low bone mass have higher mortality for cardiovascular events compared to patients with cardiovascular disease with normal bone mass. This research aims to investigate bone mineralization in patients with coronary heart disease complicated by stage II-A chronic heart failure. The study involved 33 men with coronary heart disease complicated by Stage II-A chronic heart failure. Bone mineral density was measured using dual energy x-ray densitometry of lumbar region of spine. Structural and functional changes of bone tissue of the lumbar spine have been found in 49,2% patients with coronary heart disease complicated by Stage II-A chronic heart failure, in particular, I stage of osteopenia - in 44,6%, II stage of osteopenia - in 27,7%, III stage of osteopenia - in 10,8% and osteoporosis - in 16,9%. It was established the same type of downward trend for BMD decreasing in L1 of patients with different stages of osteopenia, but in case of osteoporosis mineralization decreased equally in all vertebrae.

Capture of heavy hydrogen isotopes in a metal-organic framework with active Cu(I) sites.

The production of pure deuterium and the removal of tritium from nuclear waste are the key challenges in separation of light isotopes. Presently, the technological methods are extremely energy- and cost-intensive. Here we report the capture of heavy hydrogen isotopes from hydrogen gas by selective adsorption at Cu(I) sites in a metal-organic framework. At the strongly binding Cu(I) sites (32 kJ mol-1) nuclear quantum effects result in higher adsorption enthalpies of heavier isotopes. The capture mechanism takes place most efficiently at temperatures above 80 K, when an isotope exchange allows the preferential adsorption of heavy isotopologues from the gas phase. Large difference in adsorption enthalpy of 2.5 kJ mol-1 between D2 and H2 results in D2-over-H2 selectivity of 11 at 100 K, to the best of our knowledge the largest value known to date. Combination of thermal desorption spectroscopy, Raman measurements, inelastic neutron scattering and first principles calculations for H2/D2 mixtures allows the prediction of selectivities for tritium-containing isotopologues.

[THE INFLUENCE OF NANODISPERSE CERIUM DIOXIDE ON ONTOGENETIC CHANGES OF ANTIOXIDANT SYSTEM IN THE MUCOSA OF THE STOMACH AND COLON IN RATS].

It was established that with age the content of lipid peroxidation products increased in the mucosa of the stomach: Diene conjugates by 30%, products which react to thiobarbituric acid by 285% and Schif bases by 181%. Nanodisperse cerium dioxide (NCD) reduced the content of lipid peroxidation in the gastric mucosa in old rats: Diene conjugates by 43 %, products which react to thiobarbituric acid by 51% and Schif bases by 44% relative to the control group of rats given age. Similarly, it was established that the content of Diene conjugates increased by 40%, products which react to thiobarbituric acid by 114% and Schif bases by 132% in the mucosa of the colon of old rats. NDC significant reduced the content of products which react to thiobarbituric acid by 69% and Schyf basics by 132%. In the stomach superoxide dismutase (by 43%) and catalase activity (by 24%) decreases with age, while in the colon superoxide dismutase activity increases (by 43%). In the colon NCD significant decreased superoxide dismutase (by 34%) and catalase activity (by 21%) relative to controls. Thus, the NDC restores lipid peroxidation in the gastric mucosa and colon, in which develops oxidative stress with age.

[Role of single-nucleotide polymorphism C-1562т of the matrix metaloproteіnaza-9 gene in the development of leiomyoma in women with cervical pathology].

108 women diagnosed with leiomyoma and 84 women without this disease (control group) were examined during the research. Was conducted a comparative analysis of the genotypes distribution between women with cervical pathology of different complexity. The results of the research showed, that there is no connection between the С-1562Т polymorphism of the MMP-9 gene and the progression of leiomyoma the course of which is accompanied by false erosion of the cervix (ectopias epithelium) (p>0,521). There is also was not found any connection between the SNP in women with leiomyoma, who undergo conical electrocauterizing excision treatment because of the dysplastic epithelial changes that are considered to be precancerous (p>0,280).

[Organization of anesthesia management and advanced life support at military medical evacuation levels].

Anesthesia management and advanced life support for the severely wounded personnel at military medical evacuation levels in armed conflict (local war) is time-consuming and resource-requiring task. One of the mathematical modeling methods was used to evaluate capabilities of anesthesia and intensive care units at tactical level. Obtained result allows us to tell that there is a need to make several system changes of the existing system of anesthesia management and advanced life support for the severely wounded personnel at military medical evacuation levels. In addition to increasing number of staff of anesthesiology-critical care during the given period of time another solution should be the creation of an early evacuation to a specialized medical care level by special means while conducting intensive monitoring and treatment.

[Synergetic basis of the system of specialized medical care, specialized treatment and medical rehabilitation of minimally injured and minimally ill].

The article is devoted to analysis of the current system of specialized medical care, specialized treatment and medical rehabilitation of military casualties of minor nature. The author suggested a synergistic approach to combination of the given system with the aim of determination of development conception. Two main schemes of organization of specialized medical care are considered: medical care during the military conflict and local war; medical care during the regional and large-scale war. Taking into account the function of military field hospital for the treatment of walking wounded it was suggested to add a word combination "center of rehabilitation". The functions of the hospital are considered.

Ecology of influenza virus in wild bird populations in Central Asia.

The study provides the results of avian influenza virus surveillance in Central Asia during 2003-2009. We have analyzed 2604 samples from wild birds. These samples were collected in Kazakhstan (279), Mongolia (650), and Russia (1675). Isolated viruses from samples collected in Mongolia (13 isolates) and in Russia (4 isolates) were described. Virological analysis has shown that six isolates belong to the H3N6 subtype and five isolates belong to the H4N6 subtype. Two H1N1 influenza viruses, one H10N7 virus, two H3N8 viruses, and an H13N8 virus that is new for Central Asia have been also isolated. Samples were taken from birds of six orders, including several species preferring water and semiaquatic biotopes, one species preferring dry plain regions, and one more species that can inhabit both dry and water biotopes.

[Specific traumatologic care forwounded and injured with fractures of long bones of extremities].

The efficiency of the system to assist victims with fractures of long bones in the Russian Defense Ministry is estimated. With the help of analytic hierarchy process a system-morphological and multi-criteria are defined and explored options for implementing 21 functions of the system. The result of scientific study was mathematical basis selected and adjusted for the nine criteria of the most effective alternative version of the implementation of the system to assist injured with fractures of long bones. On the basis of information was developed the concept of trauma service of Defense Ministry of Russia.

[About the improvement of urologic care for soldiers with erectile dysfunction].

Organizational concepts of improvement of urological aid given to military men with erectile dysfunction. The reasons for insufficiency of urological aid rendered to military men with erectile dysfunction were established. The algorithm of its diagnostics was developed. Complete and reduced volume of urological aid with reference to the existing medical and diagnostic capacities of military medical and preventive treatment facilities has been developed. Organizational concepts of improvement of urological aid given to the patients with erectile dysfunction have been determined.

[Improvement of controlling system by a separated medical unit of special purpose].

The article presents a variant securing of field treatment institutes by mobile command points in combination with creation of automated system of control of a separated medical unit of special purpose and improvement of communications devices, computing and relaying of data. Such improvement of system of control permits to solve governmental tasks and make decision more effective, spending less time.

[Main directions of growth of specialized medical aid in the Armed Forces].

Systemic and process approaches permit to present a specialized medical aid (SMA) as opened, complicated, hierarchical, self-organizing system. The main tendencies of development of SMA in military and civil health care are differentiation and integration of medical specialties, standardization of types of SMA, multilevelness of SMA, development of microsurgical, endovideosurgical techniques.

[Surgical treatment of gastroesophageal reflux disease combined with duodenal ulcer].

Operations for ulcer disease of the duodenum were performed on 696 patients. In 112 (16.1%) patients there were symptoms of insufficient obturating function of the cardia, which was considered to be an indication to antireflux simultaneous operation on the cardia. The indications were worked out for the decision on operative methods in patients with ulcer disease of the duodenum in combination with gastroesophageal reflux disease. Methods of resection were used in 88 (78.5%) patients, videolaparoscopic selective proximal vagotomy with an original means of fundoplication--in 24 (21.5%) patients. Good and excellent long-term results after operation were noted in 95.5% of the patients.

[Metabolic aspects of the prediction of outcome in chronic viral hepatitis].

The researchers evaluated the condition of lipid peroxidation and antioxidant protection system together with biochemical, immunological and morphological values in 117 patients with chronic hepatitis (CH) in virus replication phase (28 patient had CH type B, 66--CH type C and 28--CH type B+C), and estimated the importance of their interrelations to the prediction of disease outcomes.

[The specific features of the course of chronic viral hepatitis concurrent with chronic opisthorchiasis]. / Osobennosti techeniia khronicheskogo virusnogo gepatita pri sochetanii s khronicheskim opistorkhozom.

A hundred and one patients with chronic viral hepatitis (CVH) in the phase of replication were examined. Group 1 comprised 53 patients with CVH in combination with chronic opisthorchiasis. Group 2 (a comparison group) included 48 patients with CVH without opisthorchiasis. According to the etiology of hepatitis, each group was divided into 3 subgroups: subgroups 1a and 2a consisted of patients with CVHB; 1b and 2b included those with CVHC, and 1c and 2c comprised those with CVHB+C. The clinical, functional, and morphological status of the liver was studied and hepatic tissue was qualitatively and quantitatively assessed in all the examinees. The findings suggest that Opisthorchis is an additional factor that aggravates hepatic damage in patients with CVH in the replicative phase of infection.

[Imitative models of the organization of treatment and evacuation measures conducted in the infantry regiment during combat]. / Imitatsionnye modeli organizatsii lechebno-évakuatsionnykh meropriiatii v motostrelkovom polku v khode boia.

During the combat the chief of medical service has to solve both the direct mission, i.e. to choose the most effective variant of organization of treatment-and-evacuation measures (TEM) and the indirect one, i.e. to define the needs of medical service in forces and resources according to the given model. To fulfill these missions the most effective method is the multi-criteria approach for practical realization of which the "successive steps" method was chosen. The main indicator of TEM effectiveness is the time from the wounding to the point of readiness for evacuation from the regimental aid station. The GPSS language of different dialects as the modelling environment is preferred on the basis of which two computerized imitative models were created: the model of TEM effectiveness in the company-battalion link and the model of regimental aid station work.