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The purpose of this work was to determine the effectiveness of acute hemorrhoid thrombosis treatment using the "Surgitron" device in combination with intravenous parenteral ozone therapy. Patients aged from 26 to 67 years, who were divided into groups, agreed to participate in the study. The main group included 34 (53.1%) patients who underwent treatment according to the generally accepted method with "Surgitron" device in combination with intravenous parenteral ozone therapy. The second group included 30 (46.8%) patients who underwent thrombectomy. To analyze the results, data on the duration of the pain syndrome, immunological changes and coagulogram parameters were used. Most pathological conditions are accompanied by inflammation, hypoxia, collateral thrombosis, activation of damage processes by lipid peroxidation products, disturbed cellular and humoral immunity, decreased local immune protection, increased incidence of inflammatory complications, changes in the hemostasis system, since damage to the blood vessel wall causes immediate vasoconstriction of both the damaged vessel itself and adjacent capillaries and arterioles, which leads to blood flow slowdown in the area of damage to the external and internal hemorrhoidal plexus. Under normal conditions, endothelial cells are responsible for the antithrombotic interaction between blood and tissues, maintaining the liquid state of the blood. They produce such anticoagulants as glucosoaminoglycans, heparin sulfates, thrombomodulin, nitric oxide, which promotes vasodilation, improves blood rheology. In our studies, the content of fibrinogen A, fibrinogen B (products of fibrin degradation), the prothrombin index decreased in patients, and the thrombin clotting time decreased. Damage to endothelial cells in the anal-hemorrhoidal zone is caused by endotoxins, leading to inflammatory edema, which results in intoxication. Ozone's detoxifying effect counter-balances these complications. This work presents and analyses the results of acute hemorrhoid thrombosis treatment with radio wave exposure, which provided non–contact incision and hemostasis of soft tissues by high frequency waves (3.8–4.0 Hz), in combination with intravenous ozone therapy to enhance the analgesic and anti-inflammatory effects characterized by oxygen supply and oxidation of mediators involved in passing nociceptive signals in the central nervous system. When carrying out the comparative analysis of the patients' treatment results, the use of ozone against the background of thrombectomy showed a positive effect.

Phytophagous mites of the superfamily Eriophyoidea are capable of inducing gall formation on various organs of higher vascular plants. However, the question of how gallogenesis affects leaf assimilation surface and photosynthetic activity of the host plants is poorly understood. We have examined the influence of gall-forming mites from the genera Eriophyes and Acalitus on leaf size, shape and photosynthetic pigment content in five deciduous tree species near the city of Tyumen, West Siberia. The gall mite infestation resulted in chlorosis, destruction of photosynthetic apparatus in gall-infected leaf parts, leaf deformation and a decrease in leaf area. The magnitude of the effects on leaf size and shape varied among the studied mite–tree systems and did not depend on the infection severity. On the contrary, chlorophyll and carotenoid amounts per leaf decreased in an infection severity-dependent manner in all mite–host plant variants. Mite-induced galls did not influence the pigment concentration in green uninfected gaps between galls. Additionally, the chlorophyll amount in the infected leaves has decreased due to the destruction of the pigment complex in the galled leaf areas and a decrease of the whole-leaf area. As a result, the losses of chlorophylls and carotenoids in leaves of all studied trees were directly related to the infection severity (quantified as the proportion of damaged leaf area to the total leaf area). Our results may help developing an approach to assess the effect of gall mites on the chlorophyll content and the photosynthetic productivity of trees, based on the direct or remote analysis of damaged leaf surface.

Introduction. Advanced technologies impress people’s imagination demonstrating the latest achievements (materials, methods, systems, technologies, devices etc.) that dramatically change the world. This, first of all, concerns nanotechnological inventions designed by scientists, engineers and specialists from different countries. Main part. The paper briefly reviews inventions made by scientists, engineers and specialists from different countries: Russia, USA, China, Belarus, Great Britain, Vietnam, Denmark, the Kyrgyz Republic. The application of the results of scientists’, engineers’ and specialists’ investigations, including inventions in the area of nanotechnology and nanomaterials allow achieving significant efficiency in construction, house and communal service, related sectors of economy. For example, the invention “A method to modify concrete with complex additive which includes hydrothermal nanoparticles SiO2 and multi-layer carbon nanotubes” refers to methods of modifying concrete by introducing combination of nanoparticles with high specific surface into concrete mixture and can be used in production of precast and monolithic parts and structures of buildings and facilities of different purpose. This method of nanomodifying concrete makes it possible to achieve increased mechanical characteristics of concrete: compressive strength (25–77% at the age of 28 days) and bending strength, resistance to damage, Young’s mod of elasticity and shearing modulus, density (up to 10%), accelerated hardening at the early age and rate of strength development, decreased water absorbtion ability and improved indicators of porous structure (pore size and pore differential size uniformity), decreased total capillary porosity, increased frost resistance. The specialists can also be interested in the following nanotechnological inventions: a method to obtain polycrystalline diamond films; phase change materials for building construction: an overview of nano-/microencapsulation, solar collector of transpiration type; a method to obtain composition for antimicrobic coating on the basis of silver sulphide associates with molecules of methylene blue; broadband electromagnetic absorbing coating; a method to produce dry building mixtures; self-organizing nanostructures and separation membrane including aquaporin water channels and the methods to produce and use them; a method to obtain nanocrystalline titanium dioxide with anatase structure, etc. Conclusion. One of the most challenging tasks the economy of every country face is to increase industrial competitiveness through technological upgrade. From the side of the state and companies the principal object to control in this process are the people and enterprises dealing with introduction of inventions and new technologies

Brain tissue transcriptomes may be organized into gene coexpression networks, but their underlying biological drivers remain incompletely understood. Here, we undertook a large-scale transcriptomic study using 508 wild-type mouse striatal tissue samples dissected exclusively in the afternoons to define 38 highly reproducible gene coexpression modules. We found that 13 and 11 modules are enriched in cell-type and molecular complex markers, respectively. Importantly, 18 modules are highly enriched in daily rhythmically expressed genes that peak or trough with distinct temporal kinetics, revealing the underlying biology of striatal diurnal gene networks. Moreover, the diurnal coexpression networks are a dominant feature of daytime transcriptomes in the mouse cortex. We next employed the striatal coexpression modules to decipher the striatal transcriptomic signatures from Huntington's disease models and heterozygous null mice for 52 genes, uncovering novel functions for Prkcq and Kdm4b in oligodendrocyte differentiation and bipolar disorder-associated Trank1 in regulating anxiety-like behaviors and nocturnal locomotion.

It performed the analysis of the literature data on the peculiarities of the influence of type 2 diabetes mellitus on the endoprosthesis replacement of the steep joints in patients with diabetes mellitus outcomes. Reviewed the risk factors for complications of endoprosthetics, it is shown that in patients with diabetes mellitus operations on the hip joints are associated with higher rates of postoperative infection, the need for blood transfusion, the development of pneumonia and urinary tract infections, and increased hospital stays and higher rates nosocomial mortality. It was noted that in the course of making a decision on the performance of arthroplasty, surgical risk should be assessed for patients with diabetes, taking into account the possible complications of diabetes and the presence of other associated diseases. The basic principles of preoperative preparation, peri-and postoperative management of this cohort of patients are characterized.

We studied the impact of fly ash produced by the thermal power station in the Middle Urals (Russia) on functional traits of two Betula species naturally colonizing ash dump lagoons. The main limiting factors for tree growth on fly ash deposits were nitrogen deficiency, high alkalinity, and unfavorable mechanical composition of substrate. Leaf area ratio (LAR) and leaf mass ratio (LMR) per tree, leaf area (LA), leaf shape coefficient (LSh), leaf thickness (LT), leaf mass per area (LMA), photosynthesis (A

Lately unmanned aerial vehicles (UAV) became an unseparated part of modern life. These machines gained their particular popularity in the field of amateur or professional video production and small cargo deliveries. But they are not only limited by civilian lines of activity. Nowadays they are also used in military conflicts either as scout or as a deadly precise weapon. Due to UAV’s easy market access, these drones can be used by the hands of terrorists groups. It’s not a rocket science to attach an explosive device to UAV, guide it to strategic area and detonate it from far away. This is one of the main danger sources for such places like nuclear power plants. A downward trend also led to new type of thread – swarm attacks, when group of small UAVs strikes their victim. A timely detection of such attacks is not a trivial task. This question is being studied by many researches from different fields. The most promising methods comes from radiolocation and computer vision areas. Next in the paper, modern algorithms of detection, classification and tracking of UAVs by using optical flow will be reviewed. Usually, the common approach for this task comes from classic computer vision methods or, highly popular today, deep learning methods.

The tick-borne encephalitis virus (TBEV) strain Lazo MP36 was isolated from the pool of mosquitoes Aedes vexans collected in Lazo region of Khabarovsk territory in August 2014. Phylogenetic analysis of the strain Lazo MP36 complete genome (GenBank accession number KT001073) revealed its correspondence to the TBEV Far Eastern subtype and differences from the following strains: 1) from ticks Ixodes persulcatus P. Schulze, 1930 [vaccine strain 205 (JX498939) and strains Khekhtzir 1230 (KF880805), Chichagovka (KP844724), Birobidzhan 1354 (KF880805) isolated in 2012-2013]; 2) from mosquitoes [strain Malyshevo (KJ744034) isolated in 1978 from Aedes vexans nipponii in Khabarovsk territory; strain Sakhalin 6-11 isolated from the pool of mosquitoes in 2011 (KF826916)]; 3) from human brain [vaccine strain Sofjin (JN229223), Glubinnoe/2004(DQ862460). Kavalerovo (DQ862460), Svetlogorie (DQ862460)]. The fusion peptide necessary for flavivirus entry to cells of the three TBEV strains isolated from mosquitoes (Lazo MP36, Malyshevo and Sakhalin 6-11) has the canonical structure 98-DRGWGNHCGLFGKGSI-113 for the tick-borne flaviviruses. Amino acid transition H104G typical for the mosquito-borne flaviviruses was not found. Structures of 5’- and 3’-untranslated (UTR) regions of the TBEV strains from mosquitoes were 85-98% homologous to the TBEV strains of all subtypes without recombination with mosquito-borne flaviviruses found in the Far East of Russia. Secondary structures of 5’- and 3'-UTR as well as cyclization sequences (CS) of types a and B are highly homologous for all TBEV isolates independently of the biological hosts and vectors. similarity of the genomes of the TBEV isolates from mosquitoes, ticks and patients as well as pathogenicity of the isolates for new-borne laboratory mice and tissue cultures might suggest a possible role of mosquitoes in the TBEV circulation in natural foci as an accidental or additional virus carrier.

Borrelia burgdorferi sensu lato (s.l.) DNA was detected by PCR in Ixodes persulcatus Schulze, 1930, Haemaphysalis concinna Koch, 1844, Haemaphysalis japonica douglasi Nuttall et Warburton, 1915 and Dermacentor silvarum Olenev, 1932 ticks collected in the Amur region, the Jewish Autonomous region, the Sakhalin region and on the Khabarovsk territory. Infection rate of I. persulcatus with B. burgdorferi s.l. 10–69% exceeded the corresponding values of three other tick species in all examined regions during 1999–2014 despite different tick abundance and dominance structure. Bacterial loads estimated on the base of quantitative real time PCR varied from 102 to 109 genome-equivalents per a tick with maximal values for I. persulcatus and H. japonica. Phylogenetic analysis of 16S rRNA gene and 5S—23S rRNA intergenic spacer nucleotide sequences revealed two species: 1) Borrelia garinii of Asian type NT29 with several isolates of European type 20047; 2) Borrelia afzelii with identical sequences of the majority of studied isolates and VS461 reference strain in all regions except the Sakhalin Island where B. afzelii was not found. Borrelia miyamotoi of the relapsing fever group was detected as monoinfection or in combination with B. burgdorferi s.l. in 4.0 ± 0.9% and 4.8 ± 0.9% I. persulcatus ticks, respectively. Multiple locus sequence analysis of three fragments of 16S rRNA, glpQ and p66 genes proved that all the Far Eastern B. miyamotoi isolates belonged to the Asian type identical to FR64b strain (GenBank CP004217) from Japan. Wide distribution of Borrelia DNA in ticks, relative genetic homogeneity with similar sequences of the coding regions and the intergenic spacer of Borrelia wild isolates and temporal stability with high homology levels of the Far Eastern isolates of B. garinii, B. afzelii and B. miyamotoi with previously described spirochetes from the surrounding regions of Russia, China and Japan allowed us to suggest multiple ecological niches as the stability factor of the parasitic system., Graphical abstract Image 1, Highlights • Borrelia DNA was detected in four species of ixodid ticks by PCR. • Bacterial loads were up to 109 Borrelia genome-equivalents per a tick. • Infection rate and bacterial loads were highest for Ixodes persulcatus. • Phylogenetic analysis showed Borrelia garinii, B. afzelii and Borrelia miyamotoi. • Genetic homogeneity of Borrelia spp. suggests multiple ecological niches.

Rickettsia spp. are intracellular Gram-negative bacteria transmitted by arthropods. Two potentially pathogenic rickettsiae, Candidatus Rickettsia tarasevichiae and Rickettsia helvetica, have been found in unfed adult Ixodes persulcatus ticks. The aim of this study was to assess the prevalence and genetic variability of Rickettsia spp. in I. persulcatus ticks collected from different locations in the Russian Far East. In total, 604 adult I. persulcatus ticks collected from four sites in the Khabarovsk Territory (continental area) and one site in Sakhalin Island were examined for the presence of Rickettsia spp. by real-time PCR. Nested PCR with species-specific primers and sequencing were used for genotyping of revealed rickettsiae. The overall prevalence of Rickettsia spp. in ticks collected in different sites varied from 67.9 to 90.7%. However, the proportion of different Rickettsia species observed in ticks from Sakhalin Island significantly differed from that in ticks from the Khabarovsk Territory. In Sakhalin Island, R. helvetica prevailed in examined ticks, while Candidatus R. tarasevichiae was predominant in the Khabarovsk Territory. For gltA and ompB gene fragments, the sequences obtained for Candidatus R. tarasevichiae from all studied sites were identical to each other and to the known sequences of this species. According to sequence analysis of gltA, оmpB and sca4 genes, R. helvetica isolates from Sakhalin Island and the Khabarovsk Territory were identical to each other, but they differed from R. helvetica from other regions and from those found in other tick species. For the first time, DNA of pathogenic Rickettsia heilongjiangensis was detected in I. persulcatus ticks in two sites from the Khabarovsk Territory. The gltA, ompA and оmpB gene sequences of R. heilongjiangensis were identical to or had solitary mismatches with the corresponding sequences of R. heilongjiangensis found in other tick species.

Electron paramagnetic resonance of spin probes was used to study the effect of low and high molecular weight CPAs on microviscosity of erythrocyte membranes. Research data on rotational mobility of the fatty acid spin probes in erythrocyte membranes after 5 min incubation in 15 % propylene glycol solution indicate the absence of strong changes in membrane microviscosity. Introduced polyethylene glycol with m. w. 1500 (PEG-1500) at a final concentration of 15% has been shown to increase the membrane microviscosity at 60 min exposure. This is explained by the fact that the molecules of PEG-1500 do not pass inside the cells and are localized on the membrane surface to cause immobilization and inhibiting the rotational mobility of the spin probe. In the initial period of time under these concentrations of PEG-1500 the injury of liquid crystal membrane structure and disorder of the protein-lipid interactions in the membrane prevail over the dehydration of cells. Probl Cryobiol Cryomed 2016; 26(1):35-44.

In our time more and more digital camera developers are beginning to use UHD resolution. This way of design evolution allows us to greatly increase overall quality of captured image. With increasing of total pixel amount, we can implement new features without dramatic resolution loss, like digital zoom or geometric aberration correction. While resolution and quality grows, either does pipeline bandwidth of video processor. In 12G-SDI video stream, pixel clock is 596 MHz, which is defining while choosing FPGA, where our video processor will be implemented in. Intel and Xilinx recommends to use very high-cost FPGA, like: Arria, Stratix, Virtex and Kintex. In this paper, we will present an approach to design a pipeline that will process demosaicing of 4K 60 FPS video stream on low-cost FPGA Intel Cyclone V.

Recently, a new Ehrlichia genetic variant, Ehrlichia sp. Khabarovsk, was identified in tissue samples of small mammals captured in the Russian Far East. To further characterize Ehrlichia sp. Khabarovsk, tissue homogenate from a naturally infected gray red-backed vole ( Myodes rufocanus ) was passaged three times in newborn laboratory mice. Using nested PCR Ehrlichia sp. Khabarovsk DNA was detected in tissue samples from infected mice at 1–4 weeks post inoculation. Electron microscopic examination revealed morulae containing gram-negative bacterial cells in monocytes of mouse spleen and liver. The size and ultrastructure of these cells corresponded to those described previously and allowed us to identify the bacteria as Ehrlichia sp. The comparison of ehrlichial 16S rRNA, groEL and gltA genes and putative GroEL and GltA amino acid sequences has demonstrated that Ehrlichia sp. Khabarovsk, like Ehrlichia ruminantium , is more distant from all other Ehrlichia species than these species are between themselves. Phylogenetic analysis has shown that Ehrlichia sp. Khabarovsk belongs to the clade formed by Ehrlichia spp. but clusters separately from other Ehrlichia species and genetic variants. These data indicate that Ehrlichia sp. Khabarovsk can be considered as a new candidate species. We propose to designate it as ‘ Candidatus Ehrlichia khabarensis’ according to the territory where this species was found.

Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating between active immunity and tolerance. We hypothesized that a similar dynamic exists in melanoma and administration of therapy during a unique phase of such oscillation could impact clinical outcome. Patients with metastatic melanoma eligible to undergo temozolomide underwent serial measurements of C-reactive protein (CRP) and immune biomarkers every 2-3 days for 2 weeks before starting therapy. Treatment was initiated prior to the estimated next CRP peak, or on day 14 post-registration if a peak was not identified. Time profiles of measured biomarkers were analyzed by fitting serially measured data points to 9 mathematical functions and were correlated to time of therapy and outcome. Data suggested that metastatic melanoma patients exhibit a dynamic immune response. The fluctuation of several biomarkers fitted cosine functions with periods which were multiples of 3-4 days. Chemotherapy delivery during a unique phase of this cycle seemed to correlate with improved response. Individualized conventional chemotherapy delivery by synchronizing treatment with pre-existing patient-specific biorhythms may improve clinical outcomes in metastatic melanoma.

We studied the impact of aridity on leaf and mesophyll traits in dominant and very abundant plant species of Eurasian steppe plant communities. We covered a 500-km latitudinal gradient across three vegetation zones in the Volga region of southern European Russia. Whole-leaf traits, volumetric fractions of leaf tissues, quantitative parameters of photosynthetic cells and chloroplasts, and chlorophyll, carbon (C) and nitrogen (N) contents were analyzed and related to plant functional type (PFT), type of mesophyll anatomy, phylogeny and climate aridity. The proportions of prevailing PFTs in the communities, such as C

Isolates of tick-borne encephalitis virus (TBEV) from arthropod vectors (ticks and mosquitoes) in the Amur, the Jewish Autonomous and the Sakhalin regions as well as on the Khabarovsk territory of the Far East of Russia were studied. Different proportions of four main tick species of the family Ixodidae: Ixodes persulcatus P. Schulze, 1930; Haemaphysalis concinna Koch, 1844; Haemaphysalis japonica douglasi Nuttall et Warburton, 1915 and Dermacentor silvarum Olenev, 1932 were found in forests and near settlements. RT-PCR of TBEV RNA in adult ticks collected from vegetation in 1999-2014 revealed average infection rates of 7.9 ± 0.7% in I. persulcatus, of 5.6 ± 1.0% in H. concinna, of 2.0 ± 2.0% in H. japonica, and of 1.3 ± 1.3% in D. silvarum. Viral loads varied in a range from 102 to 109 TBEV genome-equivalents per a tick with the maximal values in I. persulcatus and H. japonica. Molecular typing using reverse transcription with subsequent real time PCR with subtype-specific fluorescent probes demonstrated that the Far Eastern (FE) subtype of TBEV predominated both in mono-infections and in mixed infection with the Siberian (Sib) subtype in I. persulcatus pools. TBEV strains of the FE subtype were isolated from I. persulcatus, H. concinna and from a pool of Aedes vexans mosquitoes. Ten TBEV strains isolated from I. persulcatus from the Khabarovsk territory and the Jewish Autonomous region between 1985 and 2013 cluster with the TBEV vaccine strain Sofjin of the FE subtype isolated from human brain in 1937. A TBEV strain from H. concinna collected in the Amur region (GenBank accession number KF880803) is similar to the vaccine strain 205 isolated in 1973 from I. persulcatus collected in the Jewish Autonomous region. The TBEV strain Lazo MP36 of the FE subtype isolated from a pool of A. vexans in the Khabarovsk territory in 2014 (KT001073) differs from strains isolated from 1) I. persulcatus (including the vaccine strain 205) and H. concinna; 2) mosquitoes [strain Malishevo (KJ744034) isolated in 1978 from Aedes vexans nipponii in the Khabarovsk territory]; and 3) human brain (including the vaccine strain Sofjin). Accordingly, in the far eastern natural foci, TBEV of the prevailing FE subtype has remained stable since 1937. Both Russian vaccines against TBE based on the FE strains (Sofjin and 205) are similar to the new viral isolates and might protect against infection.

A method is suggested for estimating unknown velocities by combining their sparse measurements with observations of a tracer on a fine grid advected by the underlined velocity field. The dependence of the estimation error on a coarseness parameter and parameters of the flow in question is investigated numerically using synthetic velocity fields typical for real oceanic circulation. In an advanced version of the estimation procedure uncertainty in the transport equation forcing is modeled via a fuzzy sets approach. We also compare the method with a traditional interpolation which is in contrast to the developed procedure unable to capture the flow details.

Skin cancer affects more individuals in the USA than any other malignancy and malignant melanoma is particularly deadly because of its metastatic potential. Melanoma has been recognized as one of the most immunogenic malignancies; therefore, understanding the mechanisms of tumor-immune interaction is key for developing more efficient treatments. As the tumor microenvironment shows an immunosuppressive action, immunotherapeutic agents promoting endogenous immune response to cancer have been tested (interleukin-2, anticytotoxic-T-lymphocyte-associated antigen 4, and antiprogrammed cell death protein 1 monoclonal antibodies) as well as combinations of cytotoxic chemotherapy agents and inhibitors of angiogenesis (taxol/carboplatin/avastin). However, clinical outcomes are variable, with only a minority of patients achieving durable complete responses. The variability of immune homeostasis, which may be more active or more tolerant at any given time, in cancer patients and the interaction of the immune system with the tumor could explain the inconsistency in clinical outcomes among these patients. Recently, the role of the lymphocyte-to-monocyte-ratio (LMR) in the peripheral blood has been investigated and has been proven to be an independent predictor of survival in different hematological malignancies and in solid tumors. In melanoma, our group has validated the significance of LMR as a predictor of relapse after resection of advanced melanoma. In this study, we examined the dynamics in the immune system of patients with advanced melanoma by performing serial multiday concentration measurements of cytokines and immune cell subsets in the peripheral blood. The analysis of outcomes of chemotherapy administration as related to LMR on the day of treatment initiation showed that progression-free survival was improved in the patients who received chemotherapy on the day when LMR was elevated.

Hemorrhagic fever with renal syndrome (HFRS) is a serious public health issue in Far East Russia. Two different hantaviruses were isolated from rodents captured in the Khabarovsk region: Amur virus (AMRV; Khekhtsir/ AP209/2005 strain from Apodemus peninsulae) and Hantaan virus (HTNV; Galkino/AA57/2002 strain from A. agrarius). Genetic analysis of the new isolates revealed that the M and L segments were apparently different between AMRV and HTNV, but S segments of the two viruses were closer. The antigenicities of AMRV, HTNV, and Seoul virus (SEOV) were differentiated by cross-neutralization. Serological differential diagnoses of 67 HFRS patients in the Prymorsky and Khabarovsk regions of Far East Russia were conducted using a neutralization test. The results revealed that the major cause of HFRS varied with location in Far East Russia: SEOV for Vladivostok city in the Prymorsky region, AMRV in rural areas of the Primorsky region, and probably HTNV for the Khabarovsk region.

Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating between active immunity and tolerance. We hypothesized that a similar dynamic exists in melanoma and administration of therapy during a unique phase of such oscillation could impact clinical outcome. Patients with metastatic melanoma eligible to undergo temozolomide underwent serial measurements of C-reactive protein (CRP) and immune biomarkers every 2-3 days for 2 weeks before starting therapy. Treatment was initiated prior to the estimated next CRP peak, or on day 14 post-registration if a peak was not identified. Time profiles of measured biomarkers were analyzed by fitting serially measured data points to 9 mathematical functions and were correlated to time of therapy and outcome. Data suggested that metastatic melanoma patients exhibit a dynamic immune response. The fluctuation of several biomarkers fitted cosine functions with periods which were multiples of 3-4 days. Chemotherapy delivery during a unique phase of this cycle seemed to correlate with improved response. Individualized conventional chemotherapy delivery by synchronizing treatment with pre-existing patient-specific biorhythms may improve clinical outcomes in metastatic melanoma.

Totally, 2590 questing adult Ixodes persulcatus ticks and 1458 small mammals from Ural, Siberia, and the Far East as well as 53 Haemaphysalis concinna, 136 Haem. japonica, and 43 Dermacentor silvarum ticks--exclusively adults--from the Far East were examined for the presence of Ehrlichia and Anaplasma by nested PCR based on the 16S rRNA gene. Both Anaplasma phagocytophilum and Ehrlichia muris were found in I. persulcatus and small mammals from all the studied regions. Myodes spp., Microtus spp., Sorex araneus, Apodemus peninsulae, and Tamias sibiricus were naturally infected with An. phagocytophilum and E. muris. Five of the examined I. persulcatus and 5 of the examined wild rodents from Siberia and the Far East were infected with 'Candidatus Neoehrlichia mikurensis'. The determined 16S rRNA gene sequences of 'Candidatus Neoehrlichia mikurensis' were identical to the sequences of Japanese isolates, while the determined groESL sequences were unique. A new Ehrlichia sp. variant closely related to the Ehrlichia sp. EHf669 found in Haem. flava from Japan was detected in 11% of Haem. japonica ticks. New Anaplasmataceae bacteria genetically distinct from the known species of this family were found in 3 adult Derm. silvarum from the Far East and in 2 I. persulcatus from Siberia and the Far East. In the Far East, about 15% of the captured small mammals were naturally infected with recently discovered Ehrlichia sp. Khabarovsk. Ehrlichia sp. Khabarovsk was found in about 20% of Myodes spp. and S. araneus but was undetectable in any of the 236 studied Ap. peninsulae. A three-year study has demonstrated that An. phagocytophilum and E. muris were detectable in small mammals from the Far East captured only after the beginning of the tick activity season, from May to November. Ehrlichia sp. Khabarovsk was found in mammals trapped in all the examined periods, from February to November.

A total 834 Ixodes persulcatus ticks and 641 small mammals from the areas of northern and southern Ural, southeastern and southwestern Siberia, and the Far East was examined on the presence of Anaplasma spp. and Ehrlichia spp. by nested PCR based on 16S rRNA gene with subsequent sequencing. A. phagocytophilum and E. muris DNAs were found in samples from ticks and small mammals in all studied areas. A. phagocytophilum DNA was revealed in 0.3–5.1% of ticks and 3.2–16.6% of small mammals from different regions, whereas E. muris DNA was found in 4.9–15.3% of ticks and 4.1–12.6% of small mammals. One I. persulcatus tick and one east-European field vole from the Siberian region were shown to contain ‘Candidatus Neoehrlichia mikurensis’ DNA. A novel Ehrlichia species, closely related to Ehrlichia sp. EHf669, Ehrlichia sp. EH727, Ehrlichia sp. Tibet and ‘Candidatus Ehrlichia shimanensis’, was found using molecular techniques in tissue samples of 14.4% of small rodents from the Far East.

Flaviviruses are subdivided into three groups— mosquito-borne, tick-borne and no-known vector viruses. Tick-borne encephalitis virus (TBEV) is the most widely spread flavivirus in Eurasia which is transmitted to man by tick bytes and causes severe neuroinfection with lethal outcomes. Ticks are main carriers and reservoir hosts of the TBEV in nature. Their ability to feed on a variety of vertebrate animals, intracellular digestion of blood, their long life cycle up to 3-6 years at each stage of development and transovarial transmission of the TBEV make them ideal vectors. Natural TBEV infection had been revealed for 16 species of ixodid ticks. Methods: TBEV strains were isolated from a pool of mosquito Aedes vexans and ticks Ixodes persulcatus Schulze in new-born mice and porcine embryo kidney cells. Nucleotide sequences of reverse` transcription-PCR products were determined using DNA analyzer ABI 3500 (Applied Biosystems, USA). Assembling of the nucleotide sequences into complete genomes of the TBEV strains, their alignment and phylogenetic analysis were performed using MEGA 6.06.

In an epizootiologic survey of 122 rodents captured in Vladivostok, Russia, antibodies positive for hantavirus were found in Apodemus peninsulae (4/70), A. agrarius (1/39), and Clethrionomys rufocanus (1/8). The hantavirus sequences identified in two seropositive A. peninsulae and two patients with hemorrhagic fever with renal syndrome (HFRS) from the Primorye region of Far East Russia were designated as Solovey and Primorye, respectively. The nucleotide sequences of the Solovey, Primorye, and Amur (obtained through GenBank) sequences were closely related (>92% identity). Solovey and Primorye sequences shared 84% nucleotide identity with the prototype Hantaan 76-118. Phylogenetic analysis also indicated a close relationship between Solovey, Primorye, Amur, and other viruses identified in Russia, China, and Korea. Our findings suggest that the Korean field mouse (A. peninsulae) is the reservoir for a hantavirus that causes HFRS over a vast area of east Asia, including Far East Russia.

We have previously reported that tick-borne encephalitis (TBE) is endemic in a specific area of Hokkaido, Japan. In Oshima, the southern part of Hokkaido, TBE virus was isolated from sentinel dogs, ticks and rodents in 1995 and 1996. To identify when these TBE viruses emerged in Hokkaido, the times of divergence of TBE virus strains isolated in Oshima and far-eastern Russia were estimated. TBE virus was isolated in Khabarovsk in 1998 and the nucleotide sequences of viral envelope protein genes of isolates from Oshima and Khabarovsk were compared. From the synonymous substitution rate of these virus strains, the lineage divergence time of these TBE virus strains was predicted phylogenetically to be about 260–430 years ago. Furthermore, the virulence of TBE virus isolates from Oshima and Khabarovsk were compared in a mouse model. The results showed that the isolates possessed very similar virulence in mice. This report provides evidence that the Oshima strains of TBE virus in Hokkaido emerged from far-eastern Russia a few hundred years ago and this explains why these strains possess virulence similar to the TBE viruses isolated in Russia.

The antigenic relationships among 71 hantavirus strains, isolated from rodent species or humans in several geographic regions, were examined by immunofluorescence assay (IFA) using human patient sera and a panel of 22 monoclonal antibodies prepared against Hantaan, Seoul, and Puumala viruses. The study included virus strains, mainly from the former USSR, for which little or no serological data were available. Fifty-nine of the 71 isolates could be placed into five antigenic groups of hantaviruses, Hantaan (HTN), Puumala (PUU), Seoul (SEO), Prospect Hill (PH), Dobrava/Belgrade (DOB). Twelve isolates were found antigenically closely related to, but distinct from, HTN (2 strains), PUU (4 strains) and PH (6 strains), respectively. The antigenic characteristics of these 12 isolates suggested two supplementary antigenic subgroups of HTN, one of PUU, and two of PH. The two antigenic subgroups of HTN included strains isolated in the Far-East of Russia. The PUU subgroup included strains isolated in European Russia as well as strains isolated in Far-Eastern Russia. The PH group comprised two subgroups, both represented by strains isolated from M. fortis in Far-Eastern Russia. The results showed that the PUU and PH antigenic groups are more complex than previously known and that PH-like virus strains isolated in Russia are antigenically more closely related to PUU virus when compared to prototype PH virus isolated in the USA.

The specimens of 3552 questing adult Ixodes persulcatus and 1698 blood/tissue samples of small mammals collected in Ural, Siberia, and Far East of Russia were assayed for the presence of Anaplasma phagocytophilum by nested PCR based on the 16S rRNA gene. Totally, A. phagocytophilum was detected in 112 tick and 88 mammalian samples. The nucleotide sequences of the 16S rRNA gene and groESL operon (1244-1295 bp) were determined for A. phagocytophilum samples from 65 ticks and 25 small mammals. Six different 16S rRNA gene variants differing by 1-5 nucleotide substitutions were detected, and only one variant matched the sequences deposited in GenBank. Analysis of groESL sequences allowed the A. phagocytophilum samples to be divided into three groups; moreover, the samples from different groups also differed in the 16S rRNA gene sequences. The A. phagocytophilum sequences from group I were detected in 11 Myodes spp. samples from West Siberia and Far East and in 19 I. persulcatus samples from all examined regions; from group II, in 10 samples of Myodes spp. and common shrews (Sorex araneus) from Ural; and from group III, in four samples of Asian chipmunks (Tamias sibiricus) from West Siberia and Far East; and in 46 I. persulcatus samples from all examined regions. The nucleotide sequences of A. phagocytophilum groESL operon from groups I and II were strictly conserved and formed with A. phagocytophilum groESL sequence from a Swiss bank vole (Myodes glareolus) (GenBank accession no. AF192796), a separate cluster on the phylogenetic tree with a strong bootstrap support. The A. phagocytophilum groESL operon sequences from group III differed from one another by 1-4 nucleotides and formed a separate branch in the cluster generated by European A. phagocytophilum strains from roe deer (Capreolus capreolus) and Ixodes ricinus ticks.

West Nile (WN) virus has been spreading geographically to non-endemic areas in various parts of the world. However, little is known about the extent of WN virus infection in Russia. Japanese encephalitis (JE) virus, which is closely related to WN virus, is prevalent throughout East Asia. We evaluated the effectiveness of a focus reduction neutralization test in young chicks inoculated with JE and WN viruses, and conducted a survey of WN infection among wild birds in Far Eastern Russia. Following single virus infection, only neutralizing antibodies specific to the homologous virus were detected in chicks. The neutralization test was then applied to serum samples from 145 wild birds for WN and JE virus. Twenty-one samples were positive for neutralizing antibodies to WN. These results suggest that WN virus is prevalent among wild birds in the Far Eastern region of Russia.