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Implementation of new approaches for generating conventional reassortants for live attenuated influenza vaccine based on Russian master donor viruses
No full textCold-adapted influenza strains A/Leningrad/134/17/57 (H2N2) and B/USSR/60/69, originally developed in Russia, have been reliable master donors of attenuation for preparing live attenuated influenza vaccines (LAIV). The classical strategy for generating LAIV reassortants is robust, but has some disadvantages. The generation of reassortants requires at least 3 passages under selective conditions after co-infection; each of these selective passages takes six days. Screening the reassortants for a genomic composition traditionally starts after a second limiting dilution cloning procedure, and the number of suitable reassortants is limited. We developed a new approach to shorten process of preparing LAIV seed viruses. Introducing the genotyping of reassortants by pyrosequencing and monitoring sequence integrity of surface antigens starting at the first selective passage allowed specific selection of suitable reassortants for the next cloning procedure and also eliminate one of the group selective passage in vaccine candidate generation. Homogeneity analysis confirmed that reducing the number of selective passages didn't affect the quality of LAIV seed viruses. Finally, the two-way hemagglutination inhibition test, implemented for all the final seed viruses, confirmed that any amino acid substitutions acquired by reassortants during egg propagation didn't affect antigenicity of the vaccine. Our new strategy reduces the time required to generate a vaccine and was used to generate seasonal LAIVs candidates for the 2012/2013, 2014/2015, and 2015/2016 seasons more rapidly. © 2015
Frequency of type 2 diabetes in family and it's changes in diabetic patients affected or not affected with cancer
No full textAims. To study at greater than before material the prevalence of type 2 diabetes (DM2) in relatives of suffering from DM2 patients with cancer and compare the features of antidiabetic therapy in cancer patients with a familial and non-familial form of diabetes. Materials and Methods. Information about diabetes history in family was collected during two subsequent periods (May 2009-February 2011 and March 2011-July 2014 years) in cancer patients (totally,1955 people; 1351 of them with DM2 and 604 without diabetes), as well as in patients with DM2 without cancer (n=379). All patients answered questions about diabetes in their mothers, fathers, siblings, and other relatives. In cancer patients with DM2, data on the type of antidiabetic therapy for at least 6 months prior to enrolling into the hospital were collected. Results. A lower frequency of family diabetes in diabetic patients with cancer (28,5±1,2% vs 38,0±2,5%,
How to Use SNP-TATA-Comparator to Find a Significant Change in Gene Expression Caused by the Regulatory SNP of This Gene's Promoter via a Change in Affinity of the TATA-Binding Protein for This Promoter
No full textThe use of biomedical SNP markers of diseases can improve effectiveness of treatment. Genotyping of patients with subsequent searching for SNPs more frequent than in norm is the only commonly accepted method for identification of SNP markers within the framework of translational research. The bioinformatics applications aimed at millions of unannotated SNPs of the "1000 Genomes" can make this search for SNP markers more focused and less expensive. We used our Web service involving Fisher's Z-score for candidate SNP markers to find a significant change in a gene's expression. Here we analyzed the change caused by SNPs in the gene's promoter via a change in affinity of the TATA-binding protein for this promoter. We provide examples and discuss how to use this bioinformatics application in the course of practical analysis of unannotated SNPs from the "1000 Genomes" project. Using known biomedical SNP markers, we identified 17 novel candidate SNP markers nearby: rs549858786 (rheumatoid arthritis); rs72661131 (cardiovascular events in rheumatoid arthritis); rs562962093 (stroke); rs563558831 (cyclophosphamide bioactivation); rs55878706 (malaria resistance, leukopenia), rs572527200 (asthma, systemic sclerosis, and psoriasis), rs371045754 (hemophilia B), rs587745372 (cardiovascular events); rs372329931, rs200209906, rs367732974, and rs549591993 (all four: cancer); rs17231520 and rs569033466 (both: atherosclerosis); rs63750953, rs281864525, and rs34166473 (all three: malaria resistance, thalassemia). © 2015 Mikhail Ponomarenko et al
Engineering effective responses to influenza outbreaks
No full textWe present a policy-oriented summary of our six-year "service-systems-focused" research into pandemic influenza. We cover three topics: (1) R0, the basic reproductive number for the flu; (2) NPIs, non-pharmaceutical inventions to reduce the chance of becoming infected; and (3) flu vaccine allocations. We use a service-systems framing and mathematical modeling approach incorporating theories and data on the spread and control of influenza. We examine how behavioral actions and governmental policies, thoughtfully derived, can minimize influenza's societal impact. There is widespread misinterpretation that R0 is a numerical constant of a given virus. We argue that it is not, but rather that its value is largely determined by local conditions and actions, many under our individual and collective control. This control is, in the absence of vaccine, intelligent use of NPIs-highly effective in reducing the spread of influenza. Our vaccine analysis relies on government data depicting flu-like cases and vaccines administered during the 2009 H1N1 outbreak. During that outbreak, barely half of all states received allotments of vaccine in time to protect any citizens. The method of vaccine deployment-in proportion to census population-ignored the temporally uneven flu wave progression across the United States. © 2015 INFORMS
Glycyrrhizic acid derivatives as influenza A/H1N1 virus inhibitors
No full textThis Letter describes the synthesis and antiviral activity study of some glycyrrhizic acid (GL) derivatives against influenza A/H1N1/pdm09 virus in MDCK cells. Conjugation of GL with l-amino acids or their methyl esters, and amino sugar (d-galactose amine) dramatically changed its activity. The most active compounds were GL conjugates with aromatic amino acids methyl esters (phenylalanine and tyrosine) (SI = 61 and 38), and S-benzyl-cysteine (SI = 71). Thus modification of GL is a perspective route in the search of new antivirals, and some of GL derivatives are potent as anti-influenza A/H1N1 agents. © 2015 Elsevier Ltd. All rights reserved
Adipokines and a risk for metabolic disturbances in different types of female obesity
No full textAim. To investigate the effects of adiponectin and leptin on the development of metabolic disturbances in women with android and gynoid fat distribution. Subjects and methods. A total of 101 women aged 40 to 65 years were examined. Anthropometric measurements were made; overweight and obese women with a waist/hip (W/H) ratio of less than 0.83 were referred to as a gynoid fat distribution (GFD) group; and those with a W/H ratio of 0.83 or more were to an android fat distribution (AFD) group. The serum concentrations of triglycerides, high-density lipoprotein cholesterol, and glucose were measured; the levels of insulin, leptin, and adiponectin were determined by enzyme immunoassay. Insulin resistance (IR), HOMA IR, and visceral obesity index (VOI) were calculated. Results. With the same excess adipose tissue accumulation, the women with GFD had a less magnitude of hormonal and metabolic disturbances than those with AFD, whose HOMA-IR also pointed to the presence of IR. VOI was insignificantly higher in the women with GFD and 2.4-fold greater than that in normal weight (NW) women. In the women with GFD and AFD, the concentration of leptin was higher than that in the NW women, which was characteristic of obesity, but the concentration of adiponectin proved to be significantly lower in the patients with AFD and to be unchanged in those with GFD as compared with that in the NW women. Conclusion. The women with AFD are typified by a high VOI, hypoadiponectinemia, IR, and metabolic disturbances, which determine a high risk for cardiovascular events and type 2 diabetes mellitus. In the women with GFD, obesity is associated with normal adiponectinemia and a low VOI and, in terms of hormonal and metabolic characteristics, may be characterized as metabolically healthy obesity
Current report from Russian diabetic retinopathy register
No full textA pandemic expansion of diabetes mellitus (DM) observed nowadays across the globe is increasingly acknowledged as a disaster by all peoples of the world. Statistical analysis indicates an annual increase in prevalence of DM in Russian Federation that had reached 3 779 423 registered patients by 01.01.2013. Besides the humanitarian aspects, DM poses severe economic challenges for this country-challenges that stem both from high mortality and growing disability rate due to limb loss, decrease in visual acuity and need for hemodialysis, plaguing many DM patients. Aim: To produce an epidemiological evaluation based on the dynamics of prevalence of diabetic retinopathy in the Russian Federation-nationwide and in individual regions-across the last 13 years. Materials and Methods: Current survey included patients from various regions of the Russian Federation that were examined during epidemiological missions conducted by the federal Endocrinology Research Centre (2000-2009), as well as National Programmes «Health» (2007) and «Diabetes-Learn In Advance» (2012-2013). Results: In the Russian Federation registered more than 630,000 patients with different stages of diabetic retinopathy. The prevalence of diabetic retinopathy among adults (18 years and older) with type 1 diabetes is 35.25%, while in type 2 diabetes-16.67%. On average, this means that almost one in five patients (17.63%) with diabetes have certain eye problems. Conclusion: In summary, our data indicate a dramatic growth in the rate of diabetic ocular complications, with a particular increase in proliferative diabetic retinopathy, complicated cataract and neovascular glaucoma. These findings call for an even closer attention to early diagnostics, adequate management and, above everything else, timely prevention of ocular pathologies in patients with DM
Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus
No full textH2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, H2N2 is regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemagglutinins of the two different H2N2 lineages that circulated at the end of the cycle, using the well characterized A/Leningrad/134/17/57 (H2N2) master donor virus as the backbone. The vaccine strains containing the HA and NA of A/California/1/66 (clade 1) or A/Tokyo/3/67 (clade 2) showed a temperature sensitive and cold adapted phenotype and a reduced reproduction that was limited to the respiratory tract of mice, suggesting that the vaccines may be safe for use in humans. Both vaccine strains induced haemagglutination inhibition titers in mice. Vaccination abolished virus replication in the nose and lung and protected mice from weight loss after homologous and heterologous challenge with the respective donor wild type strains. In ferrets, the live attenuated vaccines induced high virus neutralizing, haemagglutination and neuraminidase inhibition titers, however; the vaccine based on the A/California/1/66 wt virus induced higher homologous and better cross-reactive antibody responses than the A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus reduction observed in the throat and nose of ferrets vaccinated with this vaccine after challenge with either of the wild type donor viruses. Moreover, both vaccines clearly reduced the infection-induced rhinitis observed in placebo-vaccinated ferrets. The results favor the vaccine based on the A/California/1/66 isolate, which will be evaluated in a clinical study. © 2014 Isakova-Sivak et al
How international tourism impacts political and ethno-religious issues in Africa? A case study of inter-governmental authority on development (IGAD)
No full textThe negative impact of political instability, religious and ethnic conflicts on tourism is well known. The article uses the example of a number of IGAD member countries to consider the reverse impact of tourism on inclusive development, weakening of ethno-religious problems, security and elimination of violence. Analysis of the tourism sector in Ethiopia, Kenya and Uganda shows that international tourism, being a driving force of economic development in these countries, is not a neutral factor in gender, religious and ethnic dynamics. Its positive impact is not automatically achieved. The article shows that the rapid growth of tourism-related industries, which is accompanied by an unequal distribution of its benefits between the state, business, local communities and religious organizations, can slow down the resolution of gender equality problems, escalate intercommunal and interreligious conflicts. However, the analysis of travel companies' business practices shows that the transition to a sustainable tourism model can contribute to the elimination of interethnic and interreligious conflicts. Formation of professional tourism communities aware of their social responsibility will help the hospitality industry together with the state to solve the problems of youth employment and education, gender inequality and security in general