Designing Controls for Network Organisations: A Value-Based Approach

Tan, Y.H. [Promotor]Paans, R. [Promotor]Gordijn, J. [Copromotor

EFFICACY AND SAFETY OF IMMUNOMODULATORS APPLICATION IN PREVENTION OF COMPLICATIONS IN PATIENTS WITH PERTUSSIS

Pertussis is an urgent pediatric problem due to its frequency and severity in the first year of life. One of the most threatening complications of pertussis is pneumonia. In a parallel, non-randomized open-label study we have demonstrated clinical efficacy and safety of immunomodulators for the prophylaxis of bacterial complications of pertussis

Evaluation of the long-term memory T cell in mice after immunization with a live tularemia vaccine

The vaccine strain F. tularensis 15 NIIEG induces long-lived cell-mediated immunity but exhibits a certain reactogenicity and genetic instability. Progress in development of a vaccine against tularemia has been limited by a lack of information regarding the mechanisms required to protect against this disease. The BALB/c mouse is the most commonly used animal to study tularemia due to its relatively low cost, well-characterized genetics, available immunological tools and mouse infection with virulent F. tularensis recapitulates human disease.CD4+ and CD8+T cells are known to be critical for the formation of protective immunity but the relative roles of memory T cell subpopulations in long lived protection against virulent strains of F. tularensis are not well established. We hypothesized that this immunity depends on central (TCM) and effector memory (TEM) T cells and their functional activity. In this study we have dissected the T cell immune response in BALB/c mice 30, 60 and 90 days after subcutaneous vaccination with 15 NIIEG.Multiparametric flow cytometry were used to characterize in vitro recall responses of splenocytes to F. tularensis antigen. TEM cells were identified as CD3+CD4+CD44+CD62L- and CD3+CD8+CD44+CD62L-, TCM cells as CD3+CD4+CD44+CD62L+ and CD3+CD8+CD44+CD62L+, respectively. The functional activity of memory T cells was assessed by the following parameters: the level of expression of the activation marker CD69 and cytokine-producing activity by staining with the intracellular cytokines IFNg and TNFa.Thus, development of a long-lived vaccine directed against F. tularensis is dependent on identifying not only the correlates of immunity present early after vaccination, but also those that persist in the host after the effector phase has ended. The maintenance of long-term protective immunity initiated by vaccination with F. tularensis strain 15 NIIEG has been shown to require the presence of antigen-specific CD4+ and CD8+ memory T cells producing IFNg and TNFa and expressing the activation marker CD69. A decrease in count and functional activity of CD8+TCM and CD8+TEM was detected in the long term after vaccination. The detected parameters of functional activity of memory T cells can be used as criteria for evaluation of protective immunity against virulent strains of F. tularensis

Динамика распространенности бронхиальной астмы у детей в Новосибирске

Six-year dynamics of epidemiology of bronchial asthma was analyzed in Novosibirsk according to a common standardized protocol of the "International Study of Asthma and Allergic Diseases in Children" (ISAAC) programme. The pathology spread was studied using a total surveying among first-form and eight-form pupils (the survey involved 7291 pupils 1996, 6631 ones in 1999 and 6943 children in 2002). The results showed stable spread of bronchial asthma symptoms among the senior and junior pupils and prevalence of mild asthma with rare exacerbations in both the groups. A progredient growth of severe asthma attack rate was noted in eight-form pupils. An increase in frequency of combined upper and lower airway pathologies was registered with reduction in skin atopy rate. A problem of underestimating of the pathology was discussed.Исследована 6-летняя динамика эпидемиологии бронхиальной астмы по единым стандартизованным протоколам программы "Международное исследование астмы и аллергических заболеваний у детей" (ISAAC) в Новосибирске. Изучение распространенности патологии проводилось при сплошном анкетировании учеников 1-х и 8-х классов (7291 школьник в 1996 г., 6631 — в 1999 г. и 6943 — в 2002 г.). В динамике выявлены стабильная распространенность симптомов бронхиальной астмы у старших и младших школьников, сохранение преобладания легких редко рецидивировавших форм патологии в обеих возрастных группах. Отмечен прогредиентный рост тяжелых приступов удушья у восьмиклассников. В популяции школьников зарегистрировано увеличение сочетанного поражения верхних и нижних отделов респираторного тракта с сокращением частоты кожных форм атопии. Отражена проблема гиподиагностики патологии

Изучение продукции некоторых цитокинов при вирусных инфекциях, протекающих с диарейным синдромом у детей

The aim of the study was to study the characteristics of the content of certain cytokines in serum as indicators of the immune response in viral infections accompanied by diarrhea syndrome in children. Materials and research methods. A survey was conducted of 92 children aged 3 months to 15 years with acute respiratory viral infections hospitalized in hospital No. 6 in Novosibirsk in the first 2 days from the onset of the disease. Two groups were formed — group 1 — patients with diarrheal syndrome and signs of respiratory system damage. Group 2 — children with isolated lesions of the respiratory tract. In all children, the genetic material of viruses was determined by polymerase chain reaction (PCR) in the nose and throat washes. Also, in all children, the determination of serum levels of IL-8, IL-17, IFN-ã by ELISA was performed. Results and discussion. When studying the levels of cytokines (IFN-ã, IL-8, IL-17) in patients with signs of gastrointestinal tract lesions in comparison with isolated respiratory manifestations, no statistically significant differences were found. However, when analyzing the levels of the studied parameters in patients with diarrheal syndrome in different age groups, significant differences in the levels of IFN-ã and IL-8 were revealed.Целью исследования явилось изучение особенностей содержания некоторых цитокинов в сыворотке крови как показателей иммунного реагирования при вирусных инфекциях, сопровождающихся диарейным синдромом у детей. Материалы и методы исследования. Проведено обследование 92 детей в возрасте от 3 месяцев до 15 лет с острыми респираторными вирусными инфекциями, госпитализированных в стационар ДКБ №6 города Новосибирска в первые двое суток от начала заболевания. Сформированы две группы: I группа — пациенты с диарейным синдромом и признаками поражения респираторной системы. Группа II — дети с изолированным поражением респираторного тракта. У всех детей провели определение генетического материала вирусов методом полимеразной цепной реакции (ПЦР) в смывах из носо- и ротоглотки. Также у всех детей было проведено определение содержания в сыворотке крови IL-8, IL-17, IFN-ã методом ИФА. Результаты и обсуждение. При исследовании уровней содержания цитокинов (IFN-ã, IL-8, IL-17) у пациентов с признаками поражения желудочно-кишечного тракта в сравнении с изолированными респираторными проявлениями статистически значимых различий выявлено не было. Однако при анализе уровней исследуемых показателей у пациентов с диарейным синдромом в различных возрастных группах выявлены достоверные различия в уровне содержания IFN-ã и IL-8

Microfluidic droplet platform for ultrahigh-throughput single-cell screening of biodiversity

© 2017, National Academy of Sciences. All rights reserved.Ultrahigh-throughput screening (uHTS) techniques can identify unique functionality from millions of variants. To mimic the natural selection mechanisms that occur by compartmentalization in vivo, we developed a technique based on single-cell encapsulation in droplets of a monodisperse microfluidic double water-in-oil-in-water emulsion (MDE). Biocompatible MDE enables in-droplet cultivation of different living species. The combination of droplet-generating machinery with FACS followed by next-generation sequencing and liquid chromatography-mass spectrometry analysis of the secretomes of encapsulated organisms yielded detailed genotype/phenotype descriptions. This platform was probed with uHTS for biocatalysts anchored to yeast with enrichment close to the theoretically calculated limit and cell-to-cell interactions. MDE-FACS allowed the identification of human butyrylcholinesterase mutants that undergo self-reactivation after inhibition by the organophosphorus agent paraoxon. The versatility of the platform allowed the identification of bacteria, including slow-growing oral microbiota species that suppress the growth of a common pathogen, Staphylococcus aureus, and predicted which genera were associated with inhibitory activity