Radiative forcing in the 21st century due to ozone changes in the troposphere and the lower stratosphere

Radiative forcing due to changes in ozone is expected for the 21st century. An assessment on changes in the tropospheric oxidative state through a model intercomparison ("OxComp'') was conducted for the IPCC Third Assessment Report (IPCC-TAR). OxComp estimated tropospheric changes in ozone and other oxidants during the 21st century based on the "SRES'' A2p emission scenario. In this study we analyze the results of 11 chemical transport models (CTMs) that participated in OxComp and use them as input for detailed radiative forcing calculations. We also address future ozone recovery in the lower stratosphere and its impact on radiative forcing by applying two models that calculate both tropospheric and stratospheric changes. The results of OxComp suggest an increase in global-mean tropospheric ozone between 11.4 and 20.5 DU for the 21st century, representing the model uncertainty range for the A2p scenario. As the A2p scenario constitutes the worst case proposed in IPCC-TAR we consider these results as an upper estimate. The radiative transfer model yields a positive radiative forcing ranging from 0.40 to 0.78 W m(-2) on a global and annual average. The lower stratosphere contributes an additional 7.5-9.3 DU to the calculated increase in the ozone column, increasing radiative forcing by 0.15-0.17 W m(-2). The modeled radiative forcing depends on the height distribution and geographical pattern of predicted ozone changes and shows a distinct seasonal variation. Despite the large variations between the 11 participating models, the calculated range for normalized radiative forcing is within 25%, indicating the ability to scale radiative forcing to global-mean ozone column change

European lipodystrophy registry: Background and structure

Background: Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each lipodystrophy subform, research in this area is difficult and international co-operation mandatory. Therefore, in 2016, the European Consortium of Lipodystrophies (ECLip) decided to create a registry for patients with lipodystrophy. Results: The registry was build using the information technology Open Source Registry System for Rare Diseases in the EU (OSSE), an open-source software and toolbox. Lipodystrophy specific data forms were developed based on current knowledge of typical signs and symptoms of lipodystrophy. The platform complies with the new General Data Protection Regulation (EU) 2016/679 by ensuring patient pseudonymization, informational separation of powers, secure data storage and security of communication, user authentication, person specific access to data, and recording of access granted to any data. Inclusion criteria are all patients with any form of lipodystrophy (with the exception of HIV-associated lipodystrophy). So far 246 patients from nine centres (Amsterdam, Bologna, Izmir, Leipzig, M\ufcnster, Moscow, Pisa, Santiago de Compostela, Ulm) have been recruited. With the help from the six centres on the brink of recruitment (Cambridge, Lille, Nicosia, Paris, Porto, Rome) this number is expected to double within the next one or 2 years. Conclusions: A European registry for all patients with lipodystrophy will provide a platform for improved research in the area of lipodystrophy. All physicians from Europe and neighbouring countries caring for patients with lipodystrophy are invited to participate in the ECLip Registry. Study registration: ClinicalTrials.gov (NCT03553420). Registered 14 March 2018, retrospectively registered

Clinical, hormonal and molecular-genetic characteristics of monogenic diabetes mellitus associated with the mutations in the <i>INS</i> gene

Background: Currently more than 50 mutations of the INS gene are known to affect the various stages of insulin biosynthesis in the beta cells of the pancreas. However only individual cases of diabetes mellitus (DM) associated with heterozygous mutations in the coding region of the INS gene were reported in Russian Federation. We report a group of patients with a clinical manifestation of DM caused by mutations in both coding and non-coding regions of the INS gene. The patients with a mutation in the intron of the INS gene are reported for the first time in Russian FederationMaterials and methods: 60 patients with an isolated course of neonatal DM (NDM), 52 patients with a manifestation of DM at the age of 7–12 months and the absence of the main autoimmune markers of type 1 DM, 650 patients with the MODY phenotype were included in the study. NGS technology was used for molecular genetic research. Author’s panel of primers (Custom DNA Panel) was used for multiplex PCR and sequencing using Ion Ampliseq™ technology. The author’s panel “­Diabetes Mellitus” included 28 genes (13 candidate genes of MODY and other genes associated with DM).Results: 13 heterozygous mutations were identified in 16 probands and 9 relatives. The majority of mutations were detected in patients with PNDM (18.75%) and in patients with an onset of DM at the age of 7–12 months (9.6%). Mutations in the INS gene were detected in 2 patients (0.3%) in the group with the MODY phenotype. Mutations in the INS gene were not detected in patients with transient NDM (TNDM). Analysis of clinical data in patients with PND and onset of diabetes at the age of 7–12 months did not show significant differences in the course of the disease. The clinical characteristics of the cases of MODY10 and diabetes caused by a mutation in the intron of the INS gene are reported in details.Conclusion: The role of INS gene mutations in NDM, MODY, and DM with an onset at the age of 7–12 months was analyzed in a large group of patients. The clinical characteristics of DM due to a mutation in the intron of the INS gene are reported for the first time in the Russian Federation

Патоморфоз заболеваний бронхолегочной системы у работающих в контакте с аэрозолями цветных металлов

Etiopathogenic features and diagnostic criteria of occupational diseases studying in workers engaged in colored metallurgy have been given in the paper. Polyvalent sensitization to metal allergens (nickel, chrome, beryllium, manganese) was found. A toxic effect of nickel on DNA was shown that could be used as a biomarker of exposure for biological monitoring in colored metallurgy workers. Biochemical investigations determined the main pathogenic mechanisms underlying pathomorphology of bronchopulmonary diseases caused by the exposure of colored metals, such as activation of lipid peroxidation, "proteolysis – antiproteolysis" imbalance, growing significance of infection. This is the first study demonstrating clinical and biochemical parallels between characteristics of development and course of respiratory pathology caused by the exposure of colored metals. Infectious, inflammatory, toxico-allergic, and destructive processes predominated in this pathology. Preventive and rehabilitation strategies have been developed.В статье представлены результаты изучения этиопатогенетических особенностей формирования профессиональных, производственно обусловленных заболеваний у работающих в цветной металлургии, определены критерии их диагностики. Выявлена поливалентная сенсибилизация к основным металлам-аллергенам (никель, хром, марганец, бериллий). Установлено токсическое влияние никеля на ДНК, что может служить биомаркером экспозиции и использоваться для биологического мониторинга у работающих в цветной металлургии.Результаты биохимических исследований определили основные патогенетические механизмы, лежащие в основе патоморфоза бронхолегочной патологии при воздействии аэрозолей цветных металлов: активация перекисного окисления липидов и дисбаланс в системе "протеолиз-антипротеолиз", возрастание роли инфекционного фактора. Впервые выявлены клинико-биохимические параллели между особенностями формирования и течением бронхолегочной патологии, сформировавшейся под воздействием аэрозоля цветных металлов с преобладанием инфекционно-воспалительного, токсико-аллергического, воспалительно-деструктивного компонентов, и биохимическим профилем организма. Разработаны методы профилактики и реабилитации

The Role of Brucella abortus I-206 Thermoextracts in L- and S-form in Shaping the Immune Response in White Mice

Background. Brucellosis is an acute infectious-allergic zoonotic disease in which sick farm animals are the main source of infection for humans. Immunization of animals and people on the territory of Russia is carried out by live vaccines, which, having a high immunogenicity, can cause clinical, hematological and immune changes. Therefore, the work on the design of new vaccines that provide high protection and do not possess reactogenicity, agglutinogenic and sensitizing activity is the current direction of the study. Methodology. The study was performed on 72 outbred white mice immunized with inactivated B. abortus 19 ВA vaccine and thermal extracts (TE) of B. abortus I-206 in L- and S-form. Morphofunctional changes in the regional lymph node, spleen, and thymus of experimental animals were examined on days 3, 7, 14, and 21 of the time of immunization. Results.The influence of single introductions thermoextracts B. abortus I-206 in L-and S-form in comparison with inactivated vaccine B. abortus 19 ВА. the removal or the morphohistologic indices of immune organs of experimental animals. Found that thermoextracts have the ability to activate immune adjustment within the structures of the spleen and lymph nodes, without causing side effects, including allergic reactions. Conclusions. Preparations obtained from B. abortus in the L- and S-forms have the ability to activate immunological rearrangement in immunocompetent organs without causing any side effects. The results indicate the promise of further research in this direction