Description of Transport Tunnel in Haloalkane Dehalogenase Variant LinB D147C+L177C from Sphingobium japonicum

The activity of enzymes with active sites buried inside their protein core highly depends on the efficient transport of substrates and products between the active site and the bulk solvent. The engineering of access tunnels in order to increase or decrease catalytic activity and specificity in a rational way is a challenging task. Here, we describe a combined experimental and computational approach to characterize the structural basis of altered activity in the haloalkane dehalogenase LinB D147C+L177C variant. While the overall protein fold is similar to the wild type enzyme and the other LinB variants, the access tunnels have been altered by introduced cysteines that were expected to form a disulfide bond. Surprisingly, the mutations have allowed several conformations of the amino acid chain in their vicinity, interfering with the structural analysis of the mutant by X-ray crystallography. The duration required for the growing of protein crystals changed from days to 1.5 years by introducing the substitutions. The haloalkane dehalogenase LinB D147C+L177C variant crystal structure was solved to 1.15 angstrom resolution, characterized and deposited to Protein Data Bank under PDB ID 6s06

ИССЛЕДОВАНИЕ АНТИБИОТИКО- И ФАГОЧУВСТВИТЕЛЬНОСТИ НОЗОКОМИАЛЬНЫХ ШТАММОВ МИКРОБОВ, ВЫДЕЛЕННЫХ ОТ ПАЦИЕНТОВ ТРАНСПЛАНТОЛОГИЧЕСКОЙ КЛИНИКИ

Antibiotic and fagosensitivity most etiologically important nosocomial strains of bacteria – Pseudomonas aeru- ginosa, Klebsiella pneumoniae, E. coli, Proteus spp., Staphylococcus spp. were studied. Multiple drug-resistant bacteria as gram-positive and gram-negative, isolated from 8 substrates, had been demonstrated. With regard to the sensitivity of Pseudomonas aeruginosa >40% was observed in 40–50% of the strains to aminoglycosides – aztreonam, amikacin, netilmicin, and only 23–25% of the strains – to gentamicin and levofloxacin (an average of antibiotic susceptibility was 27%). All strains of ESBL Klebsiella drew up and were sensitive only to imipenem, meropenem and aminoglycosides. Specific phages lysed 43–48% of the strains Pseudomonas aeruginosa and Klebsiella pneumoniae, E. coli, Pro- teus spp., multidrug resistant strains of Staphylococcus spp. It is proposed to introduce the use of phages in clinical practice. Исследована антибиотико- и фагочувствительность наиболее этиологически важных нозокомиальных штаммов микробов – синегнойных палочек, клебсиелл, кишечных палочек, протеев, стафилококков. Установлена множественная резистентность штаммов бактерий как грамположительных, так и грамотрицательных, изолированных из 8 субстратов. В отношении синегнойной палочки чувствительность >40% отмечена у 40–50% штаммов к аминогликозидам – азтреонаму, амикацину, нетилмицину и только у 23–25% штаммов – к гентамицину и левофлоксацину (в среднем антибиотикочувствительность составила 27%). Все штаммы клебсиелл вырабатывали БЛРС и были чувствительны только к имипенему, меропенему и аминогликозидам. Специфические бактериофаги лизировали 43–48% штаммов синегнойных палочек и клебсиелл, кишечные палочки, протеи, множественно резистентные штаммы стафилококков. Предлагается внедрять использование бактериофагов в клиническую практику трансплантологических клиник.

Transesterification of PHA to Oligomers Covalently Bonded with (Bio)Active Compounds Containing Either Carboxyl or Hydroxyl Functionalities

© 2015 The Authors. Published by Public Library of Science. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0120149This manuscript presents the synthesis and structural characterisation of novel biodegradable polymeric controlled-release systems of pesticides with potentially higher resistance to weather conditions in comparison to conventional forms of pesticides. Two methods for the preparation of pesticide-oligomer conjugates using the transesterification reaction were developed. The first method of obtaining conjugates, which consist of bioactive compounds with the carboxyl group and polyhydroxyalkanoates (PHAs) oligomers, is "one-pot" transesterification. In the second method, conjugates of bioactive compounds with hydroxyl group and polyhydroxyalkanoates oligomers were obtained in two-step method, through cyclic poly(3-hydroxybutyrate) oligomers. The obtained pesticide-PHA conjugates were comprehensively characterised using GPC, 1H NMR and mass spectrometry techniques. The structural characterisation of the obtained products at the molecular level with the aid of mass spectrometry confirmed that both of the synthetic strategies employed led to the formation of conjugates in which selected pesticides were covalently bonded to PHA oligomers via a hydrolysable ester bond

Антибактериальная профилактика инфекционных осложнений в практике детского хирурга

The evolution of postoperative wound infections complicates the postoperative period, prolongs the hospitalization and increases the cost of treatment. The most effective way to prevent the development of infection complications in the world is antibacterial prophylaxis. In surgery, that means the injection of an antibiotic immediately before and during twenty-four hours after the surgery. The article presents a characteristic of risk factors for postoperative complications, indications and the basic principles of antibiotic prophylaxis, and recommendations for the selection of antimicrobials, depending on the particular clinical case.Развитие послеоперационных инфекций в ране осложняет течение послеоперационного периода, продлевая сроки госпитализации, увеличивая расходы на лечение пациента. Наиболее эффективным методом предотвращения развития инфекционных осложнений во всем мире признана антибактериальная профилактика. В хирургии это подразумевает введение антибиотика непосредственно перед началом и в течение одних суток после оперативного вмешательства. В статье дана характеристика факторов риска развития послеоперационных осложнений, представлены показания, основные принципы антибиотикопрофилактики, а также рекомендации по выбору антимикробных препаратов в зависимости от конкретного клинического случая

Lancet

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries

Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and 20272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group.peer-reviewe

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3)

Background: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods: We analyzed individual data for adults (15–99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000–2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results: The study included 556,237 adults. In 2010–2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%–38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000–2004 and 2005–2009. These improvements were more noticeable among adults diagnosed aged 40–70 years than among younger adults. Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

THE NATURAL ENVIRONMENT OF THE UBSUNUR HOLLOW AND ITS ANTHROPOGENIC CONDITIONALITY

Research of the early historical epochs anthropogenic activity impact on the environment proves its influence on ecosystems dynamics and its substantial role in changing natural and climatic conditions. Methods and results. With the help of remote sensing (deciphering space images (Google resources, free access) and landscape observations on the area of Ubsunur Hollow, one of the largest arid hollows of Central Asia, in the neighbourhood of the Agar-Dag range numerous tracks of irrigation agriculture have been found. The absence of fresh water continuous supply in the area of ancient irrigation presupposes milder climatic conditions and the presence of forest flora maintaining the level of ground waters in the past. The presence of forest steppe landscapes on arid areas of Ubsunur Hollow in the recent past has been proved by the results of paleobotanic research on ancient agroirrigation landscapes to the south-west of Lake Shara Nur in the Upper Naryin Gol River. Conclusion. A big number of land allotments found in north-eastern part of Ubsunur Hollow near the Agar-Dag range (Lake Shara Nur) allows us to speak about significant water reserves (and forestry area) of this territory as well as about a big number of people living there in early epochs and who needed fuel, wood as a source of construction materials, etc., consequently forests were destroyed. They were also being destroyed during numerous wars: Central Asia is the region of constant battles between western and eastern civilizations. The conducted research proves the presence of forest flora (spruce-larch-grass-sedge communities, steppificated pine forests) in the Late Quaternary period in the central part of Ubsunur Hollow on the area which is now deserted. The most probable reason of desertisation of the area is destruction of the forest. Forest devastation is the major reason of landscape degradation not only of Ubsunur Hollow but also of the whole steppe Asian belt