Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Halo Excitation of 6^6He in Inelastic and Charge-Exchange Reactions

Four-body distorted wave theory appropriate for nucleon-nucleus reactions leading to 3-body continuum excitations of two-neutron Borromean halo nuclei is developed. The peculiarities of the halo bound state and 3-body continuum are fully taken into account by using the method of hyperspherical harmonics. The procedure is applied for A=6 test-bench nuclei; thus we report detailed studies of inclusive cross sections for inelastic $^6$He(p,p')$^6$He$^*$ and charge-exchange $^6$Li(n,p)$^6$He$^*$ reactions at nucleon energy 50 MeV. The theoretical low-energy spectra exhibit two resonance-like structures. The first (narrow) is the excitation of the well-known $2^+$ three-body resonance. The second (broad) bump is a composition of overlapping soft modes of multipolarities $1^-, 2^+, 1^+, 0^+$ whose relative weights depend on transferred momentum and reaction type. Inelastic scattering is the most selective tool for studying the soft dipole excitation mode.Comment: Submitted to Phys. Rev. C., 11 figures using eps

Опыт работы сестринских астма-школ в Архангельской области

The article summarizes a 4-year experience of nurse-guided asthma-schools at the Arkhangelsk region. This topic is of great interest in Russia as far as a doctor typically plays the main role at the education of an asthma patient. Sixteen asthma-schools have been working at the region now. The article discusses organizing problems of this activity, peculiarities due to a kind of a medical institution, a level of the nurses’ originality. The most important problem is an absence of vacancy for a training specialist on the staff of medical institutions. The results of the work show the effectiveness of nurse-guided education of asthma patients.В статье обобщен 4-летний опыт работы медсестринских астма-школ на территории Архангельской области. Тема более чем актуальна для России, где традиционно основная роль в обучении больных бронхиальной астмой принадлежала врачу-пульмонологу. В области работают 16 астма-школ. Обсуждаются вопросы их функционирования, особенности работы в зависимости от уровня медицинского учреждения, степень самостоятельности медицинских сестер. Наиболее важной проблемой является отсутствие штатных должностей специалистов по образованию в лечебных учреждениях. Результаты работы свидетельствуют об эффективности привлечения медицинских сестер к образовательному процессу у пациентов с астмой

BASOPHILE ACTIVATION TEST FOR THE DIAGNOSTICS OF FUNGAL SENSITIZATION IN THE PATIENTS WITH CYSTIC FIBROSIS

Aspergillus fumigatus colonization in the patients with cystic fibrosis (CF) may cause sensitization against A. fumigatus and/or allergic bronchopulmonary aspergillosis (ABPA), which significantly worsens the course of underlying disease. At the present time, new diagnostic tests are searched for detection of fungal sensitization in these patients. The aim of this work was to evaluate an opportunity of application of basophile activation test with A. fumigatus allergen in vitro using flow cytometry, aiming for identification of fungal sensitization in the CF patients. The study included 190 patients with CF aged 1 to 37 years. All the patients underwent common allergy screening (skin tests with fungal allergens, determination of serum levels of total IgE and specific IgE for the fungal allergens), and mycological examination (microscopy and culture of respiratory substrates). Computed tomography of the chest was performed upon clinical indications. The basophil activation test with the A. fumigatus allergen was performed in 10 CF patients with ABPA, and 10 CF patients without ABPA, in addition to the standard allergological examination. Frequency of sensitization to A. fumigatus in the patients with cystic fibrosis was 27%, the incidence of allergic bronchopulmonary aspergillosis was 5.7%. The number of eosinophils, total IgE and specific IgE levels in CF patients with ABPA were significantly higher than in CF patients without ABPA. In blood of the ABPA patients we have identified 68.5 (52.5-81.5%) of basophilic leukocytes activated by A. fumigatus allergen, with a stimulation index of 17.07 (10.30-27.70). In appropriate comparison group, the stimulation index did not exceed 1.5 (p = 0.000). Direct positive correlation between the levels of specific IgE to A. fumigatus and the number of basophils activated by A. fumigatus allergens was revealed (r = 0.77; р &lt; 0.05). FVC values and the body mass index in CF patients with ABPA were significantly lower when compared with the patients without fungal sensitization. Introduction of the basophil activation test, along with standard techniques, may enable a more differentiated assessment of ABPA development in CF patients. Timely detection of associations between A. fumigatus sensitization and clinical status of CF patients will facilitate early and effective administration of specific therapy

Expression of some molecular and biological markers in esophageal tumors of various stages and grades

Objectives: immunohistochemical study of the expression of molecular and biological markers (p53, bcl-2 and ki-67) in esophageal tumors of various stages and grades, and evaluation of the markers in the disease prognosis. Material and methods: the study included 30 patients of a retrospective group with stage II-III squamous cell carcinoma of the esophagus. Immunohistochemical study of paraffi n sections was performed using primary mouse monoclonal antibodies against p53, bcl-2 and ki67, and Reveal Polyvalent HRP-DAB Detection System. Results: diff erences in the rates and expression of molecular and biological markers (p53, bcl-2 and ki-67), controlling apoptosis and proliferation, depended on the tumor stage and grade. Conclusions: fdvanced cancer of the esophagus demonstrated an increase in rates and expression of p53+ and ki-67, as well as in the proliferative activity of tumor cells. Bcl-2 expression was more frequent and intensive in stage II tumors, compared to stage III. Esophageal tumors of higher grades were characterized with higher rates and expression of p53 and ki-67, and conversely for the bcl-2 expression. Th e revealed diff erences can be used in the disease prognosis

ПРОСТРАНСТВЕННО-ВРЕМЕННАЯ ТРАНСФОРМАЦИЯ ОСУШЕННЫХ ОРГАНОГЕННЫХ ПОЧВ СЕЛЬСКОХОЗЯЙСТВЕННЫХ ЗЕМЕЛЬ БЕЛАРУСИ

The paper demonstrates the results of systematization and generalization of the materials appropriate to the completion of soil-cartographic works on the drained and adjacent lands of agricultural organizations of the republic. Presented is the new information about the existence of peat and degropeat soils ranged at the species level of classification as a part of agricultural lands, and conducted is the analysis of spatial-time transformation of the component composition of drained organic soils between two rounds of the soil survey (1986–1998 and 2005–2015).Приведены результаты систематизации и обобщения материалов подходящих к завершению корректировочных почвенно-картографических работ на осушенных и прилегающих к ним землях сельскохозяйственных организаций страны. Представлена новая современная информация о реальном наличии торфяных и дегроторфяных почв, ранжированных на видовом уровне классификации, в составе сельскохозяйственных земель и проведен анализ пространственно-временной трансформации компонентного состава осушенных органогенных почв между двумя турами почвенного обследования (1986–1998 и 2005–2015 гг.)

Coulomb breakup of 17 Ne from the view point of nuclear astrophysics

6 pags., 5 figs. -- XII International Symposium on Nuclei in the Cosmos, August 5-12, 2012, Cairns, AustraliaBy the Coulomb breakup of 17Ne, the time-reversed reaction 15O(2p, γ) 17Ne has been studied. This reaction might play an important role in the rp process, as a break-out reaction of the hot CNO cycle. The secondary 17Ne ion beam with an energy of 500 MeV/nucleon has been dissociated in a Pb target. The reaction products have been detected with the LAND-R3B experimental setup at GSI. The preliminary differential and integral Coulomb dissociation cross section σCoul has been determined, which then will be converted into a photo-absorption cross section σphoto, and a two-proton radiative capture cross section σcap. Additionally, information about the structure of the 17Ne, a potential two-proton halo nucleus, will be received. The analysis is in progress.This project was supported by the German Federal Ministry for Education and Research (BMBF), EU(EURONS), EMMI-GSI, and HIC for FAI

Coulomb breakup of 17Ne from the viewpoint of nuclear astrophysics

By the Coulomb breakup of 17Ne, the time-reversed reaction 15O(2p,γ)17Ne has been studied. This reaction might play an important role in the rp process, as a break-out reaction of the hot CNO cycle. The secondary 17Ne ion beam with an energy of 500 MeV/nucleon has been dissociated in a Pb target. The reaction products have been detected with the LAND-R3B experimental setup at GSI. The preliminary differential and integral Coulomb dissociation cross section sCoul has been determined, which then will be converted into a photo-absorption cross section sphoto, and a two-proton radiative capture cross section σcap. Additionally, information about the structure of the 17Ne, a potential two-proton halo nucleus, will be received. The analysis is in progress. \ua9 Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike Licence

Ecto-5′-nucleotidase and intestinal ion secretion by enteropathogenic Escherichia coli

Enteropathogenic Escherichia coli (EPEC) triggers a large release of adenosine triphosphate (ATP) from host intestinal cells and the extracellular ATP is broken down to adenosine diphosphate (ADP), AMP, and adenosine. Adenosine is a potent secretagogue in the small and large intestine. We suspected that ecto-5′-nucleotidase (CD73, an intestinal enzyme) was a critical enzyme involved in the conversion of AMP to adenosine and in the pathogenesis of EPEC diarrhea. We developed a nonradioactive method for measuring ecto-5′-nucleotidase in cultured T84 cell monolayers based on the detection of phosphate release from 5′-AMP. EPEC infection triggered a release of ecto-5′-nucleotidase from the cell surface into the supernatant medium. EPEC-induced 5′-nucleotidase release was not correlated with host cell death but instead with activation of phosphatidylinositol-specific phospholipase C (PI-PLC). Ecto-5′-nucleotidase was susceptible to inhibition by zinc acetate and by α,β-methylene-adenosine diphosphate (α,β-methylene-ADP). In the Ussing chamber, these inhibitors could reverse the chloride secretory responses triggered by 5′-AMP. In addition, α,β-methylene-ADP and zinc blocked the ability of 5′-AMP to stimulate EPEC growth under nutrient-limited conditions in vitro. Ecto-5′-nucleotidase appears to be the major enzyme responsible for generation of adenosine from adenine nucleotides in the T84 cell line, and inhibitors of ecto-5′-nucleotidase, such as α,β-methylene-ADP and zinc, might be useful for treatment of the watery diarrhea produced by EPEC infection