Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial.

Background: The current tuberculosis (TB) drug development pipeline is being re-populated with candidates, including nitroimidazoles such as pretomanid, that exhibit a potential to shorten TB therapy by exerting a bactericidal effect on non-replicating bacilli. Based on results from preclinical and early clinical studies, a four-drug combination of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide (BPaMZ) regimen was identified with treatment-shortening potential for both drug-susceptible (DS) and drug-resistant (DR) TB. This trial aimed to determine the safety and efficacy of BPaMZ.

[Respiratory disorders of post-COVID-19 syndrome].

Aim: Assess the functional state of trespiratory system and effectiveness of therapeutic tactics for broncho-obstructive syndrome (BOS) in patients in the post-COVID period.

Materials And Methods: A two-center cohort prospective study included 10 456 and 89 patients, respectively. A comprehensive assessment of the respiratory system included clinical, laboratory and functional data, spirometry, body plethysmography, and a study of diffusive capacity of the lungs (DLCO).

Load in Host Cells and the Antibacterial Activity of Alveolar Macrophages Are Linked and Differentially Regulated in Various Lung Lesions of Patients with Pulmonary Tuberculosis.

Tuberculosis (TB) is a disease caused by () infection with the formation of a broad range of abnormal lung lesions within a single patient. Although host-pathogen interactions determine disease outcome, they are poorly understood within individual lesions at different stages of maturation. We compared load in a tuberculoma wall and the lung tissue distant from tuberculomas in TB patients.

Analysis of Mycobacterium tuberculosis Uptake by Alveolar Macrophages after Ex vivo Expansion Indicates Processing Host Cells with Pathogen Actually from Lung Tissue of Patients with Pulmonary Tuberculosis.

Background: Previously, the ex vivo cultures of alveolar macrophages were developed from the surgical samples of the lungs in patients with pulmonary tuberculosis (TB) to establish the unique features of Mycobacterium tuberculosis (Mtb) lifestyle in host cells, but the question has remained whether Mtb-infected cells are isolated from the human lungs or they may be the result of Mtb phagocytosis in ex vivo culture. The study was aimed to investigate Mtb uptake by TB patients' cells after ex vivo expansion.

Methods: Alveolar macrophages were infected with the Mtb clinical isolates in ex vivo culture, and the acid-fast Mtb loads in the cells were analyzed.

Electronic correlations in uranium hydride UHunder pressure.

We report results of calculations based on density functional theory and dynamical mean-field theory for the electronic structure of uranium hydride UHunder pressure, a compound of the uranium-based hydride family some members of which have been predicted to be superconducting. The effective electronic mass enhancement*/∼ 1.4 indicates that the Coulomb correlations have a moderate strength.

Influence of Molecular Orbitals on Magnetic Properties of [x].

Recent discoveries of various novel iron oxides and hydrides, which become stable at very high pressure and temperature, are extremely important for geoscience. In this paper, we report the results of an investigation on the electronic structure and magnetic properties of the hydride FeO 2 H x , using density functional theory plus dynamical mean-field theory (DFT+DMFT) calculations. An increase in the hydrogen concentration resulted in the destruction of dimeric oxygen pairs and, hence, a specific band structure of FeO 2 with strongly hybridized Fe- t 2 g -O- p z anti-bonding molecular orbitals, which led to a metallic state with the Fe ions at nearly 3+.

[Diagnostics of early signs of ocular pathology in patients with HIV/tuberculosis co-infection].

The current epidemic situation in Russia is characterized by increasing rate of co-infection (HIV/tuberculosis). Damage to the organ of vision is more common among patients with this pathology, presenting significant difficulties in diagnosis of the ophthalmic manifestations. High-tech imaging method - optical coherence tomography (OCT) allows exploration of the eye tissues with high accuracy and depth, as well as evaluation of the structure of the choroid and microcirculation parameters of the anterior and posterior eye segments.

Mycobacterium tuberculosis with different virulence reside within intact phagosomes and inhibit phagolysosomal biogenesis in alveolar macrophages of patients with pulmonary tuberculosis.

Tuberculosis (TB) is a dangerous airborne disease caused by Mycobacterium tuberculosis (Mtb) and characterized by a tight interplay between pathogen and host cells, mainly alveolar macrophages. Studies of the mechanisms of Mtb survival within human cells during TB disease are extremely important for the development of new strategies and drugs for TB treatment. We have used the ex vivo cultures of alveolar macrophages and histological sections obtained from the resected lungs of patients with pulmonary TB to establish the unique features of Mtb lifestyle in host cells.

Mycobacterium tuberculosis cording in alveolar macrophages of patients with pulmonary tuberculosis is likely associated with increased mycobacterial virulence.

Mycobacterium tuberculosis (Mtb) is an infectious agent that causes tuberculosis (TB) in humans. A study of the volume of Mtb population and the detection of Mtb virulence in the lungs of patients with pulmonary TB are of great importance for understanding the infectious process and the outcome of the disease. We analyzed the functional state of Mtb and their number in alveolar macrophages obtained from the resected lungs of patients with TB in ex vivo culture and determined that the number of Mtb, referred mainly to the Beijing genotype family (A0 and B0/W148 clusters), were significantly different in cells between different patients.

The recombinant fusion protein CFP10-ESAT6-dIFN has protective effect against tuberculosis in guinea pigs.

Development of effective vaccine candidates against tuberculosis is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein ESAT6-CFP10-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute tuberculosis. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response.

Ex vivo expansion of alveolar macrophages with Mycobacterium tuberculosis from the resected lungs of patients with pulmonary tuberculosis.

Tuberculosis (TB), with the Mycobacterium tuberculosis (Mtb) as the causative agent, remains to be a serious world health problem. Traditional methods used for the study of Mtb in the lungs of TB patients do not provide information about the number and functional status of Mtb, especially if Mtb are located in alveolar macrophages. We have developed a technique to produce ex vivo cultures of cells from different parts of lung tissues surgically removed from patients with pulmonary TB and compared data on the number of cells with Mtb inferred by the proposed technique to the results of bacteriological and histological analyses used for examination of the resected lungs.

The recombinant fusion protein CFP10-ESAT6-dIFN has protective effect against tuberculosis in guinea pigs.

Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10-ESAT6-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response.

Unexpected 3+ valence of iron in FeO, a geologically important material lying "in between" oxides and peroxides.

Recent discovery of the pyrite FeO, which can be an important ingredient of the Earth's lower mantle and which in particular may serve as an extra source of water in the Earth's interior, opens new perspectives for geophysics and geochemistry, but this is also an extremely interesting material from physical point of view. We found that in contrast to naive expectations Fe is nearly 3+ in this material, which strongly affects its magnetic properties and makes it qualitatively different from well known sulfide analogue - FeS. Doping, which is most likely to occur in the Earth's mantle, makes FeO much more magnetic.

Synthesis and biological evaluation of novel 5-aryl-4-(5-nitrofuran-2-yl)-pyrimidines as potential anti-bacterial agents.

A facile two-step synthetic approach to fluorinated and non-fluorinated 5-aryl-4-(5-nitrofuran-2-yl)-pyrimidines from readily available 5-bromo-4-(furan-2-yl)pyrimidine has been developed. All synthesized compounds were screened in vitro for their antibacterial activities against twelve various bacterial strains. It is demonstrated that some of these compounds exhibited significant antibacterial activities against strains Neisseria gonorrhoeae and Staphylococcus aureus, comparable and even higher with that commercial drug Spectinomycin.

[Clinical and morphological parallels in the validation of surgical treatment of nephrotuberculosi].

Aim: To Study clinical and morphological variants of kidney tuberculosis (KTB), for grounding a tactics of surgical treatment.

Materials And Methods: There were 107 examined patients (patients with cavitary lesions of kidneys: cavernous and multi-cavernous), operated in different phases of KTB. There were 56 men (52,3%) and women - 51(47,7%).

Synthesis and evaluation of antitubercular activity of fluorinated 5-aryl-4-(hetero)aryl substituted pyrimidines.

Various 5-(fluoroaryl)-4-(hetero)aryl substituted pyrimidines have been synthesized based on the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions starting from commercially available 5-bromopyrimidine and their antitubercular activity against Mycobacterium tuberculosis H37Rv has been explored. The outcome of the study disclose that, some of the compounds have showed promising activity in micromolar concentration against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant strains isolated from tuberculosis patients in Ural region (Russia). The data concerning the 'structure-activity' relationship for fluorinated compounds have been discussed.

Personalized Clinical Diagnosis in Data Bases for Treatment Support in Phthisiology.

The decision-making is a key event in the clinical practice. The program products with clinical decision support models in electronic data-base as well as with fixed decision moments of the real clinical practice and treatment results are very actual instruments for improving phthisiological practice and may be useful in the severe cases caused by the resistant strains of Mycobacterium tuberculosis. The methodology for gathering and structuring of useful information (critical clinical signals for decisions) is described.

Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides.

Synthetic routes to novel N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates with amino acids and glycine-containing dipeptides were developed. In vitro testing of 42 new and known compounds made it possible to reveal a series of N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates exhibiting significant antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant M. tuberculosis strain isolated from tuberculosis patients in the Ural region (Russia).

Structural γ-ε phase transition in Fe-Mn alloys from a CPA + DMFT approach.

We present a computational scheme for total energy calculations of disordered alloys with strong electronic correlations. It employs the coherent potential approximation combined with the dynamical mean-field theory and allows one to study the structural transformations. The material-specific Hamiltonians in the Wannier function basis are obtained by density functional theory.

Correlation-Driven Topological Fermi Surface Transition in FeSe.

The electronic structure and phase stability of paramagnetic FeSe is computed by using a combination of ab initio methods for calculating band structure and dynamical mean-field theory. Our results reveal a topological change (Lifshitz transition) of the Fermi surface upon a moderate expansion of the lattice. The Lifshitz transition is accompanied with a sharp increase of the local moments and results in an entire reconstruction of magnetic correlations from the in-plane magnetic wave vector, (π,π) to (π,0).

Mechanism of magnetic moment collapse under pressure in ferropericlase.

We propose a new scenario for the magnetic collapse under pressure in ferropericlase (FP) (Fe(1/4)Mg(3/4))O without the presence of intermediate spin state, which contradicts the mechanism proposed in (2013 Phys. Rev. B 87 165113).

Synthesis, and structure-activity relationship for C(4) and/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds.

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis of C(4) and/or C(5) mono(thienyl) and di(thienyl) substituted pyrimidines from commercially available 5-bromopyrimidine. All new pyrimidines were found to be active in micromolar concentrations in vitro against H37Rv, avium, terrae, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The data for acute in vivo toxicity in mice have been obtained for these compounds which appear to be promising antitubercular agents.

Draft Genome Sequence of Mycobacterium tuberculosis Strain E186hv of Beijing B0/W Lineage with Reduced Virulence.

We report a draft genome sequence of Mycobacterium tuberculosis strain E186hv, belonging to the Beijing B0/W lineage and isolated from a patient from Kurgan, Russia. This clinical isolate showed a reduced virulence phenotype unusual for this lineage and resistance to isoniazid, rifampin, ethambutol, pyrazinamide, and ofloxacin. We analyzed single nucleotide polymorphisms (SNPs) associated with virulence.

Synthesis, antimycobacterial and antifungal evaluation of some new 1-ethyl-5-(hetero)aryl-6-styryl-1,6-dihydropyrazine-2,3-dicarbonitriles.

The Petasis reaction of 6-hydroxy adducts of 1-alkyl-2,3-dicyano-5-arylpyrazinium salts with trans-styrylboronic acids proved to proceed smoothly at room temperature to give the corresponding 5-(hetero)aryl-6-styryl substituted 1,6-dihydropyrazine derivatives. Also it has been found that C(6) unsubstituted 1,6-dihydro- or 1,4,5,6-tetrahydropyrazine derivatives can be easy prepared in high yields from the corresponding pyrazinium salts by reduction with triethylsilane. All synthesized compounds were screened in vitro for their antifungal activities against seven pathogenic fungal strains and antimycobacterial activities against Mycobacterium tuberculosis H37Rv, avium, terrae and multi-drug-resistant strains isolated from tuberculosis patients in the Ural region (Russia).

Linear-temperature dependence of static magnetic susceptibility in LaFeAsO from dynamical mean-field theory.

In this Letter we report the local density approximation with dynamical mean field theory results for magnetic properties of the parent superconductor LaFeAsO in the paramagnetic phase. Calculated uniform magnetic susceptibility shows linear dependence at intermediate temperatures in agreement with experimental data. Contributions to the temperature dependence of the uniform susceptibility are strongly orbitally dependent.