TB/FLU-06E Influenza Vector-Based Vaccine in the Complex Therapy of Drug-Susceptible and Drug-Resistant Experimental Tuberculosis.

The steady rise of drug-resistant tuberculosis (TB), which renders standard therapy regimens ineffective, necessitates the development of innovative treatment approaches. Immunotherapeutic vaccines have the potential to effectively regulate the anti-TB immune response and enhance the efficacy of anti-TB treatment. In the present study, we aimed to evaluate the potency of the mucosal vector vaccine TB/FLU-06E as part of a complex treatment regimen for drug-susceptible (DS) or drug-resistant (DR) tuberculosis in C57BL/6 mice.

Molecular Periphery Design Allows Control of the New Nitrofurans Antimicrobial Selectivity.

A series of 13 new 3-substituted 5-(5-nitro-2-furyl)-1,2,4-oxadiazoles was synthesized from different aminonitriles. All compounds were screened in the disc diffusion test at a 100 μg/mL concentration to determine the bacterial growth inhibition zone presence and diameter, and then the minimum inhibitory concentrations (MICs) were determined for the most active compounds by serial dilution. The compounds showed antibacterial activity against ESKAPE bacteria, predominantly suppressing the growth of 5 species out of the panel.

Phylogenomic and genomic analysis reveals unique and shared genetic signatures of complex species.

Species belonging to the complex (MKC) are frequently isolated from humans and the environment and can cause serious diseases. The most common MKC infections are caused by the species (), leading to tuberculosis-like disease. However, a broad spectrum of virulence, antimicrobial resistance and pathogenicity of these non-tuberculous mycobacteria (NTM) are observed across the MKC.

Evaluation of composition effects on the tissue-adhesive, mechanical and physical properties of physically crosslinked hydrogels based on chitosan and pullulan for wound healing applications.

Tissue adhesion of hydrogels plays an important role in wound healing, which can improve the efficiency of wound treatment, stop bleeding, facilitate tissue growth and wound closure. However, most non-covalent crosslinked hydrogels have weak tissue adhesion and rheological properties. Furthermore, it remains a challenge to synthesize a fully physically crosslinked hydrogel with good rheological properties without compromising its tissue adhesion strength.

The Nitrofuran-Warhead-Equipped Spirocyclic Azetidines Show Excellent Activity against .

A series of 21 new 7'H-spiro[azetidine-3,5'-furo [3,4-d]pyrimidine]s substituted at the pyrimidine ring second position were synthesized. The compounds showed high antibacterial in vitro activity against . Two compounds had lower minimum inhibitory concentrations against (H37Rv strain) compared with isoniazid.

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.

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples.

Peptides show high promise in the targeting and intracellular delivery of next-generation biotherapeutics. The main limitation is peptides' susceptibility to proteolysis in biological systems. Numerous strategies have been developed to overcome this challenge by chemically enhancing the resistance to proteolysis.

Endovascular Recanalization and Carotid Stenting: The New Approach to Restore Cerebral Perfusion during Aortic Dissection.

Unlabelled: A type A aortic dissection (TAAD) is a dangerous condition requiring emergency surgery. Due to the similarity of the symptoms of cerebral malperfusion in TAAD and the signs of ischemic stroke, a differential diagnosis of these diseases is not always available. Patients with TAAD after cerebral malperfusion can have a neurological deficit.

Intrathoracic non-tuberculous mycobacteriosis with endobronchial lesion in a child aged 11 with HIV infection diagnosed by bronchoscopic biopsy, EBUS-TBNA and confocal laser endomicroscopy.

The diagnosis of intrathoracic non-tuberculous mycobacteriosis (NTM) is challenging. We report a case of a pediatric pulmonary NTM with endobronchial lesion and lymphadenitis in a child with HIV infection diagnosed by bronchoscopic biopsy, EBUS-TBNA and probe-based confocal laser endomicroscopy (pCLE). The pCLE showed a large number of highly fluorescent cells and zones of density and disorganized elastin fibers at alveolar areas.

COVID-19 and Tuberculosis: Mathematical Modeling of Infection Spread Taking into Account Reduced Screening.

The COVID-19 pandemic resulted in the cessation of many tuberculosis (TB) support programs and reduced screening coverage for TB worldwide. We propose a model that demonstrates, among other things, how undetected cases of TB affect the number of future () infections. The analysis of official statistics on the incidence of TB, preventive examination coverage of the population, and the number of patients with bacterial excretion of in the Russian Federation from 2008 to 2021 is carried out.

[Modern approaches to studying the molecular mechanisms of lung functioning in normal and pathological conditions].

Problems with breathing and lung function are caused by the development of various lung diseases associated with lifestyle, harmful environmental factors and genetic predisposition. Knowledge of the molecular mechanisms of the development of the pathological process will allow on time identification of the disease or the development of targeted therapy. The article provides an overview of modern methods that make it possible to most accurately reproduce the structural, functional and mechanical properties of the lung (organ-on-a-chip), to perform non-invasive molecular studies of biomarkers of bronchopulmonary pathology using saliva diagnostics, as well as using DNA and RNA aptamers, verify tumor markers in biological samples of human tissue.

Tuberculosis Disease in Immunocompromised Children and Adolescents: A Pediatric Tuberculosis Network European Trials Group Multicenter Case-control Study.

Background: In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe.

Methods: Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020.

Spectrum of Surgical Site Infection Pathogens in Chronic Infectious Spondylitis Requiring Revision Surgery: A 5-Year Cohort Study.

Spectrum monitoring of the pathogen in spondylitis patients plays a key role in preventing infectious complications of spinal reconstructions in chronic spondylitis (CS) and in the treatment of surgical site infection (SSI). The aim of this study is to characterize the spectrum of SSI pathogens in CS requiring revision surgery. The primary cohort encompassed 569 surgical patients with infectious CS.

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O-H insertion/base-promoted cyclization involving diazoarylidene succinimides.

A facile approach to novel medicinally relevant spiro heterocyclic scaffolds (namely furan-2(5)-ones, tetrahydrofurans and pyrans spiro-conjugated with the succinimide ring) has been developed. The protocol consists of Rh(II)-catalyzed insertion of heterocyclic carbenes derived from diazoarylidene succinimides (DAS) into the O-H bond of propiolic/allenic acids or brominated alcohols, followed by base-promoted cyclization to afford the target spirocyclic compounds in good to high yields.

Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis.

Extrapulmonary tuberculosis with a renal involvement can be a manifestation of a disseminated infection that requires therapeutic intervention, particularly with a decrease in efficacy of conventional regimens. In the present study, we investigated the therapeutic potency of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in the complex anti-tuberculosis treatment (ATT). A rabbit model of renal tuberculosis (rTB) was constructed by injecting of the standard strain Mycobacterium tuberculosis H37Rv into the cortical layer of the kidney parenchyma.

Access to Spiro Bis-β-lactams via a Metal-Free Microwave-Assisted Wolff Rearrangement/Staudinger [2+2] Cycloaddition Cascade Involving 3-Diazotetramic Acids and Imines.

Herein, we report the study of the thermally promoted reaction of 3-diazotetramic acids with imines as a rapid route to a novel spiro heterocyclic scaffold, spiro bis-β-lactams (2,6-diazaspiro[3.3]heptane-1,5-diones). The transformation proceeds via metal-free microwave-assisted Wolff rearrangement of the diazo reagent followed by Staudinger [2+2] cycloaddition of the heterocyclic ketenes with Shiff bases.

Imines with rare α-heteroatom substituted amine components generated the Staudinger/aza-Wittig tandem reaction and their application in multicomponent reactions.

A series of structurally diverse α-heteroatom substituted methyl azides (XCHN, where X = phthalimidoyl, benzotriazolyl, arylsulfanyl, aryloxy, alkoxy) have been prepared and evaluated for the generation of imines the Staudinger/aza-Wittig tandem reaction with aldehydes and triphenylphosphine. The obtained imines were successfully introduced into four types of multicomponent reactions: the Staudinger β-lactam synthesis with diazo carbonyl compounds, the Castagnoli-Cushman reaction with cyclic anhydrides, and the Ugi and azido-Ugi reactions with isocyanides and carboxylic acids or TMS-azides. These transformations allowed the preparation of four-to-seven-membered lactams, acyclic bisamides and 5-(aminomethyl)-1-alkyltetrazoles with a complex and previously poorly accessible periphery.

Utilizing Allenic Acids and Heterocyclic Diazo Compounds in the Synthesis of Polysubstituted Spirocyclic Butenolides and β-Methylidene 2-Furanones.

Herein, we report a novel approach for the assembly of spirocyclic Δ-butenolides and β-methylidene 2-furanones via Rh(II)-catalyzed O-H insertion of heterocyclic diazo compounds into allenic acids followed by base-promoted cyclization. Utilizing various diazo heterocycles, including α-diazo homophthalimides, 3-diazo tetramic acids, and diazo oxindoles, diverse spirocyclic scaffolds were produced. The research revealed that the allenic acid substitution pattern is decisive for the product type, enabling extraordinary target compound switching between two types of spirocyclic 2-furanones with exo- and endocyclic C═C bonds.

The Expression of Kisspeptins and Matrix Metalloproteinases in Extragenital Endometriosis.

Endometriosis is characterized by a condition where endometrial tissue grows outside the uterine cavity. The mechanisms of endometrium growth during endometriosis might be similar to the development of a tumor. The kisspeptin (KISS1) gene was initially discovered as a suppressor of metastasis.

Similar Patterns of Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue and Post-COVID-19 Syndromes.

Background: There is a considerable overlap between the clinical presentation of post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many of their common symptoms can be linked to dysregulation of the autonomic nervous system (dysautonomia). This study aimed to objectively assess autonomic function in a general group of patients with PCC and in a group of patients with ME/CFS whose disease was not related to COVID-19.

[Clinical and socially significant consequences of falls in elderly and senile persons (analytical review).].

Falls refers to geriatric syndromes, which is accompanied by a significant number of adverse clinically and socially consequences. For the rational organization of medical, social, psychological and other types of assistance and rehabilitation measures, separate groups of consequences developing as a result of a fall are distinguished: physical, functional, psychological, social. Every year, every fourth elderly and older person faces a fall, while about half of the victims seek medical help.

[Prevention of falls syndrome (analitic review).].

Falls in people over 60 years of age is usually interpreted as geriatric syndrome, which is one of the leading problems in geriatrics due to complications. In recent years, the frequency of falls has increased., Every third person faces a fall in old age, and every second person falls in the age over 85 years.

Assessment of Comorbidity in Patients with Drug-Resistant Tuberculosis.

A wide range of comorbidities, especially in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients, markedly complicates selecting effective treatment of tuberculosis (TB) and preventing the development of adverse events. At present, it is impossible to assess the severity of comorbid pathologies and develop indications for the administration of accompanying therapy in TB patients. The aim of this study was to identify the difference in the range of comorbidities between patients with MDR-TB and XDR-TB and assess the impact of comorbidities on TB treatment.