Novosibirsk Tuberculosis Research Institute

Nearly 300 million people globally require humanitarian assistance, primarily due to conflicts and complex emergencies (CE). Modern conflicts are increasingly prolonged, deadly and frequent, severely disrupting health systems and hindering the provision of quality tuberculosis (TB) care. Managing drug-resistant TB (DR-TB) in these settings is particularly challenging. War and post-war conditions could potentially amplify resistance. However, evidence on DR-TB in CE-affected countries remains scarce. A scoping review, including grey literature and consultation with implementing agencies, was conducted to analyse published experiences worldwide in delivering DR-TB care in CE. The review included 16 peer-reviewed articles and 11 reports. Countries affected by war exhibit multiple risk factors for amplifying TB resistance. DR-TB management in CE is ongoing, yet diagnostic access is limited, with notification rates below 20% of estimated cases. Treatment success rates among those diagnosed are comparable to global averages. Innovative approaches, such as molecular tests, shorter regimens and patient-centred approaches, have achieved higher success rates. Information on vulnerable populations, including internally displaced persons, prisoners and children, remains minimal. Only one country had reliable information on DR-TB in prisoners (Iraq), accounting for one-third of the national resistant cohort. Most CE countries rely on external funding for DR-TB programmes. Like in other infectious diseases, war significantly alters DR-TB dynamics in affected countries and bordering or refugee-hosting countries, threatening progress towards TB elimination and exacerbating the global antimicrobial resistance crisis. While innovations have improved the feasibility of DR-TB care in CE, access remains severely constrained. Identified risk factors, challenges and priorities underscore the need for expanded TB support and targeted research, particularly for vulnerable populations in CE scenarios.

Echinococcosis and alveococcosis of the lungs are zoonotic infections caused by the larval stage of Echinococcus helminths. The difficulty of diagnosing these helminth infections is due to their slow development and their similarity to several diseases, including malignant neoplasms and tuberculosis. Delay in making the correct diagnosis leads to the development of advanced cases and longer treatment. The aim of the review was to inform physiatrists, pulmonologists, infectious disease specialists, therapists, and thoracic surgeons about the complexity of the differential diagnosis of echinococcosis with atypical limited localization (with isolated lung damage). Conclusion. Diagnosis of echinococcosis presents significant difficulties due to the absence of symptoms pathognomonic for the parasitic process and a typical clinical manifestation of the disease, due to similarity with a number of nosologies of infectious and non-infectious origin, and absence of liver lesions and multilocular cysts, usually detected by CT or MRI. An immunological blood test for specific IgG should be performed at the early stages of diagnosis in patients without bacterial excretion, with suspected tuberculosis, and with an ambiguous clinical picture of pulmonary lesions. However, sometimes this blood test can be false negative because of a weak immune response.

Tuberculosis (TB),caused by Mycobacterium tuberculosis (Mtb), remains one of the leading causes of mortalityfrom infectious diseases worldwide. So, this study investigates theantimicrobial potential of [Fe­(phen)3]2+ (FEP)and FEP-loaded nanostructured lipid systems (NLS@FEP) as an innovativetherapeutic approach for TB. The FEP showed promising antimycobacterialactivity in simulated physiological environments, with minimum inhibitoryconcentrations (MIC90) from 3.92 to 0.98 μg mL–1. FEP combination with rifampicin or pretomanid significantlyreduced the MIC90, with fractional inhibitory concentrationindex (FICI) of 0.27 and 0.103, respectively. Field emission scanningelectron microscopy (FE-SEM) analysis revealed significant structuralalterations in the Mtb cell wall, suggesting thatFEP interferes with its synthesis. In silico analysesand whole-genome sequencing (WGS) supported these findings, identifyingmutations in key genes, such as ponA1, which encodesa penicillin-binding protein involved in peptidoglycan synthesis. In silico modeling predicted high FEP affinity for PonA1,in line with FE-SEM observations; however, these predictions are hypothesis-generatingand require functional validation. FEP-loaded nanostructured lipidsystem (NLS@FEP) was designed to optimize FEP activity, which improvedits stability and bioavailability. In a murine model infected with Mtb H37Rv, free FEP and NLS@FEP achieved complete eliminationof pulmonary infection.

Against the background of increasing prevalence of cardiovascular pathology, monitoring of hemodynamic indicators in children and adolescents, assessment of adaptive capabilities during the study period in an educational organization are crucial tasks of modern medicine and prevention. Objective. To identify the features of hemodynamic indicators in modern school students, to determine tendencies in the dynamics of indicators on the basis of retrospective data analysis. Materials and methods. Assessment of children’s physical development indicators was carried out on the results of a survey of 891 school students in Novosibirsk. Anthropometric and hemodynamic indicators were studied; adaptive potential was calculated. The retrospective data consisted of a sample of anthropometric and hemodynamic indicators of school students in Novosibirsk aged 7—17 years (n =4.599 children), obtained during medical examinations of school students performed in 1976 and 1997—2001. Statistical analysis was carried out using Excel spreadsheets of Statistica-10.0 package. Results. The mean values of the studied indicators, both in boys and girls corresponded to age norms, thus in 8.5% of children systolic pressure level was elevated with maximum values in 12 and 16 years age groups. Modern boys and girls are characterized by higher systolic and diastolic pressure values (by 4—6 mm Hg) and a higher heart rate compared to their peers living previously (p<0.05). It has been established in the assessment of adaptive potential that the stress of adaptive mechanisms is characteristic of most modern children (94.4%). In a large number of publications, the problem of prevalence of elevated blood pressure in modern children and adolescents is noted, as well as the decline in the proportion of children with satisfactory adaptive capabilities. Conclusion. The performed analysis has revealed age-sex features of hemodynamic indicators in modern children and adolescents and has indicated a significant deterioration in the health of school students compared to their peers living more than 40 years ago.

<title>Abstract</title> Background Maternal tuberculosis (TB) remains a significant risk factor for compromising infant immune development in high-burden TB disease settings. The integrity of B-cells in early life is important for the development of immediate and long-term immunity in infants. This study assessed circulating B-cell subset frequencies in babies born to mothers with and without active TB in Uganda. Methods A cohort of 46 mother-infant pairs (24 cases, 22 controls) was recruited between September 2021 and July 2022 from three health facilities in Kampala. Infant cases were born to mothers with active TB, whereas infant controls were born to mothers without active TB. Peripheral blood mononuclear cells (PBMCs) were collected and processed from infants at baseline (≤ 1 month of age), and at three months and six months. PBMCs were stained with a 15-marker B-cell panel for spectral flow cytometry. Data were analysed using FlowJo and R v4.4.3. Mixed-effects modelling was applied for statistical testing, with time point as a fixed effect and participant as a random effect. Post-hoc comparisons used estimated marginal means. Results At baseline, infant cases were associated with decreased mean circulating frequencies of total B cells (18.5 versus 30.2; p = 0.02), naïve B cells (55.1 versus 68.9; p = 0.01), and mature B cells (43.6 versus 66.5; p = 0.03) compared to infant controls. Additionally, the infant cases were associated with increased baseline immature (56.4 versus 33.4; p = 0.03) and antibody-secreting B cells (15.6 versus 10.5; p = 0.04) compared to infant controls. No differences were observed at three or six months, except for IgG-only memory B cells, which were increased among infant cases at six months (14.4 versus 8.3; p = 0.04). Conclusions Exposure to <italic>Mycobacterium tuberculosis</italic> in utero may decrease the preimmune B-cell repertoire in early life, potentially increasing the risk of neonatal infections and altered responses to routine infant vaccines. Prompt diagnosis and treatment of TB during pregnancy are therefore crucial to prevent poor neonatal morbidity and mortality in our setting.

Infectious diseases of farm animals are one of the most pressing problems of current livestock sector. The commonly used specific vaccine prophylaxis is not always effective due to the genetic variability and mutational variability of pathogen antigens ("antigenic drift"), the widespread prevalence of mixed polyetiological infections, heterogeneity of the immune response and reduced immune resistance. Existent specific vaccines are aimed at protecting against a specific pathogen or, in the case of multivalency, against several specific pathogens, and are based on the induction of long-term adaptive, i.e. antigen-specific immunity due to the formation of Tand B-memory cells. In the last decade, it has been established that vaccines containing microorganisms, such as BCG, provide resistance not only to a specific pathogen (for example, in the case of BCG – against M. tuberculosis), but also to a wide range of other pathogens. The main mechanism of this broad heterologous resistance is the increased reactivity of the innate immune system cells, primarily monocytes-macrophages. In response to the primary stimulus ("training"), these cells undergo a number of epigenetic and metabolic rearrangements, become "sensitized" and, when confronted with a second stimulus, the same or another pathogen, provide long-term protection against many viral and bacterial infections. Metabolites of the mevalonate metabolic pathway play an important role in the formation of non-specific or "trained" immunological memory (“trained immunity”, TI). In the present work, the hypothesis of the ability of the farnesyl pyrophosphate synthase inhibitor, aminobisphosphonate (a blocker of the mevalonate pathway at the farnesyl pyrophosphate level), to potentiate BCG-induced TI was verified in in vitro and in vivo experiments. It has been found that the aminobisphosphonate zoledronate induces the TI phenotype in monocytes and causes nonspecific protection against staphylococcal infection in mice. In addition, zoledronate significantly enhances BCG-induced TI, causing a synergistic protective effect. The phenomenon of potentiated TI that we have discovered can form the basis for the development of fundamentally new powerful universal vaccines.

Symptom-based tuberculosis (TB) screening often relies on cough reporting, which may be unreliable. Passive cough monitoring via smartphone apps offers a less subjective alternative. This study evaluated the diagnostic accuracy and implementation feasibility of smartphone-based cough frequency monitoring for identifying individuals likely to have TB in Uganda. We enrolled adults (≥15 years) screened for TB in community settings or tested at health facilities in Kampala. Participants underwent microbiological testing and 48-hour cough monitoring using the Hyfe Research app. TB status was determined using Xpert MTB/RIF Ultra and culture, and inverse probability weighting was applied to adjust for differential enrollment. We compared cough frequency between individuals with and without TB and assessed diagnostic accuracy using weighted ROC curves. We also conducted staff interviews, analyzed thematically, to explore implementation challenges. Of 884 enrolled participants, 197 had valid cough recordings and TB status (101 from community screening, 96 from health facilities). Individuals with TB had higher median cough frequency than those without: 2.2 (interquartile range 0.8-6.1) vs 0.9 (0.4-2.0) coughs per hour in the community and 6.7 (2.6-27.5) vs 2.4 (0.9-4.8) in facilities; Wilcoxon P &lt; 0.0001 for both. AUCs for smartphone-based cough recording were 0.69 (95% CI: 0.58–0.79) in the community and 0.76 (95% CI: 0.6–0.88) in health facilities. At 90% sensitivity, specificities were 20% (95% CI: 0–22%) and 46% (95% CI: 1–32%), respectively. Smartphone-recorded cough frequency was moderately correlated with self-reported cough severity, respiratory-related quality of life scores (Saint George’s Respiratory Questionnaire), and staff-observed coughs. Staff cited device visibility, stigma, and security concerns as barriers to implementation. While smartphone-recorded cough frequency was associated with TB status, it did not meet diagnostic accuracy thresholds for stand-alone screening or triage. Implementation challenges also limited data collection. Addressing operational barriers will be critical to future development and deployment of cough monitoring tools for TB screening.

Action Quality Assessment (AQA) methods combined with computer vision are used in sports. This study aims to develop tools for monitoring sports achievements. Our research advances AQA in the training process in figure skating and differs from previous studies in the following ways: 1) For preprocessing the obtained data and removing artifacts in the coordinate data array, we employ a combination of the sliding window method and the Savitzky–Golay filter, with filter parameters optimized using a genetic algorithm; 2) To identify the stages of exercise execution, we use the Pruned Exact Linear Time (PELT) algorithm combined with the Radial Basis Function (RBF); 3) We demonstrate the feasibility of using smartphone–embedded cameras to calculate performance parameters in figure skating for sports selection purposes. Methods: The study analyzed an exercise performed by an athlete on a sports disc in a gym setting. Video recording was conducted using two smartphones. Coordinate data extraction from video footage was performed using the OpenPose. The rotational speed of the athlete was calculated using of the Body-25 model. Calculations were performed using Python. Validation of the results was carried out using the Kinovea video analysis software. Results: The studied time series was divided into four segments, each exhibiting significantly different dynamics in rotational speed. The deviation between calculated speed values and those obtained using Kinovea did not exceed 3%. Conclusion: The application of the study’s results will enhance the objectivity of exercise performance evaluation in figure skating and create conditions for improving the efficiency of sports selection.

In this part of the study, the first component of the concept of "natural genome reconstruction" is being proven. It was shown with mouse and human model organisms that CD34+ hematopoietic bone marrow progenitors take up fragments of extracellular double-stranded DNA through a natural mechanism. It is known that the process of internalization of extracellular DNA fragments involves glycocalyx structures, which include glycoproteins/protein glycans, glycosylphosphatidylinositol-anchored proteins and scavenger receptors. The bioinformatic analysis conducted indicates that the main surface marker proteins of hematopoietic stem cells belong to the indicated groups of factors and contain specific DNA binding sites, including a heparin-binding domain and clusters of positively charged amino acid residues. A direct interaction of CD34 and CD84 (SLAMF5) glycoproteins, markers of hematopoietic stem cells, with double-stranded DNA fragments was demonstrated using an electrophoretic mobility shift assay system. In cells negative for CD34, which also internalize fragments, concatemerization of the fragments delivered into the cell occurs. In this case, up to five oligonucleotide monomers containing 9 telomeric TTAGGG repeats are stitched together into one structure. Extracellular fragments delivered to hematopoietic stem cells initiate division of the original hematopoietic stem cell in such a way that one of the daughter cells becomes committed to terminal differentiation, and the second retains its low-differentiated status. After treatment of bone marrow cells with hDNAgr, the number of CD34+ cells in the colonies increases to 3 % (humans as the model organism). At the same time, treatment with hDNAgr induces proliferation of blood stem cells and their immediate descendants and stimulates colony formation (mouse, rat and humans as the model organisms). Most often, the granulocyte-macrophage lineage of hematopoiesis is activated as a result of processing extracellular double-stranded DNA. The commitment process is manifested by the appearance and repair of pangenomic single-strand breaks. The transition time in the direction of differentiation (the time it takes for pangenomic single-strand breaks to appear and to be repaired) is about 7 days. It is assumed that at the moment of initiation of pangenomic single-strand breaks, a "recombinogenic situation" ensues in the cell and molecular repair and recombination mechanisms are activated. In all experiments with individual molecules, recombinant human angiogenin was used as a comparison factor. In all other experiments, one of the experimental groups consisted of hematopoietic stem cells treated with angiogenin.