Personalized Approach as a Basis for the Future Diagnosis of Tuberculosis (Literature Review)

The global spread of tuberculosis remains one of actual problems of public health despite of introduction of public health safety programs. Early, rapid and accurate identification of M. tuberculosis and determination of drug susceptibility are essential for treatment and management of this disease. Delay in delivering results prolongs potentially inappropriate antituberculosis therapy, contributing to emergence of drug resistance, reducing treatment options and increasing treatment duration and associated costs, resulting in increased mortality and morbidity. Faster, more comprehensive diagnostics will enable earlier use of the most appropriate drug regimen, thus improving patient outcomes and reducing overall healthcare costs. The treatment of infection based on the using of massive antimicrobial therapy with analysis of bacterial strains resistance to first line drugs (FLD) isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), ethambutol (EMB) and streptomycin (SM). However, the public health practitioners pay no attention to functional activity of human immune system genes. The interaction of bacterial genomes and immune system genes plays the major role in infection progress. There is growing evidence that, together with human and environmental factors, Mycobacterium tuberculosis complex strain diversity contributes to the variable outcome of infection and disease in human TB. We suppose that the future of diagnosis and treatment of tuberculosis lies in the field of personal medicine with comprehensive analysis of host and pathogen genes

The Question of Corruption During Releasement on Parole

The article notes that the existing corruption manifestations in the criminal-executive system, including when deciding on the conditional early release of a person serving a sentence of imprisonment, have become quite frequent. An analysis of the explanations of the Supreme Court of the Russian Federation is given, which pays special attention to the issue of parole. It is noted that his explanations are designed not only to streamline the process of parole, but also to really help to release those who are not dangerous to society. To exclude violations when applying parole, which are analyzed in the article, it is necessary to take a number of measures within the framework of reforming the penal system

Comparison of efficacy of laser and radio-wave methods of surgical treatment of patients with chronic rhinitis

Introduction. Chronic rhinitis occurs more often in patients; it’s symptoms deteriorate their quality of life, affect sleeping, daily activity, and sometimes cause complications. The treatment depends on the clinical symptoms. In case of inefficiency of conservative therapy, surgery is indicated. Choosing an exact surgical instrument is still controversial.Objective. The aim of our study is to compare using semiconductor laser (wavelength 1.56 mkm) and radiofrequency (4 MHz) in patients with chronic rhinitis.Materials and methods. 60 patients with chronic drug-induced rhinitis aged 19–80 years were recruited and divided into two equal groups. All patients underwent surgical procedures: semiconductor laser (IRE-Polus) and radiofrequency (Ellman Surgitron) inferior nasal turbinate reduction. To assess and compare the healing process in two groups we used endoscopy and active anterior rhinomanometry. All patients filled out the SNOT-20 questionnaire. For the mucociliary clearance evaluation saccharin test was used. We observed patients during 12 months.Conclusion. Both, laser and radiofrequency, techniques are effective in patients with chronic rhinitis. In laser group shorter healing period was observed, what leads to rehabilitation shortening and life quality improvement

Sequencing of a fragment of the leptin gene in adolescents with different weight status

Background. Obesity is a significant social problem among the population of the world. The leptin gene (LEP) is currently considered as a potential candidate gene influencing metabolic disorders associated with predisposition to overweight and obesity. Leptin plays an important role in body weight homeostasis by influencing food intake and energy expenditure and maintaining constant energy stores. A defect in the leptin gene may be one of the causes of obesity and, as a result, of various obesity-associated pathologies. The aim of the study. To search for single-nucleotide polymorphisms (SNP) of the leptin gene in adolescents with different weight status. Methods. The study involved 20  adolescents aged 11–17  years with normal body weight and  overweight/obesity. Research methods: assessment of clinical status with  anthropometry; Sanger sequencing of the leptin gene fragment localized in the  intron of this gene – (5’-AGCCTTGTTTTCATCATCTGGA, 3’-TGGGAGGAATCGCTCTCAGA). We also carried out bioinformatic processing of sequencing results. Results. As a result of the study, the optimal conditions for amplification of the 891 bps leptin gene region were selected for the above mentioned primer pair of the LEP gene (s16_L891, s16_R891). Based on the results of sequencing, 45 single nucleotide substitutions of the LEP gene were identified, including 23 single nucleotide substitutions which were not previously registered in GenBank. In the group of adolescents with overweight and obesity, 14 unregistered single nucleotide substitutions of the LEP gene and 13 registered SNPs were identified in the GenBank database. In the group of adolescents with normal body weight, these SNPs were not found

Организация медицинской помощи больным артериальной гипертензией в районах Иркутской области с низкой доступностью специализированной помощи

The complex of medical aid arrangements for arterial hypertension patients in the rural and farthest areas of Irkutsk Region which were characterized by low accessibility of specialized medical aid was developed. The complex make possible to improve awareness, treatment and control of arterial hypertension.Разработана система оказания медицинской помощи больным артериальной гипертензией в сельских и отдаленных районах Иркутской области с низкой доступностью специализированной медицинской помощи, позволяющая существенно повысить уровни осведомленности, лечения и контроля артериальной гипертензии

Online service for interpretation of the resistance prediction results to bedaquiline by the molecular data

Background. Bedaquiline is a new and promising anti-tuberculosis drug, but longterm use requires resistance. This is due to mutations in the atpE and mmpR genes in M. tuberculosis (MBT).The aim of the research was to test a system for automated interpretation of results for predicting resistance to bedaquiline by the molecular data.Materials and methods. DNA was isolated from strains of M. tuberculosis in the Irkutsk region and Yakutia. The total quantity of DNA samples was 27 strains from Yakutia and 21 strains from the Irkutsk region. The study of MBT genomes was carried out on the DNA previously obtained by the authors in the territories of the Irkutsk region (n = 5), Yakutia (n = 4), Buryatia (n = 3), Zabaykalskiy kray (n = 4) and the Far East (n = 8). We used the BSATool program to detect bedaquiline resistance based on  Sanger and genomic data. Sanger sequencing analyzed the atpE and  mmpR genes, and whole genome sequencing examined mutations in the same sequences, as well as additionally in mmpL5, mmpS5, Rv0678, Rv1979c, and pepQ.Results. Complete agreement between the phenotypic and genotypic analysis of resistance to bedaquiline was found for three strains from Yakutia. One genome with significant mutations to bedaquiline was identified. A conclusion was made about the importance of molecular analysis of target genes with subsequent detection of resistance to bedaquiline in silico

Genotypic and phenotypic characteristics of <i>Mycobacterium tuberculosis</i> drug resistance in TB children

Background. Russian Federation is included in the list of 30 countries with the highest burden of tuberculosis, including MDR tuberculosis. The most important part of this problem is the primary MDR/XDR TB in children.The aim: a comparative analysis of the phenotypic and genotypic profile of drug resistance to anti-tuberculosis drugs (ATP) according to whole genome sequencing of M. tuberculosis strains from children.Materials and methods. Whole genome sequencing (WGS) results of 61 M. tuberculosis isolates from children with tuberculosis in 2006–2020 in the Russian Federation were analyzed for anti-TB drug resistance mutations, according to the WHO catalog and were compared with the results of phenotypic drug sensitivity.Results. The M. tuberculosis belonged to two genetic groups: Beijing genotype – 82 % (50/61) dominant Central Asian Russian (31/50) and B0/W148 (16/50) subtypes, and non-Beijing (Ural, S, LAM) – 18 % (11/61). Three isolates belonged to Asian Ancestral subtype (3/50). Of the 61 isolates, only 14.7 % (9/61) were sensitive to antiTB drugs, 49.2 % (30/61) were MDR and 14.7 % (9/61) were pre-XDR. Comparison of the resistance profile (MDR/pre-XDR) with genotype revealed an upward shift for Beijing isolates, in particular Beijing B0/W148 (15/16) subline compared to other Beijing (19/34) (Chi-square with Yates correction = 5.535; p &lt; 0.05) and nonBeijing (5/12) (Chi-square with Yates correction = 6.741; p &lt; 0.05) subtypes. Discrepancies between genotypic and phenotypic drug resistance profiles were found in 11.5 % (7/61) of cases.Conclusions. Based on the analysis of WGS data, the genotypic characteristics of M. tuberculosis and the most complete set of drug resistance mutations were obtained, indicating a significant prevalence in MDR and pre-XDR TB of cases caused by epidemic subtypes of Beijing (B0/W148 and Central Asian Russian). The molecular mechanisms of adaptation of M. tuberculosis to the treatment of anti-TB drugs are not unique for the child population but reflect the general processes of the spread of MDR/XDR in Russia

Isolation and whole genome sequencing of a lipophilic anaerobic bacterium, a representative of the species complex <i>Corynebacterium tuberculostearicum</i>, from a tuberculosis focus

Background. The study of the lower respiratory tract microbiome has been actively developed inrecent years with the help of whole genome sequencing (WGS) methods. Due to this, it became clear that the nature of the lungs microbiota is very different from other microbial communities inhabiting the human body. One of the important directions in the study of pathological lungs biocenosis is the study of the role of the satellite microbiota of the tuberculosis focus. The aim of the work. To isolate and characterize oxygen-tolerant anaerobes from the necrotic contents of tuberculomas. Materials and methods. Biopsy material from 5 patients with pulmonary tuberculosis was obtained during a planned surgical treatment of tuberculoma. A pure culture was isolated from one sample during anaerobic cultivation. Lipase activity of strain was determined by plating on brain heart infusion agar (HIMEDIA, India) supplemented with 0.1 % Tween-80 and 10 mM of CaCl2. Antibiotic susceptibility was determined by RAPMYCO and SLOWMYCO of TREK Diagnostic Systems (Thermo Fisher Scientific, USA). DNA from the sediment of the broth culture was isolated by the CTAB chloroform method. Whole genome sequencing was performed on a DNBSeq-G400 NGS sequencer by Genomed (Russia). Results. Based on WGS results and phylogenetic analysis, the strain was identified as Corynebacterium kefirresidentii. The strain was characterized by high lipase activity and resistance only to Isoniazid, Ethionamide and Trimethoprim/Sulfamethoxazolin. Conclusion. The isolation of a lipophilic anaerobic representative of the Corynebacterium tuberculostearicum species complex from a tuberculous focus indicates a  possible role of the non-tuberculous microbiota in the liquefaction of caseous necrosis. We assumed that in some cases, favorable conditions are created inside the tuberculous focus for the development of satellite anaerobic lipophilic microbiota

Viral Load in COVID-19: Underestimated Clinical and Epidemiological Marker

Background. The viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the new coronavirus infection, is becoming increasingly important in clinical and epidemiological contexts. Despite this, there are significant complexities in the implementation of viral load quantitative measurement into clinical practice due to the limited approaches to its assessment.The aim of this work was to develop an approach for SARS-CoV-2 viral load analysis by the value of sample threshold cycles (Ct) relative to the Ct of the internal control sample obtained in routine PCR diagnostics of the COVID-19, and to use this approach for quantitative monitoring of viral load in patients with first positive SARS-CoV-2 test from the Irkutsk region.Materials and methods. Using regression models based on the least squares method, an approach to determine the number of copies of SARS-CoV-2 RNA in 1 ml of nasopharyngeal secretion was developed. The viral load of SARS-CoV-2 was assessed in nasopharyngeal and pharyngeal samples obtained from 1370 patients from Irkutsk and Angarsk with primary diagnosed positive PCR result in the period from July 1 to November 10, 2020.Results. A tenfold increase in the average monthly viral load among patients in September-October 2020 was revealed. We assume that the change in the epidemiological pattern of the spread of the new coronavirus infection during this period is associated with an increase in the number of contacts in the population due to the school year beginning. Higher viral loads are observed in populations at risk for COVID-19 – among healthcare workers and adults/elderly patients. Conclusion. The development of a standardized quantification of SARS-CoV-2 viral load in the nasopharyngeal samples can be a predictive clinical marker and a reliable tool for improving COVID-19 surveillance using the proposed approach to assess average viral load in a local population