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Abstract Clarithromycin (CLR) is currently a key antibiotic for Helicobacter pylori infection treatment, however, the data on CLR resistance patterns in Russia are missing. Here, we applied WGS-based approach to H. pylori clinical isolates from Russia to comprehensively investigate sequence variation, identify putative markers of CLR resistance and correlate them with phenotypic susceptibility testing. The phenotypic susceptibility of 44 H. pylori isolates (2014–2022) to CLR was determined by disc diffusion method: 23 isolates were CLR-resistant and 21-CLR-susceptible. All isolates were subjected to WGS and submitted to GenBank. Based on complete sequence analysis, we showed that among all sequence variants, the combination of mutations A2146G/A2147G in the 23S rRNA gene is the most reliable for prediction of phenotypic susceptibility. For the first time, the average number of mutations in 106 virulence-associated genes between resistant and susceptible groups were compared. Moreover, this study presents the first WGS insight into genetic diversity of H. pylori in Russia with a particular focus on the molecular basis of drug resistance: the novel mutations were described as potential markers for the resistance development. Of these, the most prominent was a frameshift deletion (252:CGGGT) in HP0820 coding region, which is a good candidate for further investigation.

BACKGROUND: The analysis of the long-term consequences of acute coronary syndrome (ACS) revealed a high incidence of complications and their probable relationship with defects in secondary prevention, which allows us to determine the direction of elimination of such defects. AIM: To assess the long-term consequences of ACS and the effectiveness of secondary prevention. MATERIALS AND METHODS: The study included 255 patients who were sequentially hospitalized in the Regional Vascular Center of Petrozavodsk for ACS in 2009–2010. In the period from October 2021 to February 2022, electronic medical record data were retrospectively analyzed to assess the effects of ACS and the effectiveness of secondary prevention. RESULTS: Data from 155 patients were analyzed, among whom men predominated (n=113, 72.9%). The mortality rate was high, with a significant prevalence of adverse effects of ACS. The 12-year mortality was 42.6% (66 people), and the average age of the deceased was 62.1±6.8 years. Chronic heart failure was diagnosed in 50 (32.3%) patients. Thirty-five of them had stage IIa (72.9% among 48 patients with a known stage), and 26 had functional class II (FC; 68.4% among 38 patients with a known FC). Stable angina pectoris was diagnosed in 41 patients (26.5%), 26 (66.7% among 39 patients with known FC) had symptoms of FC II, and 31 (20%) had recurrent ACS. Percutaneous intervention was performed in 65% of cases (n=20). Cardiac arrhythmias and conduction disorders were recorded in 41 (26.5%) patients: 15 of them (36.6%) were diagnosed with ventricular extrasystole of high grade (grade IV according to Ryan), and atrial fibrillation/flutter developed in 22 (14.2% of all observed) patients. Data indicate a lack of commitment to the principles of secondary prevention for both patients and doctors, except for quitting smoking. Six patients (3.9%) continued to smoke. Moreover, increased body weight persisted in 33 patients (21.3%). The prescription rate for necessary medications was low; acetylsalicylic acid was prescribed to 61 (39.4%) patients, blockers of the renin–angiotensin–aldosterone system to 74 (47.7%), beta-blockers to 74 (47.7%), and statins to 69 (44.5%), which does not allow achieving the target levels of therapy. The target blood pressure was achieved only in 68 patients (43.9%), heart rate in 23 (14.8%), and lipid spectrum in 2 (1.3%). CONCLUSION: This study revealed the high incidence of adverse effects of ACS in the long-term period, which, apparently, is a consequence of low adherence to lifestyle modifications and drug correction of risk factors.

Introduction. Vaccination could be the most effective means of preventing hemorrhagic fever with renal syndrome (HFRS), which is one of the leading zoonoses and a major cause of natural disease in humans. Therefore, research to develop an effective vaccine and the search for new non-toxic and effective adjuvants that can enhance and prolong the immune response, reduce the antigen concentration and reduce the frequency of dose administration is an urgent task. The aim of the study was to determine the dependence of the immunogenic activity of an experimental hantavirus vaccine based on Puumala virus (HV) on the antigen dose both in native form and in combination with carbohydrate adjuvants. Materials and methods. The immunoadjuvant effect of Ac3-LPS S. sonnei and S. flexneri 1B and emulsions of nanoemulsified squalene Sepivac SWE (SWE) as part of HV at the optimal and minimal doses was investigated by induction of neutralising antibodies after 3-fold immunisation (day 0, 14, 182) of guinea pigs (Cavia porcellus). Differences in the immunogenic activity of HV were assessed in the neutralisation reaction by 50% suppression of focal units in Vero E6 cell cultures. Results. A statistically significant increase in neutralising antibodies levels was observed after immunization both with HV at the optimal dose and for its combination with adjuvants. Ac3-LPS S. sonnei and SWE showed the most pronounced immunoadjuvant effect at concentrations of 50 and 100 μg/dose, respectively. The immunoadjuvant effect of the combination of the hantavirus vaccine with Ac3-LPS S. sonnei and SWE contributed to both an enhanced immune response and its duration. The tenfold reduction of the antigen dose in the presence of SWE allows optimization of the immune response to the vaccine. Conclusion. The results of this study show the prospects of using Ac3-LPS S. sonnei and Sepivac SWE in the vaccine for the prevention of HFRS.

Aim. To evaluate the efficacy and toxicity of second-line polychemotherapy according to FOLFOX or FOLFIRI regimen in patients with biliary tract tumours after progression during first-line chemotherapy (CT). Materials and methods. The study is based on the analysis of retrospective and prospective data on the examination and treatment of 94 patients with biliary cancer of grades T1-4N0-2M0-1 followed-up and treated at the N.N. Blokhin National Medical Research Center of Oncology from 2015 to 2023. All patients were divided into 2 groups: Group 1 (FOLFOX, n=47) and Group 2 (FOLFIRI, n=47). In Group 1, patients received the recommended FOLFOX second-line CT regimen. Patients in Group 2 received FOLFIRI regimen. The endpoints were overall survival (OS) and incidence of grade 3-4 adverse events. Results. The study included 94 patients. In the FOLFOX group, the median OS was 13.0 months (1-year OS was 57.8±7.4%); for the FOLFIRI group, the median OS was 12.3 months (1-year OS was 54.4±7.3%). The toxicity profiles of FOLFOX and FOLFIRI were acceptable and consistent with those reported for the regimens. According to the grade 3–4 toxicity data, diarrhea was significantly more common in the FOLFIRI group (p=0.014), and neurotoxicity was more common in the FOLFOX group (p=0.006). During the second-line CT, the frequency of grade 1–4 toxicities in the groups did not differ: 18 (38.3%) events in the FOLFOX group and 19 (40.0%) events in the FOLFIRI group. Conclusion. Our results of evaluating the efficacy and toxicity of the second-line polychemotherapy regimens show that the FOLFOX and FOLFIRI CT regimens have equal efficacy in patients with advanced biliary tract cancer with a good performance according to the ECOG scale, who previously received the first-line therapy with a combination of gemcitabine with a platinum agent (cisplatin or oxaliplatin); also, our data demonstrate similar toxicity profiles of these regimens.

INTRODICTION. Currently, gene therapy based on adeno-associated virus (AAV) vectors faces a number of barriers, both biomedical and technological, which require studying and overcoming for further development of this gene therapy technology.AIM. This study aimed to analyse the use of gene therapy for a range of hereditary diseases, taking into account the barriers associated with its side effects and insufficient efficacy, the determination of the therapeutic window, and individual characteristics relevant to a particular hereditary disease; additionally, the study aimed to review the approaches to lifting these barriers and increasing the availability of gene therapy through the improvement of technological approaches to production and the reduction of production costs.DISCUSSION. The authors reviewed the experience accumulated for gene therapy products that were approved or undergoing clinical trials. The study included a gene therapy applicability assessment using several hereditary diseases as a case study. The assessment showed that correct determination of the therapeutic window for a medicinal product and timely diagnosis of a hereditary disease were essential for effective and safe gene therapy. The study considered the strategies used to reduce the risks of adverse events and increase the effectiveness of AAVbased gene therapy. The authors assessed technological advancements in the manufacturing of AAV-based gene therapy products. The most perspective directions were the transition to suspension culture systems, the improvement of bioreactors, the use of new methods and materials for the purification of viral particles, the improvement of transfection systems, and the creation of new host cell lines. Ultimately, this can lead to lower production costs and an increased availability of gene therapy.CONCLUSION. Currently, gene therapy is used only for a small range of hereditary diseases. Significant barriers to its use are due to insufficient efficacy, risks of adverse events, and high costs for treatment. Ongoing biomedical and technological development should lift many of these barriers and increase access to gene therapy.

Cordyceps militaris and Lentinula edodes are known for their high extracellular proteolytic, amylolytic, and laccase activity, which is important for bakery production. This article describes the effect of enzymes obtained from mycelial biomass of C. militaris and L. edodes on such properties of flour mixes as amylolytic and proteolytic enzymic activity during baking, technological costs, and bread quality. The research featured strains of C. militaris SRG4 and L. edodes 3790 fungi; mycelial biomass powder of these fungi on a sterile grain substrate (rice, wheat); experimental flour mixes of wheat bread and first-grade baking flour with mycelial biomass powder; bread made from the experimental flour mixes. The experimental part included standard methods used in the bakery industry. The mycelial biomass of C. militaris and L. edodes fungi proved to be a promising baking additive because it possessed hydrolytic enzymes and was rich in protein substances (32.2 ± 1.5 and 26.4 ± 2.0%, respectively), specific mushroom polysaccharides (36.7 ± 0.8 and 52.2 ± 1.2%, respectively), and carotenoids (1600 ± 40 mcg/g of C. militaris biomass). The active amylases and proteinases in the mycelial biomass powder improved the sugar-forming ability and reduced the falling number. In addition, they raised the amount of washed gluten with a slight decrease in elasticity, as well as provided an acceptable structure and viscosity of the dough at 1–4% of mycelial biomass powder. This dose resulted in an optimal bread formulation of standard quality. A bigger amount caused the crumb to darken and increased its humidity while reducing the specific volume. The bread samples with C. militaris were too acid. Mycelial biomass of C. militaris and L. edodes proved to be a good source of enzymes to be used with grain substrates in bakery production. Further research is needed to define the optimal dose and processing modes.

This article presents the outcomes of a study that investigates the perceptions among residents of Russia regarding their membership in the Russian nation or society. The study employs interviews (100) and focus groups (40), carried out across five regions of Russia, as its primary data collection methods. The key methodological approach was to pose questions about societal membership and the integration of various migrant types into Russian society, thus revealing underlying beliefs about the criteria for belonging to the Russian nation or society. This approach was especially insightful for understanding perceptions about groups that are typically not questioned about their societal membership. The study identifies two distinct types of societal membership: “organic” and “acquired”. Organic membership is socially ascribed to individuals born in Russia or those with ancestors born in Russia. This category often overlaps with national identity, rendering ethnic Russians born in Russia the quintessential members of Russian society. However, organic membership is not exclusively reserved for ethnic Russians; it extends to other ethnic groups considered part of “the peoples of Russia”, though they are seen as less typical members. Interestingly, the perception of these membership categories varies between regions with distinct national identities and those without such distinctions. Acquired membership, on the other hand, is contingent upon fulfilling specific criteria, such as familiarity with Russian (or regional) culture and a desire to be part of Russian society. Exceptionally, notable achievements can override these criteria. Unlike organic members, individuals with acquired membership can lose their societal status, except in cases of betrayal, which is nearly impossible for organic members. The findings are contextualized within citizenship studies, positing that the described constructs serve as a foundation for the institution of citizenship rather than the converse. Additionally, the study contributes to the ongoing cognitive turn in ethnicity research, offering new insights into the conceptualization of national and societal belonging.