Risks of Central Russia Regions Modernization

The article deals with the development of modernization processes in regions of the Central Federal District of Russia in terms of institutional and socio-cultural risks. The territorial disparity on the criteria of modernization in Central Russia is being recorded and the denotation to all six types of modernization is being revealed. The authors consistently view the institutional and socio-cultural modernization risks represented in economic, political, administrative law and social spheres. Special attention is given to the socio-cultural risks of a family which is under the risk because of impossibility to find the balance between advantages and dangers related to the modernization processes and the transformation of family and matrimonial relations. DOI: 10.5901/mjss.2015.v6n6s7p13

Triple combination of vemurafenib, cobimetinib, and atezolizumab in real clinical practice in the Russian Federation: results of the A1 cohort of the ISABELLA study

BackgroundAmong several treatment options for BRAF-mutant metastatic melanoma, a combination of BRAF inhibitor, MEK inhibitor, and anti-PDL1 antibody seems to be a new emergent approach recently registered in the Russian Federation. It is still not clear which patient population benefits more from this simultaneous use of three drugs instead of its sequencing.AimThis study aimed to evaluate patients’ characteristics treated in real practice in 14 Russian regions by triple combination and to analyze their outcomes depending on biomarkers (PD-L1 expression).MethodsThis was a part (cohort A1) of a prospective non-interventional study of clinical outcomes and biomarkers in patients with skin melanoma. Patients were included in cohort A1 if combination treatment with vemurafenib (vem) + cobimetinib (cobi) + atezolizumab (atezo) was initiated no earlier than 12 weeks (84 days) prior to written informed consent to participate in this study. The index event was the initiation of therapy with all three drugs vem + cobi + atezo (i.e., triple combination). The primary efficacy endpoint of the study was the 24-month overall survival (OS), defined as the time from the index date to the date of death from any cause. If the patient did not experience an event, the OS will be censored at the date of the last contact. Objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) in the Intention to treat (ITT) population, in biomarker positive population, and in population with brain metastases were also evaluated. Quality of life questionnaires were pre-planned by protocol if it was a part of routine practice. Adverse events were also collected.ResultsBetween March 2021 and May 2023, 59 patients were enrolled in 19 centers from 14 regions of Russia. Thirty-one of 59 (52.4%) patients had central nervous system metastases, and 18 of 31 (58.4%) were symptomatic. Forty of 59 patients (68%) received the triple combination as the first-line treatment. The median follow-up period was 16.83 [95% confidence interval (CI) 13.8–19.8] months. The mean duration of therapy with this regimen was 9.95 months (95% CI 7.48–13.8). ORR was 55.1%; progression as the best outcome was seen in 16.3%. The median DoR was 12.95 months (95% CI 11.0–14.8 months), with a median of 20.3 months (95% CI 9.1–31.5 months) when triple therapy was administered in the first-line treatment. In patients with brain metastases (N = 31), ORR was 45.1%; the median DoR was 12.95 (95% CI 11.0–14.8 months). The median PFS in the entire population was 13.6 months (95% CI 8.6–18.6); the 24-month PFS was 22%. The estimated median OS in the entire population was 15.8 months (95% CI NA); 24-month OS was 45% (95% CI 0.32–0.64). In multivariate Cox regression model, biomarkers of interest [lactate dehydrogenase, Programmed cell death ligand-1 (PD-L1)] did not have statistically significant impact on PFS, OS, or DoR probably due to high data missing rate. No unexpected adverse events were reported. Grades 3–4 AEs were seen in 23 of 59 patients (38%) with most common were skin and liver toxicity.ConclusionTriple combination of atezolizumab, vemurafenib, and cobimetinib had proven its efficacy and tolerability in real settings. No impact of potential predictive biomarkers was seen (NCT05402059)

Ability of the sonoelastometria for deferential diagnosis of malignant and non-malignant ovarian tumors

The comparison analysis of the sonoelastomeric images with tissue density has revealed the basic laws – the greatest density of the tissues was defined in the loci painted in red color, and was in a range from 52.87 to 300 kPa. Sonoelastometric signs of malignant process presence in the ovaries have been determent at volume of the tumor not less than 15 cm3

Synthesis of Biologically Active Betulin-based Triterpene Compounds

Описаны разработанные авторами новые способы синтеза тритерпеновых соединений на основе биологически активного бетулина, перспективных для создания новых лекарственных средств. Разработан усовершенствованный способ получения бетулиновой кислоты восстановлением бетулоната натрия NaВН4 в среде воды. Предложен способ восстановления бетулоновой кислоты в бетулиновую в условиях межфазного катализа, обеспечивающий повышение выхода бетулиновой кислоты до 99 %. С использованием карбодиимидного метода синтезированы циклогексиламид бетулиновой кислоты (выход 89 %), пропиламид бетулиновой кислоты (выход 84 %), третбутиловый эфир валинбетулиновой кислоты (выход 83 %), третбутиловый эфир тирозинбетулиновой кислоты (выход 84 %). Разработаны новые одностадийные способы получения диацетата бетулина путем ацетилирования бересты березы и аллобетулина путем кипячения в толуоле илип-ксилоле бересты, пропитанной серной или ортофосфорной кислотой.Paper describes the developed by authors the novel methods of triterpene compounds synthesis from biologically active betulin, which have prospects for the design the new drugs. The improved method of betulinic acid synthesis by sodium betulonate reduction by BH4 in water medium is developed. The method of betulonic acid reduction to betulinic acid at conditions of phase-transfer catalysis was suggested which makes it possible to increase the betulinic acid yield up to 99 %. With the use of carbodiimide methods the next derivatives of betulinic acid were synthesized: cyclohexyl amide (yield 89 %), propyl amide (yield 84 %), tretbuthyl ether of valine (yield 83 %), tretbythyl ether of tyrosine (yield 84 %). The new one-step methods of synthesis of betulin diacetate by acetilation of outer bark and allobetuline synthesis by boiling in toluene or p-xylene of outer birch bark impregnated by sulphonic or ortophosphoric acids were developed

Synthesis of Biologically Active Betulin-based Triterpene Compounds

Описаны разработанные авторами новые способы синтеза тритерпеновых соединений на основе биологически активного бетулина, перспективных для создания новых лекарственных средств. Разработан усовершенствованный способ получения бетулиновой кислоты восстановлением бетулоната натрия NaВН4 в среде воды. Предложен способ восстановления бетулоновой кислоты в бетулиновую в условиях межфазного катализа, обеспечивающий повышение выхода бетулиновой кислоты до 99 %. С использованием карбодиимидного метода синтезированы циклогексиламид бетулиновой кислоты (выход 89 %), пропиламид бетулиновой кислоты (выход 84 %), третбутиловый эфир валинбетулиновой кислоты (выход 83 %), третбутиловый эфир тирозинбетулиновой кислоты (выход 84 %). Разработаны новые одностадийные способы получения диацетата бетулина путем ацетилирования бересты березы и аллобетулина путем кипячения в толуоле илип-ксилоле бересты, пропитанной серной или ортофосфорной кислотой.Paper describes the developed by authors the novel methods of triterpene compounds synthesis from biologically active betulin, which have prospects for the design the new drugs. The improved method of betulinic acid synthesis by sodium betulonate reduction by BH4 in water medium is developed. The method of betulonic acid reduction to betulinic acid at conditions of phase-transfer catalysis was suggested which makes it possible to increase the betulinic acid yield up to 99 %. With the use of carbodiimide methods the next derivatives of betulinic acid were synthesized: cyclohexyl amide (yield 89 %), propyl amide (yield 84 %), tretbuthyl ether of valine (yield 83 %), tretbythyl ether of tyrosine (yield 84 %). The new one-step methods of synthesis of betulin diacetate by acetilation of outer bark and allobetuline synthesis by boiling in toluene or p-xylene of outer birch bark impregnated by sulphonic or ortophosphoric acids were developed

Thermally modified peat additive for cement systems made using raw materials from the Kaliningrad region

Introduction. The purpose of this work is to study the thermally modified peat additive, the use of which is scientifically justified in the works of professor N.O. Kopanitsa and her colleagues. This additive is extracted from the raw materials from the Kaliningrad region, and the authors focus on its effect on the consistency, moisture-retaining capacity of the mix, and the strength characteristics of fine-grained concrete. Materials and methods. The additive was made from lowland peat extracted from the Glushkovo quarry in the Kaliningrad region. Raw materials were subjected to thermal treatment with limited access of oxygen. Results. The authors have proven an increase in the consistency and water-retaining capacity of mixes that have 4 and 8 % additive. On the 21 day, an 9 % increase in the flexural strength of concrete specimens with the 4 and 8 % additive was registered in comparison with the benchmark specimen (5.5 MPa for the benchmark mix and 6 MPa for the 4 and 8 % additive); an increase in compression strength reached 23 % when the 8 % additive was used (40.7 and 50.2 MPa for the benchmark mix and the one that contains the 8 % additive, respectively). Conclusions. The presented results of the research show a strong potential for the improvement of physical-mechanical properties of concretes by using thermally modified peat additives made from the local raw materials extracted in the Kali­ningrad region.</jats:p