Plastid DNA sequence diversity in wild grapevine samples (Vitis vinifera subsp. sylvestris) from the Caucasus region

DNA sequence diversity was investigated in three plastid regions (the trnH-psbA intergenic spacer, accDpsaI intergenic spacer and the rpl16 intron) in a group of 40 wild grape (Vitis vinifera subsp. sylvestris) samples from the South Caucasus. This group included 22 samples from Georgia, 9 samples from Azerbaijan, 2 samples from Armenia and 7 samples from Turkey. The South Caucasus region is widely believed to be the area in which grape domestication began, and the study of genetic diversity in this region is viewed as key to understanding grape domestication in general. Four plastid haplotypes are evident in the 40 samples, and are designated by their character states at each of the 4 polymorphic positions: AAAT – 22 samples, ATTT – 6 samples, GTAC – 1 sample, and ATAT – 11 samples. The AAAT haplotype is restricted to Georgia and Azerbaijan, the ATAT haplotype is distributed across the entire study area, the ATTT haplotype is distributed in the southern part of the study area from the Black Sea to the Caspian Sea. The single GTAC haplotype was only found in southwestern Georgia. The AAAT haplotype is restricted to both wild (V. vinifera subsp. sylvestris) and cultivated (V. vinifera subsp. vinifera) grape samples from the Caucasus. This observation and the presence of all other plastid haplotypes observed in a previous study of worldwide grape cultivars highlight both unique and high levels of genetic variation in wild grape (V. vinifera subsp. sylvestris) from the greater Caucasus region.

ПРИМЕНЕНИЕ ИПИЛИМУМАБА У БОЛЬНЫХ ДИССЕМИНИРОВАННОЙ МЕЛАНОМОЙ КОЖИ

Introduction: Application of ipilimumab (IPI) in the treatment of patients with disseminated melanoma, first demonstrated an increase in survival that was an important event in cancer immunotherapy. We present the results of treatment of patients within the framework of enhanced access to the drug (SA184-EAP).Materials and methods: from September 2012 to August 2014 71 patients with metastatic melanoma, with signs of tumor progression, received earlier from 1 to 6 lines of drug therapy were enrolled in protocol of treatment in Petrov Oncology Institute. Median age of patients was 51 years (range from 21 to 76 years). In 39 (60%) of patients IV stage was diagnosed, 25% of patients had metastases to the brain, 28% - had liver metastases, 19% - had bone metastases. All patients received IPI 3 mg/kg once every 3 weeks for total 4 administration.Results: A total there were 229 administrations of IPI in 71 patients (average number of administrations was 3.2). Thirty-nine patients (59%) had 4 administrations and 21 patients (35%) had 1-2 administrations. Most of the patients had at least one adverse event (AE) associated with the treatment. In 15 patients (21%) there were no adverse events. Three patients died due to adverse events possibly related to treatment: 1 – had kidney failure, 1 - had pulmonary embolism, 1 - had cerebral edema and the progression of cancer. Grade 3-4 adverse events were observed in 10 (14.1%) patients: grade 3 rash  - in 3 (4.2%) patients, grade 3 diarrhea - in 2 (2.8%) patients, grade 3 fatigue - in 2 (2 8%) patients, grade 3 dyspnea - in 1 (1.4%) patients, grade 4 of ALT and AST increasing - in 1 (1.4%) patient, grade 3 hypokalemia - in 1 (1.5%) patient. Efficacy of treatment was assessed in 54 patients, complete regression was detected in 3 (6%) patients, partial - in 6 (11%) patients. An objective response to treatment was observed in 28% of patients, the stabilization of process in 6 (11%) patients. Median follow-up was 144 days. The median time to progression was 81 days (95%; CI 73-105). The median overall survival was 411 days (95%; CI - 303-519).Conclusion: Treatment with IPI satisfactorily tolerated by most patients and has significant clinical efficacy as the second and subsequent lines of drug therapy in patients with disseminated melanoma.Введение: Применение ипилимумаба (ИПИ) для лечения больных диссеминированной  меланомой  кожи, впервые продемонстрировавшее увеличение выживаемости, явилось важным событием в иммунотерапии  злокачественных опухолей. Мы представляем  результаты лечения больных в рамках программы  расширенного  доступа к препарату (СА184-ЕАР).Материалы и методы: В ФГБУ «НИИ онкологии  им.  Н. Н. Петрова» Минздрава России в программу с сентября2012 г. по август2014 г. включен 71 больной диссеминированной меланомой, с признаками прогрессирования опухолевого процесса, получивших ранее  от 1 до 6 линий лекарственной терапии. Средний возраст составил 51 год (21–76 лет). У 39 (60%) больных установлена IV стадия M1c, 25% пациентов имели метастатическое поражение головного мозга, 28% – метастазы в печени, 19% – метастазы в костях. Все больные получали ИПИ в дозе 3 мг/кг 1 раз в 3 недели, всего 4 введения.Результаты: У  71 больного проведено 229 введений  ИПИ (в среднем-3,2).  Тридцать девять больных (59%) получили 4 введений, 21 (35%) – 1–2 введения.  Большинство пациентов имело хотя бы одно нежелательное явление (НЯ), связанное  с лечением. У  15 больных (21%) нежелательных явлений не наблюдалось. Трое больных умерло от нежелательных явлений, возможно связанных с проводимой терапией: 1 – от почечной недостаточности, 1 – от тромбоэмболии легочной артерии, 1 – от отека головного мозга на фоне прогрессирования  опухолевого процесса. НЯ 3–4 ст. наблюдались  у 10 (14,1%) больных: сыпь 3 ст.– у 3 (4,2%), диарея 3 ст. у 2 (2,8%), слабость 3 ст. у 2 (2,8%), одышка 3 ст. у 1 (1,4%), повышение уровня АЛТ и АСТ 4 ст. у 1 (1,4%), гипокалиемия 3 ст. у 1 (1,5%) больных. Эффективность лечения оценена у 54 больных, полный регресс  выявлен у 3 (6%) больных, частичный – у 6 (11%) больных. Объективный ответ на терапию наблюдался  у 28% пацинентов, стабилизация  процесса  у 6 (11%). Средняя длительность наблюдения составила 144 дня. Медиана времени до прогрессирования – 81 (95% ДИ 73–105)  дней. Медиана общей выживаемости составила 411 дней (95% ДИ – 303–519).Заключение: Терапия  ИПИ удовлетворительно переносится большинством больных и обладает значимой клинической эффективностью в качестве второй и последующих линий лекарственной  терапии у пациентов диссеминированной  меланомой  кожи

Успехи и перспективы клеточной иммунотерапии метастатической меланомы

В обзоре освещаются ключевые элементы клеточной иммунотерапии в онкологии на примере меланомы кожи как одной из наиболее иммуногенных и изученных в этом направлении опухолей. Приведена схема анализа иммунологических данных для выбора оптимальной стратегии модуляции иммунного ответа. Представлены основные концепции в разработке клеточной иммунотерапии, механизмы резистентности к данному лечебному подходу и современные способы их преодоления. Освещены принципы иммунотерапии на основе дендритных клеток, опухоль-инфильтрирующих лимфоцитов (TIL) и концепция иммунологической инженерии. Отмечена важность иммуногенетических подходов для дальнейшего развития клеточной иммуноонкологии

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

Hail Storms in Georgia in 2016-2018

The analysis of the data of the Georgian Environment Agency on the incidents of hail in Georgia and damage from them in 2016-2018 is presented. The greatest number of days with hail for the indicated three years was recorded in Kakheti (32 days with hail, 90 locations subjected to hail), the smallest - in Samegrelo-Zemo Svaneti (one day with hail, 1 subjected to hail locations). A map of hail cases has been built

Hail Storms in Kakheti (Georgia) in 2014-2018

The analysis of the data of the Georgian Environment Agency on the incidents of hail in Kakheti (Georgia) and damage from them in 2014-2018 is presented. The greatest number of days with hail for the indicated five years was recorded in municipality of Telavi (17 days with hail, 38 locations subjected to hail), the smallest - in municipality of Dedoplistskaro (2 day with hail, 2 locations subjected to hail). A map of hail cases has been built

Heavy Rainfall, Floods and Floodings in Kakheti (Georgia) in 2014-2018

The analysis of the data of the Georgian Environment Agency on the incidents of heavy rainfall, floods and floodings in Kakheti (Georgia) and damage from them in 2014-2018 is presented. The greatest number of days with heavy rainfall, floods and floodings for the indicated five years was recorded in municipality of Lagodekhi (10 day), the smallest - in municipality of Sighnaghi (2 day). And in Dedoplistskaro municipality in 2014-2018 no incidents were reported. A map of these cases has been built

Statistical analysis of the daily wind speed in Tbilisi in 1971-2016

The results of the detailed statistical analysis of the daily mean and max wind speed for Tbilisi from January 1, 1971 to December 31, 2016 are presented. In the studied period of time, the range of changes in the average daily wind speed was 0 - 14.9 m/s, and the maximum - up to 41.0 m/s. The repeatability of the average daily and maximum wind speed in Tbilisi on the Beaufort Wind Scale was obtained. In particular, it was found that the repeatability of the maximum wind speed covers the entire Beaufort scale. At the same time, the scale range of 8 and more (17.2-20.7 m/s, gale and above, the onset of destructive processes in the environment and their intensification) accounts for about 6.5% of cases (about 24 days a year). During the entire period of research with hurricane wind 3 cases were recorded (Beaufort scale range - 12, hurricane, wind speed >32.6 m/s, devastating destruction). For separate months and according to annual data, correlation and regression relationships between daily and average monthly values of the mean and max wind speed were studied

Strong Wind on the Territory of Georgia in 2014-2018

2014-2018 data on strong wind cases (V≥15 m/s) are considered. The climatic characteristics of strong winds, such as the number of days, wind speed, and direction, are studied for a five-year study period. Also, strong wind distribution areas are defined according to the municipalities. Some cases of damage caused by strong winds in 2014-2018 are described. Based on the available data a geoinformation map of the distribution of strong winds in the regions of Georgia are compiled

Analysis of Strong Precipitation in Tbilisi on August 29, 2023

Precipitation of more than 100 mm per day falls very rarely in Tbilisi (several cases in the last 120 years). On August 29, 2023, this incident repeated itself. In this work an analysis of this rare phenomenon for Tbilisi is presented