nnovative Seasonal Migrations and Subsistence System of the Mobile Pastoralists of the Desert-Steppe Zone of Eurasia:role of social groups

The study of the economic system of the earliest nomads which inhabited the Eurasian desert-steppe belt in 5000-2000 is a relevant task of contemporary studies. The data on the organization of living space and the role of social groups of early prehistoric pastoralists in the exploitation of open steppe resources are scarce. The paper presents a new methodological approach to searching camps of the earliest pastoralists. The application of this approach enabled the archaeologists to discover numerous seasonal camps in the Sal-Manych Ridge located in the western part of the Eurasian steppes, including Eneolithic camps dated to 4200-3600 BC. The study of the occupation layers at the sites, evaluation of the productivity of pasture systems made it possible to categorize such sites as short-term seasonal camps occupied by pastoralists, evaluate the role of social groups in the organization of innovative seasonal migrations and reconstruct their subsistence system. The camps emerged as a result of developing pastoral economic strategy in the Lower Don region and the abutting areas reflecting the role of special social groups of pastoralists who managed to organize seasonal moves and address the issue of exploiting pastures located beyond the permanently occupied area

Клинические варианты Helicobacter pylori-ассоциированной язвенной болезни и морфофункциональные изменения слизистой оболочки желудка и двенадцатиперстной кишки

The purpose of research was to compare cellular structure inflammatory in a gastric and a duodenal mucosa, its ratio with disregenerations at peptic ulcers of not complicated current and complicated with a bleeding, punching and its ratio with disregenerations at one peptic ulcers or plural peptic ulcers. At ulcer peptic complicated with a bleeding or punching observed more intensive character of an inflammation, a high level infiltration gastric mucosa and neutrophils, eosinophils. The density neutrophils and eosinophils infiltration correlated with disregenerations changes of gastric and a duodenal mucosa. The patients with 2 or more peptic ulcers have a high level infiltration gastric mucosa of neutrophils, plasmacytes and a high level infiltration duodenal mucosa of interepitelial neutrophils. The density neutrophils and interepitelial infiltration correlated with disregenerations changes of gastric and a duodenal mucosa.Выполнено сравнение клеточного состава воспалительного инфильтрата в слизистой оболочке желудка и двенадцатиперстной кишки (ДПК), его соотношения с дисрегенераторными процессами при дуоденальных язвах неосложненного течения и осложненных кровотечением, перфорацией, пенетрацией, при одиночных и множественных язвах. При язвенной болезни ДПК, осложненной кровотечением, перфорацией, пенетрацией, наблюдали более интенсивный характер воспаления, большую плотность инфильтрации слизистой желудка и ДПК нейтрофилами, эозинофилами. Плотность инфильтрации нейтрофилами и эозинофилами коррелировала с дисрегенераторными изменениями слизистой оболочки желудка и ДПК. У пациентов с множественными язвами выявлена более высокая плотность нейтрофильной и плазмоцитарной инфильтрации, а в луковице ДПК - выраженная межэпителиальная инфильтрация нейтрофилами. Отмечена прямая связь плотности межэпителиальной инфильтрации с дисрегенераторными изменениями в слизистой оболочке

Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma

Влияние регулятора энергетического обмена на клиническое течение и биомаркеры воспаления при лечении обострений тяжелой хронической обструктивной болезни легких

We assessed in a prospective, randomised, placebo-controlled trial the effects of «yantar-antitox» in patients with exacerbations of COPD requiring hospital admission. We recruited patients with exacerbations of severe COPD who were randomly assigned oral «Yantar-antitox» (n=33) or identical placebo (n=45) for 14 days, in addition to standard treatment with nebulised bronchodilators, antibiotics, and oxygen. We did spirometry and recorded symptom scores in inpatients. The 6-min walking distance (6MWD) was also determined. Inflammatory markers were measured in induced sputum and serum. Significant increase in the percentage predicted lung vital capacity, maximal expiratory flow volume, 6MWD were found between the patient in the «Yantar-antitox» — treated group.В проспективном рандомизированном плацебоконтролируемом исследовании изучались эффекты препарата «Янтарь-антитокс» у пациентов с обострением хронической обструктивной болезни легких (ХОБЛ), потребовавшим госпитализации. Пациенты с обострением тяжелой ХОБЛ были разделены на две группы: принимавшие «Янтарь-антитокс» (33 человека) и принимавшие плацебо (45 человек) в течение 14 дней в дополнение к стандартным мероприятиям: небулайзерная терапия бронходилататорами, антибактериальная, оксигенотерапия. Регистрировали показатели спирометрии и выраженность симптомов в баллах, проводили тест с 6-минутной ходьбой. Маркеры воспаления измеряли в индуцированной мокроте и в крови. Значимое увеличение показателей жизненной емкости легких, форсированной жизненной емкости легких, дистанции, пройденной за 6 мин было обнаружено только у пациентов основной группы

Эффективность химиотерапии по схеме GemCap + митотан во 2-й и последующих линиях лечения метастатического адренокортикального рака

Background. Combination of gemcitabine, metronomic capecitabine and mitotane (GemCap + m) is the most studied regimen in second and subsequent lines of therapy for advanced adrenocortical cancer (ACC). Previously published studies do not give a definitive answer to the question- what plays a key role in realizing the response to treatment: chemotherapy or mitotane in therapeutic concentration.Aim. Evaluation the efficacy and safety of GemCap + m combination with the standard dosing regimen of capecitabine in patients with metastatic ACC.Materials and methods. This retrospective single-center clinical study included patients over 18 years of age with histologically confirmed ACC with disease progression after completion of platinum-containing therapy. They received chemotherapy regimen gemcitabine 800 mg/m2 for days 1, 8 and capecitabine 1000 mg/m2 orally 2 times at days 1–14 of the 21-day cycle with mitotane. we evaluated objective response, stabilization of disease, 6-months disease control rate and median progression-free and overall survival. Radiological assessment according to RECIST 1.1 criteria was carried out every 6–8 weeks of treatment.Results. The study included 25 patients. mitotane concentration above 14 ng/mL was achieved in 22 (88 %) patients, of which 21 (84 %) reached therapeutic concentration in previous treatment lines. 80 % of patients received treatment as 2nd line, 20 % as 3rd and subsequent lines. The objective responses and disease stabilization was observed in 1 (4 %) and 11 (44 %) of patients, respectively. Disease control for at least 6 months rate was 24 %. median progression-free and overall survival were 3.2 months and 12.17 months, respectively. Toxicity grade 3–4 was observed in 28 % of patients. gemcitabine dose reductions due to thrombocytopenia grade 1–2 were required in 2 cases (8 %), no capecitabine reductions were necessary.Conclusion. This study demonstrates the effectiveness of a new dose regimen of chemotherapy GemCap + m in the second and subsequent lines of therapy for metastatic ACC. The progression of the disease against the background of previous lines of therapy at a therapeutic concentration of mitotane in the majority of patients indicates the effectiveness of the chemotherapeutic component of gemCap in a cohort of patients resistant to platinum and mitotane.Введение. В терапии 2-й и последующих линий метастатического адренокортикального рака (АКР) наиболее изученной является комбинация гемцитабина, метрономного капецитабина и митотана (GemCap + m). Опубликованные ранее работы, посвященные изучению данного режима, не дают однозначного ответа на вопрос, что играет ключевую роль в реализации ответа на лечение: химиотерапия или митотан в терапевтической концентрации.Цель исследования – изучение эффективности и безопасности комбинации GemCap + m со стандартным режимом дозирования капецитабина у больных метастатическим АКР.Материалы и методы. В данное ретроспективное одноцентровое клиническое исследование включались пациенты старше 18 лет с гистологически подтвержденным АКР с прогрессированием заболевания после завершения платиносодержащей терапии. Пациенты получали лечение по схеме гемцитабин 800 мг/м2 в 1-й и 8-й дни и капецитабин 1000 мг/м2 внутрь 2 раза в сутки в 1–14-й дни 21-дневного цикла на фоне приема митотана. Нами были оценены частота ответа на лечение, медианы выживаемости без прогрессирования и общей выживаемости. Радиологическая оценка эффективности терапии по критериям RECIST 1.1 проводилась каждые 6–8 нед лечения.Результаты. В исследование включено 25 пациентов. концентрация митотана выше 14 нг/мл была достигнута у 22 (88 %) пациентов, из них у 21 (84 %) – до включения в исследование. большинство пациентов (80 %) получили лечение в качестве 2-й линии, 20 % – в качестве 3-й и последующих. у 1 (4 %) пациента наблюдался частичный ответ, у 11 (44 %) – стабилизация заболевания. Частота клинической эффективности составила 24 % (n = 6), медиана выживаемости без прогрессирования и общей выживаемости – 3,2 и 12,17 мес соответственно. Нежелательные явления III–Iv степени зарегистрированы у 28 % пациентов. Редукция дозы гемцитабина в связи с тромбоцитопенией I–II степени потребовалась в 2 (8 %) случаях; редукция дозы капецитабина не требовалась.Выводы. В данной работе продемонстрирована эффективность нового дозового режима химиотерапии по схеме GemCap + m во 2-й и последующих линиях лечения метастатического АКР. у большинства пациентов в нашем исследовании прогрессирование заболевания отмечалось на фоне предыдущих линий терапии при уже достигнутой терапевтической концентрации митотана, что свидетельствует об эффективности именно химиотерапевтической составляющей GemCap при резистентности к препаратам платины и митотану

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

The origins and spread of domestic horses from the Western Eurasian steppes

Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region.Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).Descriptive and Comparative Linguistic

The Origins and Spread of Domestic Horses from the Western Eurasian Steppes

Domestication of horses fundamentally transformed long-range mobility and warfare1. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling2–4 at Botai, Central Asia around 3500 bc3. Other longstanding candidate regions for horse domestication, such as Iberia5 and Anatolia6, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association7 between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc8,9 driving the spread of Indo-European languages10. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture11,12. © 2021, The Author(s).We thank all members of the AGES group at CAGT. We are grateful for the Museum of the Institute of Plant and Animal Ecology (UB RAS, Ekaterinburg) for providing specimens. The work by G. Boeskorov is done on state assignment of DPMGI SB RAS. This project was supported by the University Paul Sabatier IDEX Chaire d’Excellence (OURASI); Villum Funden miGENEPI research programme; the CNRS ‘Programme de Recherche Conjoint’ (PRC); the CNRS International Research Project (IRP AMADEUS); the France Génomique Appel à Grand Projet (ANR-10-INBS-09-08, BUCEPHALE project); IB10131 and IB18060, both funded by Junta de Extremadura (Spain) and European Regional Development Fund; Czech Academy of Sciences (RVO:67985912); the Zoological Institute ZIN RAS (АААА-А19-119032590102-7); and King Saud University Researchers Supporting Project (NSRSP–2020/2). The research was carried out with the financial support of the Russian Foundation for Basic Research (19-59-15001 and 20-04-00213), the Russian Science Foundation (16-18-10265, 20-78-10151, and 21-18-00457), the Government of the Russian Federation (FENU-2020-0021), the Estonian Research Council (PRG29), the Estonian Ministry of Education and Research (PRG1209), the Hungarian Scientific Research Fund (Project NF 104792), the Hungarian Academy of Sciences (Momentum Mobility Research Project of the Institute of Archaeology, Research Centre for the Humanities); and the Polish National Science Centre (2013/11/B/HS3/03822). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie (grant agreement 797449). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreements 681605, 716732 and 834616)