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By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization's decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 bc, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe's first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 bc, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ∼8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ∼24,000-year-old Siberian. By ∼6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ∼4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ∼75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ∼3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin of at least some of the Indo-European languages of Europe.

The authors present the first clinical experience with intramyocardial transplantation of the mononuclear fraction of cells of the autologous bone marrow in complex surgical treatment of 10 patients with valvular heart disease. The cellular transplantation was fulfilled intraoperatively when making a prosthetic mitral (5 patients) and aortal (5 patients) valves on the open heart under conditions of extracorporeal circulation. Simultaneously direct revascularization of the myocardium (aorto-coronary and mammary-coronary shunts) was performed in 4 patients (1--with a mitral and 3--with aortal heart diseases). An investigation of the results of the examination including ECG, EchoCG and investigation of the myocardium perfusion using one-photon emission computed tomography fulfilled in the early postoperative period and within 6-12 months after operation has shown that the cell cardiomyoplasty with mononuclear fraction of cells of the autologous bone marrow improves the myocardium perfusion, however, in the early postoperative period the appearance of transitory impairments of the heart rate is possible.

The investigation of the hemostasis system performed in 47 patients with mechanical heart valves (MHV) at the terms of (3.50 +/- 0.25) years included 30 men and 17 women. There were 24 cases of aortal MHV and 23 cases of mitral MHV, I-II functional class (NYHA). The patients were given oral anticoagulants: phenylin to 35 patients (0.009 mg/day), varfarin to 12 patients (52.6 mg/a week). The primary examination of the patients has revealed insufficient anticoagulation protection and clinically asymptomatic permanent intravascular coagulation of the third degree (PIC-3), with the signs of activation of thrombocytic and/or coagulation link of hemostasis. It has been found that a complex assessment of the hemostasis system state including the vascular-thrombocytic link is an obligatory condition of the right choice and timely correction of the PIC-3 in patients with MHV. The methods of correction of impaired hemostasis depend on the primary involvement of the vascular-thrombocytic and/or coagulation link of hemostasis. The pathogenetically selected antithrombotic therapy for patients with MHV allows timely arrest of PIC-3 and less risk of the development of thrombosis and thrombo-embolic complications at long-term periods of observation.

The authors made an analysis of social-economical conditions limiting the possibilities of rendering cardiosurgical care to children. Possible ways are mapped out allowing to increase the amount of operations on children with congenital heart diseases.

Due to an increasing attention to questions of adequate protection of the myocardium and widely spread use of the method of blood cardioplegia the authors have made a comparative analysis of effectiveness of using 2 methods of cardioplegia--pharmacocrystalloid and cool blood antegrade cardioplegia: 34 patients were operated upon under conditions of extracorporeal blood circulation for aortic and mitral valve replacement. A comparison was made of 17 patients with intermittent antegrade cool crystalloid cardioplegia (group 1) and 17 patients with intermittent antegrade cold blood cardioplegia (group II). The results have shown that intermittent antegrade cool blood cardioplegia is a safe and effective method for myocardial protection during cardiopulmonary bypass.

An examination of 153 patients with valve replacement was performed at late stages of (6.8 +/- 0.2) years, in 84 patients the mitral valve replacement (MVR) was fulfilled, in 64--the aortic replacement (AVR) and in 5--two valve replacement were performed. Higher indices of hemolysis were noted in patients with AVR, in cases of two valve replacement and in patients with the paravascular fistula. The lowest indices of hemolysis take place in patients with bileaflet prostheses (MEDING/CarboMedics, St. Jude Medical), especially in patients with AVR. The complications of intravascular hemolysis are: cholelithiasis, anemia, hemosiderosis of the kidneys, sideropenia. The timely diagnosis, treatment and prophylactics are necessary to prevent these complications.

Complex estimation of the state of the lungs at the postperfusion and early postoperative periods based on roentgenological, clinical data, investigations of the parameters of oxygenation and mechanics of respiration was carried out in 32 children with septal defects of the heart, operated upon under conditions of artificial blood circulation with different kinds of the transfusion maintenance including the apparatus "Cell Saver 5" (CS) for the reinfusion of autoerythrocytes. The dynamics of endotoxicosis, hematological parameters during and after operation and requirements in transfusion media were studied. Differences in these indicators were established between the patients operated upon with the use of donor hemocomponents and those who were operated upon with CS. It allowed a conclusion about the role of the method of intraoperative reinfusion of erythrocytes in substantially less frequency and severity of the postperfusional pulmonary complications in this category of patients.

Treatment of 500 patients was used as a basis for the development of a complex stepwise programme of rehabilitation of patients with congenital heart diseases (CHD). It was noted that for a valuable social integration of people with CHD into the modern society it was necessary to perform not only the indicated, adequate and timely operations but also the inescapable measures for the improvement of their physical and psychophysiological adaptation. The following job in remote periods of observations of the patients operated upon must take into account its conformity to functional possibilities of energy expenditure for the chosen occupation and should be effected with the individually accessible (or indicated) level of the physical tension taken into consideration.

Some literature data are presented on the problem of cardiac surgery in patients with chronic renal insufficiency under regular hemodialysis and on the specificity of performing operations on such patients under conditions of artificial circulation. The authors describe their first experience of a one-step prosthezing of the aortal valve and plication of the dissecting aneurysm of the ascending part of the aorta in the patient receiving the regular hemodialysis during 5 years as well as the positive results of this original operation in dynamics of the first year of observations.

The physical working capacity was investigated in 25 men operated on for congenital heart disease and in 12 healthy men not accustomed to heavy physical load. It was shown that the main factor responsible for lower physical efficiency of the operated patients was their less pronounced ability to increase the minute circulation volume under conditions of the maximum physical load.

The correlation of most important parameters of the central hemodynamics with the intensity of anaerobic metabolism was studied in 65 patients operated on having congenital heart diseases and in 37 healthy patients under increased physical exercise. A mild decrease of the functional reserve of the cardiovascular system (by 7-15%) was revealed in the patients as compared with the control group.

The hemodynamic indices under conditions of growing physical exercise were studied in 15 healthy women and 17 patients operated for the congenital heart disease. The operated women were found to have a restricted ability to increase the stroke volume. The individual choice of the level of everyday domestic and professional activity should be made with special reference to individual hemodynamic reactions upon the physical exercise.

Under conditions of an increasing physical exercise from 25 to 100 watts the distensibility of lungs (CL) was investigated in 18 non-operated and 33 operated patients with a congenital heart disease. The decrease of CL was more pronounced in the group of non-operated patients. Changes in CL were found to depend on the blood filling of the vascular bed of the lungs. The determination of CL under an increasing physical exercise may be used for the estimation of the functional capacity of the pulmonary ventilatory apparatus.

A comparative assessment of energy losses and functional shifts in the system of circulation and respiration in various types of the professional activity in 22 patients 14,7 +/- 1,38 years after successful radical operations for the open arterial duct, defects of interatrial and interventricular septa, 64 healthy people and 12 nonoperated patients with similar congenital heart diseases was made. The patients subjected to timely radical operations were shown to possess working capacity and ability. They can fulfill a professional work with light and average strain under systematic control.

The functional cardiac reserve was studied in 26 non-operated and 42 operated patients with congenital heart diseases. The ratio of the maximum utilization of oxygen (VO2 max) to the heart volume (HV) was shown to be an objective quantitative index of the functional cardiac reserve. The authors believe that the value of the functional cardiac reserve may be used for the determination of risk as well as for the assessment of the rehabilitation of the rehabilitation significance of operations in patients with congenital heart diseases.