The Rurikids: The First Experience of Reconstructing the Genetic Portrait of the Ruling Family of Medieval Rus' Based on Paleogenomic Data.

The Rurikids were the reigning house of Rus', its principalities and, ultimately the Tsardom of Russia, for seven centuries: from the IX to the end of the XVI century. According to the Primary Chronicle (the Tale of Bygone Years), the main chronicle of Rus', the Rurik dynasty was founded by the Varangian prince Rurik, invited to reign in Novgorod in 862, but still there is no direct genetic evidence of the origin of the early Rurikids. This research, for the first time, provides a genome-wide paleogenetic analysis of bone remains belonging to one of the Rurikids, Prince Dmitry Alexandrovich (?-1294), the son of the Grand Prince of Vladimir Alexander Yaroslavich Nevsky (1221-1263). It has been established that his Y chromosome belongs to the N1a haplogroup. Most of the modern Rurikids, according to their genealogies, belonging to the N1a haplogroup, have the most similar variants of Y chromosomes to each other, as well as to the Y chromosome of Prince Dmitry Alexandrovich. Genome-wide data of the medieval and modern Rurikids unequivocally indicates that they belong to the N1a haplogroup of the Y chromosome, starting at least from the XI century (since the time of Prince Yaroslav the Wise). All the other alleged Rurikids, both ancient and modern, being carriers of other haplogroups (R1a, I2a), possess high heterogeneity of the sequence of Y chromosomes, meaning that we cannot confirm their common ancestry. The most probable ancestors of Prince Dmitry Alexandrovich in the male line were the men who left the burial ground Bolshoy Oleny Island on the coast of the Kola Peninsula about 3,600 years ago. The reconstruction of the genome of Prince Dmitry Alexandrovich indicates the contribution of three ancestral components to his origin: (1) the early medieval population of the east of Scandinavia from the island of Oland, (2) representatives of the steppe nomadic peoples of the Eurasian steppes of the Iron Age or the early medieval population of central Europe (steppe nomads from the territory of Hungary), and (3) the ancient East-Eurasian component. Reliable statistics were also obtained when the Scandinavians were replaced with the Medieval Russian Slavic populations of the XI century. Thus, for the first time, we have shown the complex nature of interethnic interactions in the formation of the nobility of medieval Rus' on the example of the ancient Rurikid.

[The use of digital radiography in the morphological evaluation of tumor response to neoadjuvant treatment of breast cancer]. / Primenenie tsifrovoi rentgenografii pri morfologicheskoi otsenke otveta opukholi na neoad"yuvantnoe lechenie raka molochnoi zhelezy.

OBJECTIVE: To optimize the morphological assessment of tumor response to neoadjuvant therapy in breast cancer. MATERIAL AND METHODS: A retro- and prospective cohort study was conducted. The object of the study was the surgical material. Macroscopic parameters of residual tumor without and with the use of digital radiography (digital X-Ray) are described and analyzed. PathVision Faxitron imaging system was used for digital X-ray samples. An analysis of dynamics of clinical characteristics was carried out. Two methods of tumor bed examination were compared. RESULTS AND DISCUSSION: The study cohort included 32 women, mean age 45.5±14 years. The correlation of the results of instrumental methods was 0.66 ([95% CI: 0.28; 1], p=0.0002). Microcalcinates were detected by digital X-Ray in 29 (90.6%) cases. Tumor bed sizes determined macroscopically (mean maximal size 6.1 (3.3) cm, median 5.2 (3.4-8.0) cm) and by using digital X-ray (mean maximal size 4.8 (2.6) cm, median 4.1 (2.7-6.2) cm), had statistically significant differences (p<0.0001). The agreement between the two methods of studying the tumor bed was 96.9%. The Cohen's kappa value was 0.95 (p<0.0001). CONCLUSION: Morphological study is an integral part of clinical trials of drug efficacy. With the help of digital X-Ray, the identification of metal markers placed in the tumor bed and microcalcinates is facilitated by the morphologist, and the visibility of the boundaries of the tumor bed is also improved. The results obtained showed that the use of digital X-Ray can improve the accuracy of assessing the degree of morphological regression of breast cancer in response to treatment.

Biodistribution of Detonation Synthesis Nanodiamonds in Mice after Intravenous Administration and Some Biochemical Changes in Blood Plasma.

Biodistribution of nanodiamonds in mice after intravenous administration, activities of AST and ALT, and the level of bilirubin in the blood plasma were studied in 2.5 h and 10, 35, and 97 days after injection of nanodiamonds. In 2.5 h after intravenous injection, nanodiamonds mainly accumulate in the lungs and liver. Then, redistribution of nanodiamonds from all organs to the liver was observed. Activities of AST and ALT and the level of bilirubin in the blood increased after 2.5 h and then decreased to the initial values.

[Remote results of infrainguinal bypass graft procedures for critical lower limb ischaemia]. / Otdalennye rezul'taty infraingvinal'nykh shuntirovanii pri kriticheskoi ishemii nizhnikh konechnostei.

AIM: The study was aimed at assessing the remote results of infrainguinal reconstructions in patients with critical lower limb ischaemia depending upon the bypass graft material used. PATIENTS AND METHODS: Analysed herein are the results of 237 infrainguinal bypass procedures performed over a 9-year period from January 1st, 2010 to December 31st, 2018. The patients were divided into three groups depending on the level of the distal anastomosis. Each group was then subdivided into subgroups based on the bypass graft material. Group One comprised 40 patients having endured femoral-proximal-popliteal bypass grafting. Group Two was composed of 77 patients after femoral-distal-popliteal bypass graft operations. Group Three included 120 patients after femorotibial bypass graft procedures. The comparative analysis was carried out in the first group between autovenous and synthetic grafts, in the second group - between autovenous, synthetic grafts and xenografts, and in the third group - between autovenous, composite grafts and xenografts. RESULTS: The primary patency rates at 1, 3, and 5 years in the first group amounted to 92, 88, and 73%, in the second group to 68, 60, 45% and in the third group - to 58, 49, and 43%, respectively. The 1-, 3-, and 5-year limb salvage rates in the first group were 100, 100, and 87%, in the second group - 90, 85, 73%; and in the third group - 90, 80, and 79%, respectively. Statistically significant differences were observed only when comparing the femoral-proximal and tibial grafts (p=0.039). Patients' survival at 1, 3, and 5 years in all groups turned out to be approximately similar, amounting in the first group to 92, 84, and 61%, in the second group to 96, 91, 71%, and in the third group to 88, 77, and 69%, respectively (p=0.87). In the first group, there were no significant differences between autovenous and synthetic grafts for any of the parameters studied. In the second group, the synthetic grafts (20%) were significantly inferior by the 5-year patency to autovenous grafts (65%) and xenografts (56%), as well as by the limb salvage rate to autovenous grafts (47 versus 84%). In the third group, the 5-year patency was the worst for the subgroup of composite grafts (15%), with the patency of xenografts being slightly inferior to that of autovenous grafts (33 vs. 55%). CONCLUSION: In patients presenting with critical ischaemia and requiring infrainguinal bypass grafting, as an alternative to an autovein if unavailable may serve synthetic prostheses when shunting to the proximal portion of the popliteal artery, or xenografts when shunting to the distal portion of the popliteal artery or tibial arteries. Despite worse patency, with their help it is possible to achieve regression of critical ischaemia and an acceptable limb salvage rate, which is comparable to the results of autovenous grafts.

Distribution of Ferrihydrite Nanoparticles in the Body and Possibility of Controlling Them in an Isolated Organ by a Permanent Magnetic Field.

We studied the distribution of ferrihydrite nanoparticles isolated from bacteria Klebsiella oxytoca in the whole body in vivo and in a cultured isolated organ (liver). The possibility of controlling these nanoparticles in the body using a magnetic field was assessed. One hour after intravenous injection of ferrihydrite nanoparticles to mice, their accumulation was observed in the liver, lungs, and kidneys. Experiment with cultured isolated rat liver showed that these nanoparticles can be controlled by a magnetic field and the influence of magnetic nanoparticles on the liver over 1 h does not lead to destruction of liver cells associated with the release of the marker enzyme AST. These results show the possibility of using magnetic nanoparticles as a system for controlled drug delivery in the body.

[On patterns of human height distributions relative to the specific length of the foot]. / O zakonomernostiakh raspredeleniia znachenii rosta cheloveka dlia konkretnoi dliny stopy.

The purpose of the study is to clarify the patterns of distribution of height measurements relative to a specific length of a foot in humans, in order to use them for more accurate and reliable determination of body length (height). 15,892 people of mixed population (9814 men and 6078 women of 49 nationalities) aged from 20 to 50 years were examined. Their heights and their foot lengths were measured, and the coefficients of the ratios were calculated. A chart was made showing the distribution of body lengths relative to different lengths of the feet, in increments of 10 mm. The nature and density distribution of body lengths for each specific foot length were analyzed. The data revealed that each individual length of the foot corresponds to several values of height with a total spread of up to 24 cm at different frequencies of occurrence, which in fact does not allow to unambiguously determine the length of the body (height) of a person relative to the length of his foot. The maximum concentration of body lengths corresponding to a specific foot length is within the proximity of the average value, while significant deviations in one direction or another are much less common - making an exception in 1-3% of cases. The main density of the distribution of height values (76-86%) relative to foot lengths falls within the range of 10-12 cm. This makes it possible with a high degree of probability to determine height relative to foot length within these limits. The ratios of foot length to height, calculated in various ways, differ from each other. In this regard, the ratio between height and foot length, established by anthropologists and shoe designers/ergonomists - including methods for determining height, based on their calculations - are poorly suited for forensic science and forensic purposes.

Bipolar pollen germination in blue spruce (Picea pungens).

Direct growth of a pollen tube is an effective mechanism of sperm delivery characteristic for the majority of seed plants. In most cases, only one tube grows from one grain to perform the delivery function; meanwhile in Picea the appearance of two tubes from a single pollen grain is quite common during in vitro germination. Here, we describe the phenomenon of bipolar germination and test two hypotheses on its nature and possible role in gametophyte functioning. The hypothesis on "trophic" function of multiple tubes provoked by poor nutrition discussed in literature was not confirmed by in vitro growth tests; bipolar germination strongly decreased with lowering sucrose availability. The highest proportion of bipolar germination occurred in optimal conditions. We then assumed that bipolar germination occurs because turgor pressure is a non-directional force and effective systems of cell wall mechanical regulation are lacking. In hypertonic medium, bipolar germination was sufficiently lower than in isotonic medium, which was consistent with prediction of the «mechanical¼ hypothesis. Scanning electron microscopy and fluorescence microscopy analysis of pollen morphology and cell wall dynamics during both types of germination showed that the appearance of a single tube or bipolar germination depends on the extension of exine rupture. Cell wall softening by short-term ·OH treatment sufficiently decreased the percent of bipolar germination without affecting total germination efficiency. We concluded that mechanical properties of the cell wall and turgor pressure could shift the balance towards one of the germination patterns.

[About the anthropometric relationship between the foot length and the height in the newborn infants and adult subjects]. / Ob antropometricheskoi zavisimosti mezhdu dlinoi stopy i rostom u novorozhdennykh detei i vzroslykh.

The objective of the present study was to clarify the relationship between the foot length and the height (body length) in the human subjects for the development of the rationale for the use of this characteristic for the estimation of the probable height of the newborn infants and adults. A total 1293 newborn babies (654 boys and 639 girls) were available for the examination. In addition, a mixed population of 12,141 men and 8213 women at the age ranging from 18 to 60 years and representing 49 ethnic groups were included in the study. We measured the height and the foot length in all the participants of the study and calculated the coefficients of correlation between these parameters. The same aspects of the anthropometric relationship between the height and the foot length were subjected to the analysis. It was shown that all the main characteristics of such dependence revealed in the adults are inherent in the newborn infant too; moreover, they are especially pronounced at birth. The differences were documented only between the relative values of the height to the foot length ratio. It is concluded that such qualitative differences can be accounted for by the fact that soon after the birth of a human being his (her) individual personality traits together with the age and gender as well as other subjective and objective factors begin to influence the above relationship. The coincidence of the height to the foot length ratios in the newborn infants and the adult subjects give evidence that such relationship is intrinsic in the anatomical structure of the human body. Therefore, it can be safely used for determining the height (body length) from the foot length for the purpose of forensic medical and criminalistic expertise.

[Multifactorial Prognostication of Remote Outcomes in Patients With Non-ST Elevation Acute Coronary Syndrome].

AIM: Creation of a mathematical nonlinear regression model for prognostication of 1 year outcomes after non-ST elevation acute coronary syndrome (NSTE ACS) for optimization of rehabilitation, secondary prevention, and personalized approach to treatment. MATERIAL AND METHODS: We included in this study 135 patients with confirmed NSTE ACS (mean age 59.1±6.1 years, 94 men and 41 women) admitted to hospital No 1 in Novosibirsk during 2010. During hospitalization and 1 year after discharge these patients received standard medical therapy. All patients underwent clinical and instrumental examination which included electrocardiography, echocardiography, Holter ECG monitoring. Program of clinical investigation also included determination of levels of inflammatory cytokines and molecular genetic studies. Effect of each of studied parameters on the probability of unfavorable one year prognosis was assessed by methods of correlation and factor analysis. RESULTS: The constructed mathematical model of multifactor prognostication of 1 year unfavorable or favorable outcomes after NSTE ACS included patient's age in years, presence of tachycardia at admission, Killip class >II, life-threatening paroxysmal tachyarrhythmias, as well as serum concentration of high-sensitivity C-reactive protein and CT genotype of a polymorphic variant rs1376251 of TAS2R50 gene. CONCLUSION: The use of the proposed model of multivariate prognostication of 1 year outcomes of NSTE ACS allows to improve the accuracy of events prediction, as it is based on data from Russian patients and takes into account the activity of subclinical inflammation and genotype of the patient. The model is simple to use and allows to personalize secondary prevention, which will facilitate lowering of total cardiovascular risk in these patients.

Detection of nanodiamonds in biological samples by EPR spectrometry.

In model experiments in vitro, the applicability of the EPR spectrometry method for the detection of modified nanodiamonds (MNDs) in blood and homogenates of mouse organs has been established. A characteristic signal (g = 2.003, ΔH ≈ 10 G) is observed in the samples of biomaterials containing MNDs, the intensity of which increases linearly with the concentration of nanoparticles in the range of 1.6-200 µg MNDs per 1 mL of the sample. The EPR method in biomaterials reveals the presence of intrinsic paramagnetic centers, signals from which are superimposed on the signal from the MNDs. However, the intensity of these signals is small, which makes it possible to register the MNDs using EPR spectrometry with the necessary accuracy. The data obtained open up the prospects of using the EPR method for studies of the interorgan distribution, accumulation, and elimination of MNDs during their intravenous injection into experimental animals.

[Two-year results of infrainguinal reconstructions using autovenous shunts and xenografts]. / Dvukhletnie rezul'taty infraingvinal'nykh rekonstruktsii s ispol'zovaniem autovenoznykh shuntov i ksenoprotezov.

The authors analysed two-year results of inftrainguinal distal arterial reconstructions using xenograft ("kemAngioprosthesis") as compared with an autovein. Ours was a retrospective study including a total of 110 patients who endured 57 femoropopliteal (distal) and 54 femorotibial bypasses by means of both an autovein and a xenograft used as a shunt. The indications for reconstructive operation in the majority of cases was critical ischaemia induced by an atherosclerotic lesion of the femoropoplitealtibial segment corresponding to type D according to the TASC II classification. A xenograft was used only in case when the patient had neither great nor small saphenous vein suitable for use. Xenografts were used in 38 operations. In femoropopliteal (distal) bypasses the primary two-year patency of the xenograft virtually did not differ from that of autovenous shunts (70.1 and 76.5%, respectively). The two-year limb salvage rate for xenografts and autoveins used as shunts amounted to 87.1 and 88.7%, respectively. In For femorotibial bypass grafting, primary 2-year patency of xenografts was considerably worse and amounted to 35.8 versus 73.7% for autovenous shunts. The two-year limb salvage rate did not depend upon the type of the shunt, amounting in both cases to 80.2%. A characteristic complication for using xenografts was aneurysmatic degeneration of the shunts, which was observed in 21% of cases averagely 2 years after surgery. A conclusion was made that using xenografts for infrainguinal bypass operations may be considered as an adequate alternative in case of no autovenous material available.

Frequency of 3' VNTR Polymorphism in the Dopamine Transporter Gene SLC6A3 in Humans Predisposed to Antisocial Behavior.

Predisposition to antisocial behavior can be related to the presence of certain polymorphic variants of genes encoding dopaminergic system proteins. We studied the frequencies of allele variants and genotypes of variable number tandem repeat polymorphism in 3' untranslated region (3' VTNR) of the dopaminergic transporter SLC6A3 gene in Caucasian men committed socially dangerous violent and non-violent crimes. Alleles with 9 and 10 repeats were most frequent in both the control group and group of men predisposed to antisocial behavior. At the same time, the 10/10 genotype was more frequently observed in the group of men prone to antisocial non-violent behavior. Hence, the presence of certain variants of 3' VTNR polymorphism of SLC6A3 gene in men is associated with predisposition to certain forms of antisocial behavior.

[MULTIDISCIPLINARY TEAM APPROACH FOR DIABETIC FOOT PATIENTS IN AN OUT-PATIENT CLINIC].

AIM: To assess the effectiveness of multidisciplinary team approach in daily practice of diabetic foot. MATERIALS AND METHODS: 376 diabetic patients (446 ulcers) treated in a diabetic foot department in 2014 were examined. All patients were screened for diabetic peripheral polyneuropathy and blood insufficiency of lower extremities in order to diagnose the type of diabetic foot ulcer: neuropathic or neuroischemic. Patients were treated by a multidisciplinary team. The number of healed ulcers, minor and major amputations was analyzed. RESULTS: 80% of diabetic foot ulcers were neuropathic with normal blood supply, 20% had signs of ischemia. 77.8% of the ulcers healed in the general group during the study period. 13 amputations (2.9%) were done in the study group: 7 minor amputations (1.6%), 2 below the knee (0.4%), and 4 above knee (0.9%). Two patients died from cardiovascular events (0.4%). The comparative analysis of outcomes of neuropathic and neuroischemic ulcers showed that 84% of neuropathic ulcers healed. Minor amputations were done in 1% of the cases, no major amputations were performed. In patients with neuroischemic ulcers, 60% of them healed, minor amputations were made in 3.4% of cases (2.3% below knee, 4.6% above knee). CONCLUSION: The majority of diabetic ulcers in the study group were neuropathic with normal blood supply. The main risk factor of major amputations is ischemia of the affected limb. The multidisciplinary team approach in daily practice of the diabetic foot department of an out-patient clinic is instrumental in healing ulcers and minimizing the risk of major amputations.

Hydrogen peroxide affects ion channels in lily pollen grain protoplasts.

Ion homeostasis plays a central role in polarisation and polar growth. In several cell types ion channels are controlled by reactive oxygen species (ROS). One of the most important cells in the plant life cycle is the male gametophyte, which grows under the tight control of both ion fluxes and ROS balance. The precise relationship between these two factors in pollen tubes has not been completely elucidated, and in pollen grains it has never been studied to date. In the present study we used a simple model - protoplasts obtained from lily pollen grains at the early germination stage - to reveal the effect of H2 O2 on cation fluxes crucial for pollen germination. Here we present direct evidence for two ROS-sensitive currents on the pollen grain plasma membrane: the hyperpolarisation-activated calcium current, which is strongly enhanced by H2 O2 , and the outward potassium current, which is modestly enhanced by H2 O2 . We used low concentrations of H2 O2 that do not cause an intracellular oxidative burst and do not damage cells, as demonstrated with fluorescent staining.

[PLASMALEMMAL ION TRANSPORT IN POLLEN TUBES IS REGULATED BY HYDROGEN PEROXIDE].

Pollen tube growth is a key step in the life cycle of seed plants, which defines the success of sexual reproduction. One of the most important contributions to this process is made by ion transport through plasmalemma, which is tightly coordinated in time and space. Different classes of signaling molecules are involved in the regulation of transmembrane ion transport including reactive oxygen species as it has been recently demonstrated. Here, using subprotoplasts isolated from pollen tubes, we have demonstrated a connection between hydrogen peroxide, on one side, and two groups of targets on the plasma membrane, on the other side: nifedipine-sensitive Ca(2+)-permeable channels and transport systems controlling membrane potential. H2O2 interaction with these targets causes the increase in cytoplasmic Ca2+ concentration and plasmalemma hyperpolarization. One of the consequences of target modification was acceleration of cell wall regeneration.

[Efficacy of intravenous iloprost (Ilomedin®) in salvage of the only extremity in a patient with thrombangiitis obliterans].

Buerger s disease, or thromboangiitis obliterans, is a severe invalidating systemic vascular disease. The present article deals with a clinical case report concerning treatment of a patient suffering from thromboangiitis obliterans with three limbs amputated (on the background of therapy with alprostadil, Karavanov s mixture, rheopolyglukin, pentoxyphyllin). The course intravenous administration of the stable analogue of prostacyclin - iloprost (IlomedinR) made it possible to save the only extremity.

[Magnesium orotate in treatment of chronic hypertension in pregnant women].

We examined 150 pregnant women with essential hypertension (EHT), EHT and connective tissue dysplasia (CTD), and healthy. Presence of CTD aggravated clinical picture of EHT and was associated with pronounced cardialgic, neurological, asthenic, vertebrogenic, visceral, and other syndromes. The use of antihypertensive, metabolic (magnesium orotate) drugs, sedative and uroseptic phytotherapy, application of other nondrug measures in conditions of multidisciplinary dynamic support of the gestational period facilitated regress of clinical symptoms of EHT and EHT+CTD, favorable course of pregnancy and successful delivery.

[Comorbidity in cardiac pathology: clinical-organizational and epidemiological problems].

Scientific (analytical) approach directs researcher to the study of nosology in isolated native view. The phenomenon under consideration- comorbidity becomes significant and to a substantial degree is able to affect all aspects of the process of medical care. This is shown in this review along such directions as frequency of overt or concealed comorbidity or real state of the problem; magnitude of intracardiac and extracardiac comorbidity; difficulties of diagnostics and treatment arising with comorbidity; problems of validity of statistical (and epidemiological) side of the matter; value of social and organizational aspects of patients care in situations when comorbidity is present.

[The application of xMAP technology in genetic typing of measles virus].

The genetic typing of measles virus in clinical samples using xMAP technology was applied. The study provided the calculation and application of specific oligonucleotide probes of genotypes D4, D6 and D7 of measles virus. The strain HobO96 genotype A of measles virus as a check sample was used. The technical approaches to the optimization of preparatory work organization and to the process of identification of measles virus genotypes are described. The presence of genotypes D4, D6 and D7 in clinical samples is proved by the sequence analysis. The genetic typing effectiveness of technique of DNA hybridization using xMAP technology on the instrumental base BioPlex (BioRad, USA) is demonstrated.