Mid-holocene Brown Bear (Ursus arctos) from the Bolshoy Lyakhovsky Island (New Siberian Islands).

A morphological description is provided for a unique find of a frozen mummified subfossil brown bear (Ursus arctos L., 1758), found for the first time ever. The find is a well-preserved bear carcass of approximately 3500 years in age. Results of computed tomography and DNA testing are discussed.

Predictors of Lethality, Remodeling, and Aorta-Related Events in Different Types of Proximal Aortic Dissection Surgery.

The aim of the study is to analyze predictors of lethality, false lumen thrombosis, enlargement of aortic diameter, and frequency of aorta-related events in the early and remote postoperative periods for various types of proximal aortic dissection surgery using the logistic regression method. Materials and Methods: A retrospective observational comparison of the results of surgical treatment of 213 patients with the diagnosis of "DeBakey type I aortic dissection" has been carried out. The participants were divided into three groups: group 1 underwent classic aortic arch reconstruction using hemiarch technique or total reconstruction of the aortic arch with a multiple-branch prosthesis (n=121); group 2 was subjected to the hemiarch technique and implantation of bare-metal (uncoated) stents (n=55); in group 3, the "frozen elephant trunk" correction technique was used (n=37). The diagnosis of all patients included into the study was preoperatively confirmed by ultrasound and tomographic examination. Predictors of negative events have been identified by building the models of logistic regressions. Results: The multivariate model of logistic regression has revealed multiplicative significant predictors of lethality: postoperative neurological complications increased the probability of lethality by 3.39 (1.24-9.18) times and presence of a patent false lumen by 4.17 (1.49-13.68) times.Among the predictors of aorta-related events, the most important were connective tissue diseases (the probability increased by 6.68 (2.98-15.62) times), presence of partial thrombosis of the false lumen (the probability of event development increased by 2.39 (1.07-5.44) times), and aortic valve repair (the probability aorta-event occurrence increased by 2.84 (1.13-7.17) times).Hybrid prosthesis implantation appeared to be the most significant predictor of false lumen thrombosis increasing its probability by 4.19 (1.90-9.44) times among aortic repair methods, while a bare-metal stent implantation in contrast reduced the likelihood of false lumen thrombosis by 0.17 (0.03-0.62) times. Eventually, the type of repair had not any significant impact on the aorta-related events and lethality in the long-term period.

Hybrid Technologies for Reconstruction of Proximal Aortic Dissection.

The aim of the study is to evaluate the efficacy of various types of hybrid technology in compare to the classical repair of the aortic arch of type I aortic dissection treatment in the in-hospital period. Materials and Methods: A retrospective observational study has been conducted, the results of surgical treatment of 213 patients with DeBakey type I aortic dissection operated on within the period from 2001 to 2017 were compared. Patients were divided into three groups: in group 1, patients undergone a hemiarch type of aortic repair or the total arch replacement (n=121); in group 2, a hemiarch aortic reconstruction and implantation of bare metal stent was performed (n=55); in group 3, a frozen elephant trunk technique was used (n=37). Taking into consideration the retrospective character of the investigation and nonequivalence of the groups by separate characteristics, they were equalized to improve the reliability of the results using the PSM (propensity score matching) pseudorandomization method. As a result, three groups of comparison were formed which were equalized by the PSM method and called PSM 1, 2, and 3. The mortality and complication rate in the in-hospital period, as well as the frequency of false lumen thrombosis development depending on the treatment method, have been analyzed. Results: The mortality rate in the PSM 1 group was 15 patients: group 1 (standard technique) - 10 patients (9%), group 2 (uncoated stents) - 5 patients (11%). A significant difference was found in the number of major bleedings (group 1 - 8%, group 2 - 21%, p=0.031) and cases of bowel ischemia (group 1 - 1%, group 2 - 9%, p=0.028). Complete false lumen thrombosis of the thoracic aorta was observed significantly more often in group 1 than in group 2 (22% vs 5%, p=0.015).In the examined group PSM 2, hospital mortality rate was 4 patients: group 1 - 3 patients (12%), group 3 - 1 patient (3%). No differences between the groups were found in the number of complications. In group 3, complete false lumen thrombosis of the thoracic aorta was observed in 59% of cases, whereas in group 1 it was found only in 4% of patients (p<0.001).In comparison group PSM 3, the mortality was 8 patients: group 2 - 5 patients (11%), group 3 - 3 patients (9%). The number of neurological complications differed significantly: in group 2 - 27%, in group 3 - 6% (p=0.019). Besides, 3% of cases of complete false lumen thrombosis were found in group 2, while there appeared 55% (p<0.001) of such patients in group 3. Conclusion: The comparative analysis showed that the use of bare metal stents and hybrid prostheses demonstrated a comparable low level of in-hospital mortality compared to the standard surgical technique of aortic arch reconstruction. At the same time, the use of the bare metal stents is associated with a higher rate of perioperative complications (bleeding, postoperative bowel ischemia, neurological complications) compared to the standard treatment and repair of the aortic dissection using hybrid prostheses. Complete thrombosis of the false lumen occurred significantly less commonly in case of using bare metal stents than with standard treatment and hybrid prostheses.

First Description of the Fur of Two Cubs of Fossil Cave Lion Panthera spelaea (Goldfuss, 1810) Found in Yakutia in 2017 and 2018.

The first description of well-preserved fur of one male and one female cubs of the fossil cave lion Panthera spelaea (finds of 2017-2018, Semyuelyakh River, Yakutia, Russia) is presented in comparison with the fur of two cubs (a male and a female) of the extant African lion P. leo and adult lions of both species: the color, differentiation, configuration, microstructure, and internal design of hair of different categories are considered. The coat of the cave lion is similar but not identical to that of the African lion, because it contains a high thick undercoat of spiral-shaped thick and airy down hair. This difference is most pronounced in the cave lion cubs, in which, however, the fur is not differentiated to the same extent as in the adult. The microstructure of hair is species-specific and subject to intraspecific age-related variability. Adaptive features of the hair structure in the cave lion are noted.

[Hybrid intervention for a ruptured thoracoabdominal aortic aneurysm]. / Gibridnoe vmeshatel'stvo pri razryve torakoabdominal'noi anevrizmy aorty.

A ruptured thoracoabdominal aortic aneurysm is an urgent situation requiring emergency surgery during which it is necessary to decrease the scope of the intervention in a patient at an extremely high surgical risk. A combination of surgical and endovascular techniques makes it possible to minimize surgical injury, blood loss, to shorten the duration of internal organs ischaemia, to reduce the risk of paraplegia. Presented herein are the results of emergency hybrid intervention for a ruptured thoracoabdominal aortic aneurysm, accompanied and followed by description of the technical aspects of performing the surgical and endovascular stages. The early postoperative period was complicated by thrombosis of the left superficial femoral artery on the background of atherosclerotic lesions, which was successfully eliminated by means of endovascular intervention with endovascular prosthetic repair. After 10 months, the patient underwent a cardiosurgical intervention. Combining surgical and endovascular techniques made it possible in an emergency situation to save the patient's life and to provide its good quality in the remote period of follow up (4 years after the hybrid operation).

[Hybrid intervention for a multilevel aneurysmatic lesion of the aorta in a patient with multifocal atherosclerosis]. / Gibridnoe vmeshatel'stvo pri mnogourovnevom anevrizmaticheskom porazhenii aorty u bol'nogo s mul'tifokal'nym aterosklerozom.

A multilevel aneurysmatic lesion of the aorta is a rare pathology. The authors describe herein a clinical case report regarding stage-wise treatment of a patient presenting with aneurysms of the thoracic and abdominal portions of the aorta and a haemodynamically significant lesion of coronary and carotid arteries. Strategy of surgical management was decided upon collegially. Successful endoprosthetic repair of the aneurysm of the thoracic portion of the aorta required closure of the left carotid artery with a graft, which, taking into consideration an existing occlusion of the right internal carotid artery, demanded preliminary carotid-subclavian bypass grafting. The clinical course of progressing angina pectoris (75% stenosis of the anterior descending artery with a poststenotic aneurysm) also increased the risk of the surgical stage. The authors provide a detailed description of the planning procedure, stages, and technical aspects of the operations performed. No complications were encountered. The duration of the follow up period amounted to 15 months. There was regression of the symptomatic manifestations, accompanied and followed by complete thrombosis of the aneurysmatic zones stented. A hybrid approach demonstrated efficacy and safety in staged treatment of complicated combined pathology of the aorta and its branches.

[Results of a Randomized Study: Multivessel Stenting and Staged Revascularization in Patients With ST-Elevation Myocardial Infarction Using Second Generation Drug Covered Stents].

Lack of evidence base on the use of 2-nd generation drug covered stents in patients with ST-elevation myocardial infarction (STEMI) with multivessel lesions in coronary vascular bed makes it important to conduct studies of new devices in a framework of multivessel stenting in primary percutaneous coronary intervention (PPCI) and staged revascularization. Controversial data on outcomes of the strategy of multiple revascularization in STEMI might be related to the use of previous generation coronary stents in this category of patients. Aim of this study was assessment of one year outcomes of multivessel stenting in a framework of PPCI and staged revascularization (8.6+/-4.2 days between stages) with the use of 2-nd generation drug covered stents. We showed that both multivessel stenting and staged revascularuzation might be effective options of revascularization in STEMI with the use of 2-nd generation drug covered stents and maintenance of limited time interval between PCI on infarct related artery and PCI on other coronary vessels with significant stenotic lesions. This strategy was associated with low rate of adverse cardiovascular events.

New data on the internal organs of a frozen Yukagir bison mummy (Bison priscus Bojanus, 1827), Yakutia, Russia.

The paper presents the first morphological description of the internal organs of a frozen corpse of the steppe bison Bison priscus (Bojanus, 1827) from the Holocene of northern Yakutia. Necropsy revealed that most of the internal organs, including the brain, heart with the main vessels, and reproductive system were well preserved. It demonstrated that the anatomy of this bison was close to that of the genera Bos and Bison. Trauma or pathological changes in the organs were not detected. The cause of death of the bison remains unknown.

Hair microstructure of the first time found calf of woolly rhinoceros Coelodonta antiquitatis.

Hair microstructure of the first calf of the woolly rhinoceros Coelodonta antiquitatis found in Sakha in 2014 (the neck and hind leg hair) was examined by the light and electron scanning microscopy. The calf hair features were compared with those of two adults studied earlier. The calf coat color was much lighter than in adults, from pale ashy to blond. The extent of hair differentiation, dimensional and pigmentation indices were lower in the calf than in adult rhinoceroses. There was no medulla in the calf hairs, while in those of adults it was occasionally found. The cortical and cuticular layer microstructure was similar in all the animals compared. In both calf and adult hairs, there were traces of mechanical damage.

Telomerase inhibitor GRN163L inhibits myeloma cell growth in vitro and in vivo.

Human telomerase, the reverse transcriptase which extends the life span of a cell by adding telomeric repeats to chromosome ends, is expressed in most cancer cells but not in the majority of normal somatic cells. Inhibition of telomerase therefore holds great promise as anticancer therapy. We have synthesized a novel telomerase inhibitor GRN163L, a lipid-attached phosphoramidate oligonucleotide complementary to template region of the RNA subunit of telomerase. Here, we report that GRN163L is efficiently taken up by human myeloma cells without any need of transfection and is resistant to nucleolytic degradation. The exposure of myeloma cells to GRN163L led to an effective inhibition of telomerase activity, reduction of telomere length and apoptotic cell death after a lag period of 2-3 weeks. Mismatch control oligonucleotides had no effect on growth of myeloma cells. The in vivo efficacy of GRN163L was confirmed in two murine models of human multiple myeloma. In three independent experiments, significant reduction in tumor cell growth and better survival than control mice was observed. Furthermore, GRN163L-induced myeloma cell death could be significantly enhanced by Hsp90 inhibitor 17AAG. These data provide the preclinical rationale for clinical evaluation of GRN163L in myeloma and in combination with 17AAG.

Common and contrasting genomic profiles among the major human lung cancer subtypes.

Lung cancer is the leading cause of cancer mortality worldwide. With the recent success of molecularly targeted therapies in this disease, a detailed knowledge of the spectrum of genetic lesions in lung cancer represents a critical step in the development of additional effective agents. An integrated high-resolution survey of regional amplifications and deletions and gene expression profiling of non-small-cell lung cancers (NSCLC) identified 93 focal high-confidence copy number alterations (CNAs), with 21 spanning less than 0.5 Mb with a median of five genes. Most CNAs were novel and included high-amplitude amplification and homozygous deletion events. Pathogenic relevance of these genomic alterations was further reinforced by their recurrence and overlap with focal alterations of other tumor types. Additionally, the comparison of the genomic profiles of the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC), showed an almost complete overlap with the exception of one amplified region on chromosome 3, specific for SCC. Among the few genes overexpressed within this amplicon was p63, a known regulator of squamous cell differentiation. These findings suggest that the AC and SCC subtypes may arise from a common cell of origin and they are driven to their distinct phenotypic end points by altered expression of a limited number of key genes such as p63.

[Use of current radiation techniques in the diagnosis and treatment of juvenile angiofibromas of the nasopharynx]. / Primenenie sovremennykh luchevykh metodov v diagnostike i lechenii iunosheskikh angiofibrom nosoglotki.

In 1992-2001 seventeen patients with juvenile nasopharyngeal angiofibromas (JNAs) were treated at Krasnoyarsk Territorial Clinical Hospital. The patients underwent a comprehensive diagnosis involving computed tomography (CT), magnetic resonance imaging (MRI), and angiography, followed by tumor vascular embolization. Later on JNAs were surgically removed in 14 patients, a course of radiation therapy was performed. In suspected JNA, the authors consider it necessary to concomitantly use CT, MRI, and angiography, which provides the most complete diagnostic picture of a pathological focus. X-ray endovascular occlusion considerably lowers blood loss, facilitates a complete angiofibroma removal, and affects the tolerability of radiation therapy in inoperable cases.

Human chromosome 3: integration of 60 NotI clones into a physical and gene map.

Sequence tagged sites generated for 60 NotI clones (NotI-STSs) from human chromosome 3-specific NotI-jumping and NotI-linking libraries were physically located using PCR screening of a radiation hybrid (RH) GeneBridge4 panel. The NotI map of chromosome 3 was generated using these RH-mapping data and those obtained earlier by FISH and sequencing of the corresponding NotI clones. The sequences of the NotI clones showed significant homologies with known genes and/or ESTs for 58 NotI-STSs (97%). These 58 NotI clones displayed 91-100% identity to 54 genes and 23 cDNA/EST clones. One known and two hypothetical protein-coding genes were localized for the first time and nine cDNA clones (unknown genes) were also carefully mapped only in this work. Three newly mapped genes are histone gene H1X (NR1-BK20C) and genes for hypothetical proteins THC1032178 and THC1024604 (NL1-243).

The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis.

Clear cell-type renal cell carcinomas (clear RCC) are characterized almost universally by loss of heterozygosity on chromosome 3p, which usually involves any combination of three regions: 3p25-p26 (harboring the VHL gene), 3p12-p14.2 (containing the FHIT gene), and 3p21-p22, implying inactivation of the resident tumor-suppressor genes (TSGs). For the 3p21-p22 region, the affected TSGs remain, at present, unknown. Recently, the RAS association family 1 gene (isoform RASSF1A), located at 3p21.3, has been identified as a candidate lung and breast TSG. In this report, we demonstrate aberrant silencing by hypermethylation of RASSF1A in both VHL-caused clear RCC tumors and clear RCC without VHL inactivation. We found hypermethylation of RASSF1A's GC-rich putative promoter region in most of analyzed samples, including 39 of 43 primary tumors (91%). The promoter was methylated partially or completely in all 18 RCC cell lines analyzed. Methylation of the GC-rich putative RASSF1A promoter region and loss of transcription of the corresponding mRNA were related causally. RASSF1A expression was reactivated after treatment with 5-aza-2'-deoxycytidine. Forced expression of RASSF1A transcripts in KRC/Y, a renal carcinoma cell line containing a normal and expressed VHL gene, suppressed growth on plastic dishes and anchorage-independent colony formation in soft agar. Mutant RASSF1A had reduced growth suppression activity significantly. These data suggest that RASSF1A is the candidate renal TSG gene for the 3p21.3 region.

Initial isolation and analysis of the human Kv1.7 (KCNA7) gene, a member of the voltage-gated potassium channel gene family.

A novel human potassium channel gene was identified and isolated. The maximal open reading frame encodes a protein of 456 amino acids. The predicted product exhibits 91% amino acid identity to the murine voltage-gated potassium channel protein Kv1.7 (Kcna7), which plays an important role in the repolarization of cell membranes. Based on the high similarity, the human gene has been classified as the ortholog of the mouse Kcna7 and given the name Kv1.7 (KCNA7). A structural prediction identified a pore region characteristic of potassium channels and six membrane-spanning domains. Northern expression analysis revealed the gene is expressed preferentially in skeletal muscle, heart and kidney. However, it is expressed at lower level in other tissues, including liver. A single mRNA isoform was observed, with a size of approximately 4.5 kb. Using fluorescence in situ hybridization, the gene was mapped to chromosomal band 19q13.4 (269.13 cR(3000)). A genomic sequence was identified in the database from this region, and the KCNA7 gene structure determined. Computational analysis of the genomic sequence reveals the location of a putative promoter and a likely muscle-specific regulatory region. Initial comparison to the published murine Kcna7 cDNA suggested a different N-terminal sequence for the human protein, however, further analysis suggests that the original mouse sequence contained an error or an unusual polymorphism.