Pathogenesis, Diagnosis, and Treatment of Hemostatic Disorders in COVID-19 Patients.

The novel coronavirus infection named COVID-19 was first detected in Wuhan, China, in December 2019, and it has been responsible for significant morbidity and mortality in scores of countries. At the time this article was being written, the number of infected and deceased patients continued to grow worldwide. Most patients with severe forms of the disease suffer from pneumonia and pulmonary insufficiency; in many cases, the disease is generalized and causes multiple organ failures and a dysfunction of physiological systems. One of the most serious and prognostically ominous complications from COVID-19 is coagulopathy, in particular, decompensated hypercoagulability with the risk of developing disseminated intravascular coagulation. In most cases, local and diffuse macro- and microthromboses are present, a condition which causes multiple-organ failure and thromboembolic complications. The causes and pathogenic mechanisms of coagulopathy in COVID-19 remain largely unclear, but they are associated with systemic inflammation, including the so-called cytokine storm. Despite the relatively short period of the ongoing pandemic, laboratory signs of serious hemostatic disorders have been identified and measures for specific prevention and correction of thrombosis have been developed. This review discusses the causes of COVID-19 coagulopathies and the associated complications, as well as possible approaches to their early diagnosis, prevention, and treatment.

Adenovirus expressing ß2-microglobulin recovers HLA class I expression and antitumor immunity by increasing T-cell recognition.

Optimal tumor cell surface expression of human leukocyte antigen (HLA) class I molecules is essential for the presentation of tumor-associated peptides to T-lymphocytes. However, a hallmark of many types of tumor is the loss or downregulation of HLA class I expression associated with ineffective tumor antigen presentation to T cells. Frequently, HLA loss can be caused by structural alterations in genes coding for HLA class I complex, including the light chain of the complex, ß2-microglobulin (ß2m). Its best-characterized function is to interact with HLA heavy chain and stabilize the complex leading to a formation of antigen-binding cleft recognized by T-cell receptor on CD8+ T cells. Our previous study demonstrated that alterations in the ß2m gene are frequently associated with cancer immune escape leading to metastatic progression and resistance to immunotherapy. These types of defects require genetic transfer strategies to recover normal expression of HLA genes. Here we characterize a replication-deficient adenoviral vector carrying human ß2m gene, which is efficient in recovering proper tumor cell surface HLA class I expression in ß2m-negative tumor cells without compromising the antigen presentation machinery. Tumor cells transduced with ß2m induced strong activation of T cells in a peptide-specific HLA-restricted manner. Gene therapy using recombinant adenoviral vectors encoding HLA genes increases tumor antigen presentation and represents a powerful tool for modulation of tumor cell immunogenicity by restoration of missing or altered HLA genes. It should be considered as part of cancer treatment in combination with immunotherapy.

[Central lymphodissection in carcinoma of the thyroid gland].

Experience with central lymphodissection (CLD) was analyzed in 93 patients with primary thyroid cancer (pT1-4aN0-1a). Prophylactic central lymphodissection was fulfilled in 48 patients, therapeutic CLD in 45 patients. The size and spread of the primary thyroid tumor had no difference in both groups of patients. In patients of the 2nd group thyroidectomy was fulfilled more often (71.1%) than in the 1st group (58.3%).The frequency of postoperative transitory hypoparathyroidism after surgery on the thyroid gland and therapeutic CLD made up 13.3%. There were no recurrent metastases of cancer after CLD fulfilled during the last 3.5 years. All cancer metastases in the postoperative period were detected in lymph nodes of the neck (2-5 levels) and their prevalence was 8.9%.

Efficient recovery of HLA class I expression in human tumor cells after beta2-microglobulin gene transfer using adenoviral vector: implications for cancer immunotherapy.

Here we report a successful use of a non-replicating adenovirus expressing the wild-type human beta2m gene in recovery of normal human leucocyte antigen (HLA) class I expression in beta2m-null cancer cells. Total loss of HLA class I expression in these cell lines is caused by a mutation in beta2m gene and a loss of heterozygosity in chromosome 15 carrying another copy of that gene. Normal HLA class I expression on the tumour cell surface is critical for the successful outcome of cancer immunotherapy as T cells can only recognize tumour-derived peptides in a complex with self-HLA class I molecules. In this report we characterize the newly generated adenoviral vector AdCMVbeta2m and demonstrate an efficient beta2m gene transfer in tumour cell lines of different histological origin, including melanoma, prostate and colorectal carcinoma. The beta2m re-expression lasted for an extended period of time both in vitro and in vivo in human tumour xenograft transplants. We propose that in a subset of cancer patients with structural defect in beta2m gene or chromosome 15, the adenoviral-mediated recovery (or even increase) of HLA class I expression on tumour cells in combination with vaccination or adoptive T-cell therapy can provide a complementary approach to improve the clinical efficacy of cancer immunotherapy.

[Sorption and contact-activating properties of the <> anastomosis zone: effect of suture material (communication II)].

The authors have carried out a comparative analysis of the interaction between two types of suture material with blood components, as well as studied the effect of heparin-mediated modification on the sorption and contact-activating processes in the zone of the anastomosis. The blood-compatible properties of the latter was assesses in vitro. It was determined that by minute 120 of the contact with blood, the largest amount of protein is had been absorbed by the anastomoses performed using the Prolene thread - 112 microg/cm2. Heparin-mediated modification made it possible to dramatically decrease the amount of the absorbed proteins. On the anastomoses performed with TiNi, additional treatment with heparin lead to an inconsiderable decrease in the protein amount. When identifying the absorbed proteins, we revealed dependence on the type of the suture material and modification with heparin. After a 60-minute contact with blood in the area of the anastomosis made with TiNi, absorbed were: albumin, immunoglobulins A, G, and transferrin. When using the Prolene thread, fibrinogen was noted to join. Additional heparinization exerted a favourable effect on the sorption processes in the area of the anastomosis wherein predominantly albumin and immunoglobulins A and G are predominantly absorbed. The parameters of the peak values and the rate of blood platelet aggregation were minimal in the area of the anastomoses done with TiNi with an additional treatment with heparin.

[Transformation of bioprosthesis-artery anastomotic area after blood exposure: the effect of suture material].

Vascular graft implantation is accompanied with tissue reaction which is determined partially by the nature of suture material. In experiments in vitro edges of arterial diepoxid-preserved bioprostheses were sutured with Prolene filament, nickelide-titanium wire (TiNi) or absorbable polydioxanone monofilament (PDS). Morphological changes in anastomotic area after blood exposure were assessed with scanning electronic microscope. Protein deposits in anastomotic area were detected 5 min after blood exposure, being more loose and bulky around Prolene sutures. The protein layer became more compact 120 min since blood exposure. Most homogeneous protein sorption was over TiNi-sutured anastomoses. Suture material affected blood cells as well - some red cells have transformed into echinocytes. Heparin-modified samples demonstrated less negative impact of suture material in anastomotic area. The worst results after 120 min of blood exposure were obtained for PDS filaments.

[Prevalence and molecular-genetic typing of nonsyndromal neurosensory deafness in the Chuvash Republic]. / Rasprostranennost' i molekuliarno-geneticheskoe tipitovanie nesindromal'noi neirosensornoi tugoukhosti v respublike Chuvashiia.

Summarized genetic epidemiological characteristics of nonsyndromic sensorineural deafness in six raions of Chuvash Republic (Cheboksary, Kanash, Morgaushi, Tsivil'sk, Mariinski Posad, and Alatyr') are presented. A total of 264,419 individuals were examined. Forty-five families (60 affected individuals) with autosomal recessive (AR) and 8 families (18 affected individuals) with autosomal dominant (AD) nonsyndromic sensorineural deafness (NSSD) were identified. The load of AD and AR NSSD in the raions examined was estimated. A correlation between the distribution of AR NSSD and genetic drift was demonstrated. Furthermore, the load of AR NSSD was substantially higher in the regions with higher differentiation level. The Spearman's correlation coefficient value was 0.87. Typing of the 35delG mutation in the gene for connexion 26 was carried out in 34 patients from 26 families with AR NSSD. Comparative estimates of the NSSD prevalence in a number of Russian populations were performed.

[Population genetic study of the Alatyr region of the Republic of Chuvashiia]. / Populiatsionno-geneticheskoe issledovanie Alatyrskogo raiona Respubliki Chuvashiia.

Population genetic characteristics were estimated in the Alatyr' raion (administrative district) of the Republic of Chuvashia, which has long been populated by three ethnic groups. The ethnic assortativeness values in the town of Alatyr' and the rural area of the district were 1.17 and 1.21, respectively, for Russians; 1.14 and 4.82, respectively, for Chuvashes; and 1.33 and 2.45, respectively, for Mordovians. Wright's statistics were as follows: Fst = 0.00358, Fit = 0.00178, and Fis = 0.00134. The migration indices were 0.0264 for Alatyr' and 0.0178 for the district. The endogamy indices for the total and the Russian populations of Alatyr' were 0.47 and 0.53, respectively. The parameters of isolation by distance were a = 0.000189 and b = 0.00959 for the urban and a = 0.000318 and b = 0.00919 for the rural area. Schemes of the genetic landscape were constructed. The influence of the polyethnic composition on the genetic structure of the population is discussed.

[Comparison of Chuvashs with Maris and Russians by vital statistics and the Crow index]. / Sravnenie Chuvashei s s Mariitsami i Russkimi po vital'nam statistikam i indeksu Krou.

Genetic demographic characteristics were calculated for Chuvash and Russian inhabitants of the Republic of Chuvashia. The generation lengths were 27.09 and 26.4 years and the sibship sizes were 2.54 and 1.82 for Chuvashes and Russians, respectively. Crow's indices and their components were as follows: Im = 0.05, If = 0.31, and Itot = 0.37 for Chuvashes and Im = 0.03, If = 0.43, and Itot = 0.46 for Russians. The genetic demographic characteristics obtained were compared with those for Highland and Meadow Maris.

[Genetic epidemiological study of populations in three regions of Chuvashia Republic]. / Genetiko-épidemiologicheskoe izuchenie naseleniia trekh raionov Respubliki Chuvashiia.

Comprehensive population genetic and medical genetic studies were performed in three raions (districts) of Chuvashia. The population of these districts is more than 90% Chuvash. About 70% of the families that completed reproduction had two or three children. The proportion of families with four or more children was 18%. The duration of generation was 27.6 years. The differential fertility and differential mortality indices in the Chuvash population were estimated at 0.33 and 0.076, respectively. The total index of differential selection was 0.403, which is typical of modern urbanized populations. Mean values of local inbreeding calculated from Malecot's model of isolation by distance were 0.00124 and 0.00377 for the urban and rural populations, respectively, of the districts studied. The prevalence rates of autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases were found to be 0.47, 0.52, and 0.35 per 1000, respectively, in the urban population and 1.62, 1.14, and 0.31 per 1000, respectively, in the rural population. Significant correlation between the local inbreeding and prevalence rates of AD and AR diseases was found. A total of 43 AD and 43 AR diseases were identified. Some of them were not found in previous studies on other populations.

[Sensitivity of biological objects to the effects of the geomagnetic field]. / O chuvstvitel'nosti biologicheskikh ob''ektov k vozdeistviiu geomagnitnogo polia.

It is shown on the basis of calculations of energy sublevels of the hyperfine structure that the effect of the geomagnetic field upon the impurity atoms in the volume of living cells should be considered in relation to the value of geomagnetic field induction pulses delta B. When delta B > or = 10 pT and the dielectric constant epsilon > or = 10, magnetodipole transitions between sublevels of the hyperfine structure within one term are possible in impurity atoms in their 2P-state. During magnetic storms with delta B > or = 100 nT magnetodipole or magnetoquadrupole forced transitions from 2P1/2 and 2P3/2 states to 2S1/2 metastable state are possible in the resonant zones formed by intersection of hyperfine energy sublevels of the corresponding excited levels.