Identification of the novel HLA-DQA1*05:107 allele.

Full length sequence characterisation of the novel HLA-DQA1*05:107 allele from whole genome sequencing data.

Sea level anomalies affect the ocean circulation at abyssal depths.

Abyssal channels are the key points controlling bottom circulation of the World Ocean. They provide meridional transport of the coldest Antarctic Bottom Water between deep-water basins influencing the meridional overturning circulation and the climate on a global scale. Here we show that the synoptic variability of deep-water flows including blocking abyssal currents between deep ocean basins is related to sea level anomalies observed over the channels. Our results demonstrate that processes at the ocean surface have a more significant connection with the bottom circulation than it was considered earlier. This study opens a discussion of the importance of mesoscale eddies and air-sea interactions on water exchange between abyssal basins, meridional heat transport in the ocean, and possible responses of the ocean to the observed sea level rise in a changing climate.

[The significance of glymphatic pathway in the relationship between the sleep-wake cycle and neurodegenerative diseases]. / Rol' glimfaticheskogo klirensa v mekhanizmakh svyazi tsikla «son­bodrstvovanie¼ i razvitiya neirodegenerativnykh protsessov.

Selective and progressive death of neurons is a characteristic feature of the process of neurodegeneration and leads to corresponding neuronal dysfunctions. Neurodegenerative diseases represent a heterogeneous group of clinically distinct disorders with similar molecular mechanisms of pathogenesis. They are based on the processes of abnormal aggregation of proteins, the formation of fibrillary insoluble structures and their deposition in the form of histopathological inclusions in the tissues of the nervous system. Disturbance of homeostatic functions that regulate neuronal ion and energy metabolism, biosynthesis and degradation of proteins and nucleotides, chronic hypoxia and the penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause metabolic changes associated with age and disorders in the sleep-wake cycle, but also contribute to the development of neurodegenerative diseases. In animal studies, clearance pathways have been identified in which solutes and specific tracers are excreted perivascular into the meningeal lymphatics. The glymphatic pathway promotes the removal of metabolites, including Aß amyloid and tau protein, from the parenchymal extracellular space of the brain. The glymphatic system is discussed to be more efficient during natural sleep, and fluid dynamics through this pathway exhibit daily fluctuations and are under circadian control. This review systematizes the key aspects and scientific data of recent studies on the role of the glymphatic pathway and astroglial AQP-4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, in particular in relation to the regulatory role of the sleep-wake cycle and in development of neurodegeneration.

[Changes in sleep patterns and the doom-scrolling (doom-surfing) phenomenon as modifiable risk factors for anxiety due to continuous stress of the COVID-19 pandemic]. / Izmeneniya rezhima sna i potreblenie informatsii s negativnym kontentom v internete («dumskrolling¼, «dumserfing¼) kak upravlyaemye faktory riska razvitiya trevogi v usloviyakh stressa pandemii COVID-19.

OBJECTIVE: To evaluate the modifiable daily behavior patterns associated with increased anxiety indicators in the general population in response to the COVID-19 pandemic. MATERIAL AND METHODS: The study examined the characteristics of the Russian population (n=7777) of the international multicenter project COMET-G. In particular, variables were targeted to describe deviations in the behavior of adults during the period of application of measures of social isolation in connection with the pandemic, and revealing a relationship with the total score on the Spielberger State Anxiety Scale (STAI-S). Among these variables, experts selected those that could potentially be subject to change in the short term, that is, act as manageable or modifiable risk factors for the development of anxiety. The selected variables were analyzed in a statistical PLS-model to identify indicators that make the most significant contribution to the increase in the total anxiety score. RESULTS: Our statistical model explained 48.4% of the variability in the STAI-S anxiety total scores related to changes in daily life habits. In particular, doom-scrolling/doom-surfing about the spread of the virus and the COVID-19 pandemic, changes in sleep patterns and usual daily life activities due to social isolation measures presented as factors significantly contributing to the increase of state anxiety. CONCLUSION: Given the manageable or modifiable risk factors that we have identified, public awareness and therapeutic recommendations, pointing to the need to (I) control the amount of time spent in the internet and monitor their internet-based content consumption, (II) regulate sleep-wake patterns, (III) maintain daily habits and household activities, may reduce the likelihood of developing anxiety disorders in the context of the impact of a global chronic stress due to the COVID-19 pandemic and associated social isolation measures.

[The significance of the glymphatic pathway in the relationship between the sleep-wake cycle and neurodegenerative diseases]. / Rol' glimfaticheskogo klirensa v mekhanizmakh vzaimosvyazi tsikla «son­bodrstvovanie¼ i razvitiya neirodegenerativnykh protsessov.

Selective and progressive death of neurons is a characteristic feature of the process of neurodegeneration and leads to corresponding neuronal dysfunctions. Neurodegenerative diseases represent a heterogeneous group of clinically distinct disorders with similar molecular mechanisms of pathogenesis. They are based on the processes of abnormal aggregation of proteins, the formation of fibrillary insoluble structures and their deposition in the form of histopathological inclusions in the tissues of the nervous system. Disturbance of homeostatic functions that regulate neuronal ion and energy metabolism, biosynthesis and degradation of proteins and nucleotides, chronic hypoxia and the penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause metabolic changes associated with age and disorders in the sleep-wake cycle, but also contribute to the development of neurodegenerative diseases. In animal studies, clearance pathways have been identified in which solutes and specific tracers are excreted perivascular into the meningeal lymphatics. The glymphatic pathway promotes the removal of metabolites, including Aß amyloid and tau protein, from the parenchymal extracellular space of the brain. The glymphatic system is discussed to be more efficient during natural sleep, and fluid dynamics through this pathway exhibit daily fluctuations and are under circadian control. This review systematizes the key aspects and the data of recent research on the role of the glymphatic pathway and astroglial AQP-4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, in particular in relation to the regulatory role of the sleep-wake cycle and in development of neurodegeneration.

Sociodemographic Factors of Depression During the COVID-19 Pandemic in Malaysia: the COVID-19 Mental Health International Study.

OBJECTIVES: To determine the prevalence of depression and the sociodemographic factors associated with depression in Malaysia during the COVID-19 pandemic METHODS. This study is part of the COVID-19 Mental Health International Study to collect data on the impact of the pandemic on mental health through an online survey. People who were aged ≥18 years, able to read Malay or English, had access to the internet, and consented to participate were asked to complete a pro forma questionnaire to collect their sociodemographic data. The presence of distress and depression was assessed using the English or Malay version of the Center for Epidemiologic Studies Depression Scale. RESULTS: Of 963 participants, 451 (46.8%) had depression and 512 (53.2%) had no depression who were either normal (n = 169, 17.5%) or had distress (n = 343, 35.6%). Participants had higher odds of having depression when living with two people (adjusted odds ratio [AOR] = 3.896, p = 0.001), three people (AOR = 2.622, p < 0.001) or four people (AOR = 3.135, p < 0.001). Participants with three children had higher odds of having depression (AOR = 2.084, p = 0.008), whereas having only one child was a protective factor for depression (AOR = 0.481, p = 0.01). Participants had higher odds of having depression when self-employed (AOR = 3.825, p = 0.003), retired (AOR = 4.526, p = 0.001), being housekeeper (AOR = 7.478, p = 0.004), not working by choice (AOR = 5.511, p < 0.001), or unemployed (AOR = 3.883, p = 0.009). Participants had higher odds of depression when living in a small town (AOR = 3.193, p < 0.001) or rural area (AOR = 3.467, p < 0.001). Participants with no chronic medical illness had lower odds of having depression (AOR = 0.589, p = 0.008). CONCLUSION: In Malaysia during the COVID-19 pandemic, people who are living with two, three, or four people, having three children, living in a small town or rural areas, and having unstable income have higher odds of having depression. Urgent intervention for those at risk of depression is recommended.

[Comparative study of Wuhan-like and omicron-like variants of SARS-CoV-2 in experimental animal models].

INTRODUCTION: The variability of SARS-CoV-2 appeared to be higher than expected, the emergence of new variants raises concerns. The aim of the work was to compare the pathogenicity of the Wuhan and BA.1.1/Omicron variants in BALB/c mice and Syrian hamsters. MATERIALS AND METHODS: The study used strains of SARS-CoV-2: Dubrovka phylogenetically close to Wuhan-Hu-1, and LIA phylogenetically close to Omicron, BALB/c mice, transgenic mice B6.Cg-Tg(K18-ACE2)2Prlmn/HEMI Hemizygous for Tg(K18-ACE2)2Prlmn, Syrian golden hamsters. Animals were infected intranasally, pathogenicity was estimated by a complex of clinical, pathomorphological and virological methods. RESULTS: Comparative studies of SARS-CoV-2 Dubrovka and LIA strains on animal models demonstrated their heterogeneous pathogenicity. In parallel infection of BALB/c mice with Dubrovka and LIA variants, the infection proceeded without serious clinical signs and lung damage. Infection with the LIA strain resulted to a systemic disease with a high concentration of viral RNA in the lungs and brain tissues of animals. The presence of viral RNA in mice infected with the Dubrovka strain was transient and undetectable in the lungs by day 7 post-infection. Unlike the mouse model, in hamsters, the Dubrovka strain had a greater pathogenicity than the LIA strain. In hamsters infected with the Dubrovka strain lung lesions were more significant, and the virus spread through organs, in particular in brain tissue, was observed. In hamsters infected with the LIA strain virus was not detected in brain tissue. CONCLUSION: The study of various variants of SARS-CoV-2 in species initially unsusceptible to SARS-CoV-2 infection is important for monitoring zoonotic reservoirs that increase the risk of spread of new variants in humans.

Immunogenic properties of SARS-CoV-2 inactivated by ultraviolet light.

Vaccination against COVID-19 is the most effective method of controlling the spread of SARS-CoV-2 and reducing mortality from this disease. The development of vaccines with high protective activity against a wide range of SARS-CoV-2 antigenic variants remains relevant. In this regard, evaluation of the effectiveness of physical methods of virus inactivation, such as ultraviolet irradiation (UV) of the virus stock, remains relevant. This study demonstrates that the UV treatment of SARS-CoV-2 completely inactivates its infectivity while preserving its morphology, antigenic properties, and ability to induce the production of virus-neutralizing antibodies in mice through immunization. Thus, the UV inactivation of SARS-CoV-2 makes it possible to obtain viral material similar in its antigenic and immunogenic properties to the native antigen, which can be used both for the development of diagnostic test systems and for the development of an inactivated vaccine against COVID-19.

[Application of modern approaches in the screening and early diagnosis programs for the orphan diseases]. / Primenenie sovremennykh tekhnologii v programmakh rannei diagnostiki orfannykh boleznei v Rossii i za rubezhom.

Orphan diseases have a prevalence ranging one patient per 10.000 population in the Russian Federation to one per 1500-2000 individuals in Australia and the USA. Many orphan diseases lead to a severe decrease in quality of life and high mortality. In this article, we discuss the problem of early diagnosis in orphan diseases in the Russian Federation, which has lagged behind global trends towards improved recognition and treatment of orphan diseases. We identify the need for improved focus at the level of national healthcare, while discussing relevant issues arising from the international experience. We review national and regional health programs and healthcare practices of Australia, Germany, Denmark, China, Norway, Slovenia, UK, and the United States, with a focus on screening and diagnosis of orphan disease. We also present a review on the state of affairs in the Russian Federation. Orphan diseases are amenable to current molecular-genetic and other diagnostic technologies, including targeted, whole exome and whole genome sequencing (targeted NGS, WES, WGS) using next generation sequencing technologies (next generation sequencing, NGS) and tandem mass spectrometry (TMS, MS/MS). We conclude with a call for major measures aimed at improving the diagnosis of orphan diseases, in particular through the expansion of the neonatal screening program, the creation of a network of orphan disease referral centers, and centralized management of patients registers.

Description of two new alleles: HLA-B*50:79 and HLA-DRB1*04:332.

Two novel HLA alleles HLA-B*50:79 and -DRB1*04:332 have non-synonymous mutations in exon 4 and exon 3, respectively.

Comparative assessment of the results of detection of СagА-positive strains of Helicobacter pylori by molecular-genetic and immunochromatographic methods in different biological materials.

A comparative analysis of the detection of CagA-positive strains of H. pylori by immunochromatographic and molecular genetic methods was carried out. We used H. pylori strains isolated from individuals with diseases of the gastrointestinal tract. The immunochromatographic method was implemented using a developed experimental model of an immunochromatographic test system for detecting the H. pylori CagA protein in various biological materials. Determination of the pathogenicity gene cagA of H. pylori was carried out using the «Helikopol SA¼ test system («Litekh¼, Russia). The assessment of the comparability of the results of detecting CagA-positive strains of H. pylori was carried out using statistical methods: Monte-Carlo, calculation of the chi-square test (χ2) and Kendall's τ-b and Somer's d coefficients. Statistical analysis was performed using the software packages «Microsoft Office Excel¼, «Statistica 10.0¼, «WinBUGS 1.4.0.¼ The study showed the absence of a statistically significant difference and the presence of a direct strong correlation between the results of detecting CagA-positive strains by molecular genetic and immunochromatographic methods, which indicates that these methods provide similar results in identifying highly pathogenic strains of H. pylori.

[The increasing of the somatic health in students using differently directed fitness].

The purpose of study is to scientifically substantiate the methodology of applying differently directed fitness tools to increase the level of somatic health, physical and mental workability of students. The experimental sampling consisted of 186 students (106 girls, 80 boys) of the Belgorod State National Research Institute and the Belgorod University of Cooperation, Economics and Law. Two groups of respondents were organized: control group (n=85; 47 girls, 38 boys) that included students involved into officially approved education program of the Chair of Physical Culture and experiment group (n=101; 59 girls, 42 boys) that included students involved into experimental program. It is established that Pilates stabilizes and topes up muscles of entire body, improves coordination abilities of students involved, improves body-build constitution, promotes reducing of back pain, improves cardio-respiratory system functioning and is the most called-for fitness direction for reducing psycho-emotional tension. The step aerobics positively effects on the cardio-respiratory system, the entire musculoskeletal system and physical workability. The level of somatic health in experiment group after the experiment improved from "below average" to "average". In control group both before and after the experiment, the level of somatic health corresponded to "below average". After the experiment, the physical performance indices in experiment group improved and remained at the same level in control group. In the experiment group all analyzed indices of mental workability increased and acquired measured character.

[Reactivation of Epstein-Barr virus (Herpesviridae: Lymphocryptovirus, HHV-4) infection during COVID-19: epidemiological features].

INTRODUCTION: Immunodeficiency underlying the development of severe forms of new coronavirus infection may be the result of mixed infection with SARS-CoV-2 and other pathogens, including Epstein-Barr virus (EBV).The aim is to study the prevalence and epidemiological features of co-infection with SARS-CoV-2 and EBV. MATERIAL AND METHODS: A cross-sectional randomized study was conducted in Moscow region from March to May 2020. Two groups were examined for EBV-markers: hospital patients (n = 95) treated for SARS-CoV-2 infection and blood donors (n = 92). RESULTS: With equal EBV prevalence the detection of active infection markers in donors (10.9%) was noticeably lower than in SARS-CoV-2 patients (80%). Significant differences in this indicator were also found when patients from subgroups with interstitial pneumonia with the presence (96.6%) and absence (97.2%) of SARS-CoV-2 in the nasopharyngeal smear were compared with the subgroup of patients with mild COVID-19 (43.3%). The average IgG VCA and IgG EBNA positivity coefficients in donor group were higher than in patient group (p < 0.05). Patients with active EBV infection markers were significantly more likely to have pneumonia, exceeding the reference values of ALT and the relative number of monocytes (odds ratio - 23.6; 3.5; 9.7, respectively). DISCUSSION: The present study examined the incidence and analyzed epidemiological features of active EBV infection in patients with COVID-19. CONCLUSION: A significantly higher rate of detection of active EBV infection markers in hospital patients indicates a combined participation SARS-CoV-2 and EBV in the development of interstitial pneumonia. Low levels of specific IgG EBV serve as predictors of EBV reactivation. Exceeding the reference values of ALT and the relative number of monocytes in patients should serve as a reason for examination for active EBV infection markers.

[The role of fibroblast growth factor 19 in pathogenesis of bile acid diarrhea of the patients who underwent cholecystectomy].

The occurrence of chronic diarrhea after cholecystectomy (CCY) has been described by many researchers. However, the main mechanisms of the development of this diarrhea are not fully understood. Supposed that dysregulation of the bile acids (ВA) absorption in the ileum is played a significant role in the development of diarrhea syndrome. AIM: To determine the role of the fibroblast growth factor 19 (FGF19) level in the serum and BA concentration in feces in pathogenesis of bile acid diarrhea (ВАD) in patients after CCY. MATERIALS AND METHODS: Sixty-one patients were examined at various times after CCY: 30 patients with chronic diarrhea that appeared after CCY (group 1) and 31 patients with normal stools (group 2). In all patients, the level of FGF19 in the blood serum, and the daily excretion of BA in the feces were studied. The control group consisted of 28 healthy individuals. RESULTS: In the 1st group we found lower concentrations of FGF19 in the blood serum 86.2 ng/ml (67.8; 117.8) compared with concentrations in the 2nd group 259 ng/ml (170.6; 318.8), p0.001. The daily excretion of bile acids with feces in the 1st group was 657.4 mg/day (524.6; 830.1), which was twice more than in the 2nd group and the control group. It was established an inverse correlation between serum concentration of the FGF19 and the BA excretion in the feces in all examined patients. It indicates a possible relationship between the low concentration of FGF19 in blood serum and malabsorption of the BA. CONCLUSION: Low level of FGF19 in the blood serum and a high excretion of BA in the feces may be one of the causes of BAD in patients undergoing cholecystectomy. Our results indicate the important role of FGF19 in the development of chronic diarrhea, which can be considered as one of the variants of postcholecystectomy syndrome.

[The increase level of somatic health in students by multi directional means of fitness].

The purpose of the study is to substantiate methodology of using multidirectional fitness tools to improve level of somatic health, and as a result, physical and mental efficiency of students. The study sampling included 186 students (106 girls, 80 boys). Two groups were formed: control group (n=85: 47 girls, 38 boys) and experimental group (n=101: 59 girls, 42 boys) in the content of educational program were included experimental method. The study demonstrated that Pilates stabilizes and topes up muscles of entire body, improves coordination abilities, improves physique, favors reducing back pain, improves cardio-respiratory system and reduces psycho-emotional tension. The step aerobics positively effect on cardio-respiratory system and entire musculoskeletal system, as well as has a on physical performance. The somatic health of students in experimental group after experiment improved from "below average" to "average". In control group, before and after the experiment, level of somatic health made to "below average". After experiment, physical performance indicators in experimental group improved. The indices of students of control group remained at the same level. In experimental group, all indices of mental performance increased and began to have regular character.

Characterization of the novel HLA-C*01:195 allele.

The new allele HLA-C*01:195 showed one nucleotide difference with HLA-C*01:02:01:01.

Two novel HLA alleles, HLA-DRB1*14:223 and HLA-DQB1*03:01:49, detected in a Buryat individual.

Two new alleles were characterized by next generation sequencing in a Buryat individual.

Superioniclike Diffusion in an Elemental Crystal: bcc Titanium.

Recent theoretical investigations [A. B. Belonoshko et al. Nat. Geosci. 10, 312 (2017)1752-089410.1038/ngeo2892] revealed the occurrence of the concerted migration of several atoms in bcc Fe at inner-core temperatures and pressures. Here, we combine first-principles and semiempirical atomistic simulations to show that a diffusion mechanism analogous to the one predicted for bcc iron at extreme conditions is also operative and of relevance for the high-temperature bcc phase of pure Ti at ambient pressure. The mechanism entails a rapid collective movement of numerous (from two to dozens) neighbors along tangled closed-loop paths in defect-free crystal regions. We argue that this phenomenon closely resembles the diffusion behavior of superionics and liquid metals. Furthermore, we suggest that concerted migration is the atomistic manifestation of vanishingly small ω-mode phonon frequencies previously detected via neutron scattering and the mechanism underlying anomalously large and markedly non-Arrhenius self-diffusivities characteristic of bcc Ti.

[Features of distribution HLAalleles and haplotypes in Kalmyks.]

Conducted high-resolution HLA-typing loci HLA-A, -B, -C, -DRB1 and -DQB1 by massively parallel sequencing of 150 potential donors of hematopoietic stem cells from the Republic of Kalmykia. In the studied population, four new alleles identified that not previously registered by the International Committee on the Nomenclature of Factors of the HLA-system of WHO. During the HLA-typing identified: 29 alleles at the HLA-A locus, 44 - at the HLA-B locus, 26 - at the HLA-C locus, 15 - at the DQB1 locus, 37 - at the HLA-DRB1 locus. The following alleles have a frequency of more than 10%: HLA-A*02:01 (11,7%), HLA-A*01:01 (11%), HLA-B*51:01 (10,3%), HLA-B*58:01 (10,3%), HLA-C*06:02 (17,7%), HLA-C*03:04 (10,3%), HLA-C*03:02 (10%), HLA-DQB1*03:01 (26,7%), HLA-DQB1*02:02 (10%), HLA-DRB1*07:01 (11,7%). The most common HLA-A-B-C-DQB1-DRB1 haplotype is A*02:05-B*50:01-C*06:02-DQB1*02:02-DRB1*07:01 (3,7%). Deviations from the Hardy - Weinberg equilibrium not identified.

[Expirience introduction of quantitative analysis of chimerism after allogenic stem cell transplantation by real-time PCR with InDel polymorphism.]

Using data obtained from domestic and foreign sources, we formed a set of primers and fluorogenic probes for analyzing twentysix specific sequence polymorphisms and one reference gene. In the course of evaluating the effectiveness of real-time PCR, using the example of one of the markers (S01a), we obtained the optimal amount of DNA per reaction (70 ng), providing a resolution of at least 0.1% of the method with the ability to estimate linear chimerism. Formed panel of primers for genetic polymorphisms - InDel has a high degree of informational content for donor-recipient pairs of Russia. From January 2018 to June 2019, a quantitative assessment of the level of linear (CD3 +, CD34 +) and general chimerism was carried out for 28 patients of the clinic of the Institution. Finally, we analyzed patients who received allografts and present 4 different clinical situations that illustrate the informativity level of this method.