The Grow It! app-longitudinal changes in adolescent well-being during the COVID-19 pandemic: a proof-of-concept study.

Adolescent mental health and well-being have been adversely impacted by the COVID-19 pandemic. In this preregistered longitudinal study, we evaluated whether adolescents' well-being improved after playing the multiplayer serious game app Grow It! During the first lockdown (May-June 2020), 1282 Dutch adolescents played the Grow It! app (age = 16.67, SD = 3.07, 68% girls). During the second lockdown (December-May 2020 onwards), an independent cohort of 1871 adolescents participated (age = 18.66, SD = 3.70, 81% girls). Adolescents answered online questionnaires regarding affective and cognitive well-being, depressive symptoms, anxiety, and impact of COVID-19 at baseline. Three to six weeks later, the baseline questionnaire was repeated and user experience questions were asked (N = 462 and N = 733 for the first and second cohort). In both cohorts, affective and cognitive well-being increased after playing the Grow It! app (t = - 6.806, p < 0.001; t = - 6.77, p < 0.001; t = - 6.12, p < 0.001; t = - 5.93, p < 0.001; Cohen's d range 0.20-0.32). At the individual level, 41-53% of the adolescents increased in their affective or cognitive well-being. Adolescents with higher risk profiles (i.e., more depressive symptoms, lower atmosphere at home, and more COVID-19 impact) improved more strongly in their well-being. Positive user evaluations and app engagement were unrelated to changes in affective and cognitive well-being. This proof-of-concept study tentatively suggests that Grow It! supported adolescents during the pandemic.

DETERMINATION OF THE SENSITIVITY OF GARDNERELLA VAGINALIS TO FENTICONAZOLE.

Objective - to determine the sensitivity of Gardnerella vaginalis to fenticonazole to justify the feasibility of using this mainly antifungal drug for local treatment of BV in cases when it is a multifactorial disease caused by Gardnerella vaginalis and Candida spp. simultaneously.; We observed 98 women with infections of the urogenital tract at the ages of 20 to 49. At the first stage of the study, we analyzed the results of laboratory data on pathological discharge from the urogenital system of these patients. 36 (%) of the examined women had Gardnerella vaginalis in the vaginal discharge. At the second stage of the study, the sensitivity of Gardnerella vaginalis to fenticonazole was determined.; The resistance to fenticonazole was registered in 1 case (2.7%). In the remaining 35 patients Gardnerella vaginalis was not stable to fenticonazole. High sensitivity to this substance was found in 22 of them (61.2%). Respectively, low sensitivity was registered in 13 people from the observation group (36.1%).; Gardnerella vaginalis is the main constituent and a marker of bacterial vaginosis. The elimination of this very microorganism is of paramount importance for its treatment. In 35 studied patients (97.3%) Gardnerella vaginalis, which was isolated by culture from vaginal discharge, had sensitivity to fenticonazole. Moreover, in 22 of them (61.2%) the sensitivity was high, and low in 13 (36.1%). Candida spp. was found in 17 (47.1%) of 36 patients with bacterial vaginosis. It is appropriate to use fenticonazole as a means of local treatment during complex therapy of women with bacterial vaginosis that improves its compliance.

QUANTITATIVE CHARACTERISTICS OF GUT MICROBIOTA IN PATIENTS WITH ARTERIAL HYPERTENSION.

The aim of the work is to study the quantitative characteristics of gut microbiota (GM) in patients with arterial hypertension AH - residents of Ukraine in comparison with practically healthy individuals. 36 patients with AH stage II, 2-3 degrees against the background of normal body weight were examined. The control group consisted of 20 apparently healthy individuals. The examination included standard clinical, laboratory and instrumental methods. For determination of the quantitative composition of GM were used the method of polymerase chain reaction with hybridization-fluorescence detection of results in real time and the test system "COLONOFLOR-16 (biocenosis)" ("ALFALAB"). Statistical analysis of the results was carried out by standard methods using Microsoft Excel 17.0. The significant changes in GM quantitative characteristics were found in patients with AH (resident of Ukraine) in comparison with healthy individuals: a significant decrease in the number of Lactobacillus spp., Bifidobacterium spp. and Faecalibacterium prausnitzii. The deficiency of Lactobacillus spp., Bifidobacterium spp. and Faecalibacterium prausnitzii in patients with AH - residents of Ukraine may indicate the important role of GM disorders in the pathogenesis of hypertension.

[ABDOMINAL OBESITY AND GUT MICROBIOTA (REVIEW)].

In review provides data on pathophysiological relationships of intestinal microbiota with body weight regulation in patients with abdominal obesity. In manuscript discusses the leading mechanisms by which the gut microbiota can contribute to obesity and metabolic diseases, analyzes its components, including gastrointestinal peptides, short-chain fatty acids, bile acids, farnesoid receptors, etc. Western diet high in salt, dysbiosis and endotoxemia can be powerful pro-inflammatory factors responsible for the development of insulin resistance and weight gain. It is promising to prescribe agonists of gastrointestinal peptides, probiotics and prebiotics, which in abdominal obesity are able to inhibit dysbiosis, regulate immune functions, and protect the organism from low-intensity chronic inflammation.

Long-term exposure to low doses of ionizing radiation and COVID-19 pandemic: oncohematological aspects.

For more than 35 years after Chornobyl catastrophe, about 5 million people in Ukraine, Republic of Belarus and Russian Federation inhabit the territories that are residually contaminated with long-lived radionuclides such as 137Cs, 90Sr. The previous studies of the Reference Laboratory operating at RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology allowed specifying the effects of the protracted low dose irradiation on the state of the hematopoietic and lymphoid tissues resulting in the increased proportion of the B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma and acute myeloid leukemia among the patients referred from the contaminated areas of Ukraine. Since the beginning of 2020, these effects of radiation were superimposed by the factors associated with COVID-19 pandemic. SARS-CoV-2 infection is associated with the significant impact on hematopoiesis and immune system. Particular attention should be given to the role of such combined burden in the development of the immunodeficiency-associated lymphoid neoplasms. The extensive studies of the combined effects of low dose irradiation and COVID-19 within the large affected populations could be made a priority in future endeavors of epidemiologists and oncohematologists.

Immunodeficiency-associated lymphoproliferative disorders and lymphoid neoplasms in post-COVID-19 pandemic era.

The 2017 revision of WHO Classification of tumors of hematopoietic and lymphoid tissues contains separate chapters on the immunodeficiency-associated lymphoproliferative disorders. In this mini-review, the brief description of pathological, immunophenotypical and clinical features of lymphoid neoplasms associated with primary immune disorders, HIV infection, those arising in post-transplant setting and other lymphoproliferative disorders (excluding those induced by radiation) is given. The heterogeneous spectrum of these lymphoid malignancies is specified by the nature of those factors that are capable to induce immune suppression or chronic antigenic stimulation of immune system. Taking into account the full swing of SARS-CoV-2 pandemic and our ignorance of the ability of this virus to induce the sustained stimulation of immune system, we could not exclude the high risk of autoimmune diseases and lymphoid neoplasms in the long-term post-pandemic period. In this context, the role of angiotensin-converting enzyme 2  as well as some recently reported cell receptors for SARS-CoV-2 cell entry should be considered as far as some of them (CD147, CD26) could be tumor-associated antigens.

Proton strings and rings in atypical nucleation of ferroelectricity in ice.

Ordinary ice has a proton-disordered phase which is kinetically metastable, unable to reach, spontaneously, the ferroelectric (FE) ground state at low temperature where a residual Pauling entropy persists. Upon light doping with KOH at low temperature, the transition to FE ice takes place, but its microscopic mechanism still needs clarification. We introduce a lattice model based on dipolar interactions plus a competing, frustrating term that enforces the ice rule (IR). In the absence of IR-breaking defects, standard Monte Carlo (MC) simulation leaves this ice model stuck in a state of disordered proton ring configurations with the correct Pauling entropy. A replica exchange accelerated MC sampling strategy succeeds, without open path moves, interfaces, or off-lattice configurations, in equilibrating this defect-free ice, reaching its low-temperature FE order through a well-defined first-order phase transition. When proton vacancies mimicking the KOH impurities are planted into the IR-conserving lattice, they enable standard MC simulation to work, revealing the kinetics of evolution of ice from proton disorder to partial FE order below the transition temperature. Replacing ordinary nucleation, each impurity opens up a proton ring generating a linear string, an actual FE hydrogen bond wire that expands with time. Reminiscent of those described for spin ice, these impurity-induced strings are proposed to exist in doped water ice too, where IRs are even stronger. The emerging mechanism yields a dependence of the long-time FE order fraction upon dopant concentration, and upon quenching temperature, that compares favorably with that known in real-life KOH doped ice.

A comprehensive assessment of potential hazard caused by organic compounds in biochar for agricultural use.

Great attention has been paid to using biochar as soil conditioner and bio-accumulator. Nevertheless, biochar application in agriculture might cause a potential hazard to ecosystems, considering that toxic organic pollutants present in biochar may enter the environment. European Biochar Certificate (EBC) set certain criteria for biochar production. Achieving the EBC established values of the molar ratio of H/Corg <0.7 and O/Corg <0.4, does not ensure that biochar will not cause phytotoxicity. The results of root growth inhibition of Sinapis alba were in the range of 9% (eucalyptus wood biochar) to 82% (maize biochar). Phytotoxicity of biochar was possibly caused by the presence of water-soluble organic compounds. In total, 62 organic compounds were identified in the leachate from noncertified biochar and 35 organic compounds in the leachate from certified biochar. Biochar safety, in terms of the presence of organic compounds, can be recognised by the evaluation of the ratio of organic carbon (OC) and elemental carbon (EC). Biochar with the highest phytotoxicity showed the ratio between OC/EC > 0.1, inhibition of Sinapis alba <30% was observed with OC/EC < 0.02. To achieve Sinapis alba inhibition <20%, these parameters should be met: volatile matter (VM) <30%; concentration of OC < 4%; aromaticity ratio AL/AR < 0.35.

Immunophenotypic features of leukemic stem cells and bulk of blasts in acute myeloid leukemia.

According to the modern concept, leukemic stem cells (LSC) in acute myeloid leukemia (AML) are distinct from the bulk of leukemic cells in bone marrow and peripheral blood of AML patients. Nevertheless, LSC are responsible for managing all the hierarchy of the bulk of leukemic blast populations. This mini-review provides brief information on the distinctive features of LSC and blast cells in cytologically recognized types of AML. The study of different phenotypes of LSC and blast cells in AML with the aid of up-to-date flow cytometric techniques is important both for the deep insight into the mechanisms of leukemogenesis and development of novel strategies of target therapy. The urgent need for extending the diagnostic panel of monoclonal antibodies used for diagnosing AML is beyond doubt.

PLASMA MICRORNA-133А LEVEL IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION.

The aim of research was to investigate the plasma microRNA (miR-133а) level in patients with essential arterial hypertension (EAH). A total of 45 patients with EAH 2-3 degrees aged 52.14 ± 8.25 years and 21 healthy individuals (control group) with comparable age and sex distributions. The following frequency of risk factors was revealed among the examined patients: overweight (53%), dyslipidaemia (73%), pre-diabetes (13%), asymptomatic hyperuricemia (29%); hypertension-mediated organ damage: increased arterial stiffness (27%), left ventricular hypertrophy (55%), atherosclerotic plaque in the carotid artery (40%), microalbuminuria (15%), moderate stage of chronic kidney disease (22%) and cardiovascular diseases: stable ischemic heart disease (11%) and heart failure with preserved ejection fraction of NYHA functional class I (18%). The plasma miR-133a level was determined by polymerase chain reaction using "CFX96 Touch" detection system (BioRad) and "TaqMan microRNA Assay" and "TaqMan® Universal PCR Master Mix" reagents (Thermo Fisher Scientific, USA). It has been established that in patients with EAH the plasma level of miR-133a was significantly lower than in practically healthy individuals (0,182 [0,102; 0,301] ), vs (0,382 [0,198; 0,474]), p <0.05). It has also been revealed a significant decrease in the level of miR-133a in the blood plasma in patients with such organs damage as LVH (0,133 [0,099;0,184]) in comparison with patients without LVH (0,238 [0,155; 0,410]), p <0.05) and also significantly lower than in healthy subjects in the control group (0,382 [0,198; 0,474]), p<0.05). There were no statistically significant differences in the plasma levels of miR-133a in the group of patients with EAH, depending on the presence of risk factors, other organ damage and cardiovascular diseases. The findings suggest the significant role of reducing of plasma levels of miR-133a in the pathogenesis of hypertension itself and in pathological remodeling of the heart.

Several aspects of descriptive epidemiology of hematological malignancies in adult population of Ukraine, Belarus and Russian Federation after Chornobyl accident.

Chornobyl impact on the health of adult population in Ukraine, Belarus and Russian Federation was a subject of several studies. However, the studies of the effects of Chornobyl on leukemia in adult populations in post-Soviet countries are scarce and the results are contradictory up to present. The results of the epidemiological studies of the oncohematological consequences of Chornobyl accident are briefly reviewed with particular focus on pre-Chornobyl and post-Chornobyl trends in leukemia incidence in Ukraine, Belarus and Russian Federation as well as in small territories of these countries with various levels of radionuclide contamination. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Overview on association of different types of leukemias with radiation exposure.

Exposure to ionizing radiation is associated with increasing risk of various types of hematological malignancies. The results of major studies on association of leukemias and radiation exposure of large populations in Japan and in Ukraine are analyzed. The patterns of different types of leukemia in 295 Chernobyl clean-up workers diagnosed according to the criteria of up-to-date World Health Organization classification within 10-25 years following Chernobyl catastrophe are summarized. In fact, a broad spectrum of radiation-related hematological malignancies has been revealed both in Life Span Study in Japan and in study of Chernobyl clean-up workers in Ukraine. The importance of the precise diagnosis of tumors of hematopoietic and lymphoid tissues according to up-to-date classifications for elucidating the role of radiation as a causative factor of leukemias is emphasized. Such studies are of high importance since according to the recent findings, radiation-associated excess risks of several types of leukemias seem to persist throughout the follow-up period up to 55 years after the radiation exposure.

Leukemic blast cells and controversies in models of hematopoiesis.

Classical and up-to-date models of hematopoietic lineage determination are briefly reviewed with the focus on myeloid-based models challenging the existence of the common progenitor for T cells, B cells and NK cells. The analysis of immunophenotype of leukemic blast cells seems to be a promising approach for interpreting some controversies in the schemes of normal hematopoiesis. The literature data as well as our own findings in the patients with various types of acute leukemias are in favor of the concept postulating that common myeloid-lymphoid progenitors giving rise to T and B cell branches retain the myeloid potential. The similarity of some immunophenotypic features of blast cells in pro-B acute lymphoblastic leukemia and acute monoblastic leukemia is consistent with monocyte origin postulated in the studies of normal hematopoiesis. Study of acute leukemias may be the challenging area of research allowing for new insight into the origin of hematopoietic cell lineages.

[About possible additions to actual scheme of normal blood formation on the basis of study of leukemic blast cells].

The issue of introduction of number of additions into actual scheme of blood formation is discussed. The long standing experience of laboratory diagnostic of oncologic hematological diseases in adults and children and the analysis of published data about normal blood formation are involved into consideration. The existence is surmised of common oligo-linear precursors for B-lymphocytes and monocytes, natural killer cells and monocytes and common cell-precursor of T-lymphocytes and dendrite cells as well. At the same time, the issue concerning the existence of human common cell-precursor of lymphization capable of differentiating into Band T-lymphocytes and natural killer cells is disputable.

[Calpains: general characteristics and role in various states of the organism].

Calpains are a family of cytoplasmic calcium-dependent proteinases with papain-like activity. They participate in a variety of processes in the body: age changes, functioning of endothelium and pulmonary system, regulation of apoptosis and necrosis, development of various hypometabolic states, arterial hypertension, diabetes and chronic kidney disease, tumor growth. It is concluded that calpains, causing limited proteolysis of substrates, play an important role in a wide range of biological phenomena. Their activity is associated with the response to the calcium-dependent signaling and the effects of aging. Inhibition of calpains activity contributes to inhibition of endothelial dysfunction, cardiovascular disease, formation of structural and functional changes in the kidney tissue, has neuroprotective effect, preventing sarcopenia, reduces inflammatory reactions caused by hyperventilation of the lungs.

Wear testing of crosslinked polyethylene: wear rate variability and microbial contamination.

The wear performance of two types of crosslinked polyethylene (Marathon™ and XLK™, DePuy Synthes Inc., Warsaw, IN) was evaluated in a pin-on-disc wear tester, a hip wear simulator, and a knee wear simulator. Sodium azide was used as the microbial inhibitor in the calf serum-based lubricant. In the pin-on-disc wear tester, the Marathon wear rate of 5.33±0.54mm(3)/Mc was significantly lower (p=0.002) than the wear rate of 6.43±0.60mm(3)/Mc for XLK. Inversely, the Marathon wear rate of 15.07±1.03mm(3)/Mc from the hip wear simulator was 2.2-times greater than the XLK wear rate of 6.71±1.03mm(3)/Mc from the knee wear simulator. Differences in implant design, conformity, GUR type, and kinematic test conditions were suggested to account for the difference between the wear rates generated in the different types of wear testing apparati. In all wear tests, sodium azide was ineffective at inhibiting microbial growth in the lubricant. Eight different organisms were identified in the lubricant samples from the wear tests, which suggested the necessity of using an alternative, more effective microbial inhibitor. Careful sample preparation and thorough cleaning has shown to improve the consistency of the wear results. The wear rates generated in the hip and knee wear simulators closely reflected the wear behaviour of Marathon and XLK reported in published data that were tested under similar conditions.

In and out: an analysis of epibiotic vs periplasmic bacterial predators.

Bdellovibrio and like organisms (BALO) are obligate predators of Gram-negative bacteria, belonging to the α- and δ-proteobacteria. BALO prey using either a periplasmic or an epibiotic predatory strategy, but the genetic background underlying these phenotypes is not known. Here we compare the epibiotic Bdellovibrio exovorus and Micavibrio aeruginosavorus to the periplasmic B. bacteriovorus and Bacteriovorax marinus. Electron microscopy showed that M. aeruginosavorus, but not B. exovorus, can attach to prey cells in a non-polar manner through its longitudinal side. Both these predators were resistant to a surprisingly high number of antibiotic compounds, possibly via 26 and 19 antibiotic-resistance genes, respectively, most of them encoding efflux pumps. Comparative genomic analysis of all the BALOs revealed that epibiotic predators have a much smaller genome (ca. 2.5 Mbp) than the periplasmic predators (ca. 3.5 Mbp). Additionally, periplasmic predators have, on average, 888 more proteins, at least 60% more peptidases, and one more rRNA operon. Fifteen and 219 protein families were specific to the epibiotic and the periplasmic predators, respectively, the latter clearly forming the core of the periplasmic 'predatome', which is upregulated during the growth phase. Metabolic deficiencies of epibiotic genomes include the synthesis of inosine, riboflavin, vitamin B6 and the siderophore aerobactin. The phylogeny of the epibiotic predators suggests that they evolved by convergent evolution, with M. aeruginosavorus originating from a non-predatory ancestor while B. exovorus evolved from periplasmic predators by gene loss.

Ab initio and shell model studies of structural, thermoelastic and vibrational properties of SnO2 under pressure.

The pressure dependences of the structural, thermoelastic and vibrational properties of SnO2 in its rutile phase are studied, as well as the pressure-induced transition to a CaCl2-type phase. These studies have been performed by means of ab initio (AI) density functional theory calculations using the localized basis code SIESTA. The results are employed to develop a shell model (SM) for application in future studies of nanostructured SnO2. A good agreement of the SM results for the pressure dependences of the above properties with the ones obtained from present and previous AI calculations as well as from experiments is achieved. The transition is characterized by a rotation of the Sn-centered oxygen octahedra around the tetragonal axis through the Sn. This rotation breaks the tetragonal symmetry of the lattice and an orthorhombic distortion appears above the critical pressure P(c). A zone-center phonon of B1g symmetry in the rutile phase involves such rotation and softens on approaching Pc. It becomes an Ag mode which stabilizes with increasing pressure in the CaCl2 phase. This behavior, together with the softening of the shear modulus (C11-C12)/2 related to the orthorhombic distortion, allows a precise determination of a value for Pc. An additional determination is provided by the splitting of the basal plane lattice parameters. Both the AI and the experimentally observed softening of the B(1g) mode are incomplete, indicating a small discontinuity at the transition. However, all results show continuous changes in volume and lattice parameters, indicating a second-order transition. All these results indicate that there should be sufficient confidence for the future employment of the shell model.

Gene expression profiling of B-CLL in Ukrainian patients in post-Chernobyl period.

BACKGROUND: Genetic mechanisms that result in the development and progression of B-cell chronic lymphocytic leukemia (B-CLL) are mainly unknown. We have analyzed gene expression patterns in Ukrainian B-CLL patients with the aim of identifying B-CLL involved / associated genes in order to shed light on the biology of this pathological entity. MATERIAL AND METHODS: The samples of the peripheral blood and bone marrow of 44 Ukrainian B-CLL patients with no characteristics indicative of unfavorable course of the disease such as CD38 were analyzed morphologically and immunocytochemically according to the new WHO classification. Total RNA was isolated, and gene expression levels were determined by microarray method comparing with the sample from 17 healthy donors. RESULTS: We investigated interactions using the Ingenuity Pathway Analysis (IPA) software and found 1191 network eligible up-regulated genes and 3398 Functions/Pathways eligible up-regulated genes, 1225 network eligible down-regulated genes and 2657 Functions/Pathways eligible down-regulated genes. CONCLUSION: In B-CLL patients, gene networks around MYC, HNF1A and HNF4A, YWHAG, NF-κB1 and SP1 are identified as up-regulated; CEBPA, YWHAG, SATB1 and RB1 -- as down-regulated. G protein coupled receptor signaling, arachidonic acid and linoleic acid metabolisms, calcium signaling, metabolism of xenobiotics by cytochrome P450 are found out as significant up-regulated pathways. EIF2 and Cdc42 signaling, regulation of eIF4 and p70S6k signaling, protein ubiquitination pathway and oxidative phosphorylation are the most significant down-regulated pathways obtained in our study. The involvement of NF-κB gene network and upregulated levels of G protein coupled receptor signaling pathway, which has an important role in transcription of NF-κB, are important and need further examination.

Ab initio studies of the para- and antiferroelectric structures and local polarized configurations in NH4H2PO4.

A study of differently polarized structures relevant to the H-bonded antiferroelectric (AFE) compound NH(4)H(2)PO(4) (ADP) is performed by first-principles calculations in the framework of the density functional theory. The calculated structures for the AFE and paraelectric (PE) phases are found in general good agreement with the available experimental data. We study the energetics and relative stability of different polarized clusters embedded in a PE matrix of ADP. We find that local ferroelectric and AFE clusters are stable and may coexist in the PE phase, which explains the coexistence of both type of microregions determined by electron spin probe measurements above the AFE-PE transition temperature. The dependency with the O-H···O bridge length of the energy barrier heights for proton transfer is studied for coordinated proton displacements along the bridges within clusters of different sizes. This dependency may have implications for the geometric isotopic effects on T(c). We analyze Mulliken orbital and bond populations which confirm the existence of a charge flow within the NH(4)(+) ion, an essential fact for the stabilization of the AFE phase over other possible polarized structures. This charge transfer is correlated with the optimization of the N-H···O bridges and with distortions of the NH(4)(+) group.