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Abstract Influenza and SARS-CoV-2 are two major respiratory pathogens that cocirculate in humans and cause serious illness with the potential to exacerbate disease in the event of co-infection. To develop a bivalent vaccine, capable of protecting against both infections, we inserted the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein into hemagglutinin (HA) molecule or into the open reading frame of the truncated nonstructural protein 1 (NS1) of live attenuated influenza vaccine (LAIV) virus and assessed phenotypic characteristics of the rescued LAIV-RBD viruses, as well as their immunogenicity in mouse and Syrian hamster animal models. A panel of 9 recombinant LAIV-RBD viruses was rescued using the A/Leningrad/17 backbone. Notably, only two variants with RBD insertions into the HA molecule could express sufficient quantities of RBD protein in infected MDCK cells. Intranasal immunization of mice induced high levels of anti-influenza antibody responses in all chimeric LAIV-RBD viruses, which was comparable to the LAIV virus vector. The RBD-specific antibody responses were most pronounced in the variant expressing RBD194 fragment as a chimeric HA protein. This candidate was further tested in Syrian hamsters and was shown to be immunogenic and capable of protecting animals against both infections.

During a survey for helminths in reindeer (Rangifer tarandus) across the Palearctic region, eggs were found in zoo reindeer feces. These were identified as eggs of Fasciola hepatica based on their morphology, morphometrics, location, and analysis of their partial sequence of ITS rDNA region. Some of the eggs had an appendage, previously unreported. Additionally, adults of F. hepatica were studied. Eggs derived from their uteri were also appendaged. Diagnostic morphological traits of F. hepatica eggs (abopercular appendage, knob, egg shell thickening, and egg shape) are discussed in this article. Three dimensional models of F. hepatica eggs were created to demonstrate the eggs features as best as possible. Since fecal examination remains gold standard in diagnosing fasciolosis in humans and animals worldwide, our findings may contribute to improved diagnostics. This research has also shown that reindeer can be a final host for F. hepatica. We also discuss whether the Novaya Zemlya archipelago might be the northernmost site of fasciolosis.

The paper was aimed at deter­mination of the quantitative activity of iNOS and Arg1, as well as M1 and M2 phenotype macrophages in women with endometrioid disease to establish their role in the pathogenesis of endometriosis. A prospective study was performed in gynecological units of the medical facilities of Poltava city. 140 women of reproductive age who made up the main group (110 women with endometrioid disease) and the control group (30 women without endometrioid disease) voluntarily participated in the study. All women underwent planned surgical treatment for existing gynecological pathology. Before surgical treatment, women were examined in accordance with the current Orders of the Ministry of Health of Ukraine. The spectrophotometric method was used to determine the enzymatic markers of macrophages (in the endometrium and peritoneal fluid) polarized into M1(iNOS) and M2 (Arg1) phenotypes. The type of macrophages was determined individually in each patient according to the ratios: in iNOS>Arg1, the M1 macrophage type prevailed; in Arg1>iNOS, the M2 macrophage type prevailed. When examining endometrial samplings in women from the main group, the iNOS indicator was by 1.4 times higher compared to women from the control group. The obtained results at the stage of entry into the abdominal cavity showed that mostly women from the main group suffered from the pelvic adhesion, especially stage 3 and stage 4. Among the obtained results, the increased quantitative activity in the peritoneal fluid of both iNOS and Arg1 in women of the main group was significant compared to the control group. When comparing the stages of endometrioid disease to the rates of quantitative activity of macrophage enzyme markers (in peritoneal fluid), it was found that the increase in the stage of the disease (from stage 3 to stage 4) caused an increase in the quantitative activity of Arg1 by 1.9 times and a decrease in the quantitative activity of iNOS by 2.9 times. Therefore, the planning of surgical intervention for women with endometrioid disease should consider a significant percentage of the pelvic adhesive disease, especially at the severe stages. Initiation of the chronic aseptic inflammatory process in endometrioid disease is caused by an increased quantitative activity of iNOS in the endometrium. In the pathogenesis of endometrioid disease, the presence of M2 phenotype macrophages in the peritoneal fluid is important, while the switching of macrophage phenotypes from a pro-inflammatory subpopulation to an anti-inflammatory one is crucial.

Spinal muscular atrophy (SMA) is an orphan disease characterized by the progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in this study. The median duration of drug treatment was over 20 months. The application of tSCS was performed during physical therapy for 20–40 min per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, and forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both type 2 and 3 SMA participants. The magnitude of functional changes was not associated with participant age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation on SMA.

The article reviews the judicial practice on the cases of compensation of damage to water bodies resulting from oil spills, during which, as a rule, a forensic environmental examination is appointed. The author analyzes the provisions of the methodology for calculating damage to water bodies regarding violations of water legislation, which are the subject of a dispute between the plaintiff and the defendant requiring expert opinion. She also gives the most common wordings of questions for forensic environmental examinations in such cases.

Mesozoic gabbro from the Stanovoy convergent margin and adakitic dacite lava from the Pliocene–Quaternary Bakening volcano in Kamchatka contain iron–titanium oxide–apatite–sulfide–sulfate (ITOASS) microinclusions along with abundant isolated iron–titanium minerals, sulfides and halides of base and precious metals. Iron–titanium minerals include magnetite, ilmenite and rutile; sulfides include chalcopyrite, pyrite and pyrrhotite; sulfates are represented by barite; and halides are predominantly composed of copper and silver chlorides. Apatite in both gabbro and adakitic dacite frequently contains elevated chlorine concentrations (up to 1.7 wt.%). Mineral thermobarometry suggests that the ITOASS microinclusions and associated Fe-Ti minerals and sulfides crystallized from subduction-related metal-rich melts in mid-crustal magmatic conduits at depths of 10 to 20 km below the surface under almost neutral redox conditions (from the unit below to the unit above the QFM buffer). The ITOASS microinclusions in gabbro and adakite from the Russian Far East provide possible magmatic links to iron oxide–apatite (IOA) and iron oxide–copper–gold (IOCG) deposits and offer valuable insights into the early magmatic (pre-metasomatic) evolution of the IOA and ICOG mineralized systems in paleo-subduction- and collision-related geodynamic environments.

Background: Influenza viruses continue to cause a significant social and economic burden globally. Vaccination is recognized as the most effective measure to control influenza. Live attenuated influenza vaccines (LAIVs) are an effective means of preventing influenza, especially among children. A reverse genetics (RG) system is required to rapidly update the antigenic composition of vaccines, as well as to design LAIVs with a broader spectrum of protection. Such a system has been developed for the Russian LAIVs only for type A strains, but not for influenza B viruses (IBV). Methods: All genes of the B/USSR/60/69 master donor virus (B60) were cloned into RG plasmids, and the engineered B60, as well as a panel of IBV LAIV reassortants were rescued from plasmid DNAs encoding all viral genes. The engineered viruses were evaluated in vitro and in a mouse model. Results: The B60 RG system was successfully developed, which made it possible to rescue LAIV reassortants with the desired antigenic composition, including hybrid strains with hemagglutinin and neuraminidase genes belonging to the viruses from different IBV lineages. The LAIV candidate carrying the HA of the B/Victoria-lineage virus and NA from the B/Yamagata-lineage virus demonstrated optimal characteristics in terms of safety, immunogenicity and cross-protection, prompting its further assessment as a broadly protective component of trivalent LAIV. Conclusions: The new RG system for B60 MDV allowed the rapid generation of type B LAIV reassortants with desired genome compositions. The generation of hybrid LAIV reassortants with HA and NA genes belonging to the opposite IBV lineages is a promising approach for the development of IBV vaccines with broad cross-protection.

Respiratory allergy takes a significant place among allergic diseases. Similar clinical manifestations occur in sensitized patients in response to various airborne allergens. Accordingly, the allergen testing by means of in vivo and in vitro techniques is necessary to identify a causally significant allergen. The main laboratory assay to estimate sensitization to the airborne allergens is based on detection of specific immunoglobulin E (sIgE). However, clinical manifestations cannot be always confirmed by this test. The aim of this work was to evaluate the potential of basophil activation test (BAT) using flow cytometry, in order to confirm sensitization to house dust mite allergens. The BAT was carried out with allergens from Dermatofagoides in 34 volunteers, 130 patients were examined at the Russian Centre of Emergency and Radiation Medicine (33 people with household and 97 people with polysensitization), and 10 patients with allergy to house dust mites confirmed by skin testing. The sensitization was assessed using two laboratory kits (Allergenicity and BD FastImmune). The total IgE and sIgE to house dust mites, as well as concentrations of eosinophilic cationic protein, were determined. Specificity of the BAT with Allergenicity kit for the house dust mites was 94%. The sensitivity was 88% in the patients with household sensitization, thus being comparable with skin testing results available from the literature. An absolute correlation was found between positive results of skin testing and the BAT. In patients with household sensitization, sIgE levels > 0.35 UA/mL were detected in 39% of cases. A positive correlation was shown between the indices of basophil activation in response to testing allergens, and total immunoglobulin E and sIgE concentrations. High degree of correlation was found between the results of Dermatofagoides sensitization testing with both BAT kits. It was shown that the use of H1 histamine receptor blockers had no effect on BAT results. A decrease in sensitivity assay for airborne allergens was revealed upon therapy with glucocorticosteroids. Due to the proven clinical significance of the basophil activation test for diagnosing sensitization to inhaled allergens, one may require to supplement the range of approved assays in Russian Clinical Guidelines with BAT testing to prove sensitization in patients with allergic rhinitis and bronchial asthma, thus contributing to better diagnosis of causally significant allergens and, accordingly, administration of proper therapy.

Objective The semen quality of stallions including sperm motility is an important target of selection as it has a high level of individual variability. However, effects of the molecular architecture of the genome on the mechanisms of sperm formation and their preservation after thawing have been poorly investigated. Here, we conducted a genome-wide association study (GWAS) for the sperm motility of cryopreserved semen in stallions of various breeds. Methods Semen samples were collected from the stallions of 23 horse breeds. The following semen characteristics were examined: progressive motility (PM), progressive motility after freezing (FPM), and the difference between PM and FPM. The respective DNA samples from these stallions were genotyped using Axiom Equine Genotyping Array. Results We performed a GWAS search for single nucleotide polymorphism (SNP) markers and potential genes related to motility properties of frozen-thawed semen in the stallions of various breeds. As a result of the GWAS analysis, two SNP markers, rs1141327473 and rs1149048772, were identified that were associated with preservation of the frozen-thawed stallion sperm motility, the relevant putative candidate genes being NME/NM23 family member 8 (NME8), olfactory receptor family 2 subfamily AP member 1 (OR2AP1), and olfactory receptor family 6 subfamily C member 4 (OR6C4). Potential implications of effects of these genes on sperm motility are herein discussed. Conclusion The GWAS results enabled us to localize novel SNPs and candidate genes for sperm motility in stallions. Implications of the study for horse breeding and genetics are a better understanding of genomic regions and candidate genes underlying stallion sperm quality, and improvement in horse reproduction and breeding techniques. The identified markers and genes for sperm cryotolerance and the respective genomic regions are promising candidates for further studying the biological processes in the formation and function of the stallion reproductive system.

Background. Gender has now been proven to have a significant impact on the development, course and outcome of a large number of diseases, including alcoholic liver disease. Alcohol consumption is one of the leading risk factors for various diseases. Alcohol-related diseases cause 10% of all deaths worldwide among young and middle-aged people. The occurrence of renal dysfunction in cirrhosis of the liver is an integral part of the natural course of the disease. At the moment, the diagnosis of gender-specific renal dysfunction that occurs against the background of liver cirrhosis is essential for the development of effective treatment strategies and the improvement of survival.Objectives. The study is aimed at identifying the features of the gender-specific renal function and urinary syndrome in patients with liver cirrhosis of alcoholic etiology and assessing the comprehensive prognostic significance of the indicators of common urine analysis in the diagnosis of renal dysfunction.Methods. An observational study was carried out using data from medical records of 158 patients with alcoholic liver cirrhosis (95 men and 63 women), aged 36 to 72 years, who were inpatients between February 2016 and March 2020. Physical examination and laboratory diagnostic data were taken into account. Binary predictors of renal dysfunction progression in patients with alcoholic liver cirrhosis were determined based on the analysis of descriptive statistics. Statistical data processing was performed using computer program Statistica 10 (StatSoft, Inc., USA) and standard Microsoft Excel software package (Microsoft Office 2016). Non-parametric statistical methods were used to describe the results. Quantitative results were analyzed using the Mann-Whitney test; comparison of two samples by a qualitatively defined feature was performed by means of the Fisher angular transformation method. Differences were considered significant at p ˂ 0.05. A multilayer neural network function from the Statistica 10 Neural Networks software was used to construct a classification scheme for renal dysfunction (yes/no). Neural network performance was assessed using descriptive and inductive statistics, calculating sensitivity, specificity, performing ROC analysis and constructing cumulative gains charts.Results. A renal function test revealed a significant decrease in glomerular filtration rate (p = 0.029) and a significant increase in urinary albumin/creatinine ratio (p < 0.0001) in women with alcoholic liver cirrhosis as compared with men. Women are also reported to have a high incidence of proteinuria, leukocyturia and bacteriuria. According to ROC-analysis, the urinalysis indicators have a high prognostic significance in identifying renal dysfunction in men and women with alcoholic liver cirrhosis (AUROC = 0.902 and sensitivity 81.82%, AUROC = 0.881 and sensitivity 75.00%, respectively).Conclusion. Renal dysfunction develops earlier and occurs twice as often in women with alcoholic cirrhosis than in men of the same age. The application of a neural network mechanism to predict renal dysfunction in men and women with alcoholic liver cirrhosis according to the indicators of urinalysis provides a high prognostic ability.

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain that has naturally high pathogenic properties in mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced. SA-M5 lost E358E/K heterogeneity and retained E358, which is the prevalent amino acid at this position among H1N1pdm09 strains. In addition, in the hemagglutinin of SA-M5, two heterogeneous substitutions (G155G/E and S190S/R) were identified. Both viruses, SA-M5 and SA-WT, were compared for their toxicity, ability to replicate, pathogenicity, and immunogenicity in mice. In mice infected with SA-M5 or SA-WT strains, toxicity, virus titer in pulmonary homogenates, and mouse survival did not differ significantly. In contrast, an increase in the immunogenicity of SA-M5 compared to SA-WT was observed. This increase could be due to the substitutions G155G/E and S190S/R in the HA of SA-M5. The prospects for using SA-M5 in studying the immunogenicity mechanisms were also discussed.

Iron and iron–manganese deposits form three closely spaced clusters within the Lesser Khingan Range of the Russian Far East. Fe-Mn mineralization is hosted in Vendian–Cambrian carbonates and composed of magnetite, hematite, braunite, haussmanite, rhodochrosite and pyrolusite. The iron–manganese ores are closely associated with explosive intermediate–felsic breccias, magnetite-rich lavas, dolerites and mineralized lithocrystalloclastic tuffs. Magmatic rocks display both concordant and discordant relationships with Fe-Mn mineralization and contain abundant xenoliths of host carbonates. Both magmatic rocks (with the exception of Nb-enriched dolerites) and Fe-Mn ores are characterized by variable enrichments in large-ion lithophile and light rare earth elements and strong depletions in high-field strength elements compatible with the broad subduction setting for explosive volcanism and associated hydrothermal Fe-Mn ore mineralization. Nd-Sr isotope systematics suggest contamination by both ancient and juvenile continental crust and the involvement of recycled pelagic sediment in the formation of Fe-Mn deposits in the Lesser Khingan Range of the Russian Far East.

Globally, preschool enrollment has surged, but its quality is often poor. We evaluate strategies to improve quality of public preschools in Colombia. The first, designed by the government and rolled out nationwide, provided extra funding, mainly earmarked for hiring teaching assistants. The second also offered low-cost training for existing teachers. The first intervention had no effect on child development, while the second improved children's cognitive development, especially for more disadvantaged children. This pattern can be explained by the interventions affecting teachers' behavior differently. The first led teachers to reduce their classroom time, including learning activities, while additional training offset the adverse effect on learning activities and improved teaching quality. [ABSTRACT FROM AUTHOR]

Introduction Many children in developing countries grow up in environments that lack stimulation, leading to deficiencies in early years of development. Several efficacy trials of early childhood care and education (ECCE) programmes have demonstrated potential to improve child development; evidence on whether these effects can be sustained once programmes are scaled is much more mixed. This study evaluates whether an ECCE programme shown to be effective in an efficacy trial maintains effectiveness when taken to scale by the Government of Ghana (GoG). The findings will provide critical evidence to the GoG on effectiveness of a programme it is investing in, as well as a blueprint for design and scale-up of ECCE programmes in other developing countries, which are expanding their investment in ECCE programmes.Methods and analysis This study is a cluster randomised controlled trial, in which the order that districts receive the programme is randomised. A minimum sample of 3240 children and 360 schools will be recruited across 72 district school cohort pairs. The primary outcomes are (1) child cognitive and socioemotional development measured using the International Development and Early Learning Assessment tool, the Strengths and Difficulties Questionnaire, and tasks from the Harvard Laboratory for Development Studies; (2) child health (measured using height/weight for age, height-for-weight Z scores). Secondary outcomes include (1) maternal mental health, (using Kessler-10 and Warwick Edinburgh Mental Wellbeing Scale) and knowledge of ECCE practices; (2) teacher knowledge, motivation and teaching quality (measured with classroom observation); (3) parental investment (using the Family Care Index and Home Observation Measurement of the Environment and the Child–Parent Relationship Scale); (4) water, sanitation, and hygiene (WASH) practices; (5) acute malnutrition (using mid-upper arm circumference). We will estimate unadjusted and adjusted intent-to-treat effects.Ethics and dissemination Study protocols have been approved by ethics boards at the University College London (21361/001), Yale University (2000031549) and Ghanaian Health Service Ethics Review Committee (028/09/21). Results will be made available to participating communities, funders, the wider public and other researchers through peer-reviewed journals, conference presentations, social and print media and various community/stakeholder engagement activities.Trial registration number ISRCTN15360698, AEARCTR-0008500.

Children from low socio-economic status (SES) households often demonstrate worse growth and developmental outcomes than wealthier children, in part because poor children face a broader range of risk factors. It is difficult to characterize the trajectories of SES disparities in low- and middle-income countries because longitudinal data are infrequently available. We analyze measures of children's linear growth (height) at ages 1, 5, 8 and 12y and receptive language (Peabody Picture Vocabulary Test) at ages 5, 8 and 12y in Ethiopia, India, Peru and Vietnam in relation to household SES, measured by parental schooling or household assets. We calculate children's percentile ranks within the distributions of height-for-age z-scores and of age- and language-standardized receptive vocabulary scores. We find that children in the top quartile of household SES are taller and have better language performance than children in the bottom quartile; differences in vocabulary scores between children with high and low SES are larger than differences in the height measure. For height, disparities in SES are present by age 1y and persist as children age. For vocabulary, SES disparities also emerge early in life, but patterns are not consistent across age; for example, SES disparities are constant over time in India, widen between 5 and 12y in Ethiopia, and narrow in this age range in Vietnam and Peru. Household characteristics (such as mother's height, age, and ethnicity), and community fixed effects explain most of the disparities in height and around half of the disparities in vocabulary. We also find evidence that SES disparities in height and language development may not be fixed over time, suggesting opportunities for policy and programs to address these gaps early in life.

The Ildeus mafic–ultramafic complex represents plutonic roots of a Triassic magmatic arc tectonically emplaced into the thickened uppermost crust beneath the Mesozoic Stanovoy collided margin. The mafic–ultramafic complex cumulates host Ni-Co-Cu-Pt-Ag-Au sulfide-native metal-alloy mineralization produced through magmatic differentiation of subduction-related primary mafic melt. This melt was sourced in the metal-rich sub-arc mantle wedge hybridized by reduced high-temperature H-S-Cl fluids and slab/sediment-derived siliceous melts carrying significant amounts of Pt, W, Au, Ag, Cu and Zn. Plutonic rocks experienced a pervasive later-stage metasomatic upgrade of the primary sulfide–native metal–alloy assemblage in the presence of oxidized hydrothermal fluid enriched in sulfate and chlorine. The new metasomatic assemblage formed in a shallow epithermal environment in the collided crust includes native gold, Ag-Au, Cu-Ag and Cu-Ag-Au alloys, heazlewoodite, digenite, chalcocite, cassiterite, galena, sphalerite, acanthite, composite Cu-Zn-Pb-Fe sulfides, Sb-As-Se sulfosalts and Pb-Ag tellurides. A two-stage model for magmatic–hydrothermal transport of some siderophile (W, Pt, Au) and chalcophile (Cu, Zn, Ag) metals in subduction–collision environments is proposed.

Igneous rocks from the Russian Far East contain Cu-Ag-Au microspherules with distinct exterior and interior structures, compositions and assemblages of Cu-rich micro-inclusions. Natural microspherules are compared in this study with technogenic Cu-Ag-Au microspherules, which are experimentally produced and extracted from gold scrap jewelry. The following set of diagnostic criteria are considered to distinguish natural from technogenic microspherules on a genetic basis as follows: (1) compacted-related features versus cellular appearance of the exterior; (2) lack of exsolution- or crystallization-related features in natural and domain-type internal structure in technogenic microspherules; (3) absence of spherical copper-oxide inclusions along with meniscus-type textural boundaries in technogenic mcirospherules; (4) pure copper-oxide composition of inclusions versus the common presence of Fe, Ni, Zn, Cu and Na in natural microspherules. The diagnostic characteristics of natural Cu-Ag-Au microspherules suggest extremely fast cooling rates during their formation, which is possible during violent explosive volcanic eruptions or injection of partially molten, pulverized metal alloys into shallow intra-crustal cavities and fault-related tectonic gashes.