[Anhedonia in mood disorders and somatic diseases: results of exploratory Mendelian randomization analysis]. / Angedoniya pri rasstroistvakh nastroeniya i somaticheskikh zabolevaniyakh: rezul'taty razvedochnogo Mendelevskogo randomizatsionnogo analiza.

OBJECTIVE: To conduct an exploratory Mendelian randomization analysis of the causal relationships of anhedonia with a wide range of psychiatric and somatic phenotypes based on the genetic data of participants in a population study. MATERIAL AND METHODS: This cross-sectional study included 4520 participants, of which 50.4% (n=2280) were female. The mean age was 36.8 (S.D.=9.8) years. Participants were pheno-nailed based on the DSM-5 criteria for anhedonia in the framework of depression. An episode of anhedonia exceeding 2 weeks during life was reported by 57.6% (n=2604) of participants. A genome-wide association study (GWAS) of the anhedonia phenotype was performed, as well as a Mendelian randomization analysis using summary statistics of large-scale GWASs on psychiatric and somatic phenotypes. RESULTS: The GWAS on anhedonia did not reveal the variants with genome-wide significant association (p<10-8). The most significant (p=9.71×10-7) was the variant rs296009 (chr5:168513184) in an intron of the slit guidance ligand 3 (SLIT3) gene. Using Mendelian randomization, nominally significant (p<0.05) causal associations of anhedonia with 24 phenotypes were identified, which can be divided into 5 main groups: psychiatric/neurological diseases, inflammatory diseases of the digestive system, respiratory diseases, oncological diseases and metabolic disorders. The most significant causal effects of anhedonia were found for breast cancer (p=0.0004, OR=0.9986, 95% confidence interval (CI) (0.9978-0.999)), minimal depression phenotype (p=0.009, OR=1.004, 95% CI (1.001-1.007)), as well as for apolipoprotein A (p=0.01, OR=0.973, 95% CI (0.952-0.993)) and respiratory diseases (p=0.01, OR=0.9988, 95% CI (0.9980-0.9997)). CONCLUSION: The polygenic nature of anhedonia may cause the risks of comorbidity of this phenotype with a wide range of somatic diseases, as well as may be associated with mood disorders.

[Forensic characteristics of injuries in cyclists in collisions with other vehicles]. / Sudebno-meditsinskaya kharakteristika povrezhdenii u velosipedistov pri stolknoveniyakh s drugimi transportnymi sredstvami.

In order to identify the features of the injuries formation in cyclists who were injured in a collision of moving vehicles with a blow to the rear wheel area of a bicycle moving at a slower speed in the same direction, the authors analyzed the results of forensic medical examinations in relation to 151 corpses of cyclists who died in road accidents aged 4 to 74 years. It was found that with this type of bicycle injury, the structures of the head, chest, lower extremities, as well as the structures of the abdomen were most often injured. Injuries to the structure of the head were characterized by the formation of depressed-comminuted fractures: more often frontal-temporal, less often occipital bone. Bilateral fractures of the ribs were also quite frequent types of damage, mainly the upper ribs (up to 5-6 ribs) were damaged, most often along the midclavicular and anterior axillary lines. Lung contusions have been identified in most of the injured persons with chest structure injury. Injuries to the abdominal organs and retroperitoneal space were recorded in 22.27% of cases, with liver and spleen ruptures in the majority of cases. Spinal injuries in cyclists were detected in 13.25% of cases, injuries in the cervical spine prevailed: cervico-occipital injuries and fracture-dislocations, mainly between 1-2 and 3-4 or 6-7 cervical vertebrae with separation or contusion of the spinal cord. Injuries to the structure and organs of the pelvis in road accidents in cyclists were observed very rarely, which made it possible to distinguish this type of bicycle injuries from other types of transport and blunt injuries, in particular from automobile injuries. Injuries to the structure of the limbs of the victims were noted quite often: fractures of the upper limbs occurred when falling on the road surface and injury to the lower limbs was formed both during the contact of two vehicles and when the victims fell on the road surface.

Identification of SOX2 Interacting Proteins in the Developing Mouse Lung With Potential Implications for Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia is a structural birth defect of the diaphragm, with lung hypoplasia and persistent pulmonary hypertension. Aside from vascular defects, the lungs show a disturbed balance of differentiated airway epithelial cells. The Sry related HMG box protein SOX2 is an important transcription factor for proper differentiation of the lung epithelium. The transcriptional activity of SOX2 depends on interaction with other proteins and the identification of SOX2-associating factors may reveal important complexes involved in the disturbed differentiation in CDH. To identify SOX2-associating proteins, we purified SOX2 complexes from embryonic mouse lungs at 18.5 days of gestation. Mass spectrometry analysis of SOX2-associated proteins identified several potential candidates, among which were the Chromodomain Helicase DNA binding protein 4 (CHD4), Cut-Like Homeobox1 (CUX1), and the Forkhead box proteins FOXP2 and FOXP4. We analyzed the expression patterns of FOXP2, FOXP4, CHD4, and CUX1 in lung during development and showed co-localization with SOX2. Co-immunoprecipitations validated the interactions of these four transcription factors with SOX2, and large-scale chromatin immunoprecipitation (ChIP) data indicated that SOX2 and CHD4 bound to unique sites in the genome, but also co-occupied identical regions, suggesting that these complexes could be involved in co-regulation of genes involved in the respiratory system.

[Establishment and development of forensic medicine in Uzbekistan]. / Stanovlenie i razvitie sudebnoi meditsiny v Uzbekistane.

The article analyzes and systematizes materials on the establishment and development of forensic medicine in Uzbekistan. It was noted that until the 1960-1970s, no independent forensic medical examinations were conducted in Turkestan, Uzbekistan in particular. The formation of scientific forensic medicine began with the establishment of the Uzbek National University (1918) with the Faculty of Medicine, where forensic medicine was taught. In the 1940-1950s, forensic medical examination bureaus (FME) were established in the regional centers of Uzbekistan. At present, the FME service includes the Republican Scientific and Practical Center for FME with its regional branches in Karakalpakstan and other regions, the departments of forensic medicine, and medical law of medical universities. The regulations and standards for all types of forensic examinations were fully updated in line with the Constitution of the Republic of Uzbekistan and the Forensic Science Act.

[Damage to the structures of the brain in acute carbon monoxide poisoning]. / Porazhenie struktur golovnogo mozga pri ostrom otravlenii ugarnym gazom.

OBJECTIVE: The aim of the study was to investigate the features of damage to the structures of the brain in acute carbon monoxide (CO) poisoning. The results of forensic, microscopic and morphometric studies of the brain of 78 corpses died from acute carbon monoxide poisoning are presented. The peculiarities of damage to the nervous tissue, the glial complex, as well as changes in the structures of blood vessels and the state of intravascular blood with the formation of aggregates, sludge, and blood clots were revealed. These changes along with perivascular and pericellular edema indicate the agonal death of the victims. When the carboxyhemoglobin concentration in the blood is about 30% the brain structures' lesions begin to appear; their intensity increases when the carboxyhemoglobin concentration is more than 60%. According to the authors, the substantiation of the thanatogenesis of various types of carbon monoxide poisoning requires further research taking into account the age of the victims, the carboxyhemoglobin concentration in the blood, the duration of the agonal period, as well as possible (competing) conditions: for example, acute alcohol intoxication, thermal injury, etc. Still urgent the studies of structures of other target organs of CO - heart and lungs.

Shannon Entropy as an Indicator for Sorting Processes in Hydrothermal Systems.

Hydrothermal processes modify the chemical and mineralogical composition of rock. We studied and quantified the effects of hydrothermal processes on the composition of volcanic rocks by a novel application of the Shannon entropy, which is a measure of uncertainty and commonly applied in information theory. We show here that the Shannon entropies calculated on major elemental chemical composition data and short-wave infrared (SWIR) reflectance spectra of hydrothermally altered rocks are lower than unaltered rocks with a comparable primary composition. The lowering of the Shannon entropy indicates chemical and spectral sorting during hydrothermal alteration of rocks. The hydrothermal processes described in this study present a natural mechanism for transforming energy from heat to increased order in rock. The increased order is manifest as the increased sorting of chemical elements and SWIR absorption features of the rock, and can be measured and quantified by the Shannon entropy. The results are useful for the study of hydrothermal mineral deposits, early life environments and the effects of hydrothermal processes on rocks.

SU-8 free-standing microfluidic probes.

We present a process for fabrication of free-standing SU-8 probes, with a dry, mechanical release of the final micro-devices. The process utilizes the thermal release tape, a commonly used cleanroom material, for facile heat-release from the sacrificial layer. For characterization of the SU-8 microfluidic probes, two liquid interfaces were designed: a disposable interface with integrated wells and an interface with external liquid reservoirs. The versatility of the fabrication and the release procedures was illustrated by further developing the process to functionalize the SU-8 probes for impedance sensing, by integrating metal thin-film electrodes. An additional interface scheme which contains electronic components for impedance measurements was developed. We investigated the possibilities of introducing perforations in the SU-8 device by photolithography, for solution sampling predominantly by diffusion. The SU-8 processes described here allow for a convenient batch production of versatile free-standing microfluidic devices with well-defined tip-geometry.

Regeneration of the lung: Lung stem cells and the development of lung mimicking devices.

Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as understanding the biomechanical properties to build artificial lung devices. In addition, the continuing efforts to better define the disease origin, progression and pathology by basic scientists and clinicians contributes to insights in the basic principles of lung biology. However, the use of different model systems, experimental approaches and readout systems may generate somewhat conflicting or contradictory results. In an effort to summarize the latest developments in the lung epithelial stem cell biology, we provide an overview of the current status of the field. We first describe the different stem cells, or progenitor cells, residing in the homeostatic lung. Next, we focus on the plasticity of the different cell types upon several injury-induced activation or repair models, and highlight the regenerative capacity of lung cells. Lastly, we summarize the generation of lung mimics, such as air-liquid interface cultures, organoids and lung on a chip, that are required to test emerging hypotheses. Moreover, the increasing collaboration between distinct specializations will contribute to the eventual development of an artificial lung device capable of assisting reduced lung function and capacity in human patients.

Millimeter-wave sensor based on a λ/2-line resonator for identification and dielectric characterization of non-ionic surfactants.

Studies of biological and artificial membrane systems, such as niosomes, currently rely on the use of fluorescent tags, which can influence the system under investigation. For this reason, the development of label-free, non-invasive detection techniques is of great interest. We demonstrate an open-volume label-free millimeter-wave sensing platform based on a coplanar waveguide, developed for identification and characterization of niosome constituents. A design based on a λ/2-line resonator was used and on-wafer measurements of transmission and reflection parameters were performed up to 110 GHz. Our sensor was able to clearly distinguish between common niosome constituents, non-ionic surfactants Tween 20 and Span 80, measuring a resonance shift of 3 GHz between them. The complex permittivities of the molecular compounds have been extracted. Our results indicate insignificant frequency dependence in the investigated frequency range (3 GHz - 110 GHz). Values of permittivity around 3.0 + 0.7i and 2.2 + 0.4i were obtained for Tween 20 and Span 80, respectively.

The Possible Role of Nonbilayer Structures in Regulating ATP Synthase Activity in Mitochondrial Membranes.

The effects of temperature and of the membrane-active protein CTII on the formation of nonbilayer structures in mitochondrial membranes were studied by 31P-NMR. Increasing the temperature of isolated mitochondrial fractions correlated with an increase in ATP synthase activity and the formation of nonbilayer packed phospholipids with immobilized molecular mobility. Computer modeling was employed for analyzing the interaction of mitochondrial membrane phospholipids with the molecular surface of CTII, which behaves like a dicyclohexylcarbodiimide-binding protein (DCCD-BP) of the F0 group in a lipid phase. Overall, our studies suggest that proton permeability toroidal pores formed in mitochondrial membranes consist of immobilized nonbilayer-packed phospholipids formed via interactions with DCCD-BP. Our studies support the existence of a proton transport along a concentration gradient mediated via transit toroidal permeability pores which induce conformational changes necessary for mediating the catalytic activity of ATP synthase in the subunits of the F0-F1 complex.

The Impact of ADH1B Alleles and Educational Status on Levels and Modes of Alcohol Consumption in Russian Male Individuals.

Alcohol abuse is one of the main reasons behind the low life span in Russia. Both social and genetic factors affect the alcohol consumption level. The genetic factors are alleles of the alcohol dehydrogenase ADH1B and aldehyde dehydrogenaseALDH2 genes. We have typed and found frequencies for the alleles in a cohort of 642 men, ethnic Russians. The individuals of the cohort were asked to complete a questionnaire in the framework of the Izhevsk Family Study (Leon et al., 2007, 2009) regarding the amount of alcohol consumed and on the type of hazardous alcohol consumption (nonbeverage alcohol consumption and the so-called "zapoï" which is a Russian term for a heavy drinking bout lasting for at least 2 days, when an individual is withdrawn from the normal social life). The ADH1B*48His allele was found among heterozygous individuals only (N=68, 10.6% of the cohort). The ALDH2*504Lys allele was also found among heterozygous individuals only (N=2, 0.3%) The effect of ADH1B alleles and the influence of the education level on the amount and type of alcohol consumed had not previously been studied in Russians. We have found that the amount of consumed alcohol is 21.6% lower (1733 g of ethanol per year) for ADH1B*48His allele carriers in the cohort of Russian men. The amount of consumed alcohol was found to be 9.8% lower (793 g of ethanol per year) in the case when individuals had a higher education as compared to those who had a secondary- or elementary school education level in the same cohort. Hence, the protective effect of the genetic factor (ADH1B*48His allele carriage) has proven to be more pronounced than the influence of the social factor (education level) at the individual level in the cohort of Russian men. Both factors have also proven to have a protective effect against hazardous types of alcohol consumption. Zapoï was not scored among individuals of the cohort with ADH1B*48His allele carriage (OR=12.6, P=0.006), as compared to 8.4% of "zapoï" individuals who did not carry the ADH1B*48His allele (genotype Arg/Arg).The percentage of individuals who consume non-beverage alcohol is lower (0.6%) in the subcohort of people with a higher education degree. This percentage is higher (6.0%, OR=10.0, P=0.004) in the subcohort of people without a higher education degree.

Immune response to pneumococcus and tetanus toxoid in patients with moderate-to-severe psoriasis following long-term ustekinumab use.

BACKGROUND: Little is known about the impact of long-term use of immunosuppressive agents on immune response. OBJECTIVES: Assess the impact of continuous maintenance ustekinumab treatment on patients' ability to mount immune responses to pneumococcal (T-cell-independent) and tetanus toxoid (T-cell-dependent) vaccines. PATIENTS AND METHODS: Ustekinumab-treated patients with moderate-to-severe psoriasis treated in the long-term extension of the Phase 3 PHOENIX 2 trial (n=60) were compared with control psoriasis patients not receiving systemic therapy (n=56). Patients were vaccinated with both 23-valent pneumococcal and tetanus toxoid vaccines. Serum samples collected pre-vaccination and 4 weeks post-vaccination were assessed for antibody responses. RESULTS: No differences in the ability of ustekinumab-treated patients to respond to pneumococcal or tetanus toxoid vaccinations were observed compared with controls. A ≥2-fold increase in antibody levels in ≥7 of 14 serotypes of the pneumococcal vaccine was observed in ustekinumab-treated (96.6%) and untreated control (92.6%) patients following vaccination. Ustekinumab-treated patients achieved a ≥4-fold increase (84.7%) in anti-tetanus antibody vs. 77.8% in the control group. No differences were detected in ex-vivo responses to anti-CD3/CD28 or tetanus toxoid between ustekinumab-treated and control groups. CONCLUSION: Long-term treatment (≥3 years) with ustekinumab does not compromise the immune response to T-cell-dependent/-independent vaccines in patients with moderate-to-severe psoriasis.

[Allele frequency distributions of -174G/C polymorphism in regulatory region of interleukin 6 gene (IL6) in Russian and worldwide populations].

Allele and genotype frequencies of the -174G/C polymorphism (rs1800795) in the regulatory region of the IL6 gene, which encode anti-inflammatory cytokine interleukin 6, were determined in seven populations representing five ethnic groups from the European part of Russia (440 individuals), as well as in small cohorts that represent populations from 24 countries of Africa and Eurasia (365 individuals). The maps of the geographic distribution of the -174G/C allele frequencies were constructed based on personal (22 populations) and the literature data (66 populations), and the data from dbSNP database obtained by the HapMap project (10 populations). The frequency of the -174G allele varied from 45 to 100% and was characterized by nonrandom geographic distribution. These data could reflect the adaptive load of the alleles examined, which was different in different regions of the world. It is suggested that the level of pathogen prevalence is one of the environmental factors that determine different adaptive values of the IL6*--174G/C alleles. This suggestion is supported by a positive correlation between the -174G allele frequency and level of pathogen prevalence calculated based on historical data (R = 0.768; p < 0.0001).

Pharmacodynamic assay of thymidylate synthase activity in peripheral blood mononuclear cells.

A simple, selective, and sensitive method utilizing tritium ((3)H) release from (3)H-deoxyuridine 5'-monophosphate (dUMP) substrate for accurate and precise determination of the low basal thymidylate synthase activity (TSA) in normal healthy peripheral blood mononuclear cells (PBMCs) was developed and validated. The method is based on the removal of the remaining substrate after the TSA reaction by absorption onto activated carbon and measurement of the supernatant fluid by liquid scintillation counting. The method background was substantially decreased by using lyophilized substrate and optimized binding conditions of remaining substrate onto carbon after TSA reaction. The concentration of cofactor N (5),N (10) methylene-(6R,S)-tetrahydrofolate was increased to obtain maximal TSA. Method sensitivity was further increased by omission of ethylenediaminetetraacetic acid from the reaction mix and by using longer reaction times. The validation parameters included specificity, linearity, sensitivity, precision, and stability. The lower limit of quantification was 25 µg PBMC cytosolic lysate, which released 1.4 pmol (3)H/h. TSA was stable in PBMC pellets stored for 6 months at -80 °C. The applicability of the method was demonstrated by the successful determination of TSA in PBMC cytosolic lysates from ten healthy volunteers with and without the specific TSA inhibitor FdUMP.

Three-electrode gas switches with electrodynamical acceleration of a discharge channel.

High voltage, high current, and high Coulomb transfer closing switches are required for many high power pulsed systems. There are a few alternatives for closing switches, for example, ignitrons, vacuum switches, solid-state switches, high pressure gas switches (spark gaps), and some others. The most popular closing switches up to date are spark gaps due to relatively simple design, robustness, easily field maintenance, and repair. Main drawback of spark gaps is limited lifetime, which is related directly or indirectly to erosion of the electrodes. Multichannel switches and switches with moving arc have been proposed to prevent the electrodes erosion. This study investigates switches, where a spark channel is initiated in a three-electrode layout and then the spark accelerates due to electrodynamic force and moves along the extended electrodes. At a given current amplitude, the diameter of the extended electrodes allows to control the spark velocity and hence, the erosion of the electrodes providing the required lifetime. The first switch is designed for 24 kV charging voltage and approximately 4 C total charge transfer. This spark gap was tested at 25 kA peak current in 40 000 shots in a single polarity discharge and in 20 000 shots in bipolar discharge. Second spark gap is designed for 24 kV charging voltage and approximately 70 C total charge transfer. It was tested in 22 000 shots, at a current of 250 kA with a pulse length of 360 mus. In this paper, we present design of these spark gaps and trigger generator, describe the test bed, and present the results of the tests.

[Protein kinase activity of immunoglobulins in human blood plasma].

Protein kinase activity of the immunoglobulins (Ig) fractions from blood plasma of clinically healthy humans has been studied. IgA, IgG and IgM preparations have been obtained using column chromatography on sorbents with rabbit antibody to H-chains of human Ig. The level of 32P incorporation in casein in the presence of [gamma-32P]ATP was used to determine protein kinase activity of the Ig-fractions. The protein kinase activity of the preparation of IgA (but not IgG or IgM) was defined. The high-purified preparation of IgA for studing the protein kinase activity has been obtained. Three stages of purifications were used--the separation of plasma proteins by polyethylenglycol 6000, gel-filtration on the column with Toyopearl HW-60 Fine and affinity chromatography on the column containing rabbit antibody to H-chains of human IgA. It was revealed that the fraction of IgA possesses the casein phosphorylation activity. Heparin and trifluoperazine completely and partially inhibited protein kinase activity of IgA while spermidine did not render essential influence. On the basis of the obtained results the conclusion is made that the blood of clinical by healthy humans contains IgA possessing the protein kinase activity.

[Microorganisms--degraders of polychlorinated biphenyls]. / Mikroorganzimy--destruktory polikhlorirovannykh bifenilov.

Four strains belonging to the genus Bacillus, capable of degrading polychlorinated biphenyls (PCB), were isolated by screening the collection strains of soil bacteria, degrading a organochlorine pesticide, hexachlorocyclohexane (HCCH). A method for production of tritium-labeled PCB was developed. Consumption and degradation of PCB by the soil bacterial strains selected were studied using tritium-labeled PCB and GLC. It was demonstrated that PCB are degradable both in culture media and under in model soil samples.

Cruising on the Internet highway.

This study evaluated differences in sexual behavior and risk for sexually transmitted diseases (STDs) among men who have sex with men (MSM) who met their partners on-line and those who did not. A self-administered questionnaire on sexual behavior was offered to a convenience sample of patients seeking public STD services. Thirty-two percent of MSM patients reported meeting a sexual partner over the Internet in the past year. MSM with on-line partners were younger, more likely to report sex with an HIV-positive person in the last year, and more likely to report casual partners in the last year compared with MSM with only off-line partners. HIV-negative MSM with on-line partners were more likely than HIV-negative MSM with only off-line partners to have received money or drugs for sex in the past year and to report sex with an HIV-positive partner in the past year. Although meeting partners on the Internet was common and associated with increased risk for STDs in MSM, it also presents new untapped opportunities for on-line health promotion and disease prevention.

[The hooded allele and selection of wild Norway rats Rattus norvegicus for behavior]. / Hooded allel' i otbor dikikh serykh krys (Rattus norvegicus) po povedeniiu.

Selection of wild gray rats for domestication (tame behavior) resulted in a sharp increase in the frequency of heterozygotes at the h allele of hooded, the main locus of rat depigmentation. The observed effect of the selection on the manifestation of the h allele is compared with similar effects giving rise to piebaldness in other animals subjected to experimental domestication. The results are discussed in terms of genetic specificity of piebaldness and of the selection vector.