The levels of relaxin and amino acids play a critical role in women with variable degree of preparedness for labour

Underlying biochemical factors that contribute towards the preparedness for labour and ripening of the cervix remain largely unknown. We aimed to characterize metabolic and hormonal determinants that constitute the preparedness for labour in women. The aim of the research was to study the content of relaxin and amino acids involved in its formation in primiparous pregnant women with various degrees of birth preparedness. Materials and methods: Prospective study has been conducted on 115 primiparous women at 38-40 weeks of gestation. Biochemical methods were used to analyse relaxin and amino acid levels in pregnant women with varying degree of birth preparedness. Results: the obtained data from the study indicate importance role of relaxin in the underlying pathogenesis in women with variable degree of preparedness for labour. The results allow to use the levels of relaxin serum as a predictor of the state of the birth canal. Furthermore, the amino acids are known to participate in various critical metabolic processes and play an important role is orchestrating many essential pathways in the body. We present the analysis of amino acids involved in the formation of relaxin in the serum of pregnant women. Our analysis has shown that amino acid imbalance leads to disruption of energy metabolism and blood flow rate, resulting in metabolic, structural and functional changes in the cervix at the onset of labour. Conclusion: considering the mechanisms of the possible influence of relaxin and amino acids on the cervical ripening, we concluded that correcting amino acid imbalance and normalising relaxin levels should be included in preinduction of labour therapeutic regimen. This would be an important step in improving the perinatal outcome

Development of a high temperature treatment device for spent nuclear fuel

Novel reprocessing schemes and techniques are the focus of the Euratom FP7 project "Actinide Recycling for Separation and Transmutation” (ACSEPT), where the Paul Scherrer Institute (PSI) is represented in the pyrochemical domain. The subject of investigation is the selective separation of fission products (FPs) from spent nuclear fuel as a head-end step to either classical hydro based or pyro processes which are not yet applied on a large scale. The selective removal of FPs that are major contributors to the overall radiation dose or bear great potentials in terms of radiotoxicity (i.e. cesium or iodine), is advantageous for further processes. At PSI a device was developed to release volatile FPs by means of inductive heating. The heating up to 2,300°C promotes the release of material that is further transported by a carrier gas stream into an inductively coupled plasma mass spectrometer for online detection. The carrier gas can be either inert (Ar) or can contain reducing or oxidizing components like hydrogen or oxygen, respectively. The development of the device by computer aided engineering approaches, the commissioning and evaluation of the device and data from first release experiments on a simulated fuel matrix are discusse

Polarization of macrophages of mice under the influence of lectin from Bacillus subtilis IMV B-7724

Macrophages (Mph) are highly plastic cells that are able to change their functional activity (polarization) and perform their functions in different physiological and pathological processes (including cancer). Changes in the functional activity of Mph can occur due to the action of a number of external stimuli (cytokines, colony-stimulating factors, products of microbial synthesis, etc.). The aim of the research was to study the effect of lectin from B. subtilis IMV B-7724 on the state of macrophage polarization in intact mice of the Balb/c strain. The cytotoxic effect of lectin from B. subtilis IMV B-7724 on the peritoneal Mph of intact Balb/c mice was evaluated in vitro; indices, characterizing the functional activity of Mph with M1 and M2 phenotypes and the levels of STAT-1 and STAT-6 mRNA expression, were determined. We have shown that the effect of bacterial lectin on peritoneal Mph is concentration-dependent: ≥0.1 mg/ml is cytotoxic while 0.02 and 0.05 mg/ml is stimulating. At low concentrations of lectin there is observed a significant increase in the ratio of NO production to the arginase activity of Mph (NO/Arg), which is characteristic of Mph with the M1 phenotype. Changes in the expression of STAT transcription factors under the influence of the lectin were similar to the changes, found under the combined action of LPS and IFN-γ on Mph. The detected changes in the functional activity of peritoneal Mph of intact mice under the influence of low concentrations of the lectin may be due to the changes in the expression of transcription factors of the JAK-STAT signaling pathway. Understanding the mechanisms of action of lectin from B. subtilis IMV B-7724 on Mph will open new perspectives for their modulation/polarizatio

Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations

Background: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. Objective: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. Methods: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kappa B) signaling. Results: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-kappa B1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. Conclusions: We present a comprehensive clinical overview of the NF-kappa B1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-kappa B1 pathway-targeted therapeutic strategies should be considered in the future.Peer reviewe

A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Geneenvironment interactions (G x E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G x E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G x E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G x E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant GxBMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer

Application of layered double hydroxides for Tc-99 immobilization

99Tc is a long-lived (T1/2=2.13•105 y) fission product (FP) of the nuclear fuel cycle (NFC). As a component of nuclear wastes it remains a FP of concern for the safety assessment of a final disposal site. In the heptavalent form Tc(VII)O4-, it is well soluble, poorly sorbed and hence, a highly mobile anion in the environment . A number of strategies have been proposed to reduce 99Tc mobility by irreversible incorporation into the structure of ubiquitous mineral. We have recently demonstrated the incorporation of TcO4- in layered double hydroxides (LDH) that were earlier proposed for 79Se and 129I remediation in water treatment technology.This work is focused on the interaction of 99Tc(VII) with Pyroaurite (PyA) and Hydrotalcite (HTC) - Mg-Fe and Mg-Al LDHs respectively, on simplified CO2- and O2-free conditions. Earlier experiments with Re(VII), considered to be a chemical analogue for 99Tc(VII), have demonstrated little to no uptake of Re(VII). Similar experiments with 99Tc(VII) however have shown a significant increase in 99Tc uptake on LDHs even in the concurrency with CO32- ions. Subsequent leaching experiments have revealed the irreversible character of 99Tc(VII)-LDH compound. Modern spectroscopic methods are applied in order to understand how 99Tc is accommodated in between the brucite layers of LDHs and whether 99Tc(VII) is reduced to Tc(IV). This information will help to verify, whether LDHs can be used as a host phase for 99Tc long-term and safe storage. Additionally, these data aquired on controlled conditions can be used for modelling of 99Tc geochemical behavior in more complex repository relevant systems

Comprehensive study of the Tobias Creek valley following the development of the Krasnaya Polyana mountain resort

The impact of environmental management on water quality carried out in the Tobias Creek watershed area and that of geological processes occurring in the given geoecosystems have been studied. The survey based on a basin approach was performed at a watercourse located in a mountainous tourist area under recreational pressure, the latter has been significantly increasing recently due to increasing domestic tourism. The types of hazardous exogenous geological processes affecting the natural environment (including water sources) and economic activities have been identified: linear and planar erosion, landslides, creep, and mudflows. The “hotel complex” and “ski slopes combined with hiking tourist routes” had the greatest negative impact on the natural environment out of the eleven types of territorial environmental management identified by experts. The ecosystem components “flora” and “soil” were subject to the greatest anthropogenic impact. The environmental conditions deteriorated gradually from the creek source to its mouth as followed by bioindication and biotesting. A comparison of geological and anthropogenic factors and the processes occurring in the catchment area within the defined ecological zones allowed us to conclude that biological parameters reflecting processes in the aquatic ecosystems may be used as indicators of the state of the natural environment

Analysis of the 207Bi, 194Hg/Au and 173Lu distribution in the irradiated MEGAPIE target

Samples obtained from different locations within the prototype liquid metal spallation target MEGAPIE irradiated in 2006 at PSI were analysed using γ-spectrometry. A variety of radionuclides formed by reaction of the target material, lead–bismuth eutectic (LBE), with the proton beam and secondary particles were identified. While nuclides representing the target material itself (207Bi) and nuclides of noble metals were found in LBE samples throughout the target, nuclides of electropositive metals were found to be quantitatively deposited on free surfaces and material interfaces within the target system. This behaviour is analysed in more detail based on results obtained for three nuclides representing groups of elements with distinct chemical behaviour, namely 207Bi, 194Hg/Au and 173Lu. Quantitative analysis results are given and compared with predictions obtained using nuclear physics calculations for those nuclides showing rather homogeneous distribution within the target. Possible reasons for the separation of radionuclides from the liquid metal and their deposition on surfaces are given, and consequences arising for nuclear facilities utilizing liquid metals are discussed