Progress with the regulation of radiation safety during recovery and removal of spent nuclear fuel from the site for temporary storage at Andreeva Bay on the Kola Peninsula.

In the 1960s, a shore technical base (STB) was established at Andreeva Bay on the Kola Peninsula, in northwest Russia. The STB maintained nuclear submarines and the nuclear icebreaker fleet, receiving and storing fresh and spent nuclear fuel (SNF) as well as solid and liquid radioactive waste (RW). It was subsequently re-designated as a site for temporary storage (STS) for SNF and RW. Over time, the SNF storage facilities partly lost their containment functions, leading to radioactive contamination of workshops and the site above permitted values. The technological and engineering infrastructure at the site was also significantly degraded as well as the condition of the stored SNF. At present, the STS Andreeva Bay facility is under decommissioning. This paper describes progress with the creation of safe working measures for workers involved in site remediation and SNF recovery operations, including the determination of safe shift times in high radiation areas, as part of overall optimization of safety. Results are presented for the successful application of these measures in the period 2019-2021, during which time significant SNF recovery and removal operations were completed without incident. Significant important experience has been gained to support safe removal of remaining SNF, including the most hazardous degraded fuel, as well as recovery of other higher level RW and decommissioning of the old storage buildings and structures.

A Novel Modulator of STIM2-Dependent Store-Operated Ca2+ Channel Activity.

Store-operated Ca2+ entry is one of the main pathways of calcium influx into non-excitable cells, which entails the initiation of many intracellular processes. The endoplasmic reticulum Ca2+ sensors STIM1 and STIM2 are the key components of store-operated Ca2+ entry in mammalian cells. Under physiological conditions, STIM proteins are responsible for store-operated Ca2+ entry activation. The STIM1 and STIM2 proteins differ in their potency for activating different store-operated channels. At the moment, there are no selective modulators of the STIM protein activity. We screened a library of small molecules and found the 4-MPTC compound, which selectively inhibited STIM2-dependent store-operated Ca2+ entry (IC50 = 1 µM) and had almost no effect on the STIM1-dependent activation of store-operated channels.

[Optical coherence tomography and optical coherence tomography-angiography in the diagnosis of chiasmo-sellar region compression]. / Opticheskaya kogerentnaya tomografiya i opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike kompressii khiazmal'no-sellyarnoi oblasti.

Preservation of visual functions in patients with chiasmo-sellar region compression (CSRC) is possible with early diagnosis and surgical decompression. PURPOSE: To analyze the parameters of optical coherence tomography (OCT) and optical coherence tomography-angiography (OCTA) in patients with CSRC. MATERIAL AND METHODS: The study included 10 patients (20 eyes) with CSRC, 15 healthy volunteers (30 eyes). OCT, OCTA was performed on Cirrus HD-OCT 5000 AngioPlex™ (Carl Zeiss Meditec, U.S.A.) with AngioVue system. RESULTS: Patients with CSRC were revealed to have decreased thickness of ILM-RPE in the nasal sector of outer circle (p<0.001) and average mGCIPL - total and for all six sectors (p<0.001), decreased RNFL in the inferior sector (p=0.017); decreased superficial vessel density (SVD) and perfusion density in the inner and outer circle areas and in all sectors of the ETDRS grid (p<0.001) except temporal; in the peripapillary area, decreased vessel perfusion density (VPD) in the inferior sector (p=0.025), capillary flux index (CFI) in all sectors (p<0.001; p=0.025 in the inferior sector). Informative diagnostic criteria included ILM-RPE in nasal sector of the outer circle (AUC=0.896); mGCIPL in the inferonasal sector (AUC=0.914), average (AUC=0.846), superior (AUC=0.829) and superonasal (AUC=0.846) sectors; average SVD (AUC=0.805) and SVD in the inner circle area (AUC=0.810); CFI in the inferior sector (AUC=0.806) with p<0.001. CONCLUSION: In CSRC, changes can be seen in OCT and OCTA parameters recorded in the macular and peripapillary regions before the changes in the central visual field. Informative diagnostic OCT and OCTA criteria can help diagnose the pathology early, expand the indications for decompression, and preserve the visual funcitons.

[Mass-spectrometric MRM analysis of FDA-verified proteins in the blood plasma of healthy volunteers]. / Mass-spektrometricheskii MRM analiz FDA-verifitsirovannykh belkov v plazme krovi zdorovykh dobrovol'tsev.

The proteomic composition of a biological sample serves as the most important feature of a biological object, and it allows discriminating normal and pathological conditions. Targeted mass spectrometric analysis, namely, multiple reaction monitoring (MRM) using synthetic isotopically-labeled internal standard (SIS), is the main alternative to the ELISA method for the analysis of diagnostically significant proteins. Based on the MRM results, a prototype test system has been developed; it employs the targeted mass spectrometric method for multiplex, quantitative analysis of FDA-verified proteins in whole blood plasma. Using this approach, it was possible to measure the content of 42 proteins in 31 samples in a concentration range spanning five orders of magnitude. The interindividual variability for 30 of the 42 registered proteins was less than 40%. The largest scatter was observed for haptoglobin (68%), immunoglobulin heavy constant delta IGHD (90%), angiotensin (72%), sex hormone-binding globulin SHBG (100%) and lipoprotein-(a) (136%). The obtained results on the concentration of proteins correlate with published data (Hortin et al., 2008, Clinical Chemistry, 54, 1608) with R2=0.84. The developed prototype test system based on targeted mass spectrometric analysis of proteins can be considered as an alternative to methods using monoclonal antibodies.

Differential Expression of Local Immune Response Genes in the Vagina: Implication for the Diagnosis of Vaginal Infections.

Transcription profiles of genes of local immune response were determined in the vagina of women with bacterial vaginosis, aerobic vaginitis, and vulvovaginal candidosis for detection of the most specific immune markers for these vaginal infections. Laboratory diagnosis of the vaginal infections was performed microscopically; the inflammatory reaction in the vagina (leukorrhea) was defined as the presence of >10 white blood cells per field of view. Transcription profiles of IL1b, IL10, IL18, TNFα, TLR4, GATA3, and CD68 were determined using reverse-transcription quantitative real-time PCR. The strongest predictors of aerobic vaginitis were increased levels of IL1b and IL10 mRNA. Bacterial vaginosis was strongly associated with reduced levels of IL18 and GATA3 mRNA. Increased levels of IL1b and TLR4 transcripts showed significant discriminatory power for vulvovaginal candidosis and leukorrhea. The results of this study suggest differential expression of local immune response genes in the vagina of women with different vaginal infections. Detection of specific immune markers in the vagina using reverse-transcriptase PCR could supplement PCR detection of abnormal vaginal microflora for the diagnosis of vaginal infections.

[The role of the endothelin system in the pathogenesis of eye diseases]. / Rol' éndotelinovoi sistemy v patogeneze glaznykh boleznei.

The endothelin system (ES) plays a complex role in the pathogenesis of various eye diseases as a local regulator of vascular tone as well as many other physiological processes. Components of ES - endothelins and their receptors - can be found nearly in all cellular structures of the eye, their concentration increases in the presence of many eye diseases. In glaucoma, ES is involved in the mechanisms of eye hypertension by influencing the secretion and outflow of aqueous humor. The increase of endothelin level leads to the decrease of perfusion pressure, hypoxia, astrocyte proliferation, increase of density and rigidity of lamina cribrosa, apoptosis of neural cells, and has a profibrogenic effect. In retinal pathology, increase of endothelins disturbs autoregulation of retinal blood vessels changing the neurovascular interactions, breaks intercellular contacts in the retina, promotes neoangiogenesis. In diabetic retinopathy, ES contributes to the development of microangiopathy and proliferative vitreoretinopathy. The review discusses the possibility of correcting ES activity in the eye with medications by influencing its synthesis, cleavage and receptor binding.

Signatures of Molecular Unification and Progressive Oxidation Unfold in Dissolved Organic Matter of the Ob-Irtysh River System along Its Path to the Arctic Ocean.

The Ob-Irtysh River system is the seventh-longest one in the world. Unlike the other Great Siberian rivers, it is only slightly impacted by the continuous permafrost in its low flow. Instead, it drains the Great Vasyugan mire, which is the world largest swamp, and receives huge load of the Irtysh waters which drain the populated lowlands of the East Siberian Plain. The central challenge of this paper is to understand the processes responsible for molecular transformations of natural organic matter (NOM) in the Ob-Irtysh river system along the South-North transect. For solving this task, the NOM was isolated from the water samples collected along the 3,000 km transect using solid-phase extraction. The NOM samples were further analyzed using high resolution mass spectrometry and optical spectroscopy. The obtained results have shown a distinct trend both in molecular composition and diversity of the NOM along the South-North transect: the largest diversity was observed in the Southern "swamp-wetland" stations. The samples were dominated with humic and lignin-like components, and enriched with aminosugars. After the Irtysh confluence, the molecular nature of NOM has changed drastically: it became much more oxidized and enriched with heterocyclic N-containing compounds. These molecular features are very different from the aliphatics-rich permafrost NOM. They witnesses much more conservative nature of the NOM discharged into the Arctic by the Ob-Irtysh river system. In general, drastic reduction in molecular diversity was observed in the northern stations located in the lower Ob flow.

[Novel agonists of melatonin receptors as promising hypotensive and neuroprotective agents for therapy of glaucoma]. / Novye agonisty melatoninovykh retseptorov kak perspektivnye gipotenzivnye i neiroprotektornye sredstva dlia terapii glaukomy.

Melatonin is a pineal hormone that has a capacity to lower intraocular pressure; it exhibits neuroprotective and antioxidant properties that make it possible to use melatonin in the therapy of glaucoma. Analogs of melatonin having affinity to melatonin receptors are promising candidates for application as antiglaucomatous drugs. Chemical modification of the melatonin structure can in-crease efficiency, bioavailability and selectivity of these analogs. We have designed and synthe-sized a number of new 2-oxindole derivatives - ligands of melatonin MT3 subtype receptors that displayed ability to lower intraocular pressure in normotensive rabbits and high antioxidant activity against hydroxyl radical and superoxide anion-radical. The antioxidant activity of new ligands was several times higher than one of melatonin that makes them prospective therapeutic tools for the diseases that include oxidative stress. The maximal hypotensive effect of analogs was comparable to that of melatonin itself but prolonged. Combination of these properties gives an opportunity of using the presented melatonin analogs in complex therapy of glaucoma.

[Hemoglobin oxygen transport capacity in surgical endotoxicosis ].

In surgical endointoxication hemoglobin oxygen transport capacity of red blood cells (hemoglobin affinity ligands: the ability to bind and release ligands) is reduced and is associated with the severity of endogenous intoxication. Violation of oxygen transport function of hemoglobin at endogenous intoxication is associated with conformational changes of a biomolecule, and its possible influence on reactive oxygen species, which confirmed in experiments in vitro: under the influence of oxygen-iron ascorbate ability of hemoglobin deteriorates. Largely similar structural and functional changes in hemoglobin occur in patients with surgical endotoxicosis.

Evaluation of polymerase chain reaction assays for the diagnosis of Trichomonas vaginalis infection in Russia.

BACKGROUND: In Russia, the microscopy- and culture-based diagnostics of trichomoniasis is mainly suboptimal. Recent years, domestically produced diagnostic PCR assays have been implemented; however, any evaluation of these PCRs has never been internationally reported. OBJECTIVE: To assess the performance characteristics of PCR assays developed and currently used in Russia to detect Trichomonas vaginalis. MATERIALS AND METHODS: Five PCR assays were assessed on 448 samples (317 vaginal and 131 male urethral) collected from symptomatic attendees of youth centres (n = 415) and patients of a dermatovenereological dispensary that were previously diagnosed with trichomoniasis (n = 33). As reference assay, a sensitive and specific real-time multiplex PCR was used. RESULTS: T. vaginalis DNA was detected in five (all females) of the 415 patients of youth centres (1.2%). All 33 patients previously diagnosed at the venereological dispensary proved to be true positive. For 445 (99.3%) of these 448 samples identical results were obtained by all PCRs, 35 positive and 410 negative. The three discordant samples were positive in all PCRs except one conventional PCR assay. The sensitivities of the PCRs were 94.3-100% and 66.7-100% for vaginal and urethral swabs, respectively. All evaluated assays were 100% specific. The detection limits of the different PCRs ranged from 0.1 to 5 genome equivalents per reaction. CONCLUSION: The PCR assays currently used in Russia for the detection of T. vaginalis have in general high sensitivities and excellent specificities for both vaginal samples and urethral samples from males.

Enhanced sensitivity of nucleoli in human proliferating cells to inhibition of protein synthesis with anisomycin.

We describe the reaction of nuclei in cultured human cells from different tissues to inhibition of total protein synthesis with anisomycin - ribotoxin, which is now considered as a potential antitumor drug. It was shown that nucleoli in sensitive cells demonstrate typical reaction: under the action of the inhibitor, labile nucleolar protein, a component of RNA polymerase I transcription complex (previously called A3 antigen), rapidly migrates from the nucleolus to numerous discrete foci in the nucleoplasm. These changes are specific for translation suppression and are not induced by other influences on the cells. Migration of A3 antigen into the nucleoplasm manifests primarily in cells at the stage of DNA replication and is absent in resting cells. These results suggest that localization of A3 antigen can be a marker of artificial suppression of translation in proliferating human cells in vitro.

Changes in the status of nucleolus during long-term culturing of human HeLa cells.

Changes in the immunocytochemical status of the nucleoli during long-term (6-8 months) in vitro culturing of HeLa (carcinoma of the cervix uteri) cells were described using new A3 monoclonal antibodies selectively reacting with human cell nucleoli. The appearance of cells with abnormal location of A3 antigen was paralleled by a significant increase of culture sensitivity to some external factors (protein synthesis inhibition and oxidative stress). The data indicate that location of one of the nucleolar antigens is an indicator of the qualitative status of HeLa cells in the culture.

Prevention of human deconditioning during prolonged immersion in water.

A 56-day immersion experiment in which two subjects participated was carried out. During the experiment the preventive effect of periodic acceleration combined with exercise and water-salt intake was assessed. Simulating an increased gravitational field, exposure to acceleration increased the static component of the load upon the musculo-skeletal system, increased the gradient of the blood hydrostatic pressure, activated mechanisms responsible for the venous return to the heart, stimulated systems regulating antidiuretic and antisodiumdiuretic reflexes. Involvement of these mechanisms restored haemodynamic parameters, fluid-electrolyte balance and blood coagulability. The prophylactic effect of acceleration was enhanced if combined with exercise and supplemented water-salt intake.

Deconditioning during prolonged immersion and possible countermeasures.

Test subjects covered with a waterproof highly elastic cloth were exposed to 13-day water immersion up to the neck. They were divided into two groups. The first (control) group consisting of six persons was exposed to immersion alone and the second (experimental) group was exposed daily to accelerations of 0.6-2 Gz for 60-90 min during the last 6 days of immersion. Before and after immersion all the test subjects were exposed to +3 Gz for 5 min which served as a provocative test. These experiments give evidence that the use of dry immersion allows experimentation during prolonged immersion without concomitant complications. Variations in the physiological parameters (cardiovascular system, fluid-electrolyte balance, blood-coagulatory system) are indicative of the preventive effect of periodic accelerations during 13-day immersion.