Drawbacks and Unexpected Advantages of the Response to Modeling Posttraumatic Stress Disorder in Old Wistar Rats.

In modeling post-traumatic stress disorder (PTSD), old Wistar rats exhibit the same general signs of a PTSD-like condition as young rats do. The ratio of testosterone to corticosterone levels was assessed as a new index and proved to provide a guideline for dividing the rat population into low- and high-anxiety groups when modeling PTSD. Several features were observed in behavior, psycho-emotional manifestations, hormone levels, and myocardial state in old rats. A sharp rise in circulating testosterone was for the first time shown to occur in old, but not young, rats in stress, contributing to a more rapid decision as to where to move in the labyrinth space. Priority data were obtained on dysfunctional accumulation of mitochondria in the myocardium in intact and stressed old rats. The information obtained may be useful in developing drugs against harmful consequences of PTSD and senile changes in the myocardium.

Role of Neurohumoral Imbalance at Post-Traumatic Stress Disorder in the Antitumor Immune Response. Experimental Study.

The aim of the study is to investigate the growth and development of B16 melanoma in mature male C57Black/6 mice with a post-traumatic stress disorder (PTSD) model. Behavioral, immunohistochemical, morphometric methods, enzyme immunoassay were used. A forced decrease in the level of corticosterone, which is characteristic for PTSD, was established, followed by intensification of the production of increased concentrations of pro-inflammatory interleukins by the cells of the immune system and, at the same time, a decrease in the secretion of anti-inflammatory cytokines. Priority data were obtained: the neurohumoral imbalance that develops in PTSD is a limiting factor to the growth of B16 melanoma, at least at the initial stages of the oncological process.

Imaging x-ray spectrometer at the high energy density instrument of the European x-ray free electron laser.

A multipurpose imaging x-ray crystal spectrometer is developed for the high energy density instrument of the European X-ray Free Electron Laser. The spectrometer is designed to measure x rays in the energy range of 4-10 keV, providing high-resolution, spatially resolved spectral measurements. A toroidally bent germanium (Ge) crystal is used, allowing x-ray diffraction from the crystal to image along a one-dimensional spatial profile while spectrally resolving along the other. A detailed geometrical analysis is performed to determine the curvature of the crystal. The theoretical performance of the spectrometer in various configurations is calculated by ray-tracing simulations. The key properties of the spectrometer, including the spectral and spatial resolution, are demonstrated experimentally on different platforms. Experimental results prove that this Ge spectrometer is a powerful tool for spatially resolved measurements of x-ray emission, scattering, or absorption spectra in high energy density physics.

Characteristic of Ultrastructure of Mice B16 Melanoma Cells under the Influence of Different Lighting Regimes.

Circadian rhythms of physiological processes, constantly being in a state of dynamic equilibrium and plastically associated with changes in environmental conditions, are the basis of homeostasis of an organism of human and other mammals. Violation of circadian rhythms due to significant disturbances in parameters of main environmental effectors (desynchronosis) leads to the development of pathological conditions and a more severe course of preexisting pathologies. We conducted the study of the ultrastructure of cells of mice transplantable malignant melanoma B16 under the condition of normal (fixed) lighting regime and under the influence of constant lighting. Results of the study show that melanoma B16 under fixed light regime represents a characteristic picture of this tumor-predominantly intact tissue with safe junctions of large, functionally active cells with highly irregular nuclei, developed organelles and a relatively low content of melanin. The picture of the B16 melanoma tissue structure and the ultrastructure of its cells under the action of constant lighting stand in marked contrast to the group with fixed light: under these conditions the tumor exhibits accelerated growth, a significant number of cells in the state of apoptosis and necrosis, ultrastructural signs of degradation of the structure and functions, and signs of embryonization of cells with the background of adaptation to oxygen deficiency.

Phenotypically Determined Liver Dysfunction in a Wistar Rat Model of Post-Traumatic Stress Disorder.

The extraordinary situation of the 2019-2022 pandemic caused a dramatic jump in the incidence of post-traumatic stress disorder (PTSD). PTSD is currently regarded not only as a neuropsychiatric disorder, but also as a comorbidity accompanied by cardiovascular diseases, circulatory disorders, liver dysfunction, etc. The relationship between behavioral disorders and the degree of morphofunctional changes in the liver remains obscure. In this study, PTSD was modeled in sexually mature male Wistar rats using predatory stress induced by a prey's fear for a predator. Testing in an elevated plus maze allowed the rat population to be divided into animals with low-anxiety (LAP) and high-anxiety (HAP) phenotypes. It was found that morphofunctional analysis of the liver, in contrast to its biochemical profiling, provides a clearer evidence that predatory stress induces liver dysfunction in rats of both phenotypes. This may indicate a decrease in the range of compensatory adaptive reactions in stressed animals. However, in HAP rats, the level of morphofunctional abnormalities in the mechanisms responsible for carbohydrate-fat, water-electrolyte and protein metabolism in the liver testified the prenosological state of the organ, while further functional loading and resulting tension of the regulatory systems could lead to homeostatic downregulation. Meanwhile, the liver of LAP animals was only characterized by insignificant diffuse changes. Thus, we demonstrate here a link between behavioral changes and the degree of morphofunctional transformation of the liver.

Two-Color Soft X-Ray Lasing in a High-Density Nickel-like Krypton Plasma.

We report evidence of strong lasing on the 4p-4s transition at 62.7 nm in nickel-like krypton occurring simultaneously with the usual 4d-4p lasing at 32.8 nm. The gain dynamics of both transitions were experimentally and numerically investigated and found comparable. The two-color amplifier was seeded by the same harmonic pulse, therefore producing a short-duration coherent two-color soft x-ray laser pulse. Both transitions offer similar prospects of pulse energy and duration and could lead to the delivery of intense and ultrashort two-color coherent soft x-ray pulses with a controllable delay.

Expansion of the "Sodium World" through Evolutionary Time and Taxonomic Space.

In 1986, Vladimir Skulachev and his colleagues coined the term "Sodium World" for the group of diverse organisms with sodium (Na)-based bioenergetics. Albeit only few such organisms had been discovered by that time, the authors insightfully noted that "the great taxonomic variety of organisms employing the Na-cycle points to the ubiquitous distribution of this novel type of membrane-linked energy transductions". Here we used tools of bioinformatics to follow expansion of the Sodium World through the evolutionary time and taxonomic space. We searched for those membrane protein families in prokaryotic genomes that correlate with the use of the Na-potential for ATP synthesis by different organisms. In addition to the known Na-translocators, we found a plethora of uncharacterized protein families; most of them show no homology with studied proteins. In addition, we traced the presence of Na-based energetics in many novel archaeal and bacterial clades, which were recently identified by metagenomic techniques. The data obtained support the view that the Na-based energetics preceded the proton-dependent energetics in evolution and prevailed during the first two billion years of the Earth history before the oxygenation of atmosphere. Hence, the full capacity of Na-based energetics in prokaryotes remains largely unexplored. The Sodium World expanded owing to the acquisition of new functions by Na-translocating systems. Specifically, most classes of G-protein-coupled receptors (GPCRs), which are targeted by almost half of the known drugs, appear to evolve from the Na-translocating microbial rhodopsins. Thereby the GPCRs of class A, with 700 representatives in human genome, retained the Na-binding site in the center of the transmembrane heptahelical bundle together with the capacity of Na-translocation. Mathematical modeling showed that the class A GPCRs could use the energy of transmembrane Na-potential for increasing both their sensitivity and selectivity. Thus, GPCRs, the largest protein family coded by human genome, stem from the Sodium World, which encourages exploration of other Na-dependent enzymes of eukaryotes.

Potassium Salt of Fullerenylpenta-N-Dihydroxytyrosine Effects on Type 2 Diabetes Mellitus Therapeutic Targets.

It was shown for the first time that pentaamino acid derivative of fullerene C60 (potassium salt of fullerenylpenta-N-dihydroxytyrosine) affects three targets of type 2 diabetes mellitus. It competitively inhibits the enzymes aldose reductase and sorbitol dehydrogenase and also has an antiglycation effect on bovine serum albumin. The inhibition constants for these enzymes were calculated.

CYTOGENETIC BIODOSIMETRY OF ACCIDENTAL EXPOSURES IN THE LONG TERMS AFTER IRRADIATION.

The group of radiation victims who had received radiation injures similar to those of Chernobyl accident victims was evaluated in terms of retrospective cytogenetic biodosimetry in the long term period of from 17 y up to 50 y after irradiation. Based on the existing results of the long-term cytogenetic examination of the victims injured after the Chernobyl accident, an original method was developed. This method of retrospective dose recovery was based on the use of a special computer program, the time elapsed after irradiation and the frequency of atypical chromosomes. Both patient groups were examined using conventional cytogenetic analysis. The new method of a retrospective biodosimetry was tested on the non-Chernobyl group. As a result the multiple regression equations which included frequency atypical chromosomes produced better results because the majority of the estimates of the retrospective doses fell into the 95%-prediction intervals for the reference group of the Chernobyl victims.

[Effect of dental implants with conditioned surface based on sodium hydroxide in patients with osteoporosis]. / Otsenka éffektivnosti primeneniia dental'nykh implantatov s konditsionirovannoi poverkhnost'iu na osnove gidroksida natriia u patsientov s osteoporozom.

The problem of improving the efficiency of implantological treatment of patients with osteoporosis (OP) today remains relevant due to the high frequency of postoperative complications. Among the main factors affecting the success of dental implant treatment, the nature of the implant surface is essential. Patients with adentia and OP especially relevant in use of dental implants with optimized surface, air conditioned component influencing bone remodelling. OBJECTIVE: Evaluation of the effectiveness of dental implants with a conditioned surface based on sodium hydroxide in men with osteoporosis. MATERIAL AND METHODS: The study included 60 men 54-65 years of age in need of dental implants of which 40 were diagnosed with OP. Patients with OP were divided into groups: I - 20 men without antiresorptive therapy; II - 20 men taking ibandronate 150 mg monthly, calcium and vitamin D (1000 mg/800 IU daily). The control group consisted of 20 men 54-65 years without OP. Microarchitectonics of the mandible was studied using cone-beam computed tomography and histomorphometry. Implants with bioactive surface based on sodium hydroxide (NaOH) were used. RESULTS: The results showed that the success of osseointegration is due to the qualitative parameters of the bone tissue of the perceived bed and the initial level of remodeling processes and does not depend on the conditioning of the implant surface NaOH. Comprehensive antiosteoporotic therapy with bisphosphonates and calcium supplementation with vitamin D leads to restoration of micro-alveolar part.

[Features of restoration of chewing efficiency in patients over 50 years with complete absence of teeth and alveolar bone atrophy.]

The base of osteoporosis is an imbalance of bone remodeling processes, with a predominance of the resorption phase that in the maxillofacial region is manifested by a partial and complete absence of teeth with a decrease in the volume of bone tissue of the jaws and a violation of its microarchitectonics. Atrophy of the alveolar bone reduces the degree of fixation of the removable prosthesis, can develop various diseases of the underlying mucosa. In this regard, the installation of dental implants as a support for removable orthopedic structures is relevant, however, in patients with osteoporosis, the risk of complications in the early and late postoperative period remains high to 44%. Objective: to improve the efficiency of dental implantation in patients with osteoporosis. 80 men over 50 years old with complete absence of teeth on the lower jaw with alveolar atrophy and osteoporosis were under observation. Carried out condition monitoring of the micro alveolar bone in patients with osteoporosis without a comprehensive antiosteoporotic therapy and in patients receiving ibandronate for 1 tablet (150 mg), 1 time a month with calcium 1 000 mg and vitamin D (cholecalciferol) 800 IU daily. It was found that taking antiresorptive therapy for 3 months improves the quality of the alveolar bone, increases the effectiveness of dental implantation in patients with complete absence of teeth and atrophy of the alveolar part.

Pulse duration of a partially coherent soft X-ray laser estimated from far-field speckle statistics.

A novel method for estimating the pulse duration of partially coherent soft X-ray pulses from a far-field intensity pattern is presented. The method is based on intensity statistics at a single point in space and time, which allows the number of coherent longitudinal modes to be measured. Utilizing the knowledge of the coherence time of the radiation, either from the measurement of the spectral bandwidth or from numerical simulations, the duration of each individual pulse can be evaluated. This method was used to estimate the pulse duration of the laser-driven nickel-like molybdenum soft X-ray laser that is based on amplified spontaneous emission from a narrow plasma column and emits at a wavelength of 18.9 nm. By varying the length of the gain medium, a clear dependence of the number of modes caused mainly by the spectral line narrowing was observed. Supported by simulations of radiative transfer and pulse propagation, the pulse duration at the end of a 3 mm long gain medium was estimated to be 3.5 ps. The experimental data from far-field intensity patterns were also analyzed by applying the generalized van Cittert-Zernike theorem, providing a lower bound of effective source size.

ACUTE MYELOID LEUKEMIA, PROSTATE AND SKIN CANCER IN ACUTE RADIATION SYNDROME SURVIVOR AFTER THE 1986 CHERNOBYL NUCLEAR ACCIDENT: CASE REPORT.

The development of hemoblastosis is often associated with the influence of various genotoxic unfavorable factors, in particular, with the effect of ionizing radiation. This article presents a case report of acute myeloid leukemia (AML) in a patient who was involved in the 1986 accident at the Chernobyl Nuclear Power Plant and suffered an acute radiation syndrome of degree II severity. Based on clinical and cytogenetic dosimetry, the average absorbed radiation dose to the whole body was estimated to be 4.3 Gy. During long-term clinical follow-up (27 years), moderate transient instability of hematological parameters was observed: lymphocytosis, leukopenia and thrombocytopenia, which was associated with chronic viral hepatitis C. Further cytogenetic investigations demonstrated a very high frequency of translocations, up to 50 times background values, that persisted over 3 decades. In 2014, the patient was diagnosed and operated on for prostate cancer and received a course of radiotherapy (total fractionated local dose of 35 Gy) in May 2015. From December 2015 through April 2016, the patient experienced general weakness and developed progressive cytopenia. A diagnosis of AML, resulting from a myelodysplastic syndrome, was confirmed by abnormal complex clones detected in 38% of metaphases by the mFISH-method, along with other chromosomal rearrangements. The patient underwent several chemotherapy treatments for AML but eventually died of bilateral pneumonia in March 2017.

Counterpropagating Radiative Shock Experiments on the Orion Laser.

We present new experiments to study the formation of radiative shocks and the interaction between two counterpropagating radiative shocks. The experiments are performed at the Orion laser facility, which is used to drive shocks in xenon inside large aspect ratio gas cells. The collision between the two shocks and their respective radiative precursors, combined with the formation of inherently three-dimensional shocks, provides a novel platform particularly suited for the benchmarking of numerical codes. The dynamics of the shocks before and after the collision are investigated using point-projection x-ray backlighting while, simultaneously, the electron density in the radiative precursor was measured via optical laser interferometry. Modeling of the experiments using the 2D radiation hydrodynamic codes nym and petra shows very good agreement with the experimental results.

Sex-Related Characteristics of Systemic Hormonal Homeostasis in Rats with Sarcoma C-45 Cells Transplanted to the Lung.

Sex-related systemic status of pituitary and thyroid hormones and cortisol was studied in rats on days 7 and 14 after transplantation of sarcoma C-45 cells into the lung. Females demonstrated slower development of the tumor process (49.0±10.7 vs. 32.0±3.9 days in males). Injection of tumor cells causes similar disorders in the levels of ACTH, thyrotropic hormone, and prolactin in males and females and opposite disorders in the thyroid and glucocorticoid homeostasis associated in males (in contrast to females) with reduction of cortisol level (by 1.9 times) and increase in the concentrations of total thyroxine forms (by 1.4 times) and triiodothyronine (by 2.9 times) by day 14. Early sex-related shifts in the status of hormone that are a component of the adaptive system attest to their possible relationship with different course of the malignant process in male and female rats.

[The Problem of the Relationship of the Chromosome Aberration Frequency in Peripheral Blood Lymphocytes with the Risk of Disease Development Including after Irradiation].

This paper presents an analysis of the data published in the scientific literature in connection with the prob- lem of forecasting the risk of development of malignant and non-malignant diseases by chromosome aberra- tion frequencies in cultures of human peripheral- blood lymphocytes. This question is closely linked with the concept of a common chromosomal instability. At the end of the twentieth century evidence of the possibility of such forecast for malignant diseases appeared when cytogenetic indices did not exceed control values on the whole. At the same time there are significant uncertainties due to interindividual and intraindividual variability. In addition, there are significant difficulties concerning distinction of chromosome aberrations induced by environmental influences (for example, radiation) and those due to the possibility of internal processes in the body. For non-malignant diseases the applicability of a similar approach to risk evaluation is not sufficiently substantiated.

[Risk factors and prevention of postoperative pancreatitis after pancreatectomy]. / Faktory riska i profilaktika posleoperatsionnogo pankreatita pri rezektsionnykh vmeshatel'stvakh na podzheludochnoi zheleze.

AIM: to improve the results of pancreatic resections through decrease of postoperative pancreatitis incidence. MATERIAL AND METHODS: It was analyzed 207 patients who underwent pancreatic surgery for pancreatic tumor (n=137) or chronic pancreatitis (n=70). 22 risk factors of postoperative pancreatitis were analyzed in 112 patients retrospectively. In prospective study of 95 patients the efficacy of lornoxicam to prevent postoperative pancreatitis was assessed. 68 parameters of immune state were studied to estimate effect of lornoxicam. RESULTS: Significant factors were mellow pancreatic parenchyma, tumoral disease, pancreatic duct diameter over 3 mm, pancreatric duct index over 0.2, body mass index over 27 kg/m2. Likelihood of postoperative pancreatitis was 40%, 63%, 74.3% and 88.9% if 2, 3, 4 and 5 factors were combined respectively. Preventive use of lornoxicam reduced significantly incidence of postoperative pancreatitis (p=0.042). Incidence of pancreatic fistula and arrosive bleeding was decreased insignificantly due to small number of observations. CONCLUSION: Assessment of significant risk factors and use of medical prevention are available to decrease likelihood of postoperative pancreatitis.

[THE AWARENESS OF MEDICAL PROFESSIONALS OF ISSUES OF STORAGE AND DESTRUCTION OF PHARMACEUTICALS].

The article presents results of analysis of awareness of medical personnel of issues of storage, maintenance of quality of pharmaceuticals, collection and transfer for destruction pharmaceuticals unsuitable for medical application. The results of analysis demonstrated inadequate level of knowledge of normative documents, violation of rules of storage of pharmaceuticals, violation of collection of medical waste products. It is established that inadequate attention is paid to these issues in programs of additional professional education. The suggestions are presented concerning organization of continuous professional education of medical professionals related to maintenance of quality of pharmaceuticals.

[Retrospective Cytogenetic Dose Evaluation. I. Chromosome Aberration Levels in Remote Periods after Acute External Exposure in Different Situations].

Cytogenetic analysis of peripheral blood lymphocyte cultures of 22 persons was performed in remote terms after acute external γ-, γ-ß- or γ-neutron irradiation as a result of various accidents using the classical me- thod. The initial dose estimates were obtained using physical calculations, the method of measuring the EPR signal in tooth enamel, according to haematological and/or cytogenetic parameters. The purpose of this study was to obtain evidence about the state of the lymphocyte chromosome apparatus of people approxi- mately 17-50 years after an accidental radiation exposure. In general, elevated levels of chromosome aberra- tions were detected. An average correlation was observed between the atypical chromosome frequency and absorbed dose. It is proposed to use the obtained results in the future to explore the possibility of retrospective dose evaluation on the basis of a special computer program.

Demonstration of a Circularly Polarized Plasma-Based Soft-X-Ray Laser.

We report the first experimental demonstration of a laser-driven circularly polarized soft-x-ray laser chain. It has been achieved by seeding a 32.8 nm Kr ix plasma amplifier with a high-order harmonic beam, which has been circularly polarized using a four-reflector polarizer. Our measurements testify that the amplified radiation maintains the initial polarization of the seed pulse in good agreement with our Maxwell-Bloch modeling. The resulting fully circular soft-x-ray laser beam exhibits a Gaussian profile and yields about 10^{10} photons per shot, fulfilling the requirements for laboratory-scale photon-demanding application experiments.