Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

Fish otoliths as biological dosimeter: internal dose calculation.

Otoliths are organs used by fish for hearing and keeping balance. They consist of biogenic crystals of hydroxyapatite and do not contain any living cells. Upon exposure to ionizing radiation, otolith hydroxyapatite accumulates radiation-induced stable CO2- radicals whose amount is proportional to absorbed dose. In electron paramagnetic resonance (EPR) dosimetry, carbonate ions are registered and, hence, the total accumulated dose in the fish otolith can be quantified. Therefore, otoliths can be used as individual fish dosimeters to support radiobiological and radioecological studies. An important aspect of otolith-based EPR dosimetry on fish from contaminated water bodies is the potential presence of bone-seeking 90Sr. Consequently, cumulative absorbed doses measured with EPR in otoliths may reflect the superposition of internal exposure to 90Sr/90Y and external exposure due to radionuclides circulating in soft tissue of the fish as well as due to environmental contamination. The objective of the present study was to develop a method that allows for an assessment of the contribution of 90Sr to the total dose in otolith. The method has been tested using otoliths from seven fish taken from reservoirs located in the Southern Urals contaminated with radionuclides including 90Sr. It has been shown that dose to otoliths is largely determined by 90Sr in the hydroxyapatite. The internal dose component can be calculated using activity concentration-to-dose conversion factors, which vary slightly in the range of 2.0-2.8 × 10-3 Gy year-1 per Bq g-1 depending on fish species and age. Internal doses to fish from water bodies with different levels of 90Sr contamination were calculated in the range from 2 mGy to ~ 200 Gy. External dose contribution was derived for two fish only to be about 100 and 40 Gy. It is concluded that EPR dosimetry on fish otoliths is a promising tool when external exposure prevails or is comparable to internal exposure due to 90Sr.

[The new approaches to legal regulation of application of medical technologies in The Russian Federation at present-day period].

The article presents analysis of legal regulation of medical technologies in Russia. The proper development of medicine and health care is impossible without permanent improvement and implementation of new medical technologies. The upcoming decades will be an era of development of bio-technologies, cellular and gene technologies included. The proposed analysis is focused on conceptual set, analysis of actual normative legal base regulating mentioned relationships and identification of perspectives of development of medical technologies. The adequate and competent legal regulation creates enabling environment developing new technological capabilities. The legislation should avoid inhibiting retributive mode and apply particularly permitting and regulating approach determining framework not to be violated. Undoubtedly, these activities should be carried out in conjunction with professional medical community to develop legislation ensuring the highest possible level of development of health care practice.

Otoliths as object of EPR dosimetric research.

Otoliths are the organs which fish use for hearing and keeping balance. Otoliths are the most calcified tissues in the fish body. In contrast to bones, otoliths are not affected by remodeling and, therefore, they are expected to accumulate any dose from ionizing radiation during lifetime. Therefore, EPR dosimetry with fish otoliths could be an important tool for dose reconstruction in radiobiology and radioecology. It could also provide useful information remediation actions to de-contaminate waterbodies. Consequently, in the present study, otoliths of three contaminated fish species (roach (Rutilus rutilus), pike (Esox lucius) and perch (Perca Fluviatilis)) were examined with Electron Paramagnetic Resonance (EPR) spectroscopy. The fish were caught at storage reservoirs of liquid radioactive waste from Mayak PA and from the upper reach of the Techa River, which have been contaminated with different levels of radionuclide activity concentrations. It is shown that the radiation-induced EPR signal of otolith is stable and characterized by a linear dose response. However, the slope of the calibration curve (corresponding to the radiation sensitivity of the material) is not the same for different species; this may be caused by differences in mineralization. The reconstructed doses were found to be in the range from undetectable (in fish from the upper stream of the Techa River) up to 265 Gy (in roach from the most contaminated waterbody). In parallel, otoliths were measured with ß-counter to detect 90Sr/90Y. Samples were also tested on the presence of alpha-emitters, but no alpha activity above background could be detected. However, a significant activity concentration of 90Sr was detected (from 1 × 101 to 2 × 104 Bq/g). The EPR doses measured correlated with the 90Sr activity concentration measured in the otolith samples.

Peculiar Effects of Electromagnetic Millimeter Waves on Tumor Development in BALB/c Mice.

The study examined the effects of millimeter electromagnetic waves at a frequency of 130 GHz corresponding to the molecular absorption and radiation spectra of NO and O2 with the total exposition time of 6 h on tumor morphogenesis in 3- and 6-month-old tumor-prone BALB/c mice of both sexes. In experimental mice exposed to electromagnetic radiation, the development of cancer process was slowed down throughout the observation period; moreover, no macroscopic signs of the tumors were revealed. However, in contrast to control mice, experimental animals demonstrated the formation of pathological reactions reflected by hepatic biochemical indices accompanied by the development of dystrophic and microcirculatory alterations in the liver tissue.

Effects of Electromagnetic Fields Modulated by Infralow Frequencies on the Production of Stem Cells.

Experimental validation of the method for regulation of stem cell proliferation and differentiation is carried out. The method consists in exposure to ultrahigh frequency electromagnetic radiation, modulated by infralow frequencies with variable parameters. A specially designed programmer, setting up the parameters of exposure, is connected to the source of radiation. The zones of anatomical location of the red bone marrow of rats were exposed for 15 min to the amplitude-modulated electromagnetic radiation of ultrahigh frequency range. The parameters of exposure were determined in previous studies. The red bone marrow was collected from the sternum and head of the femur. The cellular composition of the red bone marrow was evaluated 1, 2, 3, and 6 days after the exposure. The optimal therapeutic mode of irradiation was then chosen, leading to stem cell activation with subsequent proliferation and differentiation into mature red bone marrow cells.

[Application of the EPR and FISH Methods to Dose Reconstruction for People Exposed in the Techa River Area].

Release of liquid radioactive waste into the Techa River from the Mayak Production Association during 1949-1956 resulted in a significant exposure of about 30000 people who lived in downstream settlements. The residents were exposed to internal and external radiation. The article discusses the capability of two methods that were used 50 years after the termination of radioactive discharges for the dose reconstruction, namely EPR measurements of tooth enamel, and FISH measurements of stable chromosome aberrations in circulating lymphocytes. The Main issue in the application of these methods for the dose reconstruction was local irradiation from strontium radioisotopes incorporated in teeth and bones. The EPR and FISH assays were supported by measurements of the 90Sr content in the skeleton and teeth in order to estimate and subtract internal doses from incorporated 89, 90Sr. The resulting dose estimates obtained from EPR and FISH mea- surements were found to be consistent The settlement-averaged values in the upper-Techa Region varied from 550-570 mGy to 130-160 mGy and showed a reduction with the distance from the release site. The EPR- and FISH-based dose estimates were in agreement with the doses calculated with the dosimetry system TRDS that uses data on radionuclide contamination of the Techa River floodplain and individual residential histories.

External dose reconstruction in tooth enamel of Techa riverside residents.

This study summarizes the 20-year efforts for dose reconstruction in tooth enamel of the Techa riverside residents exposed to ionizing radiation as a result of radionuclide releases into the river in 1949-1956. It represents the first combined analysis of all the data available on EPR dosimetry with teeth of permanent residents of the Techa riverside territory. Results of electron paramagnetic resonance (EPR) measurements of 302 teeth donated by 173 individuals living permanently in Techa riverside settlements over the period of 1950-1952 were analyzed. These people were residents of villages located at the free-flowing river stream or at the banks of stagnant reservoirs such as ponds or blind river forks. Cumulative absorbed doses measured using EPR are from several sources of exposure, viz., background radiation, internal exposure due to bone-seeking radionuclides (89Sr, 90Sr/90Y), internal exposure due to 137Cs/137mBa incorporated in soft tissues, and anthropogenic external exposure. The purpose of the present study was to evaluate the contribution of different sources of enamel exposure and to deduce external doses to be used for validation of the Techa River Dosimetry System (TRDS). Since various EPR methods were used, harmonization of these methods was critical. Overall, the mean cumulative background dose was found to be 63 ± 47 mGy; cumulative internal doses due to 89Sr and 90Sr/90Y were within the range of 10-110 mGy; cumulative internal doses due to 137Cs/137mBa depend on the distance from the site of releases and varied from 1 mGy up to 90 mGy; mean external doses were maximum for settlements located at the banks of stagnant reservoirs (~500 mGy); in contrast, external doses for settlements located along the free-flowing river stream did not exceed 160 mGy and decreased downstream with increasing distance from the site of release. External enamel doses calculated using the TRDS code and derived from the EPR measurements were found to be in good agreement.

Internal in vitro dosimetry for fish using hydroxyapatite-based EPR detectors.

A number of aquatic ecosystems were exposed to ionizing radiation as a result of the activities of the Mayak Production Association in the Southern Urals, former Soviet Union, in the 1950s. Currently, fishes inhabiting contaminated lakes are being actively studied. These investigations need dosimetric support. In the present paper the results of a pilot study for elaborating an EPR dosimeter which can be used for internal dosimetry in vitro are described. Biological hydroxyapatite is proposed here to be used as a detecting substance. More specifically, small hydroxyapatite grains are proposed for use as point detectors fixed in a solid matrix. After having been pelletized, the detectors were covered by Mylar and placed in the body of a fish to be stored in the fridge for several months. Application of the detectors for internal fish dosimetry demonstrated that the enamel sensitivity is sufficient for passive detection of ionizing radiation in fishes inhabiting contaminated lakes in the Southern Urals.

[The molecular mechanisms of resistance to B-lactams of pathogens of hospital-acquired infections].

The data of local microbiologic monitoring was used to study the profiles and mechanisms of resistance to beta-lactams antibiotics of gram-negative isolates of bacteria, pathogens of hospital-acquired infections in hospital reanimation and surgical departments. The study included 210 clinical isolates of pathogens of hospital-acquired infections: Pseudomonas aeruginosa--86 (40.9%), Acinetobacter baumannii--45 (21.4%), Klebsiella pneumoniae--52 (24.8%), Escherichia coli-23 (11.0%), Enterobacter spp.--4 (1.9%). The profiles of resistance to antibiotics were analyzed using the technique of serial micro-dilutions. The detection of the most common and clinically significant gens of beta-lactamases of gram-negative bacteria was implemented using the PCR technique and sequence analysis. The most activity was detected among carbapenems and cephaperazone/sulbactam. The local characteristics of prevalence of gens coding beta-lactamases (TEM, SHV, CTX) in K. pneumoniae and E. coli were established The study detected 11 isolates of P aeruginosa resistant to carbapenems and having genetic determinants of VIM-group and coding metal-beta-lactamases. The discussed data permits to assess the indicators of resistance to beta-lactams antibiotics and basic mechanisms of resistance of causative agents of hospital-acquired infections. The studies of this kind are unique for every type of hospital-acquired infection. The results can be used in the development of the concept of etiotropic and empiric therapy.

Optimization of Spondylosynthesis for Certain Thoracolumbar Burst Fractures.

Intermediate transpedicular fixation, i.e. additional insertion of transpedicular screws into the injured vertebrae, is an improvement to the most popular surgical intervention for spinal injuries, currently gaining widespread use in clinical practice. Unilateral insertion of transpedicular screws into the injured vertebrae allows combining the advantages of intermediate transpedicular fixation with the possibility to perform anterior column support without remounting the transpedicular system. The aim of the study was to use biomechanical computer modeling for evaluating the stability of intermediate transpedicular fixation components, which allow performing anterior column support if necessary. MATERIALS AND METHODS: DICOM files obtained during CT scan of a patient with intermediate thoracolumbar spine injury and the ANSYS software were used. Stability of the transpedicular system and supportability of the complementary Mesh implant installed with unilateral intermediate transpedicular screws were evaluated using computer modeling based on the finite element method. RESULTS: The values of stress and displacement fields for spine-hardware systems with various arrangements have been obtained. The maximum loads exceeding bone tissue strength (153-161 MPa) were registered for standard 4-screw system (190 MPa) when modeling the load equivalent for walking and falling from a standing position. The use of the proposed fixation system arrangement supplemented with intermediate screws allows obtaining loads in the spine-hardware system not exceeding these thresholds. Complementary eccentric Mesh implant enhances fixation stability of the transpedicular system with intermediate screws. CONCLUSION: The results show the high degree of mechanical stability of the proposed hardware arrangement and its potential efficacy for thoracolumbar transitional vertebra stabilization.

[Genetic determinants of antibacterial resistance among nosocomial Escherichia coli, Klebsiella spp., and Enterobacter spp. isolates collected in Russia within 2003-2007].

Nosocomial bacterial isolates collected within 2003-2004 (n=411) and 2005-2007 (n=422) were highly resistant to cephalosporins III-IV and antibacterials of other groups (aminoglycosides, fluoroquinolons, chloramphenicol, and co-trimoxazole). Genes encoding TEM, SHV, CTX-M, OXA-2, and AmpC types of beta-lactamases (BLs) in the E. coli, Klebsiella spp., and Enterobacter spp. isolates were detected using polymerase chain reaction (PCR). Prevalent CTX-M-type BLs were detected in 85% of the E. coli, 87% of the Klebsiella spp., and 38% of the Enterobacter spp. isolates of the first strain collection and in 94% of the E. coli, 91% of the Klebsiella spp., and 38% of the Enterobacter spp. isolates of the second one. Genes belonging to three subtypes of blacTx-M genes were identified: bla(CTX-M-1) (228 bla(CTX-M-15) and six bla(CTX-M-3) of the first strain collection; 275 bla(CTX-M-15), three bla(CTX-M-3), and one bla(CTX-M-22) of the second one), bla(CTX-M-2) (one bla(CTX-M-5) of the first strain collection and one bla(CTX-M-2) of the second one), bla(CTX-M-9) (17 bla(CTX-M-14) and one bla(CTX-M-9) of the first strain collection; seven bla(CTX-M-14) and one bla(CTX-M-9) of the second one). Three isolates of the first strain collection and one isolate of the second one carried two genes belonging to two different subtypes, i.e., bla(CTX-M-15) and bla(CTX-M-14) simultaneously. The bacterial isolates had high levels of associative resistance to ciprofloxacin, co-trimoxazole, gentamicin, amikacin, and chloramphenicol associated with the resistance gene cassettes aadA1, aadA2, aadA5, aadB, aacA4, aac(6')Ib; dfrA1, dfrA5, dfrA12, dfrA17, cmlA1, ereA2, and catB8 in the class 1 integrons and the resistance gene cassettes dfrA1, sat1, and aadA1 in the class 2 integrons.

APPLICATION OF EPR TOOTH DOSIMETRY FOR VALIDATION OF THE CALCULATED EXTERNAL DOSES: EXPERIENCE IN DOSIMETRY FOR THE TECHA RIVER COHORT.

This study applies EPR tooth dosimetry for validation of external doses calculated with the TRDS-2016. EPR-based external dose in tooth enamel is calculated by subtraction of the contributions of natural and anthropogenic sources from the exposure of interest. These subtracted terms may contribute substantially to the overall uncertainty of the EPR-derived external dose. The validation method strongly depends on the uncertainties. The current study combines the results of a number of previous papers to propagate the uncertainty of EPR-derived external doses. It is concluded that the overall uncertainties of D ≥ 500 mGy are comparable with measurement uncertainties (≤30%); the overall uncertainties of D < 500 mGy become higher as the EPR-dose decreases because they are strongly effected by all other factors of influence. More than 70% of investigated individuals were exposed externally to doses <100 mGy with uncertainties >100%. Therefore, the validation task can be solved only based on statistical approaches. The validation of the TRDS-2016 predictions demonstrates good convergence of group-averages with EPR-based doses. The method for validation of the uncertainty of TRDS-2016 predictions should be also designed based on statistical approaches.

[Microflora in patients with systemic connective tissue diseases].

The study of microflora of skin, mucous tunic of nose and mouth, and the quantitative and qualitative structure of the intestinal and urinal microflora in cases of systemic connective tissues diseases, are reproduced. The decrease of the dominant state of typical representatives, and the increase of the role of pseudopathogenic bacteria in various biotypes, were observed. The frequency of S. aureus detection increased in skin, mucous tunic of nose and mouth. Pseudopathogenic microbes acquired greater significance in the forming of microbiocenosis of intestine, while the number of E. coli, Bifidobacterium and Lactobacterium decreased. The frequency of detection of microbes in urine decreased. The comparative analyses of the microflora in patients with systemic lupus erythromatosis and progressive systemic sclerosis demonstrated the common peculiarities for microflora character change.

[Characteristic of resistance to beta-lactam antibiotics of nosocomial strains of Proteus mirabilis].

Antibiotic resistance of bacterium Proteus mirabilis isolated from inpatients was assessed in 30 medical centres from 15 regions of Russia. The most active antibacterial preparations remained carbapenems (imipenem and meropenem). Between 3rd generation cephalosporins, the lowest minimal inhibitory concentration (MIC) was observed in inhibition-protected preparations (ceftazidime/clavulanate: MIC50 < 0.125 mcg/ml, MIC90 128 mcg/ml; cefoperazone/sulbactam: MIC50 2 mcg/ml, MIC90 64 mcg/ml). Detection of class A beta-lactamases genes (TEM, SHV, CTX) using PCR was performed in 44 strains of P. mirabilis. Genes of these enzymes was detected in 11 (25%) bacterial cultures as well as their different combinations--in 32 (72.7%) isolates of P. mirabilis. The most prevalent (56.8%) was combination of TEM and CTX genes, and in 4 nants of resistance to beta-lactams was detected.

[Etiology of nosocomial surgical infections caused by gram-negative bacteria, and profile of their antibiotic resistance].

Microbiological monitoring of microbial landscape of gram-negative bacteria--etiological agents of nosocomial surgical infections--was performed as well as their level of antibiotic resistance was studied. Two hundred forty-four strains were isolated. Antimicrobial susceptibility was assessed by the method of serial microdilutions. Spectrum of Gram-negative microorganisms was represented by 3 groups: fermenting (62.7%), nonfermenting (34.8%), and nonidentified microbes (2.5%). Spectrum of gram-negative etiological agents of nosocomial surgical infections was represented mainly by Pseudomonas aeruginosa, Acinetobacter baumanii, Escherichia coli, and Klebsiella. Most active antibacterial drugs against studied strains were carbapenems (imipenem and meropenem).

[Susceptibility and molecular mechanisms of resistance to cephalosporins of Escherichia coli strains isolated from patients with nosocomial infections].

Resistance to wide spectrum of antibiotics was studied and most widespread genetic determinants of resistance to beta-lactam antibiotics were revealed. Susceptibility testing was performed using serial broth microdilution method. Detection of class A expanded spectrum beta-lactamases genes (TEM, SHV, CTX) by polymerase-chain reaction method was performed in 90 strains. Carbapenems remained the most active antibacterial agents with respect to studied E. coli strains. Among the 3rd generation cephalosporins the lowest minimal inhibitory concentrations were observed for inhibition-protected combined agents (ceftazidime/clavulanic acid and cefoperazone/ sulbactam). Alone or in various combinations TEM, SHV, and CTX types of beta-lactamases were found in 58.9%, 14.4%, and 77.8% of strains. Combinations of 2 determinants were detected in 55.6% of the isolates, and all 3 determinants--in 5.6%. Most often E. coli was isolated in patients with urinary tract infections. Carbapenems and inhibition-protected combined 3rd generation cephalosporins are the most active agents against E. coli.

[Antimicrobial susceptibility and molecular mechanisms of resistance to beta-lactams of gram-negative microorganisms--causative agents of nosocomial infections].

Profiles and mechanisms of resistance to beta-lactam antibiotics of isolates of Gram-negative microorganisms, which are causative agents of infections in Intensive Care Unit of hospital surgery department, were studied. Two hundred and ten clinical isolates were studied: Pseudomonas aeruginosa--86 strains (40.9%), Acinetobacter baummanii--45 strains (21.4%), Klebsiella pneumoniae--52 strains (24.8%), Escherichia coli--23 strains (11%), Enterobacter spp.--4 strains (1.9%). Profiles of antibiotic resistance were studied by the method of serial microdilutions; detection of most widespread and clinically significant genes of beta-lactamases of Gram-negative bacteria was performed by polymerase chain reaction. Carbapenems and cefoperazone/sulbactam were the most active antibiotics. Local features of distribution of beta-lactamase coding genes (TEM, SHV, CTX) in K. pneumoniae and E. coli isolates were revealed. Eleven strains of P. aeruginosa resistant to carbapenems and possessing genetic determinants of VIM-group, which codes metallo-beta-lactamases, were isolated. Obtained data allows to assess the parameters of resistance to beta-lactam antibiotics and to reveal the main mechanisms of such resistance in etiologic agents of nosocomial infections, that, in its turn, allows to choose preparations for etiotropic therapy.

[Antibiotic susceptibility and molecular mechanisms of cephalosporins resistance in Klebsiella isolates from patients with hospital-acquired infections].

Antibiotic susceptibility of nosocomial Klebsiella isolates from inpatients of 30 medical centres in 15 various regions of Russia was studied. In total 212 strains were tested. The Klebsiella genus was represented by the following species: Klebsiella pmeumoniae ss. pneumoniae (182 isolates, 85.8%), Klebsiella pneumonia ss. ozaenae (1 isolate, 0.5%), Klebsiella oxytoca (29 isolates, 13.7%). The susceptibility was determined by the broth microdilution method. Carbapenems (imipenem and meropenem) remained to be the most active antibacterial agents. However, 1 imipenem resistant strain and 2 meropenem resistant strains were isolated. As for the 3rd generation cephalosporins, the lowest MICs were observed with the use of the inhibitor-protected agents, such as ceftazidime/clavulanic acid (MIC50 0.25 mcg/ml, MIC90 64 mcg/ml). 48.8%, 16.9%, 29.7% and only 10.5% of the isolates was susceptible to cefepime, cefotaxime, ceftazidime and cefoperazone respectively. Detecting of the beta-lactamase genes (TEM, SHV and CTX) was performed by PCR in 42 strains of Klebsiella pneumoniae ss. pneumoniae. Alone or in various combination the TEM type beta-lactamases were detected in 16 (38.1%) isolates. SHV and CTX were detected in 29 (69%) and 27 (64.3%) isolates respectively. Combinations of 2 and 3 different determinants of resistance to beta-lactams were revealed in 23.8% and 26.2% of the isolates respectively. No isolates producing class B MBL among the carbapenem resistant nosocomial Klebsiella strains were detected.

[Ciprofloxacin and therapy of urinary tract infections, including those due to Staphylococcus saprophyticus].

Staphylococcus saprophyticus is one of the main pathogens of cystitis in young women. The human biotopes are contaminated by the staphylococcus on direct contacts with domestic animals or after using not properly cooked food of animal origin. Young women are more susceptible to colonization of the urinary tract by S. saprophyticus vs. the other contingents. Sexual intercourse is conducive to the colonization and infection. Shifts in the urinary tract microflora due to the use of spermicide, as well as candidiasis promote colonization of the urinary tract by S. saprophyticus. At present fluoroquinolones are considered as a significant independent group of chemotherapeutics within the class of quinolones, inhibitors of DNA gyrase, characterized by high clinical efficacy in the treatment of urinary tract infections. Especially significant clinical experience with ciprofloxacin in the therapy of urinary tract infections is available.