FEATURES OF EJACULATE MICROBIOCENOSIS IN MEN WITH IMPAIRED FERTILITY, DEPENDING ON THE TYPE OF CONSUMED ALCOHOLIC BEVERAGES.

Due to the lack of both common conception concerning etiology of male infertility and data about disorders of immune homeostasis concomitant with dysbiosis of urogenital tract in men with damages of reproductive function depending on features of alcoholic anamnesis, the aim of our research is studying influence of microbiocenoses in ejaculate on nonspecific immune factors in males suffering from fertile function damages depending on kind and amount of alcohol used. This article deals with findings concerning condition of semen analysis, cellular agents in innate immunity, bacteriological investigation of ejaculate in 73 males divided in 5 groups, depending on amount and kind of alcohol. According to data obtained it was established that all patients in groups under research suffered from incomplete phagocytosis in neutrophils links secondary to retaining functional and metabolic reserve in using strong alcoholic drinks and in its exhaustion in drinking excess bear and mixed alcohol. Studying microflora in ejaculate has shown presence only G+ flora (Staphylococcus haemolyticus, Staphylococcus epidermidis, Enterococcus faecalis) in drinking excess strong alcohol but in drinking excess bear and mixed alcohol both G+ microflora (Staphylococcus epidermidis, Enterococcus faecalis) and G- microflora (Escherichia coli, Klebsiella pneumoniae) have been observed. Associations of microorganisms have been revealed in males of all groups under research, in this case the most number of them has been revealed in drinking excess bear. In turn, the semen analysis showed that the most evident changes in ejaculate fertile properties were being observed at middle and high risk in consumption of beer and alcohol mixed, as astenoteratozoospermia. Proceeding from the data obtained one may suppose that drinking alcohol mixed is the factor causing development of incompetence for nonspecific protection, because it might lead to damages of microbiocenoses in ejaculate and male fertility reduced consequently.

[MENTAL DERANGEMENT AS A MANDATORY MEDICAL CRITERION OF LIMITED SANTY].

The aim of the article is scientific conceptualization of the problem of mental derangement as a mandatory medical criterion of limited sanity according to criminal legislation by experience of Ukraine and some foreign countries and development of new approaches to such status assessment. Empirical study base of the problem consists of judgments of conviction taken from Unified State Register of Court Rulings of Ukraine and carried out on persons who commit crimes in the state of limited sanity from March 1st, 2014, till August 1st, 2020. Results of some foreign researchers' studies of the problem in question have been used as well. A combination of general and special scientific methods (comparative method, system structural method, method of statistical analysis, method of legal phenomenon system analysis etc.) has been applied to reach the aim in view. In conclusion: medical criterion of limited sanity ("mental derangement") used by lawmaker does not allow defining clearly types of illnesses, represent all possible types of psychiatric pathology and also causes complications in law enforcement practice. It has been proved that increase of quantity of people having mental derangements and quantity of crimes committed by such people shows that non-application of compulsory measures of medical care, correlational programs leads to repeated crimes commitment. Taking into account absence of duration of compulsory measures of medical care application, it has been suggested to stipulate this by Ukrainian legislation and to develop classification of mental derangements and criteria of their division into severe and non-severe.

[Floating structure of the carotid artery as a cause of microembolism in the basin of cerebral arteries]. / Flotiruiushchaia struktura sonnoi arterii kak prichina mikroémbolii v basseine mozgovykh arterii.

This article describes a rare clinical and diagnostic case report regarding a female patient presenting with frequent transitory attacks in the basin of both middle cerebral arteries. Based on the findings of duplex scanning of the cervical arteries we revealed floating structures with the presence of pronounced slow turbulent blood flow. After excluding all known causes of cerebral artery microembolism, associated with heart pathology or with the presence of unstable atherosclerotic plaques, the leading hypothesis of transitory ischaemic attacks in the woman concerned was the formation of microthrombi in the zone of motility of the structures revealed. The results of bitemporal transcranial Doppler monitoring carried out during 30 minutes detected more than 10 microembolic signals in the middle cerebral artery, thus confirming the embolic nature of transitory ischaemic attacks.

Study of p-(3-carboxy-1-adamantyl)-calix[4]arene with hydrogen bonds along the upper and lower rim by IR spectroscopy and DFT.

The IR spectra of p-(3-carboxy-1-adamantyl)-calix[4]arene (AdC4A) were studied. Using IR spectroscopy, it has been shown that in calixarene in dilute solution in CCl4, there was no free hydroxyl absorption band. The hydroxyl group band was characterized by a very low frequency, which indicates a strong intramolecular hydrogen bond on the lower rim of the calixarene molecules. On the upper rim of the calixarene, the carboxyl groups form cyclic dimer or tetramer complexes via intermolecular hydrogen bonds. The cone conformation persists, but there is a mutual influence of the hydrogen bonds along the top and bottom rims of the calixarene molecule. The structure with dimeric hydrogen bonds between the carboxyl groups is 16.5 KJ/mol more preferable than the structure with tetrameric cyclic hydrogen bonds for AdC4A. The reactivity depends on the type of association on the upper rim, whether these are hydrogen-bonded dimers or cyclic tetrameric association. Graphical abstract .

Generation of two clonal iPSC lines, ICGi019-A and ICGi019-B, by reprogramming peripheral blood mononuclear cells of a patient suffering from hypertrophic cardiomyopathy and carrying a heterozygous p.M659I mutation in MYH7.

Hypertrophic cardiomyopathy (HCM) is one of the most frequent cardiovascular diseases but no methods to prevent its progression have been developed. Cardiomyocytes derived from patient-specific induced pluripotent stem cells can become a platform to study pathogenesis of the disease and to search for more effective therapy methods. We generated two iPSC lines from peripheral blood mononuclear cells of an HCM patient with heterozygous p.M659I mutation in MYH7 using episomal vectors. The iPSC lines expressed pluripotency markers, demonstrated ability to spontaneously differentiate into derivatives of three germ layers, and retained the mutation.

[PREVENTION OF CORRUPTION OFFENCES IN THE HEALTHСARE: THE EXPERIENCE OF UKRAINE AND GEORGIA].

The aim of the article is a comparative and legal study of corruption and measures to combat corruption in health care in Ukraine, using the experience of Georgia and the European Union. The materials of the research are the legislation of the European Union, Georgia, Ukraine, statistical information. The authors of the research have used the systematization method, comparative and legal method, analysis and generalization of statistical data. Corruption and corruption offences in the health system may lead to unpredictable consequences impacting accessibility, equity and health outcomes. Fighting against corruption in the health sector consists of the identification of specific forms of corruption and the implementation of effective anti-corruption measures, which must be designed to fit the context of a country's health system. A study of the experience of Georgia and the EU countries shows that, changes in the organization and management of the health system, financing of health care, provision of health services, increase access to medical services, reducing inequalities, financial risks reduction regarding expenditures on medical services, changing public opinion of the perception of corruption, transparency and accountability in the funding of medicine, the anti-corruption examination of legislative acts regulating the activity of healthcare in Ukraine, the formation of anti-corruption behaviour in society, active cooperation with civil society institutions are therefore of primary importance for Ukraine during the period of medical reform. Elimination of the reasons and conditions promoting the commission of corruption offences in the health system and the introduction of an effective anti-corruption strategy based on good governance, transparency and zero tolerance are among the priority areas for improving the current legislation of Ukraine in fighting against corruption in the field of healthcare.

Synthesis, structure-activity relationship and biological evaluation of tetracationic gemini Dabco-surfactants for transdermal liposomal formulations.

In this study, we report the relationship between structure, self-assembly behavior and antimicrobial activity of multicationic gemini surfactants and their successful use as stabilizers of a new liposomal formulation for transdermal drug delivery. New surfactants containing natural moiety 1,4-diazabicyclo[2.2.2]octane with four charges and two hydrophobic chains (n-Dabco-s-Dabco-n, where s = 2, 6, 12 and n = 12, 14, 16, 18) were synthesized. A linear dependence of the CMC decrease, with the increase of the number of carbon atoms in alkyl groups (slope 0.23) was shown. The aggregation numbers of n-Dabco-2-Dabco-n are smaller than 30 and they decrease with increasing alkyl chain length. This is in compliance with the larger surface area per n-Dabco-2-Dabco-n molecule. New liposomal formulations loading Rhodamine B phosphatidylcholine (with mean size about 100 nm and increased zeta potential from -7 ± 2 mV to +55 ± 2 mV) have been successfully stabilized by n-Dabco-s-Dabco-n surfactants. These formulations were designed to improve the bioavailability and skin permeation of loaded compound. The antibacterial activity of Dabco-surfactants was shown to be strongly affected by their structure (alkyl chain length and number of charged nitrogen). 12-Dabco-2-Dabco-12 was the most active (MIC = 0.48, 0.98 and 15.6 µg/mL against S. aureus, B. cereus and E. coli, respectively) without hemolytic activity at 3.1 µg/mL concentration. PC/14-Dabco-2-Dabco-14-liposomes were shown to be the best formulation, with the highest antibacterial activity against Sa (MIC = 7.8 µg‧mL-1) and lowest cytotoxicity (IC50 > 125). The modification of liposomes by Dabco-surfactants stabilizes the membrane of the vesicles, preventing the release of rhodamine B and impairing the penetration of the dye across Strat-M® membrane. Cellular uptake of rhodamine B-loaded PC/12-Dabco-2-Dabco-12-liposomes was also reported. This is the first example of cationic mixed liposomes containing Dabco-surfactants of potential interest for transdermal drug delivery.

Generation of two iPSC lines, (ICGi015-A and ICGi015-B), by reprogramming peripheral blood mononuclear cells from a patient with Parkinson's disease.

Studying Parkinson's disease (PD), one of the most common neurodegenerative disorders worldwide, requires different model systems, including patient-specific induced pluripotent stem cell lines. With the help of non-integrating episomal vectors the iPSC lines ICGi015-A and ICGi015-B were generated from blood mononuclear cells of PD patient, carrying three SNPs, associated with PD development. The obtained iPSC lines express pluripotency markers and demonstrate the ability to in vitro differentiate into the three germ layers. These cell lines may be useful for studying molecular mechanisms of PD and for drug screening.

Formation of Alcohol Motivation in Monkeys (Macaca mulatta) Kept in Isolation.

The effects of environmental factors (flavors, different ethanol concentration, alcoholic deprivation, and food reinforcement) on the formation of alcohol motivation was studied in rhesus macaques (Macaca mulatta, n=6). Motivation for alcohol intake was induced in two stages: initiation (sessions 1-160) and formation of motivation (sessions 161-516). Monkeys preferred multifruit flavor and 4% ethanol solution, while ethanol deprivation did not stimulate alcohol consumption. The pronounced individual differences in the pattern of alcohol motivation were revealed: the intake of 4% ethanol solution ranged from 0.21±0.03 to 0.43±0.06 g/kg without food reinforcement and increased from 0.78±0.03 to 1.22±0.09 g/kg with food reinforcement. The results suggest that the proposed method is valid and can be used as an experimental model of alcohol dependence in non-human primates.

Applying Patient-Specific Induced Pluripotent Stem Cells to Create a Model of Hypertrophic Cardiomyopathy.

Generation of patient-specific induced pluripotent stem cells (iPSCs) and their subsequent differentiation into cardiomyocytes opened new opportunities for studying pathogenesis of inherited cardiovascular diseases. One of these diseases is hypertrophic cardiomyopathy (HCM) for which no efficient therapy methods have been developed so far. In this study, the approach based on patient-specific iPSCs was applied to create a model of the disease. Genetic analysis of a hypertrophic cardiomyopathy patient revealed R326Q mutation in the MYBPC3 gene. iPSCs of the patient were generated and characterized. The cells were differentiated into cardiomyocytes together with the control iPSCs from a healthy donor. The patient's iPSC-derived cardiomyocytes exhibited early HCM features, such as abnormal calcium handling and increased intracellular calcium concentration. Therefore, cardiomyocytes obtained by directed differentiation of iPSCs from the HCM patient can be used as a model system to study HCM pathogenesis.

Vibrational spectroscopic investigation of the gold complexation within the cascade structure of phosphorus-containing dendrimer.

The interaction of the phosphoric dendrimer with gold was performed by means of vibrational spectroscopy and quantum chemistry. Stable complexes are formed with a PN-PS linkage, whereas with an isolated PS bond this does not occur. The change in geometric parameters and delocalization of electric charge under the influence of gold was discovered. The classification of bands in the experimental vibrational spectra of the dendrimer and its complex was carried out. HOMO of molecule of the dendrimer is localized on the SPNP linkage, whereas the LUMO is located on the terminal group. In the SPNP linkage there is a noticeable delocalization of the charge which leads to a change in the reactivity of this group. Interaction energy was estimated as the difference between the energies of the complex and the energies of the molecules of the dendrimer G'0 and two molecules AuCl and is equal to 25.2 eV. The ionization energy IE and electron affinity EA for AuCl are higher than for dendrimer, therefore, when the complex is formed, these quantities increases. Chemical potential and the electrophilicity index in the complex also increases.

[Preventability of perinatal losses by the example of the large industrial cities Chelyabinsk and Novosibirsk]. / Predotvratimost' perinatal'nykh poter' v Cheliabinske i Novosibirske.

Perinatal mortality rate is an indicator that characterizes the quality of medical care, as well as the social and economic situation in the region. OBJECTIVE: to audit perinatal losses in large regional centers of the Russian Federation with a population of over 1 million inhabitants, such as Chelyabinsk and Novosibirsk. MATERIAL AND METHODS: A comprehensive postmortem examination of 309 cases of perinatal losses in 2016 was made, which was supplemented with an assessment of preventability according to the Scandinavian-Baltic classification. RESULTS: The rate of preventable deaths in Chelyabinsk and Novosibirsk amounted to 91 and 81.5% of cases, respectively; the deaths were due to stillbirths at more than 28 weeks' gestation and to dead newborns in almost half of cases. The proportion of intranatal deaths was shown to increase in Chelyabinsk; the number of neonatal deaths at more than 33 weeks' gestation rose in Novosibirsk. CONCLUSION: Supplementing the traditional clinical and postmortem analysis with an assessment of the preventability of perinatal loss makes it possible to ensure a unified approach to evaluating these conditions and the comparability of autopsy results in different subjects of the Russian Federation and to determine regional reserves for reducing perinatal mortality rates.

Vibrational spectroscopic study of cationic phosphorus dendrimers with aminoethylpiperidine terminal groups.

Two generations of phosphoric dendrimers with piperidine functional groups were synthesized for use in biology and medicine. Neutral samples are soluble in organic solvents but after protonation these dendrimers become water soluble and can be used for biological experiments. The FTIR and FT Raman spectra of two generations of dendrimers Gi constructed from the cyclotriphosphazene core, repeating units OC6H4CHNN(CH3)P(S)< and aminoethylpiperidine end groups NH(CH2)2C5NH11 were recorded. The study of the IR spectra shows that the NH groups form hydrogen bonds. The calculation of the molecular structure and vibrational spectra of the first generation dendrimer was performed by the method of DFT. This molecule has flat, repeating units and a plane of symmetry passing through the core. The calculation of the distribution of potential energy made it possible to classify the bands in the experimental spectra of dendrimers. Amine groups are manifested in the form of a band of NH stretching vibrations at 3389 cm-1 in the IR spectrum of G1. NH+ stretching bands located at 2646 and 2540 cm-1 in the IR spectrum of G2. The stretching vibrations of NH+ groups are noticeably shifted to low frequencies due to the formation of a hydrogen bond with the chlorine atom. The line at 1575 cm-1 in the Raman spectrum of G1 is characteristic for repeating units.

The BiPo-3 detector.

The BiPo-3 detector is a low radioactive detector dedicated to measuring ultra-low natural contaminations of 208Tl and 214Bi in thin materials, initially developed to measure the radiopurity of the double ß decay source foils of the SuperNEMO experiment at the µBq/kg level. The BiPo-3 technique consists in installing the foil of interest between two thin ultra-radiopure scintillators coupled to low radioactive photomultipliers. The design and performances of the detector are presented. In this paper, the final results of the 208Tl and 214Bi activity measurements of the first enriched 82Se foils are reported for the first time, showing the capability of the detector to reach sensitivities in the range of some µBq/kg.

Cyclic cooperative intramolecular hydrogen bond in p-tert-butylcalix[6]arene according to FTIR spectroscopy and DFT studies.

This article describes a comparative research of IR spectra and H-bonds in the p-tert-butylcalix[6]arene (TB6) and calix[6]arene (C6). IR spectra were computed for compressed cone conformation by DFT method. The assignment of the bands in the IR spectra of the TB6 and C6 was made. The effect of the bulky tert-butyl substituents on the structure and H-bonding in TB6 was established. Our research has shown that in TB6 and C6 the cyclic H-bond is realized, which ensures the existence of a compressed cone conformation. Introduction of tert-butyl substituents in TB6 leads to hardening of H-bonds. Examination of IR spectra showed that when heated TB6 remains in a compressed cone conformation. In a molecule of TB6 and C6 oxygen atoms are in a "boat" conformation.

Repeated administration of ethambutol in therapeutic dose causes testes alteration and spermatogenesis disruption in Wistar rats.

Ethambutol (EMB) is conventionally used to treat tuberculosis and atypical Mycobacterium infections in combination with other antimycobacterial drugs. Eventually, EMB testicular toxicity has not been explored extensively yet. The aim of the study is to evaluate testicular toxicity of EMB. We explored the impact of EMB on male rats' fertility, testosterone level and germ cells state, testicular pro- and anti-oxidant status and DNA damage, as well as identified EMB effects on cytochrome P-450 2E1 (CYP2E1) both with computer simulation and in vivo. We demonstrated that EMB administration to male rats decreased in epididymal sperm count (19%) and fertility index (53%). These events were accompanied by reduction in serum testosterone content (1.6 times) and appearance of spermatogenic epithelium damages. It was also found in testes the intensification of lipid peroxidation, decrease in reduced glutathione content and changes in DNA fragmentation. Additionally, computer simulation showed direct interaction of EMB with CYP2E1 active site and heme. On the top of this, we demonstrated that level of testicular CYP2E1 messenger RNA in EMB-treated rats was increased 8.7 folds and p-nitrophenol hydroxylase activity in testes rose three folds. As this shows, EMB-caused CYP2E1 induction, oxidative stress, and apoptosis in the testes contribute to inhibition of steroidogenesis enzymes and spermatogenesis disruption.

Search for Neutrinoless Quadruple-ß Decay of

We report the results of a first experimental search for lepton number violation by four units in the neutrinoless quadruple-ß decay of ^{150}Nd using a total exposure of 0.19 kg yr recorded with the NEMO-3 detector at the Modane Underground Laboratory. We find no evidence of this decay and set lower limits on the half-life in the range T_{1/2}>(1.1-3.2)×10^{21} yr at the 90% C.L., depending on the model used for the kinematic distributions of the emitted electrons.

[Some aspects of examining the images of tracer hyperfixation foci in osteoscintigrams by computer-assisted automated analysis].

OBJECTIVE: to analyze the numerical characteristics of bone metastases according to scintigraphic data. MATERIAL AND METHODS: Computer-assisted automated analysis was used to examine planar skeletal osteoscintigrams in patients with breast cancer who had both complete remission and disease progression with skeletal metastases. Brightness in the image was used as an analyzed indicator. RESULTS: Examination of physiological tracer accumulation in patients without skeletal metastases suggests that there is a wide variability of brightness values in the scintigrams of individual skeletal areas. At the same time, the skeletal anatomic areas show significant differences in the average image brightness values (p < 0.01). In virtually all skeletal areas, the average brightness values in the pathological tracer hyperfixation foci (HFFs) in the scintigrams are dominant over the similar values of physiological HFFs. CONCLUSION: There is a direct relationship between the tracer accumulation levels in the skeletal areas without metastatic involvement and the bone metastases occurring in the same areas.

Structure, IR and Raman spectra of phosphotrihydrazide studied by DFT.

The FTIR and FT Raman measurements of the phosphotrihydrazide (S)P[N(Me)-NH2]3 have been performed. This compound is a zero generation dendrimer G0 with terminal amine groups. Structural optimization and normal mode analysis were obtained for G0 by the density functional theory (DFT). Optimized geometric bond length and angles obtained by DFT show good agreement with experiment. The amine terminal groups are characterized by the well-defined bands at 3321, 3238, 1614cm(-1) in the experimental IR spectrum and by bands at 3327, 3241cm(-1) in the Raman spectrum of G0. The experimental frequencies of asymmetric and symmetric NH2 stretching vibrations of amine group are lower than theoretical values due to intramolecular NH⋯S hydrogen bond. This hydrogen bond is also responsible for higher experimental infrared intensity of these bands as compared with theoretical values. Relying on DFT calculations a complete vibrational assignment is proposed for the studied dendrimer.

[SURGICAL TREATMENT OF THE INJURED PERSONS WITH SPLENIC TRAUMA IN THE CLOSED COMBINED ABDOMINAL TRAUMA].

The results of treatment of the injured persons, suffering splenic injury, in closed com- bined abdominal trauma, depending on its severity and the splenic injury degree, are presented.