Endothelin Level in Menopausal Women with Comorbidity of the Acute Phase Middle Severity COVID-19 with Arterial Hypertension and Type 2 Diabetes Mellitus.

The levels of endothelins were assessed in menopausal women with arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) in the acute phase of the moderate COVID-19. Women under observation (age 45-69 years) were divided into two groups. Control group consisted of women (n=16) who did not have COVID-19, were not vaccinated, and had no antibodies to SARS-CoV-2 (IgG). The main group included women (n=63) in the acute phase of the moderate COVID-19 accompanied by pneumonia. According to the clinical and anamnestic data analysis, the main group was divided into subgroups: without AH and T2DM (n=21); with AH and without T2DM (n=32); and with AH and T2DM (n=10). The parameters of clinical blood analysis, as well as endothelin-1, endothelin-2, and endothelin-3 levels were assessed. In women with a moderate COVID-19, the endothelin-1 and endothelin-2 levels were increased compared to the control regardless of AH and T2DM status. We found no statistically significant differences in the studied parameters of endothelial dysfunction between the subgroups of menopausal women in the acute phase of the moderate COVID-19.

Selective synthesis of A-ring Е-arylidene derivatives from ß-sitosterol and their activity.

A series of 24-ethylcholest-4-ene-3,6-dione 2E-arylidene-derivatives has been synthesized by a Claisen-Schmidt reaction from a natural phytosterol ß-sitosterol with yields of 80-85%. The structure of the obtained compounds was confirmed by NMR spectroscopy, including two-dimensional correlation experiments. The synthesized compounds were evaluated for their in vitro cytotoxicity and α-glucosidase inhibitory activity. It was established that compound 3 with pyridin-3-ylmethylene moiety exhibited a selective cytotoxic effect against the U251 cancer cell line with 99.31% inhibition of cancer cell growth. Compounds with pyridin-4-ylmethylene 4 and furan-2-ylmethylene-5 fragments were the most active inhibitors of α-glucosidase with IC50 64.00 and 38.95 µM, being 3- and 5-times more active than acarbose. Binding mode to α-glucosidase and ADMET characteristics for the lead molecule 5 were proposed computationally. To sum up, an efficient approach to the derivatives with promising antidiabetic activity based on available natural product ß-sitosterol is suggested.

[Neuroendocrine changes among 45-60 years old women with COVID-19 and 12 months after the disease.]

Climacteric women have the post-COVID period clinical features, which can lead to an acceleration of the aging. The study consists in assessing individual parameters of the neuroendocrine system in climacteric women with a moderate course of COVID-19 and 12 months after the disease. Under observation were women aged 45-69 years, who were divided into groups: women who did not have COVID-19, not vaccinated, with no antibodies to COVID-19 (IgG) - control group (n=16); women in the acute phase of COVID-19 with a moderate course, accompanied by pneumonia - main group (n=63); patients from the main group who agreed to be examined 12 months after COVID-19 (n=15). The prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, cortisol, testosterone, 17-OH-progesterone, dihydroepiandrosterone sulfate (DHEA-S) levels were assessed. In women with COVID-19 compared with the control the prolactin level was increased (p=0,0002) and the estradiol (р=0,032), testosterone (p=0,004), cortisol (p=0,009), 17-OH-progesterone (p=0,025) and DHEA-S (p=0,003) levels were reduced. Intragroup comparison of hormones showed a decrease in the prolactin level (р=0,041) and increase in the 17-OH-progesterone (р=0,011) and DHEA-S (р=0,0006) levels 12 months after the disease. With a personalized consideration of this group a decrease in the prolactin level is observed in 73,3% of these patients. In the same period, there was an increase in testosterone levels in 46,7% of women, cortisol - in 73,3% of women, 17-OH-progesterone - in 80% of women, DHEA-S - in 100% of cases. When comparing these hormonal parameters between the group of patients who recovered from COVID-19 12 months ago and the control, no statistically significant differences were found, however, patients were identified in whom prolactin and cortisol exceeded the reference values, although in the acute phase of COVID-19 the values of these indicators corresponded to the reference values.

Modifying Distant Effect of High Dilutions of Inorganic and Biological Substances.

It is known that highly diluted substances can exert a modifying effect on the initial substances without direct contact with them (distant interaction). The capability of high dilutions of IFNγ and Na2SO4 for the distant modifying effect was studied by the method of terahertz spectroscopy. Statistically significant differences were shown between terahertz characteristics of the initial solution of IFNγ protein and solution that had interacted with high dilutions of IFNγ; in case of sodium sulfate, no such differences were detected. Thus, high dilutions exert a distant modifying effect on the initial substances with complex spatial structure typical of biological molecules.

Study of the Effects of Highly Diluted Sodium Sulfate and Interferon-Gamma.

High dilutions of solutions containing extremely small amounts of the initial substance can modify the biological effects of the initial substance molecules. Using terahertz spectroscopy, we studied the possibility of modifying the physicochemical properties of the initial substance by adding high dilutions of high-molecular-weight (IFNγ) and low-molecular-weight (Na2SO4) compounds. In addition, the modifying effect produced by high dilutions of a low-molecular electrolyte (a solution of Na2SO4 salt) on the initial substance was confirmed by conductometry. This method allows measuring electrical conductivity that also depends on the physicochemical properties of the solution, namely, the number of ions and velocity of their movement. Statistically significant differences were shown between terahertz and conductometric characteristics of the initial solution (inorganic salt Na2SO4 or a protein IFNγ) and a solution, where high dilutions of the same substances were added in different concentrations. Interestingly, the differences were more pronounced for the biological molecule. Thus, it has been shown that high dilutions can change the properties of the initial solution; the effect is more pronounced for the protein solution.

Length of Leukocyte Telomeres in Newborns of HIV-Infected Mothers.

We studied the relative length of telomeres in newborns with unrealized perinatal transmission of HIV (zero viral load according to PCR results). A cross-sectional survey of 62 newborns of HIV-infected mothers (Apgar score 8); the control group consisted of 80 healthy newborns (Apgar score 8). DNA extracted from whole venous blood samples was analyzed. In newborns of HIV-infected mothers, the relative length of telomeres was significantly lower (0.69 (0.66; 0.72)) than in newborns of the control group (1.1 (0.97; 1.22)) (p<0.001). No significant differences in the relative length of telomeres were found between newborns of mothers with a viral load at the time of delivery and with undetectable viral load: 0.69 (0.66; 0.73) and 0.69 (0.63; 0.72). These findings indicate that HIV-infection in mothers or exposure to antiretroviral therapy has an impact on the relative telomere length in leukocytes of newborns.

Mutation Effect of Ionizing and Non-Ionizing Electromagnetic Radiation on Drosophila melanogaster.

The frequency of D. melanogaster embryonic death was estimated using the method of dominant lethal mutations after exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field. γ-Radiation had a dose-dependent mutational effect on D. melanogaster. A pronounced increase in embryonic death was observed starting from a dose of 3 Gy and reaches a plateau at 60 Gy due to the maximum death of eggs. When D. melanogaster was exposed to pulsed magnetic field, the effect did not depend on the exposure time; a statistically significant genotoxic effect was detected after 5-h exposure.

Features of the Free Radical Oxidation Process and Antioxidant System in Newborns Born to HIV-Infected of Mothers Who Received Antiretroviral Therapies to Prevent HIV Transmission.

The LPO processes and the state of the antioxidant system in perinatally HIV-exposed newborns were studied. Perinatally HIV-exposed (n=62) and healthy newborns (n=80; control) were examined retrospectively (Apgar score 8 in both groups). Blood plasma and erythrocyte hemolysate were used as the material for biochemical tests. Using spectrophotometric, fluorometric, and statistical methods, we found enhanced LPO processes insufficiently compensated by the antioxidant system with excessive accumulation of damaging metabolites in the blood of perinatally HIV-exposed newborns. These changes can be a consequence of oxidative stress during the perinatal period.

Pro-and Antioxidant Status in Newborn with COVID-19.

There is practically no information on the state of oxidative stress reactions in newborns with coronavirus infections. At the same time, such studies are extremely important and can contribute to better understanding of the process of reactivity in patients of different ages. The content of pro- and antioxidant status indicators was assessed in 44 newborns with confirmed COVID-19. It was found that the content of compounds with unsaturated double bonds, primary, secondary, and final LPO products were elevated in newborns with COVID-19. These changes were accompanied by higher SOD activity and retinol level and reduced activity of glutathione peroxidase. Contrary to popular opinion, newborns can be a COVID-19-susceptible age group and require more close monitoring of metabolic reactions during the period of neonatal adaptation that is an aggravating background during infection.

[Withdrawal syndrome after tyrosine kinase inhibitors discontinuation in patients with chronic myeloid leukemia].

BACKGROUND: Withdrawal syndrome (WS) a musculoskeletal pain after discontinuation of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) has been described in the treatment-free remission (TFR) studies. The pathophysiological mechanisms and predisposing factors of WS have not been well established. AIM: Our aim was to evaluate clinical features and factors associated with WS in the Russian cohort of CML patients who discontinued TKI therapy. MATERIALS AND METHODS: WS was evaluated in total of 183 CML patients with chronic phase and sustained deep molecular response (DMR). WS was defined as a musculoskeletal pain newly observed after TKI cessation or as a worsening of previously observed symptoms. RESULTS: DMR loss free survival at 36 months was 49% and 43% in prospective and retrospective groups respectively (p=0.96) with mеdian (Me) time of observation 33 months (range 1136). WS was observed in 49 (27%) patients: grade 12 was in 45 (92%) patients, grade 3 in 4 (8%) patients. Me time to WS occurrence was 2 months (range 17), Ме duration of WS was 5 months (range 135). WS was resolved in 14 of 15 patients with molecular relapse after 13 months of TKI re-initiation and was decreased in 1 patient. WS was completely resolved in 31 of 34 patients who continued remained in TFR and decreased in 3 patients. WS was resolved spontaneously or with nonsteroidal anti-inflammatory drugs in 14 (45%) and 17 (55%) patients accordingly. Older age (p0.0001), longer duration of TKI therapy (p0.0001) and presence of locomotion system diseases (p=0.022) were observed in patients with WS. No WS was observed in pregnant patients (р0.001). Survival without DMR loss at 12 months after TKI stop was 66 and 42% in patients with and without WS accordingly (р=0.095). CONCLUSION: The rate of WS was 27% that is in a good concordance with the data of the other TFR studies. A longer period of TKI exposure, older age and the history of locomotion system diseases were associated with the development of the WS. We found for the first time that WS was not observed in patients with pregnancy. There was no association of WS development and the rate of molecular relapses.

Review: Tertiary cell wall of plant fibers as a source of inspiration in material design.

The review summarizes the plant lifehacks on material design on the example of the impressive cellulose-enriched cell wall deposited by fibers of many plants. This specific cell wall type is called tertiary since it is deposited after the secondary cell wall and is very distinct in the machinery of formation and function. The basic principles of tertiary cell wall performance include: 1) original composition (two major players - cellulose microfibrils and the version of rhamnogalacturonan I that forms specific supramolecular structures); 2) original cell wall design with axial orientation of all cellulose microfibrils, pronounced lateral interactions between them and the presence of the entrapped rhamnogalacturonan I; 3) dynamic changes in cell wall supramolecular organization due to rhamnogalacturonan I modifications in muro in the course of fiber maturation; 4) the built-in sensors that trace the cell wall state; 5) incorporation of tertiary cell wall into the system with higher level of organization.

Quantitative system for diagnosis of vulvovaginal candidiasis.

INTRODUCTION: Vaginal infections are one of the most common reason for gynecological consultations. Many of them are the result of overgrowth of resident microorganisms. The clinical symptoms of vulvovaginal candidiasis are nonspecific and an accurate diagnosis is a problem that often leads to inadequate treatment or delays in treatment. The lack of an exact and practical diagnostic method is a common cause of misdiagnosis. AIM: To create a complex, quantitative method for the diagnosis of vulvovaginal candidiasis which to enables differentiation from vaginal fungal colonization. MATERIAL AND METHODS: A total of 2306 vaginal samples were examined. Clinical, microbiological, epidemiological methods and statistical models are used. RESULTS AND DISCUSSION: The proposed score system is a specific, sensitive and inexpensive method to routinely diagnose vulvovaginal candidiasis. Statistical processing of the obtained data shows the impact of the individual components on which the method is based: the presence of vaginal discharge, pruritus, direct microscopy and assessment of the fungal growth. The data analysis reveals good sensitivity (71%) and high specificity (98%) of the method. This allows accurate interpretation of the result of the clinical and microbiological examination of each patient. CONCLUSION: The system for diagnosing vulvovaginal candidiasis is complex and based on quantitative indicators. The method can be used to differentiate vulvovaginal candidiasis from vaginal fungal colonization (the cut-off value is 5.5 points) and to more accurately interpret a Candida positive result from quantitative real-time PCR in asymptomatic patients or in women with mixed vaginal infection.

Superoxide Dismutase Activity in Male and Female Patients of Different Age with Moderate COVID-19.

The study involved 271 patients (132 men and 139 women) with moderate COVID-19. Superoxide dismutase (SOD) activity in erythrocytes was measured spectrophotometrically. In total group of patients (divided into age groups of 18-35, 36-45, 46-60, and 61-90 years), higher SOD activity was found in the 18-35 age group in comparison with the groups 46-60 years (p<0.01) and 61-90 years (p<0.05). Then, the groups were additionally divided by sex. In men, no differences in enzyme activity were found between the age groups. In women of early reproductive age, SOD activity was higher than in groups 36-45, 46-60, and 61-90 years. The sex differences consisted in higher SOD activity in women aged 18-35 years in comparison with men of this age. These data should be taken into account when choosing the tactics of therapy for patients with moderate COVID-19 course.

Ultra-rapid and automatic interplay between L1 and L2 semantics in late bilinguals: EEG evidence.

Converging behavioral and neuroimaging evidence suggests parallel activation of native (L1) and second (L2) language codes in bilinguals, with the modulation of the N400 as the most likely neural correlate of such L1-L2 interplay at lexico-semantic level. However, this relatively late effect may reflect secondary controlled processes, in contrast to earlier modulations found in monolinguals (<200 msec) indicative of fast and automatic lexico-semantic L1 access, which has so far not been documented for bilingualism. To address this, we investigated early neurophysiological crosslinguistic activation during bilingual word access. EEG signals were recorded from a group of late bilinguals during a masked-priming crosslinguistic task in which L1 (Russian) words were presented as subliminal primes for 50 msec before L2 (English) target words. Prime-target pairs matched either phonologically only, semantically only, both phonologically and semantically, or did not match. Cluster-based random permutation analyses revealed a main effect of semantic similarity at 40-60 msec over centro-posterior scalp sites, reflecting a negative-going shift of ERP amplitudes for semantically similar prime-target pairs. Importantly, neural source reconstruction showed activations within a left-hemispheric network comprising the middle and superior temporal cortex and the angular gyrus as the most likely neural substrate of this early semantic effect. Furthermore, analyses also revealed significant differences over frontocentral sites for the main effect of semantic and phonological similarity, ranging from 312 to 356 and 380-444 msec respectively, thus confirming previously described N400 crosslinguistic effects. Our findings confirm the existence of an integrated brain network for the bilingual lexicon and reveal the earliest (∼50 msec) crosslinguistic effect reported so far, suggesting fast and automatic L1-L2 interplay, followed by later (possibly top-down controlled) processing stages.

Urinary levels of energy metabolism hormones in association with the proportional intake of maternal milk and weight gain in very preterm neonates.

BACKGROUND: This study prospectively investigated the levels of energy metabolism hormones in very preterm neonates to identify their change over time and association with intake of maternal milk as well as weight gain velocity. METHODS: We measured and compared the leptin, adiponectin, ghrelin, and insulin-like growth factor I (IGF-1) levels in the urine of 70 very preterm neonates, before the initiation of any enteral feeding (baseline level) and twice within 14 days on full enteral feeding (FEF). Regression models identified the role of intake of maternal milk on the levels of the tested energy metabolism hormones in the enteral-fed infants. We also analyzed the adequacy of the weight gain velocity defined by the fetal-infant growth reference (FIGR). Additionally, we collected and analyzed the infants' clinical and feeding characteristics during the birth hospitalization. RESULTS: The preterm infants' baseline levels of the energy metabolism hormones significantly predicted their increase at the end of two weeks of observation on FEF. The leptin level was associated with increased intake of maternal milk, whereas the feeding volume was associated with increased ghrelin and IGF-1, and decreased leptin and adiponectin. Infants with comparable FIGR had higher leptin levels than those with inadequate weight gain velocity. CONCLUSION: Early postnatal levels of leptin, adiponectin, ghrelin, and IGF-1 predicted the increase of these hormones in the fully enteral fed very preterm neonates. Moreover, greater intake of maternal milk by the study infants contributed to an increased leptin-associated weight gain velocity.

Synthesis of C17-[5-methyl-1,3]-oxazoles by N-propargylation of triterpenic acids and evaluation of their cytotoxic activity.

A series of unexpected triterpenic C17-[5-methyl-1,3]-oxazoles along with targeted N-propargylamides was synthesized by an interaction of acid chlorides with propargylamine hydrochloride. We proposed that the formation of methyl oxazole passes through an alternative pathway by the participation of the terminal alkyne carbon atom and acid chloride intermediate with following intramolecular rearrangements. The synthesized compounds were evaluated for their cytotoxicity at the U.S. National Cancer Institute. 28-Nor-17-(5-methyloxazol-2-yl)-2-cyano-2,4-seco-3-nor-lup-4(23),20(29)-diene has demonstrated the highest activity with GI50 ranged from 1.03 to 16.4 µM against different cancer cell lines. Molecular docking in Kelch domain of Keap1 protein was performed to study a possible molecular target. Thus, we have shown for the first time that triterpenic C17-[5-methyl-1,3]-oxazoles are alternative products of the interaction of triterpenic acid chlorides with propargylamine hydrochloride and they have an advantage over corresponding N-propargylamides as cytotoxic agents.

THE EFFECTIVENESS OF MELATONIN IN THE COMPLEX TREATMENT OF HYPERTENSION IN PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE.

In recent years, there has been a progressive increase in the number of patients with chronic kidney disease (CKD), whose mortality risk is significantly higher than in general patients, which is associated with cardiovascular risks.In patients with CKD stage 5D before the start of replacement renal therapy for hypertension exceeds 90%. The aim -to analyze the efficacy and safety of the use of melatonin in the complex treatment of arterial hypertension (AH) in patients with CKD of 5 stage with impaired melatonin-forming function of the epiphysis (MFE). 60 people (35 women and 25 men) with a chronic kidney disease of 5 stage, which have violated MFE and AH were examined. For all patients in addition to antihypertensive therapy were prescribed the drug melatonin at a dose of 3 mg, which was taken once a day at 22:00 for 8 weeks. For all examined, before and after the course of treatment, were measured blood pressure (BP), Ambulatory Blood Pressure Monitoring (ABPM) and determination of the concentration of melatonin in the salivaby immunosorbent method. The examined patients showed a high frequency of MFE disturbance both in the daytime and at night - respectively, in 52,4% (p<0,001) and 82,6% (p<0,001). The dynamics of the diurnal BP on the background of treatment was due to changes in the degree of nocturnal decrease of BP, the number of patients in the main group with the "non-dipper" profile, decreased from 44,5% to 27,6% (p<0,05%), the proportion of patients with a daily profile of BP "night-peakear" from 22,4% to 4,8% (p<0,05%). Besides, a statistically significant of the number of persons with a daily profile of BP "dipper" increase in 30,2%. Against the background of complex treatment, there was a decrease in the patient's need for the dose and amount of antihypertensive drugs to achieve BP targets. Our data show a high incidence of MFE disorders in patients with CKD stage VD, and adding to the antihypertensive therapy of the drug melatonin in patients with CKD of 5 stage is effective and safe.

Multipotent Mesenchymal Stromal Cells in Patients with Chronic Myeloid Leukemia before Discontinuation of Tyrosine Kinase Inhibitors.

We analyzed changes in multipotent mesenchymal stromal cells of patients with chronic myeloid leukemia before discontinuation of tyrosine kinase inhibitors. Withdrawal syndrome was significantly more common in patients who have been taking tyrosine kinase inhibitors for a longer time and in patients of older age and with lower body weight. In patients with withdrawal syndrome, the total production of mesenchymal stromal cells and expression of FGFR2 and MMP2 genes were significantly lower; loss of deep molecular response was also less frequent in this group of patients. At the same time, the expression of genes important for the maintenance of stem cells (SOX9, PDGFRa, and LIF) was significantly lower in the mesenchymal stromal cells of patients with withdrawal syndrome and loss of deep molecular response. We observed a clear-cut relationship between the development of withdrawal syndrome and the loss of deep molecular response. The decrease in the expression of FGFR2 and MMP2 genes in the mesenchymal stromal cells of patients with chronic myeloid leukemia before discontinuation of treatment can be a predictor of withdrawal syndrome, while simultaneous decrease in the expression of SOX9, PDGFRa, and LIF in these cells attests to undesirability of therapy discontinuation at the moment.

[The intraoperative prophylaxis of local ischemical brain damage in neurosurgical patients with cerebral aneurysm]. / Intraoperatsionnaia profilaktika lokal'nogo ishemicheskogo povrezhdeniia golovnogo mozga u neirokhirurgicheskikh patsientov s tserebral'noi anevrizmoi.

AIM: To study the effectiveness of intraoperative administration of Cytoflavine for the prevention of ischemic brain injury during cerebral aneurysm (CA) clipping with temporary occlusion of the leading artery under general anesthesia. MATERIAL AND METHODS: The prospective cohort single-center study included 40 patients with CA ( the main group - 27 patients with intraoperative administration of cytoflavine; the comparison group -13 patients without use of cytoflavine), who underwent aneurism clipping with temporary occlusion of the afferent artery. We assesed the intraoperative state of the brain, the time of awakening and extubation of patients after surgery, neurological deficit and local ischemic changes in the area of surgery according to the CT of the brain in the early postoperative period, resuscitation bed-day and the relationship of these indicators with the duration of temporary occlusion of the afferent artery in the selected groups of patients. RESULTS: In intergroup comparison, patients of the main group treated with intraoperative cytoflavin showed a reduction in the time of awakening (p=0.013) and the time of extubation (p=0.01) both with temporary occlusion of the afferent artery and in patients without temporary occlusion (p<0.05). The duration of resuscitation bed-day decreased in the main group of patients receiving intraoperatively cytoflavine (p=0.01), as well as in patients in the comparison group without temporary occlusion (p<0.05). CONCLUSION: Temporary occlusion of the afferent artery with short intervals of vessel occlusion in combination with intraoperative intravenous administration of cytoflavine expands the tolerability to artery occlusion in patients operated in the 'cold' period, reduces the possibility of neurological deficit, reduces the recovery period and resuscitation bed-day after surgical clipping CA.

[Problems of diagnostics and treatment of transtiretinum amyloidosis with destruction of the heart in the elderly: Clinical experience.]

The article presents a modern understanding of the treatment of cardiac amyloidosis, provides data on the frequency of occurrence, classification and variants of clinical manifestations of transthyretin amyloidosis. This pathology is a slowly progressive disease, the symptoms of which usually appear in the elderly and senile age. This diagnosis may become more common in the future as the population ages and diagnostic methods improve. As an illustration, a description of the clinical case of transtritin amyloidosis of the heart in a 77-year-old patient, which occurred with a primary lesion of the heart and symptoms of chronic heart failure, is given. It shows the difficulties in the lifetime diagnosis of transthyretin amyloidosis.