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The Covid-19 pandemic has posed a major challenge to the entire world. Even for the countries with big economics this challenge turned out to be hard to overcome. The “paused” world tried to fight against the most inexplicable economic crisis with the use of digital technologies. The era of digital technology development is a period of limitless possibilities for modern managers. Managing a company easily and efficiently is already unthinkable without information technology and digital platforms maintaining competitiveness in the market, relieving employees from routine tasks, optimizing processes, taking care of development - these are the minimum requirements, that are difficult to achieve in modern conditions without technological progress. The issue of information security and integration of modern technologies, in the management process, during the COVID-19 pandemic, became even more urgent and vital for some organizations, as many of them had to work remotely for quite a long time during the entire period. Every good project manager knows that one of the main tools for effectively developing a team and completing a project with the best results is fast and quality communication. To ensure this, companies use platforms where employees can centrally and transparently communicate with each other and monitor the progress of the work process. In the conditions of switching to remote work mode, it has become a daily necessity to hold meetings, trainings, conferences and lectures or lessons online, therefore, it is important to select programs tailored to the specifics of our activity, which are specially designed for this purpose. In this case, Georgia turned out to be quite ready, too. Within just couple of days the country managed to organize the transition of the state as well as private sector to the remote working mode, and got the 2nd place among the top 50 countries, where remote working is the most convenient and comfortable

The present empirical paper investigates the following issues: the formation of the Georgian currency system that started after the collapse of the Soviet Union, when the country has declared its independence, establishing the National Bank of Georgia and issuing the national currency. Also is discussed financial market where foreign exchange and transaction are made. As it is known today, in the international currency market, 90% of the world market holds the FOREX (Foreign Exchange Market), which makes it the largest foreign exchange market in the world. FOREX currency traders, together with traditional forms, offers the most modern and comfortable form of trade - Online trading. The existing currencies are largely proportional to the ongoing processes of the FOREX market. Keywords: Currency, Currency Exchange Rate, Currency Market, Interbank Exchange Market, Foreign Exchange, FOREX Market.

One of the most unsolvable problems for developing countries still remains the drop of their national currency course, it is the result of many factors that take place in economy overall and also of the errors that are committed by the central banks of these countries. All that triggers the impoverishment and decreases the level of earning of population. The central bank should choose floating or fixed currency system, as for developing countries it is extremely important to stabilize the national currency course.

Objective— Abnormalities in nitric oxide (NO) bioavailability have been reported in blacks. Whether there are differences in endothelium-derived hyperpolarizing factor (EDHF) in addition to NO between blacks and whites and how these affect physiological vasodilation remain unknown. We hypothesized that the bioavailability of vascular NO and EDHF, at rest and with pharmacological and physiological vasodilation, varies between whites and blacks. Approach and Results— In 74 white and 86 black subjects without known cardiovascular disease risk factors, forearm blood flow was measured using plethysmography at rest and during inhibition of NO with N G -monomethyl- l -arginine and of K + Ca channels (EDHF) with tetraethylammonium. The reduction in resting forearm blood flow was greater with N G -monomethyl- l -arginine ( P =0.019) and similar with tetraethylammonium in whites compared with blacks. Vasodilation with bradykinin, acetylcholine, and sodium nitroprusside was lower in blacks compared with whites (all P G -monomethyl- l -arginine was greater in whites compared with blacks with bradykinin, acetylcholine, and exercise. Inhibition with tetraethylammonium was lower in blacks with bradykinin, but greater during exercise and with acetylcholine. Conclusions— The contribution to both resting and stimulus-mediated vasodilator tone of NO is greater in whites compared with blacks. EDHF partly compensates for the reduced NO release in exercise and acetylcholine-mediated vasodilation in blacks. Preserved EDHF but reduced NO bioavailability and sensitivity characterizes the vasculature in healthy blacks. Clinical Trial Registration— URL: http://clinicaltrials.gov/ . Unique identifier: NCT00166166.

a Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States b Division of Pulmonary Medicine, Emory University School of Medicine, Atlanta, GA, United States c Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, United States d Department of Dermatology, Atlanta VA Medical Center and Emory University School of Medicine, Atlanta, GA, United States e Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, United States

Aims: Bradykinin (BK) stimulates tissue plasminogen activator (t-PA) release from human endothelium. Although BK stimulates both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) release, the role of EDHF in t-PA release remains unexplored. This study sought to determine the mechanisms of BK-stimulated t-PA release in the forearm vasculature of healthy human subjects. Methods: In 33 healthy subjects (age 40.3 ± 1.9 years), forearm blood flow (FBF) and t-PA release were measured at rest and after intra-arterial infusions of BK (400 ng/min) and sodium nitroprusside (3.2 mg/min). Measurements were repeated after intra-arterial infusion of tetraethylammonium chloride (TEA; 1 µmol/min), fluconazole (0.4 µmol·min-1·l-1), and NG-monomethyl-L-arginine (L-NMMA, 8 µmol/min) to block nitric oxide, and their combination in separate studies. Results: BK significantly increased net t-PA release across the forearm (p < 0.0001). Fluconazole attenuated both BK-mediated vasodilation (-23.3 ± 2.7% FBF, p < 0.0001) and t-PA release (from 50.9 ± 9.0 to 21.3 ± 8.9 ng/min/100 ml, p = 0.02). TEA attenuated FBF (-14.7 ± 3.2%, p = 0.002) and abolished BK-stimulated t-PA release (from 22.9 ± 5.7 to -0.8 ± 3.6 ng/min/100 ml, p = 0.0002). L-NMMA attenuated FBF (p < 0.0001), but did not inhibit BK-induced t-PA release (nonsignificant). Conclusion: BK-stimulated t-PA release is partly due to cytochrome P450-derived epoxides and is inhibited by K+Ca channel blockade. Thus, BK stimulates both EDHF-dependent vasodilation and t-PA release.

Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective β1 -antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12-week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-N(G) -monomethylarginine (L-NMMA) and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P

The role of endothelium-derived hyperpolarizing factor (EDHF) in either the healthy circulation or in those with hypercholesterolemia is unknown. In healthy and hypercholesterolemic subjects, we measured forearm blood flow (FBF) using strain-gauge plethysmography at rest, during graded handgrip exercise, and after sodium nitroprusside infusion. Measurements were repeated after l-NMMA, tetraethylammonium (TEA), and combined infusions. At rest, l-NMMA infusion reduced FBF in healthy but not hypercholesterolemic subjects. At peak exercise, vasodilation was lower in hypercholesterolemic compared to healthy subjects (274% vs 438% increase in FBF, p=0.017). TEA infusion reduced exercise-induced vasodilation in both healthy and hypercholesterolemic subjects (27%, p

Unlike traditional beta receptor antagonists, nebivolol activates nitric oxide. We hypothesized that therapy with nebivolol compared with metoprolol would improve arterial stiffness, increase levels of circulating progenitor cells (PC), and decrease oxidative stress (OS). In a randomized, double–blind, cross–over study, 30 hypertensive subjects received either once daily nebivolol or metoprolol succinate for 3 months each. Pulse wave velocity and augmentation index were measured using tonometry. Flow cytometry was used to measure circulating PC. OS was measured as plasma aminothiols. Measurements were performed at baseline, and repeated at 3 and 6 months. No significant differences were present between the levels of OS, arterial stiffness, and PC numbers during treatment with metoprolol compared with nebivolol. In subgroup analyses of beta–blocker naive subjects (n = 19), nebivolol reduced pulse wave velocity significantly compared with metoprolol (−1.4 ± 1.9 vs. −0.1 ± 2.2; P = .005). Both nebivolol and metoprolol increased circulating levels of CD34+/CD133 + PC similarly ( P = .05), suggesting improved regenerative capacity.

Heritable factors play a key role in the development of coronary heart disease.1 Early unbiased genome-wide approaches have led to the identification of more than a dozen novel risk loci for myocardial infarction (MI) in predominantly Caucasian cohorts.2–8 Many loci have replicated in large cohorts, yet of these only four appear to have a mechanistically relevant basis through lipid metabolism pathways (1p13, 1p32, 19p13, 6q26).9,10 The remaining loci span genomic regions that as yet have no clearly defined mechanism to explain MI risk. Valuable insights into the functions of these variants may be gleaned by studying their effects on related or intermediate phenotypes which may be causal in the pathway to developing MI. This is best illustrated by the initial association of 1p13 with MI and then with the intermediate phenotype of lipid levels, with subsequent functional studies identifying its role in cellular cholesterol transport through the sortillin protein.11 Another intermediate phenotype of interest in vascular disease is abnormal pressure wave reflection within the arterial tree. Abnormalities in these arterial tree properties occur due to complex composite changes in parameters such as arterial stiffness and vasomotor tone, ultimately leading to increased left ventricular after-load and cardiovascular events such as myocardial ischemia, MI, and stroke.12–15 We therefore investigated the association of variants at eight MI risk loci, whose mechanisms of action are currently unknown, with noninvasively derived pulse wave analysis (PWA) indexes including the magnitude and timing of reflected arterial pressure waveforms in two separate Caucasian populations. The first consisting of very healthy subjects, free of confounding risk factors to enable an assessment of direct genetic risk and the second, an unselected community-based population that allowed determination of genetic effects in the context of common risk factors. We hypothesized that some or all of these markers would demonstrate association with indexes of adverse arterial wave reflection.

Background— We assessed the contribution of endothelium-derived hyperpolarizing factors to resting and agonist-stimulated vasodilator tone in health and disease. Tetraethylammonium chloride (TEA) was used to inhibit K + Ca channel activation and fluconazole was used to inhibit cytochrome P450 2C9–mediated epoxyeicosatrienoic acid synthesis. We hypothesized that endothelium-derived hyperpolarizing factors contribute to resting vascular tone by K + Ca channel activation and epoxyeicosatrienoic acid release and that endothelium-derived hyperpolarizing factors compensate for reduced nitric oxide bioavailability at rest and with endothelium-dependent vasodilators. Methods and Results— In 103 healthy subjects and 71 nonhypertensive subjects with multiple risk factors, we measured resting forearm blood flow (FBF) using venous occlusion plethysmography before and after intra-arterial infusions of N G -monomethyl- l -arginine (L-NMMA), TEA, fluconazole, and their combination. The effects of these antagonists on resting FBF and on bradykinin- and acetylcholine-mediated vasodilation were studied. Resting FBF decreased with TEA and L-NMMA in all subjects ( P P =0.04) and to TEA was lower ( P =0.04) in healthy subjects compared with those with risk factors. Fluconazole decreased resting FBF in all subjects, and the addition of TEA further reduced FBF after fluconazole, suggesting that cytochrome P450 metabolites and other hyperpolarizing factor(s) activate K + Ca channels. Both L-NMMA and TEA attenuated bradykinin-mediated vasodilation in healthy and hypercholesterolemic subjects ( P P Conclusions— First, by activating TEA-inhibitable K + Ca channels, endothelium-derived hyperpolarizing factors, together with nitric oxide, contribute to resting microvascular dilator tone. The contribution of K + Ca channel activation compared with nitric oxide is greater in those with multiple risk factors compared with healthy subjects. Second, activation of K + Ca channels is only partly through epoxyeicosatrienoic acid release, indicating the presence of other hyperpolarizing mechanisms. Third, bradykinin, but not acetylcholine, stimulates K + Ca channel–mediated vasodilation in healthy subjects, whereas in hypercholesterolemia, K + Ca channel-mediated vasodilation compensates for the reduced nitric oxide activity. Thus, enhanced endothelium-derived hyperpolarizing factor activity in conditions of nitric oxide deficiency contributes to maintenance of resting and agonist-stimulated vasodilation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00166166.

Arterial stiffening may lead to hypertension, greater left ventricular after-load and adverse clinical outcomes. The underlying mechanisms influencing arterial elasticity may involve oxidative injury to the vessel wall. We sought to examine the relationship between novel markers of oxidative stress and arterial elastic properties in healthy humans.We studied 169 subjects (mean age 42.6 ± 14 years, 51.6% male) free of traditional cardiovascular risk factors. Indices of arterial stiffness and wave reflections measured included carotid-femoral Pulse Wave Velocity (PWV), Augmentation Index (Aix) and Pulse Pressure Amplification (PPA). Non-free radical oxidative stress was assessed as plasma oxidized and reduced amino-thiol levels (cysteine/cystine, glutathione/GSSG) and their ratios (redox potentials), and free radical oxidative stress as derivatives of reactive oxygen metabolites (dROMs). Inflammation was assessed as hsCRP and interleukin-6 levels. The non-free radical marker of oxidative stress, cystine was significantly correlated with all arterial indices; PWV (r=0.38, p0.001), Aix (r=0.35, p0.001) and PPA (r=-0.30, p0.001). Its redox potential, was also associated with PWV (r=0.22, p=0.01), while the free radical marker of oxidative stress dROMS was associated with Aix (r=0.25, p0.01). After multivariate adjustment for age, gender, arterial pressure, height, weight, heart rate and CRP, of these oxidative stress markers, only cystine remained independently associated with PWV (p=0.03), Aix (p=0.01) and PPA (p=0.05).In healthy subjects without confounding risk factors or significant systemic inflammation, a high cystine level, reflecting extracellular oxidant burden, is associated with increased arterial stiffness and wave reflections. This has implications for understanding the role of oxidant burden in pre-clinical vascular dysfunction.

Background: Physical activity is a determinant of cardiovascular performance and a predictor of risk. Levels of progenitor cells that contribute to repair of tissues including the cardiovascular system are modulated by cardiovascular risk factors and disease. Similarly, adiponectin levels, an anti-inflammatory adipokine, may be modulated by the sedentary state. We hypothesized that the benefits of physical activity may include enhancing the circulating progenitor cell counts and raising adiponectin levels. We investigated this relationship in healthy subjects. Methods: We studied 61 healthy, non-obese subjects free of risk factors (age 43±13 years, BMI 24.2±3.4 kg/m 2 ). Levels of light (6 METS) and total physical activity, expressed as MET-minutes/day of energy expenditure, were derived from the validated Cross-Cultural Activity Participation Study (CAPS) Typical Week Activity questionnaire. Levels of CD34+ hematopoetic progenitor cells and the sub-populations enriched for endothelial progenitors including CD34+/CD133+, CD34+/KDR+ and CD34+/CD133+/KDR+ cells were measured by flow cytometry. Adiponectin was measured by ELISA (n= 32). Results: The CD34+ count correlated with light (r = 0.30, p Conclusion: We show for the first time in a healthy, non-obese population that vigorous physical activity is associated increased levels of hematopoeitic and endothelial progenitors. Greater activity is also associated with increased adiponectin levels. These findings provide insights into the mechanisms underlying the protective role of regular exercise in cardiovascular and metabolic health.

We previously suggested that women with endometriosis have increased oxidative stress in the peritoneal cavity. To assess whether antioxidant supplementation would ameliorate endometriosis-associated symptoms, we performed a randomized, placebo-controlled trial of antioxidant vitamins (vitamins E and C) in women with pelvic pain and endometriosis. Fifty-nine women, ages 19 to 41 years, with pelvic pain and history of endometriosis or infertility were recruited for this study. Patients were randomly assigned to 2 groups: vitamin E (1200 IU) and vitamin C (1000 mg) combination or placebo daily for 8 weeks before surgery. Pain scales were administered at baseline and biweekly. Inflammatory markers were measured in the peritoneal fluid obtained from both groups of patients at the end of therapy. Our results indicated that after treatment with antioxidants, chronic pain (“everyday pain”) improved in 43% of patients in the antioxidant treatment group ( P = 0.0055) compared with the placebo group. In the same group, dysmenorrhea (“pain associated with menstruation”) and dyspareunia (“pain with sex”) decreased in 37% and 24% patients, respectively. In the placebo group, dysmenorrhea-associated pain decreased in 4 patients and no change was seen in chronic pain or dyspareunia. There was a significant decrease in peritoneal fluid inflammatory markers, regulated upon activation, normal T-cell expressed and secreted ( P ≤ 0.002), interleukin-6 ( P ≤ 0.056), and monocyte chemotactic protein-1 ( P ≤ 0.016) after antioxidant therapy compared with patients not taking antioxidants. The results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers in the peritoneal fluid.

Objective To determine the contribution of endometrial cells in the development of endometriosis. Specifically the response of the mesothelium to endometrial cells in the production of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), and IL-8 was studied. Design In vitro study. Setting University Research Laboratory. Patients None. Intervention(s) None. Main outcome measure(s) Cellular MCP-1, IL-6 secretion and MCP-1, and IL-6 and IL-8 messenger RNA expression were evaluated by ELISA and reverse transcription-polymerase chain reaction (RT-PCR) assay. Result(s) The mesothelial cells produced more MCP-1 and IL-6 than endometrial epithelial and stromal cells. Mesothelial cells cultured in the presence of endometrial epithelial cells produced even greater levels of MCP-1 and IL-6 than those cultured in the presence of stromal cells or cultured alone. The MCP-1, IL-6, and IL-8 mRNA expression also increased when mesothelial cells were co-cultured with endometrial epithelial cells. Conclusion(s) The results suggest that endometrial epithelial cells may be important in evoking the inflammatory reaction in the peritoneal cavity during retrograde menstruation and that mesothelial cells may play an important role in the chemotaxis of monocytes and in the inflammatory process during the development of endometriosis.

Background Epoxyeicosatrienoic acids are arachidonic-acid-derived products of cytochrome P450 (CYP450) epoxygenases. Endothelium-derived hyperpolarizing factor (EDHF) stimulates calcium dependent potassium channels by CYP450 metabolites that can be inhibited with fluconazole (FLU). The role of EDHF in impaired endothelial function remains undefined. We hypothesised a differential contribution of EDHF in diabetics (DM) compared to healthy subjects. Methods In 16 healthy and 14 DM subjects, we measured forearm blood flow (FBF) with venous occlusion strain gauge plethysmography at rest and after endothelium-dependent and -independent vasodilation with acetylcholine (7.5, 15, 30 μg/min) or bradykinin (100, 200, 400 ng/min) and sodium nitroprusside (1.6 and 3.2 μg/min), respectively. Measurements were repeated after NO blockade with LNG monomethyl arginine (L-NMMA, 8 μmol/min), CYP450 blockade with fluconazole (0.4–1.6 μmol/min) and combined NO and CYP450 blockade. Results L-NMMA reduced resting FBF by −1.75 mls/min (p Conclusions NO is the major contributor to resting vasodilator tone in healthy subjects, whereas both NO and hyperpolarisation via CYP450 metabolites contribute to resting tone in DM. However, in the absence of NO in healthy subjects CYP450 metabolites were observed to have an important contribution suggesting an upregulation of EDHF activity via CYP450 metabolites when there is a decreased NO bioavailability. CYP450 metabolites do not contribute to pharmacologically stimulated vasodilation in either DM or healthy subjects, but whether other EDHFs play a role needs to be studied.

ObjectivesThe primary objective of this study was to elucidate mechanisms underlying the link between vitamin D status and cardiovascular disease by exploring the relationship between 25-hydroxyvitamin D (25-OH D), an established marker of vitamin D status, and vascular function in healthy adults.BackgroundMechanisms underlying vitamin D deficiency-mediated increased risk of cardiovascular disease remain unknown. Vitamin D influences endothelial and smooth muscle cell function, mediates inflammation, and modulates the renin-angiotensin-aldosterone axis. We investigated the relationship between vitamin D status and vascular function in humans, with the hypothesis that vitamin D insufficiency will be associated with increased arterial stiffness and abnormal vascular function.MethodsWe measured serum 25-OH D in 554 subjects. Endothelial function was assessed as brachial artery flow-mediated dilation, and microvascular function was assessed as digital reactive hyperemia index. Carotid-femoral pulse wave velocity and radial tonometry-derived central augmentation index and subendocardial viability ratio were measured to assess arterial stiffness.ResultsMean 25-OH D was 31.8 ± 14 ng/ml. After adjustment for age, sex, race, body mass index, total cholesterol, low-density lipoprotein, triglycerides, C-reactive protein, and medication use, 25-OH D remained independently associated with flow-mediated vasodilation (β = 0.1, p = 0.03), reactive hyperemia index (β = 0.23, p < 0.001), pulse wave velocity (β = −0.09, p = 0.04), augmentation index (β = −0.11, p = 0.03), and subendocardial viability ratio (β = 0.18, p = 0.001). In 42 subjects with vitamin D insufficiency, normalization of 25-OH D at 6 months was associated with increases in reactive hyperemia index (0.38 ± 0.14, p = 0.009) and subendocardial viability ratio (7.7 ± 3.1, p = 0.04), and a decrease in mean arterial pressure (4.6 ± 2.3 mm Hg, p = 0.02).ConclusionsVitamin D insufficiency is associated with increased arterial stiffness and endothelial dysfunction in the conductance and resistance blood vessels in humans, irrespective of traditional risk burden. Our findings provide impetus for larger trials to assess the effects of vitamin D therapy in cardiovascular disease.