54 research outputs found
Critical illness induces alternative activation of M2 macrophages in adipose tissue
INTRODUCTION: We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown. METHODS: We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n=20) and non-surviving prolonged critically ill patients (n=61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients. RESULTS: Subcutaneous and visceral adipose tissue biopsies from nonsurviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-alpha and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-gamma PPARgamma a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARgamma protein levels. CONCLUSIONS: Unlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2 macrophages, which have local anti-inflammatory and insulin sensitizing features. This M2 macrophage accumulation may contribute to the previously observed protective metabolic activity of adipose tissue during critical illness.status: publishe
Impact of Parenteral Nutrition Versus Fasting on Hepatic Bile Acid Production and Transport in a Rabbit Model of Prolonged Critical Illness
Cholestatic liver dysfunction frequently occurs during critical illness. Administration of parenteral nutrition (PN) is thought to aggravate this. Underlying mechanisms are not clear.status: publishe
Changes in the central component of the hypothalamus-pituitary-thyroid axis in a rabbit model of prolonged critical illness
Introduction: Prolonged critically ill patients reveal low circulating thyroid hormone levels without a rise in thyroid stimulating hormone (TSH). This condition is labeled "low 3,5,3'-tri-iodothyronine (T3) syndrome" or "nonthyroidal illness syndrome (NTI)" or "euthyroid sick syndrome". Despite the low circulating and peripheral tissue thyroid hormone levels, thyrotropin releasing hormone (TRH) expression in the hypothalamus is reduced and it remains unclear which mechanism is responsible. We set out to study whether increased hypothalamic T3availability could reflect local thyrotoxicosis and explain feedback inhibition-induced suppression of the TRH gene in the context of the low T3syndrome in prolonged critical illness.Methods: Healthy rabbits were compared with prolonged critically ill, parenterally fed animals. We visualized TRH mRNA in the hypothalamus by in situ-hybridization and measured mRNA levels for the type II iodothyronine diodinase (D2), the thyroid hormone transporters monocarboxylate transporter (MCT) 8, MCT10 and organic anion co-transporting polypeptide 1C1 (OATP1C1) and the thyroid hormone receptors α (TRα) and ÎČ (TRÎČ) in the hypothalamus. We also measured the activity of the D2 and type III iodothyronine deiodinase (D3) enzymes.Results: In the hypothalamus of prolonged critically ill rabbits with low circulating T3 and TSH, we observed decreased TRH mRNA, increased D2 mRNA and increased MCT10 and OATP1C1 mRNA while MCT8 gene expression was unaltered as compared with healthy controls. This coincided with low hypothalamic thyroxine (T4) and low-normal T3concentrations, without a change at the thyroid hormone receptor level.Conclusions: Although expression of D2 and of the thyroid hormone transporters MCT10 and OATP1C1 were increased in the hypothalamus of prolonged critical ill animals, hypothalamic T4and T3content or thyroid hormone receptor expression were not elevated. Hence, decreased TRH gene expression, and hereby low TSH and T3 during prolonged critical illness, is not exclusively brought about by hypothalamic thyrotoxicosis, and infer other TRH suppressing factors to play a role
ĐĐœĐ”ŃĐœĐ”ŃĐŸŃĐłĐŸĐČĐŸĐ” ŃĐŸŃŃŃĐŽĐœĐžŃĐ”ŃŃĐČĐŸ Đ Đ”ŃĐżŃблОĐșĐž ĐĐŸŃĐ”Ń ŃĐŸ ŃŃŃĐ°ĐœĐ°ĐŒĐž ĐĄĐ”ĐČĐ”ŃĐŸ-ĐĐŸŃŃĐŸŃĐœĐŸĐč ĐзОО
ĐŃлДЎŃŃĐČОД бŃŃŃŃĐŸĐłĐŸ ŃĐ°Đ·ĐČĐžŃĐžŃ Đž ŃŃĐ»ĐŸĐ¶ĐœĐ”ĐœĐžŃ ĐŒĐžŃĐŸŃ
ĐŸĐ·ŃĐčŃŃĐČĐ”ĐœĐœŃŃ
ŃĐČŃĐ·Đ”Đč Đž ŃĐŸŃĐłĐŸĐČĐŸ-ŃĐșĐŸĐœĐŸĐŒĐžŃĐ”ŃĐșĐŸĐłĐŸ ĐČĐ·Đ°ĐžĐŒĐŸĐŽĐ”ĐčŃŃĐČĐžŃ ĐłĐŸŃŃĐŽĐ°ŃŃŃĐČ, ŃĐ”ĐœĐŽĐ”ĐœŃОО ŃĐ°Đ·ĐČĐžŃОД ĐŒĐ”Đ¶ĐŽŃĐœĐ°ŃĐŸĐŽĐœĐŸĐłĐŸ ŃĐŸŃŃŃĐŽĐœĐžŃĐ”ŃŃĐČĐ° ĐżŃĐžĐŸĐ±ŃĐ”ŃĐ°ŃŃ ĐŸŃĐŸĐ±ŃŃ Đ°ĐșŃŃĐ°Đ»ŃĐœĐŸŃŃŃ. ĐĄĐ”ĐČĐ”ŃĐŸ-ĐĐŸŃŃĐŸŃĐœĐ°Ń ĐĐ·ĐžŃ (ĐĄĐĐ) â ŃŃĐŸ ŃĐ”ĐłĐžĐŸĐœ, ĐČ ĐșĐŸŃĐŸŃĐŸĐŒ ĐŸŃĐ”ĐœŃ ŃĐŸĐœĐșĐŸ пДŃДплДŃĐ°ŃŃŃŃ ĐžŃŃĐŸŃĐžŃĐ”ŃĐșОД, ĐžĐŽĐ”ĐŸĐ»ĐŸĐłĐžŃĐ”ŃĐșОД, ĐżĐŸĐ»ĐžŃĐžŃĐ”ŃĐșОД ĐŸŃĐŸĐ±Đ”ĐœĐœĐŸŃŃĐž Đž ŃĐșĐŸĐœĐŸĐŒĐžŃĐ”ŃĐșĐ°Ń ŃДлДŃĐŸĐŸĐ±ŃĐ°Đ·ĐœĐŸŃŃŃ ŃĐŸŃĐłĐŸĐČлО. ĐĄŃŃĐ°ĐœĐŸĐČĐŸĐč ŃĐŸŃŃĐ°ĐČ ŃĐ”ĐłĐžĐŸĐœĐ° ĐĄĐ”ĐČĐ”ŃĐŸ-ĐĐŸŃŃĐŸŃĐœĐŸĐč ĐзОО ĐŒĐŸĐ¶Đ”Ń ŃĐ°ŃŃĐŒĐ°ŃŃĐžĐČĐ°ŃŃŃŃ Ń ŃĐ°Đ·ĐœŃŃ
ŃĐŸŃĐ”Đș Đ·ŃĐ”ĐœĐžŃ, ĐČ ŃĐ°ĐŒĐșĐ°Ń
ĐŽĐ°ĐœĐœĐŸĐłĐŸ ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ ĐżĐŸĐŽ ŃŃŃĐ°ĐœĐ°ĐŒĐž ĐŽĐ°ĐœĐœĐŸĐłĐŸ ŃĐ”ĐłĐžĐŸĐœĐ° ĐżĐŸĐœĐžĐŒĐ°ŃŃŃŃ Đ Đ”ŃĐżŃблОĐșĐ° ĐĐŸŃĐ”Ń, ĐĐžŃĐ°Đč, ĐŻĐżĐŸĐœĐžŃ Đž ĐČŃŃ Đ ĐŸŃŃĐžŃ.
ĐĐ·Đ°ĐžĐŒĐŸĐŽĐ”ĐčŃŃĐČОД Đ Đ”ŃĐżŃблОĐșĐž ĐĐŸŃĐ”Ń Ń ĐșажЎŃĐŒ Оз ŃŃĐ”Ń
ĐłĐŸŃŃĐŽĐ°ŃŃŃĐČ ĐžĐŒĐ”Đ”Ń ŃĐœĐžĐșĐ°Đ»ŃĐœŃŃ ĐžŃŃĐŸŃĐžŃ, ĐŽĐŸŃŃĐ°ŃĐŸŃĐœŃĐč ĐżĐŸŃĐ”ĐœŃОал ĐŽĐ»Ń ŃĐ°Đ·ĐČĐžŃĐžŃ ŃĐŸŃĐłĐŸĐČлО, Đ° ŃĐ°ĐșжД ŃĐČĐŸĐž ĐŸŃĐŸĐ±Đ”ĐœĐœĐŸŃŃĐž ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐČĐœĐ”ŃĐœĐ”ŃĐșĐŸĐœĐŸĐŒĐžŃĐ”ŃĐșĐžŃ
ŃĐČŃĐ·Đ”Đč. ĐŁŃĐžĐ»Đ”ĐœĐžĐ” ŃĐŸĐ»Đž ĐĐžŃĐ°Ń ĐČ ĐșĐ°ŃĐ”ŃŃĐČĐ” ŃĐŸŃĐłĐŸĐČĐŸĐłĐŸ паŃŃĐœĐ”ŃĐ°, ŃĐœĐžĐ¶Đ”ĐœĐžĐ” Đ·ĐœĐ°ŃĐžĐŒĐŸŃŃĐž ĐŻĐżĐŸĐœĐžĐž Đž ŃĐ»ĐŸĐ¶ĐœĐ°Ń ŃĐșĐŸĐœĐŸĐŒĐžŃĐ”ŃĐșĐ°Ń ŃĐžŃŃĐ°ŃĐžŃ ĐČ Đ ĐŸŃŃОО ĐœĐ° ŃĐ”ĐșŃŃĐžĐč ĐŒĐŸĐŒĐ”ĐœŃ ĐŸĐșĐ°Đ·ŃĐČĐ°ŃŃ ŃŃŃĐ”ŃŃĐČĐ”ĐœĐœĐŸĐ” ĐČлОŃĐœĐžĐ” ĐœĐ° ŃĐ°Đ·ĐČĐžŃОД Đ Đ”ŃĐżŃблОĐșĐž ĐĐŸŃĐ”Ń, ĐŸĐżĐŸŃĐŸĐč ŃĐșĐŸĐœĐŸĐŒĐžŃĐ”ŃĐșĐŸĐłĐŸ ŃĐŸŃŃĐ° ĐșĐŸŃĐŸŃĐŸĐč ŃŃĐ°ĐŽĐžŃĐžĐŸĐœĐœĐŸ ŃĐČĐ»ŃлаŃŃ ŃĐŸŃĐłĐŸĐČĐ»Ń. ĐŃĐž ŃŃĐž ŃŃŃĐ°ĐœŃ ŃĐČĐ»ŃŃŃŃŃ ĐŸĐŽĐœĐžĐŒĐž Оз ĐČĐ°Đ¶ĐœĐ”ĐčŃĐžŃ
паŃŃĐœĐ”ŃĐŸĐČ ĐŽĐ»Ń Đ Đ”ŃĐżŃблОĐșĐž ĐĐŸŃĐ”Ń, ĐżĐŸŃŃĐŸĐŒŃ ĐžĐ·ŃŃĐ”ĐœĐžĐ” ĐżŃĐŸŃĐ”ŃŃĐŸĐČ ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐČĐœĐ”ŃĐœĐ”ŃĐșĐŸĐœĐŸĐŒĐžŃĐ”ŃĐșĐžŃ
ŃĐČŃĐ·Đ”Đč ĐČ ŃĐ°ĐŒĐșĐ°Ń
ŃĐ”ĐłĐžĐŸĐœĐ° ĐĄĐ”ĐČĐ”ŃĐŸ-ĐĐŸŃŃĐŸŃĐœĐŸĐč ĐзОО ĐœĐ”ĐŸĐ±Ń
ĐŸĐŽĐžĐŒĐŸ ĐŽĐ»Ń ĐŸĐżŃĐ”ĐŽĐ”Đ»Đ”ĐœĐžŃ ĐŸŃĐœĐŸĐČĐœŃŃ
ŃĐ”ĐœĐŽĐ”ĐœŃĐžĐč, ĐșĐ°ŃĐ”ŃŃĐČĐ”ĐœĐœŃŃ
ĐžĐ·ĐŒĐ”ĐœĐ”ĐœĐžĐč Đž ŃĐ°ĐșŃĐŸŃĐŸĐČ, ĐŸĐżŃДЎДлŃŃŃĐžŃ
ĐČĐ”ĐșŃĐŸŃ ŃĐŸŃĐłĐŸĐČŃŃ
ĐŸŃĐœĐŸŃĐ”ĐœĐžĐč.
ĐŠĐ”Đ»Ń ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ â ĐČŃŃĐČĐžŃŃ ĐŸŃĐœĐŸĐČĐœŃĐ” ŃĐ”ĐœĐŽĐ”ĐœŃОО ŃĐŸŃŃŃĐŽĐœĐžŃĐ”ŃŃĐČĐ° Đ Đ”ŃĐżŃблОĐșĐž ĐĐŸŃĐ”Ń Đž ŃŃŃĐ°Đœ ĐĄĐ”ĐČĐ”ŃĐŸ-ĐĐŸŃŃĐŸŃĐœĐŸĐč ĐзОО ĐČ ŃŃĐ”ŃĐ” ĐČĐœĐ”ŃĐœĐ”Đč ŃĐŸŃĐłĐŸĐČлО. ĐŃĐ°ĐșŃĐžŃĐ”ŃĐșĐ°Ń Đ·ĐœĐ°ŃĐžĐŒĐŸŃŃŃ ŃĐ°Đ±ĐŸŃŃ ŃĐŸŃŃĐŸĐžŃ ĐČ ĐČĐŸĐ·ĐŒĐŸĐ¶ĐœĐŸŃŃĐž ĐżĐŸĐ»ŃŃĐ”ĐœĐžŃ ĐČŃĐ”ŃŃĐŸŃĐŸĐœĐœĐ”ĐłĐŸ Đ°ĐœĐ°Đ»ĐžĐ·Đ° ĐČĐœĐ”ŃĐœĐ”ŃĐŸŃĐłĐŸĐČĐŸĐłĐŸ ŃĐŸŃŃŃĐŽĐœĐžŃĐ”ŃŃĐČĐ° Đ Đ”ŃĐżŃблОĐșĐž ĐĐŸŃĐ”Ń Đž ŃŃŃĐ°Đœ ĐĄĐ”ĐČĐ”ŃĐŸ-ĐĐŸŃŃĐŸŃĐœĐŸĐč ĐзОО, глŃĐ±ĐŸĐșĐŸ ŃĐ°ŃĐșŃŃŃĐžŃ ĐŽĐ°ĐœĐœĐŸĐč ŃĐ”ĐŒĐ°ŃĐžĐșĐž, ŃŃĐŸ ĐŒĐŸĐ¶Đ”Ń ĐżĐŸŃĐ»ŃжОŃŃ ĐŸŃĐœĐŸĐČĐŸĐč ĐŽĐ»Ń ĐŽĐ°Đ»ŃĐœĐ”ĐčŃĐžŃ
ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžĐč ŃĐŸŃĐłĐŸĐČлО Đ Đ”ŃĐżŃблОĐșĐž ĐĐŸŃĐ”Ń ŃĐŸ ŃŃŃĐ°ĐœĐ°ĐŒĐž ŃĐ”ĐłĐžĐŸĐœĐ° Đž ĐŸĐżŃĐ”ĐŽĐ”Đ»Đ”ĐœĐžŃ Đ±ŃĐŽŃŃĐžŃ
пДŃŃпДĐșŃĐžĐČ ĐČ ŃĐŸŃŃŃĐŽĐœĐžŃĐ”ŃŃĐČĐ” ĐŽĐ»Ń ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐČĐœĐ”ŃĐœĐ”ŃĐŸŃĐłĐŸĐČĐŸĐč ĐżĐŸĐ»ĐžŃĐžĐșĐž ŃŃŃĐ°ĐœŃ.The final project is devoted to trade cooperation of the Republic of Korea and North-East Asian countries. This region is influenced by many factors and analyses of dynamics and structure of trade are extremely significant to reveal the reasons of current trends of international cooperation between countries
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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (nâ=â143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (nâ=â152), or no hydrocortisone (nâ=â108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (nâ=â137), shock-dependent (nâ=â146), and no (nâ=â101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707
ĐДжЎŃĐœĐ°ŃĐŸĐŽĐœŃĐč ĐŒŃĐ·ŃĐșĐ°Đ»ŃĐœŃĐč ĐșĐŸĐœĐșŃŃŃ ĐČ ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžĐž ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ ĐżŃĐŸĐČĐ”ĐŽĐ”ĐœĐžŃ (ĐœĐ° ĐżŃĐžĐŒĐ”ŃĐ” ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ 2017)
ĐĐœĐœĐŸŃĐ°ŃĐžŃ ĐČŃĐżŃŃĐșĐœĐŸĐč ĐșĐČалОŃĐžĐșĐ°ŃĐžĐŸĐœĐœĐŸĐč ŃĐ°Đ±ĐŸŃŃ ĐŃĐ»ĐŸĐČ ĐĐžĐșĐžŃĐ° ĐĄĐ”ŃгДДĐČĐžŃ Â«ĐĐĐĐĐŁĐĐĐ ĐĐĐĐ«Đ ĐĐŁĐĐ«ĐĐĐĐŹĐĐ«Đ ĐĐĐĐĐŁĐ ĐĄ РЀĐĐ ĐĐĐ ĐĐĐĐĐĐ ĐĐĐĐĐРХйРĐĐĐ« ĐĐ ĐĐĐĐĐĐĐĐŻ (ĐĐ ĐĐ ĐĐĐĐ Đ ĐĐĐ ĐĐĐĐĐĐĐĐŻ-2017)» Đ. ŃŃĐș. - ĐŃĐșĐŸĐČĐ° ĐĐ»Đ”ĐœĐ° ĐĐ»Đ°ĐŽĐžĐŒĐžŃĐŸĐČĐœĐ°, ĐŽĐŸĐșŃĐŸŃ ŃĐžĐ»ĐŸĐ»ĐŸĐłĐžŃĐ”ŃĐșĐžŃ
ĐœĐ°ŃĐș, ĐŽĐŸŃĐ”ĐœŃ ĐĐ°ŃДЎŃĐ° ŃĐČŃĐ·Đ”Đč Ń ĐŸĐ±ŃĐ”ŃŃĐČĐ”ĐœĐœĐŸŃŃŃŃ ĐŃĐœĐ°Ń ŃĐŸŃĐŒĐ° ĐŸĐ±ŃŃĐ”ĐœĐžŃ ĐĐșŃŃĐ°Đ»ŃĐœĐŸŃŃŃ: ĐŒĐ”Đ¶ĐŽŃĐœĐ°ŃĐŸĐŽĐœŃĐč ĐŒŃĐ·ŃĐșĐ°Đ»ŃĐœŃĐč ĐșĐŸĐœĐșŃŃŃ ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžĐ” ĐșĐ°Đș ŃĐ°ĐŒĐŸĐ” ĐŒĐ°ŃŃŃĐ°Đ±ĐœĐŸĐ” ŃДгŃĐ»ŃŃĐœĐŸĐ” ĐČŃŃĐŸĐșĐŸŃĐ”Ń
ĐœĐŸĐ»ĐŸĐłĐžŃĐœĐŸĐ” ŃДлДĐČĐžĐ·ĐžĐŸĐœĐœĐŸĐ” Đž ĐŒĐ”ĐŽĐžĐ°-ŃĐŸĐ±ŃŃОД, ĐșĐŸŃĐŸŃĐŸĐ” . Đ Đ”Đ¶Đ”ĐłĐŸĐŽĐœĐŸ Đ°ĐșŃĐ”ĐœŃĐžŃŃĐ”Ń ĐČĐœĐžĐŒĐ°ĐœĐžĐ” Đ°ŃĐŽĐžŃĐŸŃОО ĐœĐ° ĐœĐ°ŃĐžĐŸĐœĐ°Đ»ŃĐœĐŸ-ĐșŃĐ»ŃŃŃŃĐœŃŃ
ĐŸŃĐŸĐ±Đ”ĐœĐœĐŸŃŃŃŃ
ŃŃŃĐ°ĐœŃ-ĐŸŃĐłĐ°ĐœĐžĐ·Đ°ŃĐŸŃĐ° ĐșĐŸĐœĐșŃŃŃĐ°, ŃĐŸŃĐŒĐžŃŃĐ”Ń Đ·ĐœĐ°ŃĐžŃДлŃĐœŃĐ” ŃŃŃĐžŃŃĐžŃĐ”ŃĐșОД ĐżĐŸŃĐŸĐșĐž Đž ŃĐ”ĐŒ ŃĐ°ĐŒŃĐŒ ŃĐżĐŸŃĐŸĐ±ŃŃĐČŃĐ”Ń ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐžĐŒĐžĐŽĐ¶Đ° ŃĐ”ŃŃĐžŃĐŸŃОО. ĐĐŸĐ»Đ”Đ” ŃĐŸĐłĐŸ, ĐżĐŸĐ±Đ”ĐŽĐ° ŃŃŃĐ°ĐœŃ-ŃŃĐ°ŃŃĐœĐžŃŃ ĐșĐŸĐœĐșŃŃŃĐ° ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ Đ·Đ°ŃĐ°ŃŃŃŃ ĐŸŃŃĐ°Đ¶Đ°Đ”Ń ĐžĐŽĐ”ĐŸĐ»ĐŸĐłĐŸ-ĐżĐŸĐ»ĐžŃĐžŃĐ”ŃĐșĐžĐč ĐČĐ”ĐșŃĐŸŃ ĐĐČŃĐŸĐżŃ Đž ĐżĐŸ ŃŃŃĐž ЎДла ĐČŃĐżĐŸĐ»ĐœŃĐ”Ń ŃŃĐœĐșŃĐžŃ ĐżĐŸĐ»ĐžŃĐžŃĐ”ŃĐșĐŸĐłĐŸ PR ŃŃŃĐ°ĐœŃ-ĐżĐŸĐ±Đ”ĐŽĐžŃĐ”Đ»Ń Đž ŃŃŃĐ°ĐœŃ-Ń
ĐŸĐ·ŃĐčĐșĐž ĐŒĐ”ŃĐŸĐżŃĐžŃŃĐžŃ. ĐĄĐ»Đ”ĐŽĐŸĐČĐ°ŃДлŃĐœĐŸ Đ°ĐœĐ°Đ»ĐžĐ· ĐžŃĐżĐŸĐ»ŃĐ·ŃĐ”ĐŒŃŃ
ĐœĐ° ĐŒĐ”ŃĐŸĐżŃĐžŃŃОО ĐșĐŸĐŒĐŒŃĐœĐžĐșĐ°ŃĐžĐČĐœŃŃ
ŃĐ”Ń
ĐœĐŸĐ»ĐŸĐłĐžĐč ŃĐČĐ»ŃĐ”ŃŃŃ Đ°ĐșŃŃĐ°Đ»ŃĐœŃĐŒ Đž ĐČĐŸŃŃŃĐ”Đ±ĐŸĐČĐ°ĐœĐœŃĐŒ ĐŽĐ»Ń ŃĐŸĐ±ŃŃĐžĐčĐœĐŸĐłĐŸ Đž ŃŃŃŃĐŸĐžŃДлŃĐœĐŸĐłĐŸ PR ĐбŃĐ”ĐșŃ ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ: ĐșĐŸĐŒĐŒŃĐœĐžĐșĐ°ŃĐžĐŸĐœĐœŃĐ” Đ°ĐșŃĐžĐČĐœĐŸŃŃĐž ĐŒĐ”Đ¶ĐŽŃĐœĐ°ŃĐŸĐŽĐœĐŸĐłĐŸ ĐŒŃĐ·ŃĐșĐ°Đ»ŃĐœĐŸĐłĐŸ ĐșĐŸĐœĐșŃŃŃĐ° (ĐœĐ° ĐżŃĐžĐŒĐ”ŃĐ” ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ ĐČ ĐОДĐČĐ” ĐČ 2017 Đł.). ĐŃĐ”ĐŽĐŒĐ”Ń ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ: ŃŃĐœĐșŃĐžŃ ŃŃĐ°ŃŃŃĐœĐŸĐłĐŸ PR-ĐŒĐ”ŃĐŸĐżŃĐžŃŃĐžŃ ĐČ ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžĐž ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ. ĐŠĐ”Đ»Ń ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ: ĐŽĐŸĐșĐ°Đ·Đ°ŃŃ, ŃŃĐŸ ĐŒĐ”Đ¶ĐŽŃĐœĐ°ŃĐŸĐŽĐœŃĐč ĐŒŃĐ·ŃĐșĐ°Đ»ŃĐœŃĐč ĐșĐŸĐœĐșŃŃŃ ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžĐ” ŃĐżĐŸŃĐŸĐ±ŃŃĐČŃĐ”Ń ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ ĐżŃĐŸĐČĐ”ĐŽĐ”ĐœĐžŃ. ĐĐ°ĐŽĐ°ŃĐž ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ: ŃĐ°Đ·ŃĐ°Đ±ĐŸŃĐ°ŃŃ ŃĐ”ŃĐŒĐžĐœĐŸĐ»ĐŸĐłĐžŃĐ”ŃĐșĐžĐč аппаŃĐ°Ń ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ ĐœĐ° ĐŸŃĐœĐŸĐČĐ” ĐœĐ°ŃŃĐœĐŸĐč лОŃĐ”ŃĐ°ŃŃŃŃ ĐżĐŸ ĐžĐŒĐžĐŽĐ¶ĐŒĐ”ĐčĐșĐžĐœĐłŃ, бŃĐ”ĐœĐŽĐžĐœĐłŃ Đž ĐžĐČĐ”ĐœŃ-ĐŒĐ”ĐœĐ”ĐŽĐ¶ĐŒĐ”ĐœŃŃ; ĐŸĐżŃДЎДлОŃŃ Đ°ĐșŃŃĐ°Đ»ŃĐœŃĐ” ĐșĐŸĐŒĐŒŃĐœĐžĐșĐ°ŃĐžĐŸĐœĐœŃĐ” ŃĐ”Ń
ĐœĐŸĐ»ĐŸĐłĐžĐž, ĐżŃĐžĐŒĐ”ĐœŃĐ”ĐŒŃĐ” ĐČ ŃĐ°ĐŒĐșĐ°Ń
ŃпДŃОалŃĐœŃŃ
ŃĐŸĐ±ŃŃĐžĐč ĐŽĐ»Ń ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ; ĐŸĐżĐžŃĐ°ŃŃ ŃĐŸĐ»Ń ĐĐČŃĐŸĐżĐ”ĐčŃĐșĐŸĐłĐŸ ĐĐ”ŃĐ°ŃДлŃĐœĐŸĐłĐŸ ĐĄĐŸŃĐ·Đ° ĐșĐ°Đș ĐŸŃĐłĐ°ĐœĐžĐ·Đ°ŃĐŸŃĐ° ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ ĐČ ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžĐž ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ ĐżŃĐŸĐČĐ”ĐŽĐ”ĐœĐžŃ ĐșĐŸĐœĐșŃŃŃĐ°; ĐŸŃĐ”ĐœĐžŃŃ ŃŃŃĐ”ĐșŃĐžĐČĐœĐŸŃŃŃ ŃĐ”Đ°Đ»ĐžĐ·ĐŸĐČĐ°ĐœĐœŃŃ
ĐșĐŸĐŒĐŒŃĐœĐžĐșĐ°ŃĐžĐČĐœŃŃ
ŃĐ”Ń
ĐœĐŸĐ»ĐŸĐłĐžĐč ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ ĐČ ŃĐ°ĐŒĐșĐ°Ń
ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ; ĐŽĐ°ŃŃ ŃĐ”ĐșĐŸĐŒĐ”ĐœĐŽĐ°ŃОО ĐżĐŸ ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ Ń ĐżĐŸĐŒĐŸŃŃŃ ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ. ĐąĐ”ĐŸŃĐ”ŃĐžŃĐ”ŃĐșĐ°Ń Đ±Đ°Đ·Đ°: ĐœĐ°ŃŃĐœŃĐ” ŃŃŃĐŽŃ Đ. ĐŃĐșĐŸĐČĐŸĐč, Đ. ĐĐ°ĐČŃŃ, Đ. ĐĐ°ĐœĐșŃŃŃ
ĐžĐœĐ°, Đ. ĐĐ¶Đ”ĐœĐ”ŃĐ°, Đ. ĐĐ°ĐČĐ”ŃĐžĐœĐŸĐč, ĐŁ. Đ„Đ°Đ»ŃŃбаŃŃĐ°, Đж. ĐĐŸĐ»ĐŽĐ±Đ»Đ°ŃŃĐ° Đ° ŃĐ°ĐșжД ŃŃŃĐŽŃ Đ. ĐĐ°ŃŃĐŒĐ°ĐœĐ° ĐŸ ĐŒŃĐ·ŃĐșĐ°Đ»ŃĐœĐŸĐŒ Đ±ĐžĐ·ĐœĐ”ŃĐ”, Đ. ĐĐ¶ĐŸŃĐŽĐ°ĐœĐ° ĐŸ ĐżŃĐŸĐŽĐČĐžĐ¶Đ”ĐœĐžĐž ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°Đœ Ń ĐżĐŸĐŒĐŸŃŃŃ ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ Đž ĐŽŃ. ĐĐŒĐżĐžŃĐžŃĐ”ŃĐșĐ°Ń Đ±Đ°Đ·Đ°: PR-ĐŽĐŸĐșŃĐŒĐ”ĐœŃŃ, ŃĐ°Đ·ĐŒĐ”ŃĐ”ĐœĐœŃĐ” ĐœĐ° ŃĐ°ĐčŃĐ” ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ Đž ĐĐČŃĐŸĐżĐ”ĐčŃĐșĐŸĐłĐŸ ĐĐ”ŃĐ°ŃДлŃĐœĐŸĐłĐŸ ĐĄĐŸŃĐ·Đ°; Đ±ĐŸĐ»Đ”Đ” ĐżĐŸĐ»ŃŃĐŸŃĐ° ĐŒĐžĐ»Đ»ĐžĐŸĐœĐ° ŃŃĐ°ŃĐ”Đč ĐŸĐ± ĐŁĐșŃĐ°ĐžĐœĐ” ĐČ Đ”ĐČŃĐŸĐżĐ”ĐčŃĐșĐžŃ
ĐĄĐĐ, ŃĐ°Đ·ĐŒĐ”ŃĐ”ĐœĐœŃĐ” ĐČ Đ±Đ°Đ·Đ” ĐżŃĐŸĐ”ĐșŃĐ° ĐŒĐŸĐœĐžŃĐŸŃĐžĐœĐłĐ° ĐŒĐ”Đ¶ĐŽŃĐœĐ°ŃĐŸĐŽĐœĐŸĐłĐŸ ĐžĐŒĐžĐŽĐ¶Đ° ĐŁĐșŃĐ°ĐžĐœŃ Â«Oko»; ĐŽĐ°ĐœĐœŃĐ” Đ±Đ°Đ·Ń ĐŒĐ°ŃĐ”ŃĐžĐ°Đ»ĐŸĐČ ĐĄĐĐ Đž ŃĐŸŃОалŃĐœŃŃ
ĐŒĐ”ĐŽĐžĐ° Factiva; ĐŽĐ°ĐœĐœŃĐ” Google.Analytics. ĐŃĐ°ĐșŃĐžŃĐ”ŃĐșĐ°Ń Đ·ĐœĐ°ŃĐžĐŒĐŸŃŃŃ: ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžĐ” ĐŽĐŸĐșĐ°Đ·ŃĐČĐ°Đ”Ń, ŃŃĐŸ ĐŒĐ”Đ¶ĐŽŃĐœĐ°ŃĐŸĐŽĐœŃĐč ĐŒŃĐ·ŃĐșĐ°Đ»ŃĐœŃĐč ĐșĐŸĐœĐșŃŃŃ ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžĐ” ŃĐŸŃĐŒĐžŃŃĐ”Ń ĐžĐŒĐžĐŽĐ¶ ŃŃŃĐ°ĐœŃ ĐżŃĐŸĐČĐ”ĐŽĐ”ĐœĐžŃ ĐœĐ”Đ·Đ°ĐČĐžŃĐžĐŒĐŸ ĐŸŃ ŃŃпДŃĐœĐŸŃŃĐž ĐžŃĐżĐŸĐ»ŃĐ·ĐŸĐČĐ°ĐœĐžŃ ĐșĐŸĐœĐșŃĐ”ŃĐœŃŃ
ŃĐ”Ń
ĐœĐŸĐ»ĐŸĐłĐžĐč ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ. йДзОŃŃ ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ Đ±ŃлО Đ°ĐżŃĐŸĐ±ĐžŃĐŸĐČĐ°ĐœŃ ĐœĐ° ĐŒĐ”Đ¶ĐŽŃĐœĐ°ŃĐŸĐŽĐœĐŸĐŒ ĐœĐ°ŃŃĐœĐŸĐŒ ŃĐŸŃŃĐŒĐ” «ĐДЎОа ĐČ ŃĐŸĐČŃĐ”ĐŒĐ”ĐœĐœĐŸĐŒ ĐŒĐžŃĐ”. 57-Đ” ĐĐ”ŃĐ”ŃбŃŃĐłŃĐșОД ŃŃĐ”ĐœĐžŃ», ĐŸĐżŃблОĐșĐŸĐČĐ°ĐœŃ ĐČ ŃĐ±ĐŸŃĐœĐžĐșĐ” ĐŒĐ°ŃĐ”ŃĐžĐ°Đ»ĐŸĐČ ŃŃĐ°ŃĐ”Đč ŃĐŸŃŃĐŒĐ° Đž ĐžĐŒĐ”ŃŃ ŃŃĐ°ŃŃŃ ĐœĐ°ŃŃĐœĐŸĐč ŃŃĐ°ŃŃĐž, ŃĐ°Đ·ĐŒĐ”ŃĐ”ĐœĐœĐŸĐč ĐČ Đ±Đ°Đ·Đ” Đ ĐĐĐŠ. ĐĄŃŃŃĐșŃŃŃĐ° ŃĐ°Đ±ĐŸŃŃ: Đ Đ°Đ±ĐŸŃĐ° ŃĐŸŃŃĐŸĐžŃ ĐžĐ· ĐČĐČĐ”ĐŽĐ”ĐœĐžŃ, 3 глаĐČ: «ŃŃĐœĐșŃĐžŃ ŃпДŃОалŃĐœĐŸĐłĐŸ ŃĐŸĐ±ŃŃĐžŃ ĐČ ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžĐž ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ», «ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžĐ” ĐșĐ°Đș ŃпДŃОалŃĐœĐŸĐ” ŃĐŸĐ±ŃŃОД ĐĐČŃĐŸĐżĐ”ĐčŃĐșĐŸĐłĐŸ ĐĐ”ŃĐ°ŃДлŃĐœĐŸĐłĐŸ ĐĄĐŸŃза» Đž «ĐșĐŸĐŒĐŒŃĐœĐžĐșĐ°ŃĐžĐŸĐœĐœŃĐč ĐżĐŸŃĐ”ĐœŃОал ĐĐČŃĐŸĐČĐžĐŽĐ”ĐœĐžŃ ĐșĐ°Đș ĐżĐ»ĐŸŃĐ°ĐŽĐșĐž ĐŽĐ»Ń ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐžĐŒĐžĐŽĐ¶Đ° ŃŃŃĐ°ĐœŃ», Đ·Đ°ĐșĐ»ŃŃĐ”ĐœĐžŃ, ŃпОŃĐșĐ° ĐžŃĐżĐŸĐ»ŃĐ·ĐŸĐČĐ°ĐœĐœĐŸĐč лОŃĐ”ŃĐ°ŃŃŃŃ ĐžĐ· 67 ĐżĐŸĐ·ĐžŃĐžĐč Đž 12 ĐżŃĐžĐ»ĐŸĐ¶Đ”ĐœĐžĐč. ĐбŃĐžĐč ĐŸĐ±ŃĐ”ĐŒ 76 ŃŃŃĐ°ĐœĐžŃ.Abstract of graduating qualification thesis Mikita Arlou INTERNATIONAL MUSIC CONTEST IN HOST COUNTRY IMAGE FORMATION (ON THE EXAMPLE OF EUROVISION 2017) Supervisor associate professor Elena Bykova, doctor of philology Department of PR in business full-time study Relevance: the international music contest Eurovision as the most wide scale regular high tech TV and Media event which annually emphasizes audience attention on national cultural features of the host country, forms tourist flows which have huge influence on territorial image formation. Besides the win of a participating in the Eurovision country often shows the ideological and political European vector and in fact serves as political PR of the winning or host country. Consequently the analysis of applied communication technologies is relevant and in-demand for event PR. Research object: communication activities of international music contest (on the example of Eurovision in Kyiv in 2017). Research subject: function of status PR event in country image formation. The aim of research: to prove that international music contest Eurovision contributes host country image formation. The tasks of research: to develop research terminology based on scientific literature on image making, branding and event management; to define actual communication technologies applied in special PR events on country image formation; to describe European Broadcasting Union role in host country image formation; to appreciate effectiveness of applied communication technologies on host country image formation in Eurovision; to give recommendations for host country image formation with the help of Eurovision. Theoretical base: scientific works written by E. Bykova, D. Gavra, A. Pankrukhin, B. Jenes, E. Kaverina, U. Halcbaur, J. Goldblatt and D. PassmanÂŽs works on music business and P. Jordan on county image building with the help of Eurovision, etc. The empirical base: PR documents from official Eurovision and European Broadcasting Union websites; more than 1.5 million articles on Ukraine in European media stored in the base of international Ukrainian image monitoring project Oko; content of the mass media and social media base Factiva; Google.Analytics data. Practical significance: the research proves that international music contest Eurovision is relevant for the host country image formation independently of the success level of applied country image formation communication technologies. Approbation: General positions of current thesis were aprobated on international scientific forum Media in modern world and were published at the collection of articles of the forum and have the status of a scientific article posted in the RINC database. Thesis structure: Research consists of introduction, 3 chapters: Special event function in country image formation, Eurovision as EBU special event and communication potential of Eurovision as a platform for image formation; conclusion, literature list from 67 positions and 12 attachments. The total volume is 76 pages
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Nutrients, insulin and muscle wasting during critical illness
Critical illness develops upon acute
life-threatening insults, which require acute intervention to support vital
organs in order to avoid imminent death of the patt. This condition is
characterized by abiphasic stress response. The acute phase of critical
illness is an evolutionary programmed response to a stressor, and the
adaptations are considered to be beneficial for short-term survival. Its main
purpose is to provide endogenous substrates for protein synthesis and energy
metabolism and this by increasing protein catabolism. The evolution of intensive care medicine has allowed patients to
survive diseases and trauma that were previously lethal. However, about 30% of
thepatients who survive the acute phase remain dependent on vital organ
support for a prolonged period and enter a chronic phase of critical illness.
During this unnatural phase of critical illness, the hypercatabolic response
is sustained. Skeletal muscle is the largest proteinsource and patients can
thus lose up to 10% of their muscle mass in one week, despite nutritional
support. Muscle atrophy, together with the development of muscle membrane
inexcitability, compromises musclestrength and function. This myopathy results
in severe muscle weakness, which exposes the patients to serious risks for
delayed recovery,prolonged rehabilitation and adverse outcome.
Because the gastro-intestinal tract is often
dysfunctional during critical illness, intravenous nutrition has been evaluated
to counteract hypercatabolism and improve outcome, but unfortunately with poor
success. As the nutritional intervention studies were performed without
controlling for hyperglycemia, aggravation of hyperglycemia, together with the
negativeeffects of untreated hyperglycemia, may explain why intravenous
nutrition alone was ineffective. Indeed, the development of hyperglycemia,
which is very common in critically ill patients, has been shown to increase the
risk for organ failure and death, and to promote catabolism. The general aim of
this thesis was to gain more insight in the effect on muscle proteolysis of the
combination of intravenous nutrition with the infusion of insulin to maintain
normoglycemia. We hypothesized that this intervention would be safe for organ
function and survival, and effective to prevent severe muscle wasting during
prolonged critical illness.
In a first study, we investigated the
effect of strict blood glucose control with intensive insulin therapy on
proteolytic pathways in skeletal muscle of intravenously fed critically ill
patients. Interestingly, markers
of muscle atrophy were not ameliorated by this intervention, possibly
indicating that the amountof nutrition was insufficient tocounteract the
catabolic response. However, we also observed signs of myofiber degeneration
and an accumulation of potentially toxic protein aggregates, irrespective of
insulin therapy, which is suggestive of incomplete or insufficiently activated
autophagy. The fact that nutrients inhibit this pathway, combined with the
failure of feeding in the presence of normoglycemia to counteract muscle
wasting, emphasizes the importance to study the potentialrole of inadequate
(artificial) feeding, either too little or too much, during critical illness in
relation to these pathways.
We
addressed the question on the impact of feeding versus fasting on these
catabolic pathways in our animal model of prolonged criticalillness. We
assessed the efficacy to attenuate protein degradation as well as safety for
vital organ function and survival of different intravenous nutritional
interventions.status: publishe
Dynamic movement primitives for human movement recognition
Due to copyright restrictions, the access to the full text of this article is only available via subscription.Dynamic Movement Primitives (DMPs)-originally a method for movement trajectory generation [1] has been also used for recognition tasks [2, 3]. However there has not been a systematic comparison between other recognition methods and DMPs using human movement data. This paper presents a comparison of commonly used Hidden Markov Model (HMM) based recognition with DMP based recognition using human generated letter trajectories. As the working principles of these two methods are very different, in addition to the performance, the numbers of adaptable parameters that are used in each method and, process time were compared. The results, indicate that HMM gives better results than DMP, with possible noise robustness advantage in DMPs for human movement.Ministry of Internal Affairs and Communication
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