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

Effect of withholding early parenteral nutrition in PICU on ketogenesis as potential mediator of its outcome benefit

Background: In critically ill children, omitting early use of parenteral nutrition (late-PN versus early-PN) reduced infections, accelerated weaning from mechanical ventilation, and shortened PICU stay. We hypothesized that fasting-induced ketogenesis mediates these benefits. Methods: In a secondary analysis of the PEPaNIC RCT (N = 1440), the impact of late-PN versus early-PN on plasma 3-hydroxybutyrate (3HB), and on blood glucose, plasma insulin, and glucagon as key ketogenesis regulators, was determined for 96 matched patients staying ≥ 5 days in PICU, and the day of maximal 3HB-effect, if any, was identified. Subsequently, in the total study population, plasma 3HB and late-PN-affected ketogenesis regulators were measured on that average day of maximal 3HB effect. Multivariable Cox proportional hazard and logistic regression analyses were performed adjusting for randomization and baseline risk factors. Whether any potential mediator role for 3HB was direct or indirect was assessed by further adjusting for ketogenesis regulators. Results: In the matched cohort (n = 96), late-PN versus early-PN increased plasma 3HB throughout PICU days 1–5 (P < 0.0001), maximally on PICU day 2. Also, blood glucose (P < 0.001) and plasma insulin (P < 0.0001), but not glucagon, were affected. In the total cohort (n = 1142 with available plasma), late-PN increased plasma 3HB on PICU day 2 (day 1 for shorter stayers) from (median [IQR]) 0.04 [0.04–0.04] mmol/L to 0.75 [0.04–2.03] mmol/L (P < 0.0001). The 3HB effect of late-PN sta

Reduced Cortisol Metabolism during Critical Illness

Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism.status: publishe

Внешнеторговое сотрудничество Республики Корея со странами Северо-Восточной Азии

Вследствие быстрого развития и усложнения мирохозяйственных связей и торгово-экономического взаимодействия государств, тенденции развитие международного сотрудничества приобретают особую актуальность. Северо-Восточная Азия (СВА) – это регион, в котором очень тонко переплетаются исторические, идеологические, политические особенности и экономическая целесообразность торговли. Страновой состав региона Северо-Восточной Азии может рассматриваться с разных точек зрения, в рамках данного исследования под странами данного региона понимаются Республика Корея, Китай, Япония и вся Россия. Взаимодействие Республики Корея с каждым из трех государств имеет уникальную историю, достаточный потенциал для развития торговли, а также свои особенности формирования внешнеэкономических связей. Усиление роли Китая в качестве торгового партнера, снижение значимости Японии и сложная экономическая ситуация в России на текущий момент оказывают существенное влияние на развитие Республики Корея, опорой экономического роста которой традиционно являлась торговля. Эти три страны являются одними из важнейших партнеров для Республики Корея, поэтому изучение процессов формирования внешнеэкономических связей в рамках региона Северо-Восточной Азии необходимо для определения основных тенденций, качественных изменений и факторов, определяющих вектор торговых отношений. Цель исследования – выявить основные тенденции сотрудничества Республики Корея и стран Северо-Восточной Азии в сфере внешней торговли. Практическая значимость работы состоит в возможности получения всестороннего анализа внешнеторгового сотрудничества Республики Корея и стран Северо-Восточной Азии, глубоко раскрытия данной тематики, что может послужить основой для дальнейших исследований торговли Республики Корея со странами региона и определения будущих перспектив в сотрудничестве для формирования внешнеторговой политики страны.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

Dynamics and prognostic value of the hypothalamus–pituitary–adrenal axis responses to pediatric critical illness and association with corticosteroid treatment: a prospective observational study

Purpose: Increased systemic cortisol availability during adult critical illness is determined by reduced binding-proteins and suppressed breakdown rather than elevated ACTH. Dynamics, drivers and prognostic value of hypercortisolism during pediatric critical illness remain scarcely investigated. Methods: This preplanned secondary analysis of the PEPaNIC-RCT (N = 1440), after excluding 420 children treated with corticosteroids before PICU-admission, documented (a) plasma ACTH, (free)cortisol and cortisol-metabolism at PICU-admission, day-3 and last PICU-day, their prognostic value, and impact of withholding early parenteral nutrition (PN), (b) the association between corticosteroid-treatment and these hormones, and (c) the association between corticosteroid-treatment and outcome. Results: ACTH was normal upon PICU-admission and low thereafte

Nicole Stott

Nicole has explored from the heights of outer space to the depths of our oceans. She marveled at the awesomeness of our planet experienced from these vantage points, and she believes that sharing this perspective has the power to increase everyone’s appreciation of and obligation to care for our home planet and all who inhabit it. Nicole is a veteran NASA Astronaut with two spaceflights, one spacewalk, and 104 days living and working in space as a crewmember on both the Space Shuttle and the International Space Station (ISS). She is also a NASA Aquanaut and was a crewmember on the longest duration saturated dive mission on the Aquarius undersea laboratory. Always an Artist, Nicole was the First Astronaut to Paint in Space. Nicole combines her spaceflight experience and artwork to inspire creative thinking about solutions to our planetary and personal challenges, and to increase awareness of the outstanding work being done every day in space to improve life here on Earth. She uniquely shares the impression of our planet from the orbital and undersea perspectives, while stressing the significance of our planetary community and environment, a renaissance approach to education and wellness, and the surprising interplay between science and art.https://commons.erau.edu/space-congress-bios-2018/1012/thumbnail.jp

Tumour necrosis factor-alpha, interleukin-6 and interleukin-8 do not promote adhesion of human endometrial epithelial cells to mesothelial cells in a quantitative in vitro model

BACKGROUND: A key factor in the pathogenesis of endometriosis is the endometrial-peritoneal adhesion. To study the pathogenesis of endometriosis, a quantitative in vitro assay (QIVA) was developed to measure in vitro adhesion between human endometrial epithelial cells and mesothelial cells using commercially available cell lines. Using the QIVA, the hypothesis was tested that tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) promote adhesion of endometrial epithelial cells to mesothelial cells. METHODS: Mesothelial cells were pre-treated with TNF-alpha, IL-6 or IL-8 in various concentrations (ranging from 0 to 1000 IU/ml) for 24 h. Confluent endometrial epithelial cells were labelled with [35S]methionine, added to the confluent mesothelial cells and incubated for 1 h. After incubation, non-adhering cells were removed and adherent cells were solubilized and their [35S]methionine radioactivity was counted to quantify the adherence of endometrial epithelial cells to mesothelial cells. RESULTS: The in vitro adhesion of human endometrial epithelial cells to human mesothelial cells was inhibited in a dose-dependent manner by TNF-alpha (P=0.0007), IL-6 (P<0.0001) and IL-8 (P=0.0004). CONCLUSIONS: Using a quantitative in vitro adhesion assay, we were unable to confirm our hypothesis that TNF-alpha, IL-6 and IL-8 promote the in vitro adhesion between endometrial epithelial cells and mesothelial cells.status: publishe

Circulating 3-T1AM and 3,5-T2 in critically ill patients: a cross-sectional observational study

BACKGROUND: Critical illness is hallmarked by low circulating thyroxine (T4) and triiodothyronine (T3) concentrations, in the presence of elevated reverse T3 (rT3) and low-normal thyrotropin (TSH), referred to as nonthyroidal illness (NTI). Thyroid hormone (TH) metabolism is substantially increased during NTI, in part explained by enhanced deiodinase 3 (D3) activity. T4- and T3-sulfate concentrations are elevated, due to suppressed D1 activity in the presence of unaltered sulfotransferase activity, and 3,3'-diiodothyronine (3,3'-T2) concentrations are normal. To elucidate further the driving forces behind increased TH metabolism during NTI, two other potential T4 metabolites-3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM)-were measured and related to their potential TH precursors. METHODS: Morning blood samples were collected cross-sectionally from 83 critically ill patients on a University Hospital intensive care unit and from 38 demographically matched healthy volunteers. Serum TH and binding proteins were quantified with commercial assays, and 3,5-T2 and 3-T1AM with in-house developed immunoassays. RESULTS: Critically ill patients revealed, besides the NTI, a median 44% lower serum 3-T1AM concentration (p  0.2) concentrations than other patients did. Multivariable linear regression analysis adjusted for potential precursors revealed that the reduced serum 3-T1AM was positively correlated with the low serum T3 (p < 0.001) but unrelated to serum T4 or rT3. The elevated 3,5-T2 concentration did not independently correlate with TH. CONCLUSIONS: Increased TH metabolism during NTI could not be explained by increased conversion to 3-T1AM, as circulating 3-T1AM was suppressed in proportion to the concomitantly low T3 concentrations. Increased conversion of T4 and/or T3 to 3,5-T2 could be possible, as serum 3,5-T2 concentrations were elevated. Whether 3-T1AM or 3,5-T2 plays a functional role during critical illness needs further investigation.status: publishe

Critical illness induces alternative activation of M2 macrophages in adipose tissue

status: publishe