Role of epicardial adipose tissue in the development of cardiovascular diseases

Epicardial adipose tissue (EAT) has unique properties due to its special anatomical structure, thermoregulation, and metabolic activity. Dysregulated EAT provokes the synthesis of pro-inflammatory cytokines, disorders in the metabolism of fats and glucose, as well as contributes to fatty degeneration of the myocardium and heart failure development. EAT may serve as a risk factor and biomarker for cardiovascular diseases, and is also a potential therapeutic target. The purpose of this review was to highlight current research data on EAT, secreted adipokines, their effect on target tissue metabolism, and to systematize the relationship between EAT and cardiovascular diseases. In particular, its function, role in heart failure, atrial fibrillation, as well as the prognostic value of various microRNAs determined in EAT are highlighted

Five decades of terrestrial and freshwater research at Ny-Ålesund, Svalbard

For more than five decades, research has been conducted at Ny-Ålesund, in Svalbard, Norway, to understand the structure and functioning of High-Arctic ecosystems and the profound impacts on them of environmental change. Terrestrial, freshwater, glacial and marine ecosystems are accessible year-round from Ny-Ålesund, providing unique opportunities for interdisciplinary observational and experimental studies along physical, chemical, hydrological and climatic gradients. Here, we synthesize terrestrial and freshwater research at Ny-Ålesund and review current knowledge of biodiversity patterns, species population dynamics and interactions, ecosystem processes, biogeochemical cycles and anthropogenic impacts. There is now strong evidence of past and ongoing biotic changes caused by climate change, including negative effects on populations of many taxa and impacts of rain-on-snow events across multiple trophic levels. While species-level characteristics and responses are well understood for macro-organisms, major knowledge gaps exist for microbes, invertebrates and ecosystem-level processes. In order to fill current knowledge gaps, we recommend (1) maintaining monitoring efforts, while establishing a long-term ecosystem-based monitoring programme; (2) gaining a mechanistic understanding of environmental change impacts on processes and linkages in food webs; (3) identifying trophic interactions and cascades across ecosystems; and (4) integrating long-term data on microbial, invertebrate and freshwater communities, along with measurements of carbon and nutrient fluxes among soils, atmosphere, freshwaters and the marine environment. The synthesis here shows that the Ny-Ålesund study system has the characteristics needed to fill these gaps in knowledge, thereby enhancing our understanding of High-Arctic ecosystems and their responses to environmental variability and change

Five decades of terrestrial and freshwater research at Ny-Ålesund, Svalbard

For more than five decades, research has been conducted at Ny-Alesund, in Svalbard, Norway, to understand the structure and functioning of High Arctic ecosystems and the profound impacts on them of environmental change. Terrestrial, freshwater, glacial and marine ecosystems are accessible year-round from Ny-Alesund, providing unique opportunities for interdisciplinary observational and experimental studies along physical, chemical, hydrological and climatic gradients. Here, we synthesize terrestrial and freshwater research at Ny-Alesund and review current knowledge of biodiversity patterns, species population dynamics and interactions, ecosystem processes, biogeochemical cycles and anthropogenic impacts. There is now strong evidence of past and ongoing biotic changes caused by climate change, including negative effects on populations of many taxa and impacts of rain-on-snow events across multiple trophic levels. While species-level characteristics and responses are well understood for macro-organisms, major knowledge gaps exist for microbes, invertebrates and ecosystem-level processes. In order to fill current knowledge gaps, we recommend (1) maintaining monitoring efforts, while establishing a longterm ecosystem-based monitoring programme; (2) gaining a mechanistic understanding of environmental change impacts on processes and linkages in food webs; (3) identifying trophic interactions and cascades across ecosystems; and (4) integrating long-term data on microbial, invertebrate and freshwater communities, along with measurements of carbon and nutrient fluxes among soils, atmosphere, freshwaters and the marine environment. The synthesis here shows that the Ny-Alesund study system has the characteristics needed to fill these gaps in knowledge, thereby enhancing our understanding of High-Arctic ecosystems and their responses to environmental variability and change

Высокая суммарная доза облучения улучшает выживаемость больных локализованной формой мелкоклеточного рака легкого: результаты одноцентрового ретроспективного анализа

The overall survival of patients with locally advanced small cell lung cancer who received at least 2 courses of chemotherapy and external beam radiation therapy at a total dose >50 Gy delivered to the primary tumor was retrospectively studied. Patients were dividedinto 2 groups. Patients in the standard treatment group (n=71) were treated to 50–58 Gy total dose. The dose escalation group (n=69) was treated to 60–74 Gy. Accelerated fractionation regimen in radiotherapy was more frequently given in dose escalation treatment group. The 1-, 3- and 5-year survival rates in the dose escalated and standard dose groups were respectively 54 % (95 % CI 42–65 %) and 32 % (95 % CI 23–44 %), р=0,11; 25 % (95 % CI 16–36 %) and 1 % (95% CI 0–8 %), р=0,0003; 17 % (95 % CI 10–28 %) and 0 % (95 % CI 0–5 %) (р=0.0007). The median survival was 14 months (95 % CI 10–17 months) in the dose escalated treatment group and 9 months (95 % CI 8–11months) in patients of the standard treatment group (χ2=16,8, р<0,0001). Multifactorial analysis showed that a total dose of ≥60 Gy resulted in reduction in risk of death (RR 0,57 (CI 0,37–0,88), р=0,012). Radiation dose escalation can result in improvement of local control for patients with locally advanced small cell lung cancer. Prospective randomized studies are required to finally confirm this hypothesis. Проведено ретроспективное изучение общей выживаемости больных Л-МРЛ, получавших не менее 2 курсов химиотерапии и дистанционную ЛТ в СОД не менее 50 Гр на первичный очаг. Больные группы СОДст (n=71) получили облучение грудной клетки в стандартно рекомендованной дозе, в группе СОДэск (n=69) суммарная доза составляла 60–74 Гр по биологическому эквиваленту. Лучевую терапию в режиме ускоренного фракционирования с эскалацией дозы (УГФЭД) чаще применяли в группе СОДэск. Более 1, 3 и 5 лет жили пациенты из группы СОДэск и СОДст соответственно в 54 % (95 % ДИ 42–65 %) и 32 % (95 % ДИ 23–44 %), р=0,11; в 25 % (95 % ДИ 16–36 %) и 1 % (95% ДИ 0–8 %), р=0,0003; в 17 % (95 % ДИ 10–28 %) и 0 % (95 % ДИ 0–5 %) случаях (р=0,0007). Медиана выживаемости в группах составила 14 (95 % ДИ 10–17 мес) и 9 (95 % ДИ 8–11 мес) мес, χ2=16,8, р<0,0001 соответственно. При многофакторном анализе только СОД 60 Гр и выше независимо снижала риск смерти (ОР 0,57 (ДИ 0,37–0,88), р=0,012). Увеличение СОД выше стандартно рекомендуемых 50–58 Гр может привести к улучшению выживаемости больных Л-МРЛ. Окончательное подтверждение этой гипотезы возможно только в рамках проспективного рандомизированного исследования

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance.

Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large sample sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14-17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium

The Pore-Forming Toxin Listeriolysin O Mediates a Novel Entry Pathway of L. monocytogenes into Human Hepatocytes

Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin listeriolysin O (LLO) facilitates bacterial escape from the internalization vesicle into the cytoplasm, where bacteria divide and undergo cell-to-cell spreading via actin-based motility. In the present study we demonstrate that in addition to InlA and InlB, LLO is required for efficient internalization of L. monocytogenes into human hepatocytes (HepG2). Surprisingly, LLO is an invasion factor sufficient to induce the internalization of noninvasive Listeria innocua or polystyrene beads into host cells in a dose-dependent fashion and at the concentrations produced by L. monocytogenes. To elucidate the mechanisms underlying LLO-induced bacterial entry, we constructed novel LLO derivatives locked at different stages of the toxin assembly on host membranes. We found that LLO-induced bacterial or bead entry only occurs upon LLO pore formation. Scanning electron and fluorescence microscopy studies show that LLO-coated beads stimulate the formation of membrane extensions that ingest the beads into an early endosomal compartment. This LLO-induced internalization pathway is dynamin-and F-actin-dependent, and clathrin-independent. Interestingly, further linking pore formation to bacteria/bead uptake, LLO induces F-actin polymerization in a tyrosine kinase-and pore-dependent fashion. In conclusion, we demonstrate for the first time that a bacterial pathogen perforates the host cell plasma membrane as a strategy to activate the endocytic machinery and gain entry into the host cell

Five decades of terrestrial and freshwater research at Ny-Ålesund, Svalbard

For more than five decades, research has been conducted at Ny-Ålesund, in Svalbard, Norway, to understand the structure and functioning of High-Arctic ecosystems and the profound impacts on them of environmental change. Terrestrial, freshwater, glacial and marine ecosystems are accessible year-round from Ny-Ålesund, providing unique opportunities for interdisciplinary observational and experimental studies along physical, chemical, hydrological and climatic gradients. Here, we synthesize terrestrial and freshwater research at Ny-Ålesund and review current knowledge of biodiversity patterns, species population dynamics and interactions, ecosystem processes, biogeochemical cycles and anthropogenic impacts. There is now strong evidence of past and ongoing biotic changes caused by climate change, including negative effects on populations of many taxa and impacts of rain-on-snow events across multiple trophic levels. While species-level characteristics and responses are well understood for macro-organisms, major knowledge gaps exist for microbes, invertebrates and ecosystem-level processes. In order to fill current knowledge gaps, we recommend (1) maintaining monitoring efforts, while establishing a long-term ecosystem-based monitoring programme; (2) gaining a mechanistic understanding of environmental change impacts on processes and linkages in food webs; (3) identifying trophic interactions and cascades across ecosystems; and (4) integrating long-term data on microbial, invertebrate and freshwater communities, along with measurements of carbon and nutrient fluxes among soils, atmosphere, freshwaters and the marine environment. The synthesis here shows that the Ny-Ålesund study system has the characteristics needed to fill these gaps in knowledge, thereby enhancing our understanding of High-Arctic ecosystems and their responses to environmental variability and change