48 research outputs found

    Muscle spindles of the rat sternomastoid muscle

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    The sternomastoid (SM) muscle in rodents presents a peculiar distribution of fiber types with a steep gradient from the ventral, superficial, white portion to the dorsal, deep, red region, where muscle spindles are restricted. Cross section of the medial longitudinal third of the rat SM contains around 10,000 muscle fibers with a mean diameter of 51.28±12.62 (μm +/- SD). Transverse sections stained by Succinate Dehydrogenase (SDH) reaction clearly presents two distinct regions: the dorsal deep red portion encompassing a 40% cross section area contains a high percentage of packed SDH-positive muscle fibers, and the ventral superficial region which contains mainly SDH-negative muscle fibers. Indeed, the ventral superficial region of the rat SM muscle contains mainly fast 2B muscle fibers. These acidic ATPase pH 4.3-negative and SDH-negative 2B muscle fibers are the largest of the SM muscle, while the acidic ATPase pH 4.3-positive and SDH-positive Type 1 muscle fibers are the smallest. Here we show that in thin transverse cryosections only 2 or 3 muscle spindle are observed in the central part of the dorsal deep red portion of the SM muscle. Azan Mallory stained sections allow at the same time to count the spindles and to evaluate aging fibrosis of the skeletal muscle tissue. Though restricted in the muscle red region, SM spindles are embedded in perimysium, whose changes may influence their reflex activity. Our findings confirm that any comparisons of changes in number and percentage of muscle spindles and muscle fibers of the rat SM muscle will require morphometry of the whole muscle cross-section. Muscle biopsies of SM muscle from large mammals will only provide partial data on the size of the different types of muscle fibers biased by sampling. Nonetheless, histology of muscle tissue continue to provide practical and low-cost quantitative data to follow-up translational studies in rodents and beyond

    Mural cell-derived chemokines provide a protective niche to safeguard vascular macrophages and limit chronic inflammation

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    Maladaptive, non-resolving inflammation contributes to chronic inflammatory diseases such as atheroscle-rosis. Because macrophages remove necrotic cells, defective macrophage programs can promote chronic inflammation with persistent tissue injury. Here, we investigated the mechanisms sustaining vascular mac-rophages. Intravital imaging revealed a spatiotemporal macrophage niche across vascular beds alongside mural cells (MCs)-pericytes and smooth muscle cells. Single-cell transcriptomics, co-culture, and genetic deletion experiments revealed MC-derived expression of the chemokines CCL2 and MIF, which actively pre-served macrophage survival and their homeostatic functions. In atherosclerosis, this positioned macro-phages in viable plaque areas, away from the necrotic core, and maintained a homeostatic macrophage phenotype. Disruption of this MC-macrophage unit via MC-specific deletion of these chemokines triggered detrimental macrophage relocalizing, exacerbated plaque necrosis, inflammation, and atheroprogression. In line, CCL2 inhibition at advanced stages of atherosclerosis showed detrimental effects. This work presents a MC-driven safeguard toward maintaining the homeostatic vascular macrophage niche

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo

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    Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features

    European Atlas of Natural Radiation

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    Natural ionizing radiation is considered as the largest contributor to the collective effective dose received by the world population. The human population is continuously exposed to ionizing radiation from several natural sources that can be classified into two broad categories: high-energy cosmic rays incident on the Earth’s atmosphere and releasing secondary radiation (cosmic contribution); and radioactive nuclides generated during the formation of the Earth and still present in the Earth’s crust (terrestrial contribution). Terrestrial radioactivity is mostly produced by the uranium and thorium radioactive families together with potassium. In most circumstances, radon, a noble gas produced in the radioactive decay of uranium, is the most important contributor to the total dose. This Atlas aims to present the current state of knowledge of natural radioactivity, by giving general background information, and describing its various sources. This reference material is complemented by a collection of maps of Europe displaying the levels of natural radioactivity caused by different sources. It is a compilation of contributions and reviews received from more than 80 experts in their field: they come from universities, research centres, national and European authorities and international organizations. This Atlas provides reference material and makes harmonized datasets available to the scientific community and national competent authorities. In parallel, this Atlas may serve as a tool for the public to: • familiarize itself with natural radioactivity; • be informed about the levels of natural radioactivity caused by different sources; • have a more balanced view of the annual dose received by the world population, to which natural radioactivity is the largest contributor; • and make direct comparisons between doses from natural sources of ionizing radiation and those from man-made (artificial) ones, hence to better understand the latter.JRC.G.10-Knowledge for Nuclear Security and Safet

    Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

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    Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

    European Atlas of Natural Radiation

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    Natural ionizing radiation is considered as the largest contributor to the collective effective dose received by the world population. The human population is continuously exposed to ionizing radiation from several natural sources that can be classified into two broad categories: high-energy cosmic rays incident on the Earth’s atmosphere and releasing secondary radiation (cosmic contribution); and radioactive nuclides generated during the formation of the Earth and still present in the Earth’s crust (terrestrial contribution). Terrestrial radioactivity is mostly produced by the uranium and thorium radioactive families together with potassium. In most circumstances, radon, a noble gas produced in the radioactive decay of uranium, is the most important contributor to the total dose.This Atlas aims to present the current state of knowledge of natural radioactivity, by giving general background information, and describing its various sources. This reference material is complemented by a collection of maps of Europe displaying the levels of natural radioactivity caused by different sources. It is a compilation of contributions and reviews received from more than 80 experts in their field: they come from universities, research centres, national and European authorities and international organizations.This Atlas provides reference material and makes harmonized datasets available to the scientific community and national competent authorities. In parallel, this Atlas may serve as a tool for the public to: • familiarize itself with natural radioactivity;• be informed about the levels of natural radioactivity caused by different sources;• have a more balanced view of the annual dose received by the world population, to which natural radioactivity is the largest contributor;• and make direct comparisons between doses from natural sources of ionizing radiation and those from man-made (artificial) ones, hence to better understand the latter.Additional information at: https://remon.jrc.ec.europa.eu/About/Atlas-of-Natural-Radiatio

    Microclimate and Weathering in Cultural Heritage: Design of a Monitoring Apparatus for Field Exposure Tests

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    An innovative experimental method for the long-term monitoring of outdoor microclimate and material decay at cultural heritage sites was developed to aid the formulation of new damage functions and models for climate-change risk assessment. To that end, an apparatus for field exposure tests was designed to monitor a variety of historical building materials in different environmental settings. The data series acquired, i.e., surface temperature and moisture, are compared with the corresponding meteorological datasets on a local and regional scale. The apparatus is designed for supporting also the monitoring of the physical and chemical changes caused by weathering. This novel method is expected to provide insights into the interaction between historical materials and the environment, which can be exploited for the protection and conservation of cultural heritage

    Terrestrial gamma dose rate mapping (Euganean Hills, Italy): comparison between field measurements and HPGe gamma spectrometric data

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    Terrestrial gamma radiation is mostly due to radionuclides in soil and rocks, primarily the 238U, 235U and 232Th radioactive families and 40K. This radiation contributes 15% to public exposure from all ionizing radiation sources, considering global population. Moreover, it can be used to estimate radon flux and included as one of the quantities relevant to the geogenic radon hazard model. Therefore, effort has been put into developing maps of terrestrial gamma dose rate at the regional, national or European scale, using different input data and methods. In the present work, two distinct approaches to map terrestrial gamma dose rate have been tested in the Euganean Hills district of NE Italy. The first one is based on 41 in situ measurements of ambient dose equivalent rates using a rate meter equipped with a NaI scintillator probe. The second one estimates terrestrial gamma dose rate from the U, Th and K activity concentrations in rock samples collected at the same locations of the dose rates measurements. The results obtained indicate good agreement between the two approaches, and as such suggest that the UNSCEAR 2008 prescription to derive ambient dose equivalent rate from laboratory gamma measurements produces reliable data, provided that cosmic and fall-out contributions are included. Moreover, the study proved that mapping the ambient dose equivalent rate (or terrestrial gamma dose rate) using only one database – i.e. either measured data or estimates derived from radionuclide activity concentration – yields valid results.JRC.G.10-Knowledge for Nuclear Security and Safet
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