In contrast to venous thromboembolism, little is known about arterial thromboembolism in patients with cancer. The aim of this study was to quantify the risk and explore clinical risk factors of ...arterial thromboembolism in patients with cancer, and investigate its potential impact on mortality. Patients with newly-diagnosed cancer or progression of disease after remission were included in a prospective observational cohort study and followed for two years. Between October 2003 and October 2013, 1880 patients (54.3% male; median age 61 years) were included. During a median follow up of 723 days, 48 (2.6%) patients developed arterial thromboembolism 20 (41.7%) myocardial infarction, 16 (33.3%) stroke and 12 (25.0%) peripheral arterial events, 157 (8.4%) developed venous thromboembolism, and 754 (40.1%) patients died. The cumulative 3-, 6-, 12-, and 24-month risks of arterial thromboembolism were 0.9%, 1.1%, 1.7%, and 2.6%, respectively. Male sex (subdistribution hazard ratio=2.9, 95%CI: 1.5-5.6;
=0.002), age (subdistribution hazard ratio per 10 year increase=1.5, 1.2-1.7;
<0.001), hypertension (3.1, 1.7-5.5;
<0.001), smoking (2.0, 1.1-3.7;
=0.022), lung cancer (2.3, 1.2-4.2;
=0.009), and kidney cancer (3.8, 1.4-10.5;
=0.012) were associated with a higher arterial thromboembolism risk. Furthermore, the occurrence of arterial thromboembolism was associated with a 3.2-fold increased risk of all-cause mortality (hazard ratio=3.2, 95%CI: 2.2-4.8;
<0.001). Arterial thromboembolism is a less common complication in patients with cancer than venous thromboembolism. The risk of arterial thromboembolism is high in patients with lung and kidney cancer. Patients with cancer who develop arterial thromboembolism are at a 3-fold increased risk of mortality.
We present a study of γ-ray emission from the core-collapse supernova remnant Cas A in the energy range from 0.1 GeV to 10 TeV. We used 65 hr of the Very Energetic Radiation Imaging Telescope Array ...System (VERITAS) data to cover 200 GeV-10 TeV, and 10.8 yr of Fermi-Large Area Telescope (LAT) data to cover 0.1-500 GeV. The spectral analysis of Fermi-LAT data shows a significant spectral curvature around 1.3 0.4stat GeV that is consistent with the expected spectrum from pion decay. Above this energy, the joint spectrum from Fermi-LAT and VERITAS deviates significantly from a simple power law, and it is best described by a power law with a spectral index of 2.17 0.02stat and a cutoff energy of 2.3 0.5stat TeV. These results, along with radio, X-ray, and γ-ray data, are interpreted in the context of leptonic and hadronic models. Assuming a one-zone model, we exclude a purely leptonic scenario and conclude that proton acceleration up to at least 6 TeV is required to explain the observed γ-ray spectrum. From modeling of the entire multiwavelength spectrum, a minimum magnetic field inside the remnant of Bmin 150 G is deduced.
Background Hemodynamic differentiation between pulmonary arterial hypertension (PAH) and postcapillary pulmonary hypertension (PH) is important because treatment options are strikingly different for ...the two disease subsets. Whereas patients with PAH can be treated effectively with targeted therapies, their use in postcapillary PH is currently not recommended. Our aim was to establish an algorithm to identify patients who are likely to experience a significant hemodynamic treatment response. Methods We determined hemodynamic cutoffs to discriminate between idiopathic PAH and postcapillary PH in a large database of 4,363 stable patients undergoing first diagnostic right and left heart catheterizations. In a second step, we performed a patient-level pooled analysis of four randomized, placebo-controlled trials including 541 patients with PAH who received treprostinil or placebo, to validate hemodynamic cutoffs with regard to treatment response. Results Receiver operating characteristic analysis identified mean pulmonary arterial wedge pressure (mPAWP) < 12 mm Hg and diastolic pulmonary vascular pressure gradient (DPG) ≥ 7 mm Hg as the best hemodynamic discriminators between idiopathic PAH and postcapillary PH. In our treatment study, only patients with mPAWP < 12 mm Hg, DPG > 20 mm Hg or a combination of both had a significant placebo-corrected improvement in hemodynamics. Conclusions mPAWP < 12 mm Hg and DPG > 20 mm Hg identify patients with PAH who are likely to have significant hemodynamic improvement with prostacyclin treatment.
BACKGROUND Deficient nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling results from endothelial dysfunction and may underlie impaired cardiac relaxation in patients with ...heart failure with preserved left ventricular ejection fraction (HFpEF) and pulmonary hypertension (PH). The acute hemodynamic effects of riociguat, a novel soluble guanylate cyclase stimulator, were characterized in patients with PH and HFpEF. METHODS Clinically stable patients receiving standard HF therapy with a left ventricular ejection fraction > 50%, mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg, and pulmonary arterial wedge pressure (PAWP) > 15 mm Hg at rest were randomized to single oral doses of placebo or riociguat (0.5, 1, or 2 mg). The primary efficacy variable was the peak decrease in mPAP from baseline up to 6 h. Secondary outcomes included hemodynamic and echocardiographic parameters, safety, and pharmacokinetics. RESULTS There was no significant change in peak decrease in mPAP with riociguat 2 mg (n = 10) vs placebo (n = 11, P = .6). However, riociguat 2 mg significantly increased stroke volume (+9 mL 95% CI, 0.4-17; P = .04) and decreased systolic BP (−12 mm Hg 95% CI, −22 to −1; P = .03) and right ventricular end-diastolic area (−5.6 cm2 95% CI, −11 to −0.3; P = .04), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or pulmonary vascular resistance. Riociguat was well tolerated. CONCLUSIONS In patients with HFpEF and PH, riociguat was well tolerated, had no significant effect on mPAP, and improved exploratory hemodynamic and echocardiographic parameters. TRIAL REGISTRY: ClinicalTrials.gov ; No.: NCT01172756; URL: www.clinicaltrials.gov
Delayed bone fracture healing and the formation of non-unions represent an important clinical problem, particularly in polytrauma patients who suffer from posttraumatic systemic inflammation. ...However, the underlying pathomechanisms remain unclear. Neutrophil granulocytes are crucial effector cells in the systemic immune response and represent the most abundant immune cell population in the early fracture haematoma. Here we investigated the role of neutrophils in a mouse model of uncomplicated fracture healing and compromised fracture healing induced by an additional thoracic trauma. Twenty four hours before injury, 50 % of the mice were systemically treated with an anti-Ly-6G-antibody to reduce neutrophil numbers. In the isolated fracture model, Ly-6G-Ab treatment significantly increased the concentration of both pro- and anti-inflammatory cytokines, including interleukin (IL)-6 and IL-10, and chemokines, for example, C-X-C motif ligand 1 (CXCL1) and monocyte chemotactic protein-1 (MCP-1), in the fracture haematoma. Monocyte/macrophage recruitment was also significantly enhanced. After 21 d, bone regeneration was considerably impaired as demonstrated by significantly diminished bone content and impaired mechanical properties of the fracture callus. These results indicate that undisturbed neutrophil recruitment and function in the inflammatory phase after fracture is crucial to initiate downstream responses leading to bone regeneration. In the combined trauma model, the reduction of neutrophil numbers ameliorated pulmonary inflammation but did not provoke any significant effect on bone regeneration, suggesting that neutrophils may not play a crucial pathomechanistic role in compromised fracture healing induced by an additional thoracic trauma.
Global-Scale Structure of the Eelgrass Microbiome Fahimipour, Ashkaan K; Kardish, Melissa R; Lang, Jenna M ...
Applied and environmental microbiology,
2017-Jun-15, Letnik:
83, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Plant-associated microorganisms are essential for their hosts' survival and performance. Yet, most plant microbiome studies to date have focused on terrestrial species sampled across relatively small ...spatial scales. Here, we report the results of a global-scale analysis of microbial communities associated with leaf and root surfaces of the marine eelgrass
throughout its range in the Northern Hemisphere. By contrasting host microbiomes with those of surrounding seawater and sediment, we uncovered the structure, composition, and variability of microbial communities associated with eelgrass. We also investigated hypotheses about the assembly of the eelgrass microbiome using a metabolic modeling approach. Our results reveal leaf communities displaying high variability and spatial turnover that mirror their adjacent coastal seawater microbiomes. By contrast, roots showed relatively low compositional turnover and were distinct from surrounding sediment communities, a result driven by the enrichment of predicted sulfur-oxidizing bacterial taxa on root surfaces. Predictions from metabolic modeling of enriched taxa were consistent with a habitat-filtering community assembly mechanism whereby similarity in resource use drives taxonomic cooccurrence patterns on belowground, but not aboveground, host tissues. Our work provides evidence for a core eelgrass root microbiome with putative functional roles and highlights potentially disparate processes influencing microbial community assembly on different plant compartments.
Plants depend critically on their associated microbiome, yet the structure of microbial communities found on marine plants remains poorly understood in comparison to that for terrestrial species. Seagrasses are the only flowering plants that live entirely in marine environments. The return of terrestrial seagrass ancestors to oceans is among the most extreme habitat shifts documented in plants, making them an ideal testbed for the study of microbial symbioses with plants that experience relatively harsh abiotic conditions. In this study, we report the results of a global sampling effort to extensively characterize the structure of microbial communities associated with the widespread seagrass species
, or eelgrass, across its geographic range. Our results reveal major differences in the structure and composition of above- versus belowground microbial communities on eelgrass surfaces, as well as their relationships with the environment and host.
Measurements of atmospheric CH4 from air samples collected weekly at 46 remote surface sites show that, after a decade of near‐zero growth, globally averaged atmospheric methane increased during 2007 ...and 2008. During 2007, CH4 increased by 8.3 ± 0.6 ppb. CH4 mole fractions averaged over polar northern latitudes and the Southern Hemisphere increased more than other zonally averaged regions. In 2008, globally averaged CH4 increased by 4.4 ± 0.6 ppb; the largest increase was in the tropics, while polar northern latitudes did not increase. Satellite and in situ CO observations suggest only a minor contribution to increased CH4 from biomass burning. The most likely drivers of the CH4 anomalies observed during 2007 and 2008 are anomalously high temperatures in the Arctic and greater than average precipitation in the tropics. Near‐zero CH4 growth in the Arctic during 2008 suggests we have not yet activated strong climate feedbacks from permafrost and CH4 hydrates.
The phases of swallowing are controlled by central pattern-generating circuitry of the brain stem and peripheral reflexes. The oral, pharyngeal, and esophageal phases of swallowing are independent of ...each other. Although central pattern generators of the brain stem control the timing of these phases, the peripheral manifestation of these phases depends on sensory feedback through reflexes of the pharynx and esophagus. The dependence of the esophageal phase of swallowing on peripheral feedback explains its absence during failed swallows. Reflexes that initiate the pharyngeal phase of swallowing also inhibit the esophageal phase which ensures the appropriate timing of its occurrence to provide efficient bolus transport and which prevents the occurrence of multiple esophageal peristaltic events. These inhibitory reflexes are probably partly responsible for deglutitive inhibition. Three separate sets of brain stem nuclei mediate the oral, pharyngeal, and esophageal phases of swallowing. The trigeminal nucleus and reticular formation probably contain the oral phase pattern-generating neural circuitry. The nucleus tractus solitarius (NTS) probably contains the second-order sensory neurons as well as the pattern-generating circuitry of both the pharyngeal and esophageal phases of swallowing, whereas the nucleus ambiguus and dorsal motor nucleus contain the motor neurons of the pharyngeal and esophageal phases of swallowing. The ventromedial nucleus of the NTS may govern the coupling of the pharyngeal phase to the esophageal phase of swallowing.
Abstract
Hair follicles undergo cycles of regeneration fueled by hair follicle stem cells (HFSCs). While β-catenin-dependent canonical Wnt signaling has been extensively studied and implicated in ...HFSC activation and fate determination, very little is known about the function of β-catenin-independent Wnt signaling in HFSCs. In this study, we investigate the functional role of ROR2, a Wnt receptor, in HFSCs. By analyzing
Ror2
-depleted HFSCs, we uncover that ROR2 is not only essential to regulate Wnt-activated signaling that is responsible for HFSC activation and self-renewal, but it is also required to maintain proper ATM/ATR-dependent DNA damage response, which is indispensable for the long-term maintenance of HFSCs. In analyzing HFSCs lacking β-catenin, we identify a compensatory role of ROR2-PKC signaling in protecting
β-catenin
-null HFSCs from the loss of stem cell pool. Collectively, our study unveils a previously unrecognized role of ROR2 in regulation of stem cell self-renewal and maintenance.
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