Abstract Background Many computed tomography (CT) parameters have been proposed as potential predictors of outcome in acute pulmonary embolism. We sought to summarize available evidence on the ...predictive value of CT severity parameters for short-term clinical outcome in pulmonary embolism. Methods We searched PubMed and EMBASE through February 2014 for studies that reported on the association between CT parameters of acute pulmonary embolism severity and short-term (≤6 months) clinical outcome. Risk estimates for quantitative parameters of right ventricular (RV) dysfunction (abnormally increased RV/left ventricular LV diameter ratio on transverse sections and 4-chamber views), qualitative parameters of RV dysfunction (abnormal septal morphology and contrast reflux), thrombus load, and central thrombus location were derived using random effect regression analysis. Meta-regression analysis was performed to quantify and explain study heterogeneity. Results A total of 49 studies with 13,162 patients with acute pulmonary embolism (median age of 61 years, 55.1% were women) who underwent diagnostic CT imaging were included in the analysis. An abnormally increased RV/LV diameter ratio measured on transverse sections was associated with an approximately 2.5-fold risk for all-cause mortality (pooled odds ratio OR, 2.5; 95% confidence interval CI, 1.8-3.5) and adverse outcome (OR, 2.3; 95% CI, 1.6-3.4) and a 5-fold risk for pulmonary embolism-related mortality (OR, 5.0; 95% CI, 2.7-9.2). Thrombus load (OR, 1.6, 95% CI, 0.7-3.9; P = .2896) and central location (OR, 1.7; 95% CI, 0.7-4.2; P = .2609) were not predictive for all-cause mortality, although both were associated with adverse clinical outcome. Conclusions Across all end points, the RV/LV diameter ratio on transverse CT sections has the strongest predictive value and most robust evidence base for adverse clinical outcomes in patients with acute pulmonary embolism.
Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies. Following exposure to cold, BAT is activated by the sympathetic nervous ...system with concomitant release of catecholamines and activation of β-adrenergic receptors. Because BAT therapies based on cold exposure or β-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat. However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A2A receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A2A receptors in mice causes a decrease in BAT-dependent thermogenesis, whereas treatment with A2A agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A2A receptors or injection of lentiviral vectors expressing the A2A receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A2A agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A2A signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.
To determine the feasibility of computed tomography (CT)-based dynamic myocardial perfusion imaging for the detection of hemodynamically significant coronary artery stenosis, as defined with ...fractional flow reserve (FFR).
Institutional review board approval and informed patient consent were obtained before patient enrollment in the study. The study was HIPAA compliant. Subjects who were suspected of having or were known to have coronary artery disease underwent electrocardiographically triggered dynamic stress myocardial perfusion imaging. FFR measurement was performed within all main coronary arteries with a luminal narrowing of 50%-85%. Estimated myocardial blood flow (MBF) was derived from CT images by using a model-based parametric deconvolution method for 16 myocardial segments and was related to hemodynamically significant coronary artery stenosis with an FFR of 0.75 or less in a blinded fashion. Conventional measures of diagnostic accuracy were derived, and discriminatory power analysis was performed by using logistic regression analysis.
Of 36 enrolled subjects, 33 (mean age, 68.1 years ± 10 standard deviation; 25 76% men, eight 24% women) completed the study protocol. An MBF cut point of 75 mL/100 mL/min provided the highest discriminatory power (C statistic, 0.707; P <.001). While the diagnostic accuracy of CT for the detection of anatomically significant coronary artery stenosis (>50%) was high, it was low for the detection of hemodynamically significant stenosis (positive predictive value PPV per coronary segment, 49%; 95% confidence interval CI: 36%, 60%). With use of estimated MBF to reclassify lesions depicted with CT angiography, 30 of 70 (43%) coronary lesions were graded as not hemodynamically significant, which significantly increased PPV to 78% (95% CI: 61%, 89%; P = .02). The presence of a coronary artery stenosis with a corresponding MBF less than 75 mL/100 mL/min had a high risk for hemodynamic significance (odds ratio, 86.9; 95% CI:17.6, 430.4).
Dynamic CT-based stress myocardial perfusion imaging may allow detection of hemodynamically significant coronary artery stenosis.
Neuroinflammation is a devastating pathophysiological process that results in brain damage and neuronal death. Pathogens, cell fragments and cellular dysfunction trigger inflammatory responses. ...Irrespective of the cause, inflammasomes are key intracellular multiprotein signalling platforms that sense neuropathological conditions. The activation of inflammasomes leads to the auto‐proteolytic cleavage of caspase‐1, resulting in the proteolysis of the pro‐inflammatory cytokines interleukin (IL)1β and IL18 into their bioactive forms. It also initiates pyroptosis, a type of cell death. The two cytokines contribute to the pathogenesis in acute and chronic brain diseases and also play a central role in human aging and psychiatric disorders. Sex steroids, in particular oestrogens, are well‐described neuroprotective agents in the central nervous system. Oestrogens improve the functional outcome after ischaemia and traumatic brain injury, reduce neuronal death in Parkinson′s and Alzheimer′s disease, as well as in amyotrophic lateral sclerosis, attenuate glutamate excitotoxicity and the formation of radical oxygen species, and lessen the spread of oedema after damage. Moreover, oestrogens alleviate menopause‐related depressive symptoms and have a positive influence on depressive disorders probably by influencing growth factor production and serotonergic brain circuits. Recent evidence also suggests that inflammasome signalling affects anxiety‐ and depressive‐like behaviour and that oestrogen ameliorates depression‐like behaviour through the suppression of inflammasomes. In the present review, we highlight the most recent findings demonstrating that oestrogens selectively suppress the activation of the neuroinflammatory cascade in the brain in acute and chronic brain disease models. Furthermore, we aim to describe putative regulatory signalling pathways involved in the control of inflammasomes. Finally, we consider that psychiatric disorders such as depression also contain an inflammatory component that could be modulated by oestrogen.
Compound optics such as lens systems can overcome the limitations concerning resolution, efficiency, or aberrations which fabrication constraints would impose on any single optical element. In this ...work we demonstrate unprecedented sub-5 nm point focusing of hard x-rays, based on the combination of a high gain Kirkpatrick-Baez (KB) mirror system and a high resolution W/Si multilayer zone plate (MZP) for ultra-short focal length f. The pre-focusing allows limiting the MZP radius to below 2 μm, compatible with the required 5 nm structure width and essentially unlimited aspect ratios, provided by enabling fabrication technology based on pulsed laser deposition (PLD) and focused ion beam (FIB).
DNA‐sensitive fluorescent light‐up probes based on berberine are presented. This biogenic fluorophore was chosen as central unit to use its potential biocompatibility and its DNA‐binding properties. ...To provide predictable fluorescence quenching in aqueous solution and a fluorescence light‐up effect upon DNA binding, aryl substituents were attached at the 9‐position by Suzuki‐Miyaura coupling reactions. The 9‐arylberberine derivatives have a very low fluorescence quantum yield (Φfl=<0.02), which is caused by the radiationless deactivation of the excited state by torsional relaxation about the biaryl axis. In addition, these berberine derivatives intercalate into DNA with high affinity (Kb=2.0−22×104 M−1). Except for the nitrophenyl‐ and hydroxyphenyl‐substituted derivatives, all tested compounds exhibited a pronounced fluorescence light‐up effect upon association with DNA, because the deactivation of the excited‐state by torsional relaxation is suppressed in the DNA binding site. Most notably, it was shown exemplarily with the 9‐(4‐methoxyphenyl)‐ and the 9‐(6‐methoxynaphthyl)‐substituted derivatives that these properties are suited for fluorimetric cell analysis. In particular, these probes generated distinct staining patterns in eukaryotic cells (NIH 3T3 mouse fibroblasts), which enabled the identification of nuclear substructures, most likely heterochromatin or nucleoli, respectively.
Staining subcompartments of eukaryotic cells: The high affinity of 9‐aryl‐substituted berberine derivatives to DNA and the resulting fluorescent light‐up effect were used for fluorimetric staining of eukaryotic cells, specifically for the distinct visualization of the heterochromatin or the nucleoli.
Virtual reality exposure therapy (VRET) is a promising treatment for patients with fear of driving. The present pilot study is the first one focusing on behavioral effects of VRET on patients with ...fear of driving as measured by a post-treatment driving test in real traffic.
The therapy followed a standardized manual including psychotherapeutic and medical examination, two preparative psychotherapy sessions, five virtual reality exposure sessions, a final behavioral avoidance test (BAT) in real traffic, a closing session, and two follow-up phone assessments after six and twelve weeks. VRE was conducted in a driving simulator with a fully equipped mockup. The exposure scenarios were individually tailored to the patients' anxiety hierarchy. A total of 14 patients were treated. Parameters on the verbal, behavioral and physiological level were assessed.
The treatment was helpful to overcome driving fear and avoidance. In the final BAT, all patients mastered driving tasks they had avoided before, 71% showed an adequate driving behavior as assessed by the driving instructor, and 93% could maintain their treatment success until the second follow-up phone call. Further analyses suggest that treatment reduces avoidance behavior as well as symptoms of posttraumatic stress disorder as measured by standardized questionnaires (Avoidance and Fusion Questionnaire: p < .10, PTSD Symptom Scale-Self Report: p < .05).
VRET in driving simulation is very promising to treat driving fear. Further research with randomized controlled trials is needed to verify efficacy. Moreover, simulators with lower configuration stages should be tested for a broad availability in psychotherapy.
Context.
Carbonic acid (H
2
CO
3
) is a weak acid relevant to astrobiology which, to date, remains undetected in space. Experimental work has shown that the
β
-polymorph of H
2
CO
3
forms under space ...relevant conditions through energetic (UV photon, electron, and cosmic ray) processing of CO
2
- and H
2
O-rich ices. Although its
α
-polymorph ice has been recently reassigned to the monomethyl ester of carbonic acid, a different form of H
2
CO
3
ice may exist and is synthesized without irradiation through surface reactions involving CO molecules and OH radicals, that is to say
γ
-H
2
CO
3
.
Aims.
We aim to provide a systematic set of vacuum ultraviolet (VUV) photoabsorption spectroscopic data of pure carbonic acid that formed and was destroyed under conditions relevant to space in support of its future identification on the surface of icy objects in the Solar System by the upcoming Jupiter ICy moons Explorer mission and on interstellar dust by the
James Webb
Space Telescope spacecraft.
Methods.
We present VUV photoabsorption spectra of pure and mixed CO
2
and H
2
O ices exposed to 1 keV electrons at 20 and 80 K to simulate different interstellar and Solar System environments. Ices were then annealed to obtain a layer of pure H
2
CO
3
which was further exposed to 1 keV electrons at 20 and 80 K to monitor its destruction pathway. Fourier-transform infrared (FT-IR) spectroscopy was used as a secondary probe providing complementary information on the physicochemical changes within an ice.
Results.
Our laboratory work shows that the formation of solid H
2
CO
3
, CO, and O
3
upon the energetic processing of CO
2
:H
2
O ice mixtures is temperature-dependent in the range between 20 and 80 K. The amorphous to crystalline phase transition of H
2
CO
3
ice is investigated for the first time in the VUV spectral range by annealing the ice at 200 and 225 K. We have detected two photoabsorption bands at 139 and 200 nm, and we assigned them to
β
-H
2
CO
3
and
γ
-H
2
CO
3
, respectively. We present VUV spectra of the electron irradiation of annealed H
2
CO
3
ice at different temperatures leading to its decomposition into CO
2
, H
2
O, and CO ice. Laboratory results are compared to Cassini UltraViolet Imaging Spectrograph observations of the 70−90 K ice surface of Saturn’s satellites Enceladus, Dione, and Rhea.
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