Using energetic particle and wave measurements from the Van Allen Probes, Polar Orbiting Environmental Satellites (POES), and Geostationary Operational Environmental Satellite (GOES), the ...acceleration mechanism of ultrarelativistic electrons (>3 MeV) in the center of the outer radiation belt is investigated statistically. A superposed epoch analysis is conducted using 19 storms, which caused flux enhancements of 1.8–7.7 MeV electrons. The evolution of electron phase space density radial profile suggests an energy‐dependent acceleration of ultrarelativistic electrons in the outer belt. Especially, for electrons with very high energies (~7 MeV), prevalent positive phase space density radial gradients support inward radial diffusion being responsible for electron acceleration in the center of the outer belt (L*~3–5) during most enhancement events in the Van Allen Probes era. We propose a two‐step acceleration process to explain the acceleration of ~7 MeV electrons in the outer belt: intense and sustained chorus waves locally energize core electron populations to ultrarelativistic energies at high L region beyond the Van Allen Probes' apogee, followed by inward radial diffusion which further energizes these populations to even higher energies. Statistical results of chorus wave activity inferred from POES precipitating electron measurements as well as core electron populations observed by the Van Allen Probes and GOES support this hypothesis.
Key Points
Electron phase space density (PSD) evolution was studied for 19 storms with 1.8–7.7 MeV electron enhancements in the Van Allen Probes era
Prevalent positive PSD radial gradients support inward radial diffusion being responsible for ~7 MeV electron acceleration at L*~3–5
Two‐step acceleration mechanism is proposed to explain the acceleration of very high energy electrons in the outer belt
Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia.
We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it ...reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem.
We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla.
Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.
Background:
The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC).
...Methods:
GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed.
Results:
A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS.
Conclusion:
The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.
To retrospectively assess the value of computed tomographic (CT) bronchial arteriography (BA) with 320-row multidetector CT in the management of patients with recurrent hemoptysis immediately after ...bronchial artery embolization (BAE).
Among 135 consecutive patients treated with BAE between April 2014 and March 2016, recurrent hemoptysis developed in 15, and 10 subsequently underwent multidetector CT. Vascular abnormalities and associated anatomy were evaluated to determine the potential cause of BAE failure, and the clinical impacts of CT BA were analyzed.
CT BA revealed an additional 22 abnormal vessels in the qualified 10 patients, and 8 patients were treated again within 24 hours after the first BAE based on multidetector CT findings. Of the 22 abnormal vessels, 16 were embolized, including 4 orthotopic arteries, 8 ectopic arteries, and 4 nonbronchial systemic arteries (NBSAs); the remaining 6 abnormal arteries were not embolized because of normal BA (n = 1), anatomic inaccessibility (n = 2), or cessation of hemoptysis with conservative therapy (n = 3). There were no further cases of recurrent hemoptysis after the second intervention, with a mean follow-up of 7.7 months ± 6.7. Overall, initial conventional BA missed 65% of potential bleeding arteries (22 of 34). After CT BA, 73% of the newly identified vessels (16 of 22) were embolized.
Multiple unrecognized abnormal ectopic bronchial arteries and NBSAs are the major causes of failure of initial BAE. Multidetector CT BA can precisely identify a large number of feeding vessels that are missed on conventional BA, allowing for repeat embolization with a high success rate.
Acute ischemic stroke patients with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) thrombolysis have different outcomes. The degree of thrombolysis depends largely on the delicate ...balance of coagulation and fibrinolysis. Thus, our study aimed to investigate the prognostic value of routine coagulation parameters in acute stroke patients treated with rt-PA. From December 2016 to October 2018, consecutive patients treated with standard-dose IV rt-PA within 4.5 h of stroke onset were collected in Beijing Tiantan Hospital. Routine coagulation parameters, including platelet count, mean platelet volume, platelet distribution width, prothrombin time (PT), activated partial thromboplastin time, thrombin time, and fibrinogen, were measured at baseline (h0) and 24 h (h24) after thrombolysis. The change of coagulation parameters was defined as the (h24-h0)/h0 ratio. The prognosis included short-term outcome at 24 h and functional outcome at 3 months. A total of 267 patients were investigated (188 men and 79 women) with a mean age of 60.88 ± 12.31 years. In total, 9 patients had early neurological deterioration within 24 h, and 99 patients had an unfavorable outcome at the 3-month visit. In multivariate logistic regression, the (h24-h0)/h0 of PT was associated with unfavorable functional outcomes at 3 months (odds ratio: 1.42, 95% confidence interval: 1.02-2.28). While the change of other coagulation parameters failed to show any correlation with short-term or long-term prognosis. In conclusion, the prolongation of PT from baseline to 24 h after IV rt-PA increases the risk of 3-month unfavorable outcomes in acute stroke patients.
Hypoxia-reoxygenation of cultured macrovascular endothelial cells is used to study ischemia-reperfusion (IR)-related cellular and molecular changes; however, these models do not accurately depict ...events in pulmonary microvascular endothelial cells (PMVECs) during conventional lung retrieval and transplantation. We used rat PMVECs in a new non-hypoxic cell-based lung transplantation model to assess these events.
To simulate cold storage, rat PMVECs were preserved in 95% O2-5% CO2 at 4°C for 6 hours in low-potassium dextran solution. Dishes were warmed for 1 hour to room temperature for simulating implantation. Medium was added at 37°C in 50% O2-5% CO2-45% N2 to simulate reperfusion. Additional PMVECs were transfected with siRNA targeting mitogen-activated protein kinases (MAPKs) and then subjected to simulated IR.
MAPKs and NF-κB were activated during simulated reperfusion, and AP-1 was activated during ischemia and reperfusion. Increased malondialdehyde levels were found during cold ischemia, and apoptosis and production of IL-1β, IL-6, and TNF-α were observed during reperfusion. Silencing of MAPKs attenuated oxidative stress, inflammation and apoptosis. Silencing of JNK and p38 decreased NF-κB phosphorylation and increased inhibitor of NF-κB (IκB)α levels. Knockdown of ERK1/2 increased NF-κB phosphorylation but had no effect on IκBα expression. Silencing of JNK and ERK1/2, but not p38, decreased AP-1 phosphorylation.
Exposing rat PMVECs to simulated non-hypoxic IR caused lipid peroxidation, inflammation and apoptosis, which required MAPK-mediated NF-κB and AP-1 activation and distinct regulation of MAPKs by these 2 transcription factors. This model could be used to uncouple mechanisms of IR and evaluate potential therapeutics in alleviating IR injury.
Background: Patients with diabetes mellitus (DM) are considered to increase the risk of thrombosis and bleeding. However, whether DM is an independent risk factor for events in patients ...anticoagulated with bivalirudin during elective percutaneous coronary intervention (PCI) is not clear. Methods: Patients anticoagulated with bivalirudin during elective PCI from January 2017 to August 2018 in 3 centers were enrolled. The primary endpoint of thrombotic events was major adverse cardiac and cerebrovascular events (MACCE, including all-cause death, myocardial infarction, ischemic revascularization, stent thrombosis, and stroke); the primary endpoint of bleeding events was Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding. Results: 1152 patients were finally enrolled. After one-year follow-up, 89 (7.7%) MACCE and 21 (1.8%) BARC 2, 3 or 5 bleeding occurred. Multivariate Cox regression analysis showed DM was not an independent risk factor for MACCE (hazard ratio HR: 1.029, 95% confidence interval CI: 0.674-1.573, P = .893), but peripheral artery disease (PAD) history (HR: 2.200, 95%CI: 1.290-3.751, P = .004) was an independent risk factor for MACCE. DM was not an independent risk factor for BARC 2, 3 or 5 bleeding (HR: 0.732, 95%CI: 0.293-1.831, P = .505), but PAD history (HR: 3.029, 95%CI: 1.102-8.332, P = .032) and low hemoglobin level (HR = 0.972, 95%CI: 0.947-0.998, P = .036) were independent risk factors for BARC 2, 3 or 5 bleeding. Conclusions: DM was not an independent risk factor for one-year thrombotic and bleeding events in patients anticoagulated with bivalirudin during elective PCI. More attention should be paid to PAD history and hemoglobin level to identify high-risk patients.
Background Leukoaraiosis (LA) is an indicator of small vessel disease, but little is known about the relationship between the severity of LA and etiologic subtype of ischemic stroke. Our study aimed ...to investigate the factors associated with the severity of LA and the relationship between the severity of LA and etiologic subtype of ischemic stroke. Methods A total of 791 patients with first-ever ischemic stroke within 7 days were enrolled in our study. We evaluated cranial magnetic resonance imagings including severity of LA in periventricular and deep white matter, severity of silent lacunar infarcts (SLIs), etiologic subtype of ischemic stroke, and topographic patterns of acute cerebral infarcts. Severity of LA was graded as grade 0 when Fazekas scores = 0, grade 1 when Fazekas scores ranged from 1 to 2, and grade 2 when Fazekas scores were greater than or equal to 3. Multivariable ordinal logistic regression was used to analyze the factors associated with the severity of LA. Results A total of 748 patients (94.6%) had LA, the numbers and proportions of grade 0, grade 1, and grade 2 LA were 43 patients (5.4%), 413 patients (52.2%), and 335 patients (42.4%), respectively. In multivariable ordinal logistic regression analysis, increasing age, higher diastolic blood pressure, admission National Institutes of Health Stroke Scale scores less than or equal to 3, presence of SLIs, and small artery occlusion (SAO) subtype of ischemic stroke were found to be independently associated with higher grade of LA. Conclusions LA is prevalent in first-ever ischemic stroke patients. Severe LA is more frequently associated with higher grades of SLIs and ischemic stroke due to SAO.
The importance of the stabilizing effect of the distal interosseous membrane on the distal radioulnar joint, especially in patients with a distal oblique bundle, has been described. The purpose of ...this study was to evaluate the stability of the distal radioulnar joint after an ulnar shortening osteotomy and to quantify longitudinal resistance to ulnar shortening when the osteotomy was proximal or distal to the ulnar attachment of the distal interosseous membrane. These relationships were characterized for forearms with or without a distal oblique bundle.
Ten fresh-frozen cadavers were used. A transverse osteotomy and ulnar shortening was performed proximal (proximal shortening) and distal (distal shortening) to the ulnar attachment of the distal interosseous membrane. Distal radioulnar joint laxity was evaluated as the volar and dorsal displacements of the radius relative to the fixed ulna with 20 N of applied force. Testing was performed under controlled 1-mm increments of ulnar shortening up to 4 mm, with the forearm in neutral alignment, 60° of pronation, and 60° of supination. Resistance to ulnar shortening was quantified as the slope of the load-displacement curve obtained by displacing the distal ulnar segment proximally.
In proximal shortening, significantly greater stability of the distal radioulnar joint was obtained with even 1 mm of shortening compared with the control, whereas distal shortening demonstrated significant improvement in stability of the distal radioulnar joint only after shortening of ≥4 mm in all rotational positions. Significantly greater stability of the distal radioulnar joint was achieved with proximal shortening than with distal shortening and in specimens with a distal oblique bundle than in those without a distal oblique bundle. The longitudinal resistance to ulnar shortening was significantly greater in proximal shortening than in distal shortening. The stiffness in proximal shortening was not affected by the presence of a distal oblique bundle in the distal interosseous membrane.
Ulnar shortening with the osteotomy carried out proximal to the attachment of the distal interosseous membrane had a more favorable effect on stability of the distal radioulnar joint compared with distal osteotomy, especially in the presence of a distal oblique bundle.
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