Citations

Aims and background Id helix-loop-helix proteins function as regulators of cell growth and differentiation. However, they can induce malignant transformation when overexpressed. The EWS/ETS chimeric proteins in Ewing sarcoma act as aberrant transcription factors leading to tumorigenic processes. An enhanced expression of the Id2 gene in Ewing sarcoma cells was previously shown by gene array techniques. We investigated the expression of Id2 at the protein and gene level in Ewing sarcoma. Methods We evaluated the expression of Id2 protein using immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a total of 71 cases of Ewing sarcoma. Additionally, a Ewing sarcoma cell line was examined by real-time quantitative PCR. Results Id2 expression was observed in 65 cases (91.5%) of the 71 total cases examined and a high level of Id2 expression was observed in 45 of these cases (63.8%). In tumor cells, Id2 proteins displayed cytoplasmic as well as nuclear localization. The amplification of the Id2 gene was not noted in a Ewing sarcoma cell line using real-time quantitative PCR. The crossing points of Id2 in the Ewing sarcoma cell line, control fibroblast, and osteosarcoma cell line were 18.54 ± 0.16, 18.25, and 18.34, respectively. Conclusions Our data support a role for increased Id2 protein expression in Ewing sarcoma. However, this overexpression of the Id2 protein could not be confirmed by a corresponding change at the gene level in a Ewing sarcoma cell line.

AbstractThis study used resting state functional magnetic resonance imaging (rsfMRI) to investigate whole brain networks in patients with persistent postural perceptual dizziness (PPPD). We compared rsfMRI data from 38 patients with PPPD and 38 healthy controls using whole brain and region of interest analyses. We examined correlations among connectivity and clinical variables and tested the ability of a machine learning algorithm to classify subjects using rsfMRI results. Patients with PPPD showed: (a) increased connectivity of subcallosal cortex with left superior lateral occipital cortex and left middle frontal gyrus, (b) decreased connectivity of left hippocampus with bilateral central opercular cortices, left posterior opercular cortex, right insular cortex and cerebellum, and (c) decreased connectivity between right nucleus accumbens and anterior left temporal fusiform cortex. After controlling for anxiety and depression as covariates, patients with PPPD still showed decreased connectivity between left hippocampus and right inferior frontal gyrus, bilateral temporal lobes, bilateral insular cortices, bilateral central opercular cortex, left parietal opercular cortex, bilateral occipital lobes and cerebellum (bilateral lobules VI and V, and left I–IV). Dizziness handicap, anxiety, and depression correlated with connectivity in clinically meaningful brain regions. The machine learning algorithm correctly classified patients and controls with a sensitivity of 78.4%, specificity of 76.9%, and area under the curve = 0.88 using 11 connectivity parameters. Patients with PPPD showed reduced connectivity among the areas involved in multisensory vestibular processing and spatial cognition, but increased connectivity in networks linking visual and emotional processing. Connectivity patterns may become an imaging biomarker of PPPD.

Background and purpose Vertebrobasilar dolichoectatic and fusiform aneurysms (VBDAs) are known to have a poor natural history, with high rates of growth, rupture, and stroke. The purpose of this study was to identify hemodynamic characteristics that differ between VBDAs associated with growth, rupture, and stroke. Materials and methods VBDAs with CT angiography or MR angiography followed longitudinally without treatment were studied. Unstable aneurysms were defined as those that grew or ruptured during follow-up. Aneurysms associated with stroke were defined as those associated with posterior circulation infarct at follow-up. Baseline data, including demographics, comorbidities, and aneurysm morphology and size were collected. Image based computational fluid dynamics models were created and run under pulsatile flow conditions. Relevant hemodynamic and geometric variables were calculated and compared between groups (stable vs unstable and no stroke vs stroke) using the Wilcoxon test. Results A total of 37 VBDAs were included (24 stable, 13 unstable; 30 no stroke, 7 stroke). Unstable aneurysms had lower shear rates (P=0.05), blood flow velocity (P=0.03), and lower vorticity (P=0.049) than stable aneurysms. In addition, unstable aneurysms had higher mean oscillatory shear indices (P=0.001). There were no differences in the hemodynamic characteristics of aneurysms in the stroke group compared with the non-stroke group. Conclusion This small study suggests there may be hemodynamic differences between unstable and stable VBDAs. Unstable VBDAs appear to be under lower flow conditions with lower velocity, vorticity, and shear rates, and have more oscillatory flow. There was no difference in the hemodynamic characteristics of aneurysms in the stroke and no stroke group.

Aims and Background HuR is a member of the family of ELAV (embryonic lethal abnormal vision)-like proteins that stabilize several cellular mRNAs by binding to AU-rich elements in the 3’ untranslated region of the mRNA. Cyclooxygenase-2 (COX-2) is a well known enzyme that promotes tumor growth and metastasis. Recent studies have shown that HuR can stabilize the mRNA of COX-2, and cytoplasmic expression of HuR is associated with increased COX-2 expression in some cancers. The aim of this study was to investigate the correlation between COX-2 and HuR in Ewing sarcoma. Methods The expression patterns for HuR and COX-2 were assessed via immunochemical analysis of 70 Ewing sarcoma samples. Results Nuclear HuR expression was observed in 12 of 70 (17.1%) cases, but cytoplasmic expression was not observed. COX-2 expression was seen in 25 of 70 (35.7%) samples. Nuclear HuR and COX-2 were simultaneously expressed in 8 of 70 (11.4%) samples. The expression of nuclear HuR was significantly associated with COX-2 expression (P = 0.014). Neither HuR nor COX-2 expression showed a correlation with age or sex. Conclusions COX-2 expression in Ewing sarcoma may not be directly related to mRNA stabilization by HuR. However, a correlation between COX-2 expression and nuclear HuR expression through indirect mRNA stabilization can be suggested.

Background: Use of magnetic resonance imaging (MRI) brain is restricted in patients with cardiovascular implantable electronic devices (CIEDs). We proposed to determine whether mortality difference exists for patients with non–MRI-conditional CIEDs undergoing brain MRI compared with controls. Methods and Results: Retrospective analysis of prospectively collected data was performed to compare all-cause mortality in patients with CIEDs undergoing brain MRI (CIED-MRI) with 3 control groups matched for age, sex, imaging year, and type of CIED: (1) no CIED, brain MRI (no–CIED-MRI); (2) CIED, brain computerized tomography (CT) scan (CIED-CT); and (3) no CIED, brain CT (no–CIED-CT). The primary outcome was a significant difference ( P <0.05) between estimated mortality rates. Secondary outcomes were changes in device function before and after brain MRI. The estimated all-cause mortality at 5 years for the CIED-MRI group [mean age (±SD), 68.2 years (15.3 years); 61.2% men] was not significantly different from patients who underwent CT with or without a device (CIED-CT group: hazard ratio, 0.814; 95% confidence interval, 0.593–1.117; P =0.2; no–CIED-CT group: hazard ratio, 1.149; 95% confidence interval, 0.818–1.613; P =0.4). There was a significant increase in mortality between CIED-MRI and no–CIED-MRI groups (hazard ratio, 1.463; 95% confidence interval, 1.019–2.099; P =0.04). Conclusions: Brain MRI in patients with CIEDs does not carry an increased mortality risk compared with brain CT and can be performed with adherence to appropriate procedural protocols.

AbstractBackgroundTransthoracic impedance measurements (TIM) is primarily used for minute ventilation rate adaptive sensors in pacemakers. With elevated impedance, the TIM electrical signal itself is oversensed, causing device malfunction.ObjectiveWe report an increased incidence of TIM oversensing.MethodRetrospective chart review. We review existing records of 18 patients who have demonstrated device malfunction with TIM oversensing.ResultsWe have found a 1.8% incidence of TIM‐related oversensing in our patient population of 959 patients with contemporary Boston Scientific (Marlborough, MA, USA) pacemakers and cardiac resynchronization therapy pacemakers. One patient experienced a syncopal episode.ConclusionOversensing with pacing inhibition is apparent with the potential of adverse effects to patients.

Background Intracranial aneurysms represent a significant health concern and are poorly understood despite decades of research. Our study focused on understanding temporal patterns of endothelial cell distribution in different spatial locations within the aneurysm early after creation in a rabbit model. Methods Elastase induced saccular aneurysms were created in rabbits and harvested on day 1 (n=3) and after 2 (n=5), 4 (n=4), 8 (n=5), and 12 (n=6) weeks. Sham operated controls (n=3) were harvested on the same day. Aneurysm and control tissue samples were subjected to en face whole mount CD31 staining for endothelial cells. Semiquantitative scoring was performed on the basis of endothelial coverage of the vessel wall (proximal, middle, and distal portions of the aneurysm dome). Mixed effects models were used to assess the effect of time and aneurysm section on endothelial coverage. Results Aneurysmal segments were near completely de-endothelialized at 4 and 8 weeks but had re-endothelialized by 12 weeks. Compared with controls, aneurysms at all time points showed decreased endothelialization, but the difference was only significant compared with the 4 and 8 week groups. Both time (P=0.03) and aneurysm section (P=0.07) were significantly associated with the degree of endothelialization. Proximal locations showed increased endothelialization compared with distal locations (P=0.03). Conclusion In experimental aneurysms of rabbits, endothelial cells regress during the first month after creation, followed by ascending re-endothelialization that stays incomplete. These findings suggest that re-population of endothelial cells comes from resident cells in the adjacent parent artery and that deranged hemodynamics may affect full reconstitution of endothelial cells long term.