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Blood vessel tortuosity results from increased diameter and length in response to higher hemodynamic loads. Tortuosity metrics have not been determined for abnormal superior cerebral veins (SCVs) draining cerebral arteriovenous malformations (AVMs). Draining vein (DV) tortuosity may influence safety and efficacy of retrograde microcatheter navigation during transvenous treatment of pial AVMs. Here, we quantify SCV tortuosity in normal subjects and AVM patients using two image segmentation methods. We used contrast-enhanced brain magnetic resonance (MR) images to define the axis of each SCV through a regularly spaced set of three-dimensional (3D) points defining its skeleton curve. We then calculated two metrics the "sum of angles metric" (SOAM), which adds all angles of curvature along a vessel and normalizes by vessel length, and the "distance metric" (DM), a tortuosity measure providing a ratio of vessel length to linear distance between vessel endpoints. We analyzed 168 metrics in 43 veins of eight normal subjects and 41 veins of seven AVM patients. In normal subjects, the mean SOAM and DM for SCVs were 21.34 ± 7.49 °/mm and 1.42 ± 0.25, respectively. In AVM patients, DVs had a significantly higher mean SOAM of 30.43 ± 11.38 °/mm (p = .02) and DM of 2.79 ± 1.77 (p = .01) than normal subjects. In AVM patients, DVs were significantly more tortuous than matched contralateral uninvolved SCVs, which were similar in tortuosity to normal subject SCVs. We thus report normative tortuosity metrics of brain SCVs and show that AVM cortical DVs are significantly more tortuous than normal SCVs. Knowledge of these comparative tortuosities is valuable in planning endovenous AVM embolotherapies. © 2020 Wiley Periodicals, Inc.BACKGROUND Circular RNAs (circRNAs), proven as single-stranded closed RNA molecules, have been implicated in the onset and development of multiple cancers. This study aimed to summarize existing evidences regarding the clinicopathologic, diagnostic, and prognostic significances of circRNAs in gastric cancer (GC). METHODS Eligible studies were identified using online databases. The quality of the included studies was judged, and patients' clinical characteristics, diagnostic data, and overall survival (OS) were extracted from the electronic medical record. Fisher's method was adopted to determine P values for clinicopathologic features. The diagnostic and prognostic data from all included studies were merged. RESULTS Thirty eligible studies were comprised of 2687 GC patients were enrolled in the meta-analyses. Altered expressions of circRNAs in GC tissues were significantly associated with worse clinicopathologic features. Abnormally expressed circRNAs yielded a pooled sensitivity of 0.76 (95% CI 0.69-0.81) and a specificity of 0.77 (95% CI 0.70-0.83) in distinguishing GC from noncancerous controls, which corresponded to an area under the curve (AUC) of 0.83. The survival analysis showed that the oncogenic circRNA signature could be an independent risk factor of OS (HR = 2.11, 95% CI 1.60-2.78, P = .000). Patients with down-regulated circRNAs (tumor suppressor genes) presented a significantly shorter OS time than those with high-level circRNAs (HR = 0.33, 95% CI 0.27-0.42, P = .000). Stratified analyses based on sample type, control source, circRNA expression status, and cutoff setting also produced robust results. CONCLUSIONS CircRNAs may play an important role as potential diagnostic and prognostic biomarkers of GC. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.BACKGROUND Red cell distribution width (RDW) and mean platelet volume (MPV) are considered to be associated with tumors. We investigated the diagnostic value of RDW, MPV, and cancer antigen 125 (CA125), alone or in combination, in the diagnosis of endometrial cancer and endometrial hyperplasia. METHODS This study included 144 patients with endometrial cancer (stage I 32; II 42; III 48; and IV 22), 104 patients with endometrial hyperplasia, and 80 healthy control subjects. The whole blood cell parameters were analyzed by a Mindray Blood Cell Analyzer (CAL8000), whereas CA125 was analyzed using an Architect i2000 Analyzer (Abbott). RESULTS Significant differences in RDW, MPV, and CA125 level were observed in the endometrial cancer, endometrial hyperplasia, and control groups (P less then .05). Red cell distribution width was positively correlated (r = .735) whereas MPV was negatively correlated with (r = -.736) endometrial cancer staging. The area under the receiver operating characteristic curve of the combined diagnosis of endometrial cancer based on RDW, MPV, and CA125 was 0.924 (95% CI 0.881-0.955). The sensitivity and specificity of the combined diagnosis were larger than those of the independent detections involving RDW, MPV, and CA125. CONCLUSIONS The combination of RDW, MPV, and CA125 can improve the differential diagnosis of endometrial cancer and endometrial hyperplasia. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.OBJECTIVES ABP 959 is a proposed biosimilar to eculizumab, a monoclonal antibody targeting the human C5 complement protein. The objective of this randomized, double-blind, three-arm, study was to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity of ABP 959 relative to the eculizumab reference product (RP) in healthy adult male subjects. METHODS Eligible subjects aged 18-45 years were randomized to receive a 300-mg IV infusion of ABP 959, or FDA-licensed eculizumab (eculizumab US), or EU-authorized eculizumab (eculizumab EU). Primary PK endpoint was area under the total serum concentration-time curve from 0 to infinity (AUC0-∞ ); primary PD endpoint was area between the effect curve (ABEC) of CH50-time data. RESULTS The geometric mean of PK and PD parameters were similar between ABP 959 versus eculizumab US and eculizumab EU; PK and PD similarity was established based on 90% confidence intervals of the geometric mean ratio being within prespecified equivalence margin of 0.8 and 1.25. The incidence of treatment-emergent adverse events was similar across groups. The incidence of binding anti-drug antibodies was similar across treatments; no subjects developed neutralizing antibodies. CONCLUSIONS This study demonstrated PK and PD similarity of ABP 959 to eculizumab RP; safety and immunogenicity profiles were also similar. This article is protected by copyright. All rights reserved.Observational studies showed alcohol drinking behaviors may be associated with the risk of ALS, whereas contradictory findings emerged and whether such association is causal is unclear. We here investigate the causal relationship between alcohol consumption and ALS. By leveraging instruments from large-scale genome-wide association studies, we performed a comprehensive Mendelian randomization analysis and found alcohol consumption was causally associated with ALS, leading to ~1.5 fold (95%CI 1.4 - 3.4) higher risk of ALS for each approximately 10g/d increase in alcohol intake. Our finding therefore suggests accumulative alcohol consumption may serve as a crucial risk factor in the pathogenesis of ALS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The objective of study was to compare clinical outcome of cryoplasty, tandem stents, and cutting balloon ureteroplasty as "bailout procedures" to prevent surgical intervention or stent dependency in renal transplant patients with refractory ureteral stricture. All patients who underwent a bailout procedure from 11/6/2003 to 8/21/2015 at a single institution were reviewed retrospectively. Refractory ureteral stricture was defined as ureteral stenosis not responding to at least two prior percutaneous plain balloon ureteroplasties. Primary patency was defined as stable allograft function following the procedure with unobstructed urine outflow, not requiring indwelling ureteral stent, repeat ureteroplasty, or surgical revision. Sixty-one procedures were performed on 51 patients. Patients were followed-up for a median of 286 days. Overall primary patency rate was 26.1%. Primary patency rate by method was 38.1%, 23.1%, and 14.3% after cryoplasty, tandem stent placement, and cutting balloon dilatation, respectively (p= 0.260). Primary patency rate was higher in early ( less then 3 months post-transplant) ureteral strictures (35.7% vs. 13.3%; p= 0.047). More complications identified in patients who had tandem ureteral stents (p=0.00754). As some renal transplant patients may not be good operative candidates for ureteral revision, it would be reasonable to attempt one of these "bailout" interventions as long as the clinical team and patient are aware of overall low potential for achieving primary patency. This article is protected by copyright. All rights reserved.OBJECTIVE Assess occurrence of the dendritic spine scaffolding protein Drebrin as pathophysiologically relevant autoantibody target in patients with recurrent seizures and suspected encephalitis as leading symptoms. METHODS Sera of four patients with adult onset epilepsy and suspected encephalitis of unresolved etiology and equivalent results in autoantibody screening were subjected to epitope identification. We combined a wide array of approaches ranging from immunoblotting, immunoprecipitation and mass-spectrometry, subcellular binding pattern analyses in primary neuronal cultures, immunohistochemistry in brains of wildtype and Drebrin knockout mice to in vitro analyses on impaired synapse formation, morphology and aberrant neuronal excitability by antibody exposure. RESULTS In the serum of a patient with adult onset epilepsy and suspected encephalitis, a strong signal at ~70 kDa was detected by immunoblotting, for which mass-spectrometry revealed Drebrin as putative antigen. Three other patients whose sera by copyright. All rights reserved.BACKGROUND The information on mortality after an acute stroke patient is still limited. OBJECTIVES The aim of this study was to investigate the prognostic potential of procalcitonin (PCT) serum levels in acute ischemic stroke. METHODS A total of 748 patients were enrolled in this study. Prognostic potential of PCT was evaluated by Kaplan-Meier analysis and multivariable Cox hazard regression analyses. RESULTS Procalcitonin levels were found to be significantly higher in acute ischemic stroke patients who died in 30 days than those who survived. Univariate logistic regression analysis showed that PCT was significantly associated with 30-day mortality, and Cox regression analysis revealed that PCT was a strong predictor of 30-day overall mortality. Kaplan-Meier analysis revealed that overall cumulative 30-day mortality was significantly higher in those with PCT levels >1.5 ng/mL when compared to those with PCT levels less then 1.5 ng/mL. CONCLUSIONS Procalcitonin is a significant independent prognostic marker of 30-day mortality after the one set of acute ischemic stroke. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.Streptococcus mutans is a major cause of tooth decay due to its promotion of biofilm formation and acid production. Several plant extracts have been reported to have multiple biological activities such as anti-inflammation and anti-bacterial effects. In this study, we investigated the antibacterial activity of three plant extracts, phellodendron bark (PB), yucca, and black ginger, and found that PB had a stronger effect than other extracts. Then, we investigated the minimum inhibitory concentration (MIC) of PB against 100 S. mutans strains. The MIC range of PB was 9.8-312.5 µg/mL. PB suppressed the growth kinetics of S. mutans in a dose-dependent manner, even at sub-MICs of PB. Then, we investigated the effect of PB on S. mutans virulence. PB suppressed biofilm formation at high concentrations, although PB did not affect the expression of glucosyltransferase genes. Additionally, PB suppressed the decrease in pH from adding excess of glucose. The expression of genes responsible for acid production was increased by the addition of excess glucose without PB, whereas their expression levels were not increased in the presence of 1× and 2× MIC of PB.
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