Value of whole breast magnetic resonance elastography added to MRI for lesion characterization

The purpose of this work was to assess the diagnostic value of magnetic resonance elastography (MRE) in addition to MRI to differentiate malignant from benign breast tumors, and the feasibility of performing MRE on the whole breast. MRE quantified biomechanical properties within the entire breast (50 slices) using an 11 min acquisition protocol at an isotropic image acquisition resolution of 2 × 2 × 2 mm³. Fifty patients were included. Finally, 43 patients (median age 52) with a suspect breast lesion detected by mammography and/or ultrasound were examined by MRI and MRE at 1.5 T. The viscoelastic parameters, i.e. elasticity (G_d), viscosity (G_l), the magnitude of the complex shear modulus , and the phase angle , were measured via MRE and correlated with MRI Breast Imaging—Reporting and Data System (BI‐RADS) score, histological type, and histological grade. Stroma component and angiogenesis were also correlated with viscoelastic properties. In the 43 lesions, G_d decreased and y increased with the MRI BI‐RADS score (p_Gd = 0.02, p_y = 0.002), whereas (G_l) and y were increased in malignant lesions (p_Gl = 0.045, p_y = 0.0004). The area under the curve increased from 0.84 for MRI BI‐RADS alone to 0.92 with the MRI BI‐RADS and y (AUC increase +0.08; 95% CI (?0.003; 0.16)). Lesion characterization using the y parameter increased the diagnostic accuracy. The phase angle y was found to have a significant role (p = 0.01) in predicting malignancy independently of the MRI BI‐RADS. Interestingly, histological analysis showed no correlation between viscoelastic parameters and percentage and type of stroma, CD34 quantification of vessels, or histological grade. The combination of MRE and MRI improves the diagnostic accuracy for breast lesions in the studied cohort. In particular, the phase angle y was found to have a significant role in predicting malignancy in addition to BI‐RADS.     

Consciousness Indexing and Outcome Prediction with Resting-State EEG in Severe Disorders of Consciousness

We applied the following methods to resting-state EEG data from patients with disorders of consciousness (DOC) for consciousness indexing and outcome prediction: microstates, entropy (i.e. approximate, permutation), power in alpha and delta frequency bands, and connectivity (i.e. weighted symbolic mutual information, symbolic transfer entropy, complex network analysis). Patients with unresponsive wakefulness syndrome (UWS) and patients in a minimally conscious state (MCS) were classified into these two categories by fitting and testing a generalised linear model. We aimed subsequently to develop an automated system for outcome prediction in severe DOC by selecting an optimal subset of features using sequential floating forward selection (SFFS). The two outcome categories were defined as UWS or dead, and MCS or emerged from MCS. Percentage of time spent in microstate D in the alpha frequency band performed best at distinguishing MCS from UWS patients. The average clustering coefficient obtained from thresholding beta coherence performed best at predicting outcome. The optimal subset of features selected with SFFS consisted of the frequency of microstate A in the 2–20 Hz frequency band, path length obtained from thresholding alpha coherence, and average path length obtained from thresholding alpha coherence. Combining these features seemed to afford high prediction power. Python and MATLAB toolboxes for the above calculations are freely available under the GNU public license for non-commercial use (https://qeeg.wordpress.com)     

An Evaluation of the Accuracy of Labeling of Percent Sodium Hypochlorite on Various Commercial and Professional Sources: Is Sodium Hypochlorite from These Sources Equally Suitable for Endodontic Irrigation?

Introduction

The shelf life of sodium hypochlorite (NaOCl) is limited, and a previous article showed that there can be a discrepancy between the expected concentration of free available chlorine (FAC) and the actual FAC concentration in NaOCl solutions intended for endodontic irrigation. The current study investigates the FAC content of domestic and professional NaOCls and evaluates the influences of dilution and storage on FAC concentration.

Methods

First, domestic and professional NaOCls not obtained from manufacturers were iodometrically titrated. Then, NaOCls were diluted with demineralized water or tap water and stored at 4°C or 18°C and analyzed at baseline and 2 and 22 weeks. Statistical analyses included paired samples, independent samples t tests and repeated multivariate analysis of variance. Correlations were calculated with the Pearson or Spearman rank correlation test. A P < .05 was considered significant.

Results

Label specifications of domestic NaOCl were very imprecise (ie, <5% NaOCl). Domestic NaOCl contained 1.8%–3.5% NaOCl (w/v). Professional NaOCl varied from 14.3% relative less FAC than specified on the label to 23.5% relative more FAC than specified. After 22 weeks, the relative average loss of FAC in all conditions was 5.4% FAC (P = .002). Dilution, diluents, or storage temperature had no effect on the decline of FAC caused by aging.

Conclusions

There is a great variation in NaOCl concentrations, with domestic NaOCl being the least accurate. NaOCl can be stored up to 5 months. The FAC concentration of domestic NaOCl is unpredictable, and, therefore, it appears less suitable for clinical application as root canal irrigant.     

Women's angiographic vitamin and estrogen trial: design and methods

The Women's Angiographic Vitamin and Estrogen trial was a randomized, double-blind, placebo-controlled study designed to test the efficacy of estrogen replacement and antioxidant vitamins for preventing angiographic progression of coronary artery disease. Postmenopausal women with one or more angiographically documented coronary stenoses of 15-75% at baseline were assigned in a 2 x 2 factorial randomization to active hormone replacement therapy (conjugated estrogens for women who had had a hysterectomy or conjugated estrogens with medroxyprogesterone for women with intact uteri) or placebo and to active vitamins E and C or their placebos. Seven clinical centers, five in the United States and two in Canada, randomized 423 women between July 1997 and July 1999. Quantitative coronary angiography was performed at baseline and repeated after projected mean follow-up of 3 years.     

Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase Mps1

Mps1 is a dual specificity protein kinase that is essential for the bipolar attachment of chromosomes to the mitotic spindle and for maintaining the spindle assembly checkpoint until all chromosomes are properly attached. Mps1 is expressed at high levels during mitosis and is abundantly expressed in cancer cells. Disruption of Mps1 function induces aneuploidy and cell death. We report the identification of MPI-0479605, a potent and selective ATP competitive inhibitor of Mps1. Cells treated with MPI-0479605 undergo aberrant mitosis, resulting in aneuploidy and formation of micronuclei. In cells with wild-type p53, this promotes the induction of a postmitotic checkpoint characterized by the ATM- and RAD3-related-dependent activation of the p53-p21 pathway. In both wild-type and p53 mutant cells lines, there is a growth arrest and inhibition of DNA synthesis. Subsequently, cells undergo mitotic catastrophe and/or an apoptotic response. In xenograft models, MPI-0479605 inhibits tumor growth, suggesting that drugs targeting Mps1 may have utility as novel cancer therapeutics.     

Effect of clindamycin on intracellular replication, protein synthesis, and infectivity of Toxoplasma gondii.

We studied the effects of clindamycin and a combination of clindamycin and pyrimethamine on the proliferation of Toxoplasma gondii in cultured mammalian cells and the effect of clindamycin on the parasite's RNA and protein syntheses. Infected macrophages were treated for 48 h with clindamycin or a combination of clindamycin and pyrimethamine, and the 50% inhibitory concentrations for parasite growth were 32.50 +/- 1.30 and 10.78 +/- 0.56 micrograms/ml, respectively. A modified susceptibility assay was also used to measure the effect of low concentrations of clindamycin on T. gondii. Macrophages and bovine turbinate cells were infected with low numbers of tachyzoites and were exposed to low concentrations of clindamycin for 5 days. In these systems, a concentration of 10 ng of clindamycin per ml inhibited 50% of the growth of the parasite in macrophages, while it completely prohibited the growth of the parasite in epithelial cells. When free tachyzoites were preexposed to clindamycin for 4 h, the reduction of parasite infectivity was proportional to the amount of drug; 100 ng of clindamycin per ml reduced the infectivity of T. gondii to 46.5% +/- 8.5% of that of the untreated control. A concentration of 40 micrograms of clindamycin per ml reduced protein synthesis by 56.2% +/- 6.0% but had no effect on RNA synthesis after a 4-h exposure of free tachyzoites of T. gondii to the drug. Our results show that long-term exposure to low concentrations of clindamycin reduces the level of replication of T. gondii, that clindamycin affects the protein synthesis of free parasites, and that clindamycin impairs the ability of tachyzoites to infect host cells.     

Trans‐Ethnic Meta‐Analysis Identifies Common and Rare Variants Associated with Hepatocyte Growth Factor Levels in the Multi‐Ethnic Study of Atherosclerosis (MESA)

Hepatocyte growth factor (HGF) is a mesenchyme‐derived pleiotropic factor that regulates cell growth, motility, mitogenesis, and morphogenesis in a variety of cells, and increased serum levels of HGF have been linked to a number of clinical and subclinical cardiovascular disease phenotypes. However, little is currently known regarding which genetic factors influence HGF levels, despite evidence of substantial genetic contributions to HGF variation. Based upon ethnicity‐stratified single‐variant association analysis and trans‐ethnic meta‐analysis of 6201 participants of the Multi‐Ethnic Study of Atherosclerosis (MESA), we discovered five statistically significant common and low‐frequency variants: HGF missense polymorphism rs5745687 (p.E299K) as well as four variants (rs16844364, rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC. We also identified two significant ethnicity‐specific gene‐level associations (A1BG in African Americans; FASN in Chinese Americans) based upon low‐frequency/rare variants, while meta‐analysis of gene‐level results identified a significant association for HGFAC. However, identified single‐variant associations explained modest proportions of the total trait variation and were not significantly associated with coronary artery calcium or coronary heart disease. Our findings indicate that genetic factors influencing circulating HGF levels may be complex and ethnically diverse.     

Comparison between anatomy and resistance of upper airway in normal subjects, snorers and OSAS patients.

Upper airway (UA) anatomical abnormalities are frequently observed in obstructive sleep apnea syndrome (OSAS). The correspondence between UA anatomical modifications and UA resistance (UAR) had not been studied. We aimed to determine if cephalometric characteristics could be related to segmental UAR. In twenty-five patients (21 males) (15 OSAS patients, 10 snorers) and 10 control subjects (8 males), segmental UAR were measured in supine position and cephalometry was performed. Inspiratory and expiratory UAR were calculated at peak flow. Length of the soft palate (LP), posterior airway space (PAS), distance from hyoid bone to mandibular plane and to posterior pharyngeal wall were different between the groups (P<0.01). Inspiratory and expiratory, total and segmental, UAR were higher in OSAS (P<0.001). Segmental UAR were correlated with PAS and distance from hyoid bone to mandibular plane and to pharyngeal posterior wall (P<0.05). In conclusion, OSAS patients had higher UAR depending on anatomical variables, especially the place of the hyoid bone.