Notes

CD123 Is Consistently Expressed on NPM1-Mutated AML Cells.
A new procedure for the determination of 12 naturally occurring hormones and some related synthetic chemicals in milk, commonly used as growth promoters in cattle, is reported. The method is based on liquid-liquid extraction followed by solid-phase extraction (SPE) using a new one-pot synthesized ordered mesoporous silica (of the SBA-15 type) functionalized with octadecyl groups (denoted as SBA-15-C18-CO) as reversed-phase sorbent. The analytes were eluted with methanol and then submitted to HPLC with diode array detection. Under optimal conditions, the method quantification limit for the analytes ranged from 0.023 to 1.36μg/mL. The sorbent affored the extraction of estrone, 17β-estradiol, estriol, progesterone, hexestrol, diethylstilbestrol, 4-androstene-3,17-dione, ethinylestradiol, 17α-methyltestosterone, nandrolone, prednisolone and testosterone with mean recoveries ranging from 72% to 105% (except for diethylstilbestrol) with RSD less then 11%. These results were comparable and, in some cases, even better than those obtained with other extraction methods, therefore SBA-15-C18-CO mesoporous silica possess a high potential as a reversed-phase sorbent for SPE of the 12 mentioned endocrine disrupting compounds in milk samples.Comprehensive on-line two-dimensional liquid chromatography is an attractive technique to enhance peak capacity and deal with complex samples. Yet, its optimization is not straightforward and requires to take into account a huge number of parameters to finally obtain a good compromise between different criteria which are often conflicting. In this study, we propose a procedure for RPLC×RPLC separations able to define, for a given analysis time, the optimized LC×LC parameters for achieving the best compromise between high peak capacity and low dilution. This procedure makes use of both a prediction tool based on theoretical relationships and a Pareto-optimality approach to optimize these two criteria. The possibility to split the flow-rate of the first dimension before the interface is taken into account as well as the focusing effect in the second dimension. This optimization procedure is applied to the prediction of optimized conditions for the separation of peptides. The need for very short and efficient columns (typically 30 mm as column length and 1.3 μm as particle diameter) in the second dimension is clearly established whatever the geometry of the first dimension column. Furthermore it is shown that several sets of quite different conditions in the first dimension can lead to similar results and hence that additional quality descriptors are required to make a decision. RPLC×RPLC separations of a protein digest were carried out and the obtained results were found in very good accordance with the predicted ones. Our results were compared to the top results reported in the literature for 1D-RPLC separations of peptides. More than 4-fold increase in peak capacity (5100 vs 1150) at 200 min has been obtained. Furthermore a 40-fold gain in analysis time (1h vs 40 h) was obtained for achieving 1800 as effective peak capacity which is close to the highest peak capacity reported in 1D-RPLC for the separation of peptides.A capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) method for the simultaneous assessment of nine biogenic amines (spermine, spermidine, putrescine, cadaverine, histamine, phenylethylamine, tryptamine, tyramine, and urocanic acid) in commercial samples of beer and wine is introduced. The samples were submitted to a simple clean-up step with poly(vinylpolypyrrolidone) followed by filtration. Electrophoretic separation in a polyvinyl alcohol (PVA)-coated capillary using 0.5 mol L(-1) acetic acid (pH 2.5) as background electrolyte and detection by electrospray-tandem mass spectrometry was employed. The range of the correlation coefficients of the calibration curves of the analyzed compounds was 0.996-0.999, and the limits of detection and limits of quantification were in the range of 1-2 μg L(-1) and 3-8 μg L(-1), respectively. The recovery values for samples spiked at three concentration levels (0.2, 0.5, and 1.0 mg L(-1)) ranged from 87 to 113% with standard deviation not greater than 5.8%. The use of a PVA-coated silica capillary allows suppressing the electroosmotic flow and, consequently, increasing of the separation efficiency. The method was successfully used to determine biogenic amines in commercial samples of beer and wine.Conventional mass spectrometric analysis of raw samples commonly requires sample pretreatment and chromatographic separation using high performance liquid chromatography or gas chromatography, which could be time-consuming and laborious. In this study, thin layer chromatography (TLC) coupled with electrospray ionization mass spectrometry (ESI-MS) was developed for direct analysis of raw samples. The sorbent material of the TLC plate was found to be able to retain the interfering compounds and allow interested analytes to be extracted, ionized and detected by ESI-MS with much reduced matrix interference. Our results showed that this method could be effectively applied in direct analysis of samples containing common interfering compounds, e.g., salts and detergents, and rapid detection and quantitation of target analytes in raw samples. Offline and online separation and detection of different components in mixture samples, e.g., plant extracts, using TLC-ESI-MS were also demonstrated. Overall, this study revealed that TLC-ESI-MS could be a simple, rapid and efficient method for analysis of raw samples.Over the past 30 years a vast number of studies have demonstrated the presence of pharmaceutical residues in the environment. But still knowledge is scarce regarding the interaction of these emerging pollutants with various matrices in nature. A chromatographic system with on-line detection was developed to perform a sorption study of six selected pharmaceuticals to four natural sediments and dewatered digested sewage treatment plant sludge with differing physicochemical characteristics. Sorption effects, measured as asymmetry factors and recoveries, differed pronouncedly among the pharmaceuticals and between the matrices, which could be explained by basic physicochemical properties of the investigated compounds in relation to matrix characteristics. Protonated and deprotonated molecular properties had the greatest importance for sorbate-sorbent interactions. Atenolol, with cationic properties, showed the highest degree of sorption regardless of the matrix studied. Diclofenac and furosemide, both acids, showed the least tendency towards interactions to natural matrices. Among the neutral compounds bendroflumethiazide, carbamazepine and oxazepam, weaker forces, such as van der Waals, aromatic electron donor-acceptor interactions, and hydrogen forces, seemed more important to determine sorption differences. Results revealed that sorption of pharmaceuticals on natural sediments decreased in the order atenolol (+)>bendroflumethiazide>oxazepam>carbamazepine>diclofenac (-)>furosemide (-). The matrix content of organic matter measured as total organic carbon (TOC) clearly dictated drug sorption. Beside from studying matrix interaction, these results and the developed technique and methodology might find use in the development of new removal processes of pharmaceuticals from wastewater based on improved knowledge concerning chemical interactions to filter materials.Low mammographic breast density (MBD) and increased hyaluronan (HA) synthesis have been shown to have adverse effects on breast cancer prognosis. We aimed at elucidating the background of risk associated with mammographic characteristics, MBD and HA and its synthesizing isoforms in an attempt to uncover potential underlying biological mechanisms. MBD and mammographic characteristics of 270 patients were classified according to percentile density (very low density VLD, ≤25 %; mixed density MID, >25 %) and the BI-RADS 5th edition lexicon. Breast density and mammographic features were correlated with the localization and expression of HA, CD44, and HAS1-3 isoforms, and their combined effect on patients' survivals was explored. VLD showed an increased level of HA-positive carcinoma cells and stromal HA, HAS2, and HAS3. Tumors presenting as masses had more HA-positive carcinoma cells and more stromal HAS2 and HAS3. Indistinct margin tumors showed more stromal HA and HAS3. Patients who combined both VLD breasts with either high HA in carcinoma cells or stroma showed a worse prognosis compared to low levels (carcinoma cells 58.0 vs. 80.5 %, p = 0.001; stroma 64.2 vs. 79.6 %, p = 0.017), while no similar HA-related effect was observed in MID breasts. Our findings suggest a strong reciprocal relationship between low MBD and HA expression and synthesis. The expression of both factors simultaneously leads to an especially adverse prognostic effect which might have an impact on treatment decision in the future. Moreover, HA around cancer cells may inhibit chemotherapy agents and antibody treatments from reaching cancer cells.Inbreeding depression is usually quantified by regressing individual phenotypic values on inbreeding coefficients, implicitly assuming there is no correlation between an individual's phenotype and the kinship coefficient to its mate. If such an association between parental phenotype and parental kinship exists, and if the trait of interest is heritable, estimates of inbreeding depression can be biased. Here we first derive the expected bias as a function of the covariance between mean parental breeding value and parental kinship. Subsequently, we use simulated data to confirm the existence of this bias, and show that it can be accounted for in a quantitative genetic animal model. Finally, we use long-term individual-based data for white-throated dippers (Cinclus cinclus), a bird species in which inbreeding is relatively common, to obtain an empirical estimate of this bias. We show that during part of the study period, parents of inbred birds had shorter wings than those of outbred birds, and as wing length is heritable, inbred individuals were smaller, independent of any inbreeding effects. This resulted in the overestimation of inbreeding effects. Similarly, during a period when parents of inbred birds had longer wings, we found that inbreeding effects were underestimated. We discuss how such associations may have arisen in this system, and why they are likely to occur in others, too. Overall, we demonstrate how less biased estimates of inbreeding depression can be obtained within a quantitative genetic framework, and suggest that inbreeding and additive genetic effects should be accounted for simultaneously whenever possible.The purpose of this study was to explore the factors associated with Pap testing among married immigrant women of Vietnamese origin residing in Taiwan, including demographics, knowledge of cervical cancer, knowledge of Pap tests, fatalism, attitudes toward cervical cancer, and barriers to receiving Pap tests. A cross-sectional correlational design was used. Data were collected from July 2012 to January 2013. Participants were recruited through snowball sampling in two communities in Southern Taiwan. A total of 451 married immigrant women of Vietnamese origin aged 30 years and over were invited to participate in the study and 427 participated. Data analysis included descriptive statistics and multivariate logistic regression. Participants with no children were significantly less likely to have received a Pap test (odds ratio = 0.278, 95% confidence interval [CI] = 0.135-0.569); each additional point of knowledge about Pap tests increased the likelihood of having a Pap test by 19% (odds ratio = 1.190, 95% CI = 1.
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