Sensitive and fast identification of bacteria in blood samples by immunoaffinity mass spectrometry for quick BSI diagnosis

Bloodstream infections rank among the most serious causes of morbidity and mortality in hospitalized patients, partly due to the long period (up to one week) required for clinical diagnosis. In this work, we have developed a sensitive method to quickly and accurately identify bacteria in human blood samples by combining optimized matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) and efficient immunoaffinity enrichment/separation. A library of bacteria reference mass spectra at different cell numbers was firstly built. Due to a reduced sample spot size, the reference spectra could be obtained from as few as 10 to 10(2) intact bacterial cells. Bacteria in human blood samples were then extracted using antibodies-modified magnetic beads for MS fingerprinting. By comparing the sample spectra with the reference spectra based on a cosine correlation, bacteria with concentrations as low as 500 cells per mL in blood serum and 8000 cells per mL in whole blood were identified. The proposed method was further applied to positive clinical blood cultures (BCs) provided by a local hospital, where Escherichia coli and Staphylococcus aureus were identified. Because of the method's high sensitivity, the BC time required for diagnosis can be greatly reduced. As a proof of concept, whole blood spiked with a low initial concentration (10(2) or 10(3) cells per mL) of bacteria was cultured in commercial BC bottles and analysed by the developed method after different BC times. Bacteria were successfully identified after 4 hours of BC. Therefore, an entire diagnostic process could be accurately accomplished within half a day using the newly developed method, which could facilitate the timely determination of appropriate anti-bacterial therapy and decrease the risk of mortality from bloodstream infections

Measuring euthymia within the Neuroticism Scale from the NEO Personality Inventory: A Mokken analysis of the Norwegian general population study for scalability

Background Whereas the Eysenck Neuroticism Scale only contains items covering negative mental health to measure dysthymia, the NEO Personality Inventory (NEO-PI) contains neuroticism items covering both negative mental health and positive mental health (or euthymia). The consequence of wording items both positively and negatively within the NEO-PI has never been psychometrically investigated. The aim of this study was to perform a validation analysis of the NEO-PI neuroticism scale. Methods Using a Norwegian general population study we examined the structure of the negatively and positively formulated items by principal component analysis (PCA). The scalability of the identified two groups of euthymia versus dysthymia items was examined by Mokken analysis. Results With a response rate of 90%, 1082 individuals with a completed NEO-PI were available. The PCA identified the neuroticism scale as the most distinct where 14 items had acceptable loadings for the euthymia subscale, another 14 items for the dysthymia subscale. However, the Mokken analysis coefficient of homogeneity only found acceptable scalability for the euthymia subscale. Limitations A comparison with the Eysenck Neuroticism Scale was not performed. Conclusion The NEO-PI neuroticism scale contains two subscales consisting of items worded in an opposite direction where only the positive euthymia items have an acceptable scalability

Natural Products as Starting Materials for Development of Second Generation Serca Inhibitors Targeted Towards Prostate Cancer Cells

An analysis of the binding of the 8 O N tert butoxycarbonyl 12 aminododecanoyl derivative of 8 O debutanoylthapsigargin to the target molecule, the SERCA pump, has revealed the importance of the length and flexibility of the side chain attached to O 8. Based on the analysis a series of analogues to the 2 unsubstituted analogue trilobolide has been constructed and shown to be equipotent with thapsigargin as SERCA inhibitors. Only the 12 Boc aminododecaonoyl derivative, however, was found to be apoptoti