Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacteremia: Results From a Large Multicenter Cohort Study.

Background: We assessed the impact of infectious disease (ID) consultation on management and outcome in patients with Staphylococcus aureus bacteremia (SAB).

Methods: A retrospective cohort study examined consecutive SAB patients from 6 academic and community hospitals between 2007 and 2010. Quality measures of management including echocardiography, repeat blood culture, removal of infectious foci, and antibiotic therapy were compared between ID consultation (IDC) and no ID consultation (NIDC) groups.

Comparative effectiveness of cefazolin versus cloxacillin as definitive antibiotic therapy for MSSA bacteraemia: results from a large multicentre cohort study.

Objectives: We compared the effectiveness of cefazolin versus cloxacillin in the treatment of MSSA bacteraemia in terms of mortality and relapse.

Methods: A retrospective cohort study examined consecutive patients with Staphylococcus aureus bacteraemia from six academic and community hospitals between 2007 and 2010. Patients with MSSA bacteraemia who received cefazolin or cloxacillin as the predominant definitive antibiotic therapy were included in the study.

Application of multiple-locus variable number tandem repeat analysis to identify outbreak-associated Neisseria meningitides serogroup C sequence type 4821 in China.

Neisseria meningitidis (N. meningitidis) serogroup C sequence type (ST)-4821 caused an outbreak in 2010 in Shandong province of China. Twenty-one non-outbreak-associated strains were isolated, along with twenty-eight N.

Design of hyperthermophilic lipase chimeras by key motif-directed recombination.

Recombination of diverse natural evolved domains within a superfamily offers greater opportunity for enzyme function leaps. How to recombine protein modules from distant parents with less disruption in cross-interfaces is a challenging issue. Here, we identified the existence of a key motif, the sequence VVSVN(D)YR, within a structural motif ψ loop in the α/β-hydrolase fold superfamily, by using a MEME server and the PROMOTIF program.

Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs.

Acid ceramidase (ACDase) is being recognized as a therapeutic target for cancer. B13 represents a moderate inhibitor of ACDase. The present study concentrates on the lysosomal targeting of B13 via its N,N-dimethylglycine (DMG) esters (DMG-B13 prodrugs).

Novel rare earth tungstoarsenate heteropolyoxometalates K11[Ln(AsW 11O 39) 2]·xH 2O (Ln = La, Nd, Sm) binding to bovine serum albumin: spectroscopic approach.

The rare earth salts of heteropoly have been widely applied in many fields. In this study, the biological activity of rare earth tungstoarsenate heteropolyoxometalates K11[Ln(AsW11O39)2]·xH2O (abbr. LnW11, Ln = La (x = 24), Nd (x = 17), and Sm (x = 19)) were investigated by spectroscopic methods including fluorescence spectroscopy and UV-vis absorption spectroscopy at different temperatures.

Advances in treatment of ulcerative colitis with herbs: from bench to bedside.

Ulcerative colitis (UC), an idiopathic inflammatory disorder in the colon, has become a clinical challenge, owing to the increasing incidence and poor prognosis. The conventional treatments for UC including aminosalicylates, corticosteroids, and immunosuppressants, induce remission in only half of patients. Meanwhile, the treatments often come with serious side effects which can be life-threatening.

Regulatory roles of KDR antisense oligonucleotide on the proliferation of human prostate cancer cell line PC-3.

Purpose: To explore the regulatory roles of antisense oligonucleotide (ASODN) of vascular endothelial growth factor receptor 2/ VEGFR2 (kinase insert domain-containing receptor, KDR) on the proliferation of PC-3 human prostate cancer cell line.

Methods: Different concentrations of synthetic sense and antisense KDR oligonucleotides were transfected into PC-3 human prostate cancer cell line. The inhibitory effects of oligonucleotides on tumor cell proliferation, KDR mRNA expression, cell cycle distribution and cell apoptosis were analyzed.

Characterization of the PH1704 protease from Pyrococcus horikoshii OT3 and the critical functions of Tyr120.

The PH1704 protease from hyperthermophilic archaean Pyrococcus horikoshii OT3 is a member of DJ-1/ThiJ/PfpI superfamily with diverse functional subclasses. The recombinant PH1704 was efficiently purified and was systematically characterized by a combination of substrate specificity analysis, steady-state kinetics study and molecular docking research. The homogeneous protease was obtained as a presumed dodecamer with molecular weight of ∼240 kDa.

CD39 and CD161 modulate Th17 responses in Crohn's disease.

CD39 (ENTPD1) is expressed by subsets of pathogenic human CD4(+) T cells, such as Th17 cells. These Th17 cells are considered important in intestinal inflammation, such as seen in Crohn's disease (CD). Recently, CD161 (NKR-P1A) was shown to be a phenotypic marker of human Th17 cells.

Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells.

Aim: To investigate the effects of osteopontin (OPN) gene expression knockdown on colon cancer Lovo cells in vitro.

Methods: Four candidate small interfering RNA (siRNA) constructs targeting the OPN gene and a scrambled control sequence (NC-siRNA) were synthesized and inserted into a pGPU6/GFP/Neo expression vector. After confirmation by restriction enzyme digestion and DNA sequencing, the recombinant plasmids were subsequently transfected into a human colon cancer cell line (Lovo) using a liposome transfection method.

Green synthesis and physical characterization of Au nanoparticles and their interaction with bovine serum albumin.

In this study, we used morin as a reducing agent for the synthesis of stable and nearly spherical Au nanoparticles (M-AuNPs), which were characterized by UV-vis, transmission electron microscopy (TEM) and X-ray diffraction (XRD). The binding characteristics and molecular mechanism of the interaction between the M-AuNPs and bovine serum albumin (BSA) were explored by UV-vis absorbance, fluorescence spectroscopy, and circular dichroism spectra (CD). The results showed that the quenching mechanisms were based on static quenching.

All-trans retinoic acid attenuates experimental colitis through inhibition of NF-κB signaling.

Inflammatory bowel disease (IBD) is characterized by excessive innate immune cell activation, which is responsible for tissue damage and induction of adaptive immune responses. All-trans retinoic acid (ATRA), the ligand of retinoic acid receptors (RAR), has been previously shown to regulate adaptive immune responses and restore Th17/Treg balance, while its role in regulation of innate immune cell function such as macrophages remains to be elucidated. The study was performed to explore the effect of ATRA on regulation of innate immune responses during dextran sulfate sodium (DSS) induced murine colitis.

Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation.

Objective: To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0-3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations.

A new nanoPCR molecular assay for detection of porcine bocavirus.

Nanoparticle-assisted polymerase chain reaction (nanoPCR) is a novel method for the rapid amplification of DNA and has been used for the detection of virus. For detection of porcine bocavirus (PBoV), a sensitive and specific nanoPCR assay was developed with a pair of primers that were designed based on NS1 gene sequences available in GenBank. Under the optimized conditions of the PBoV nanoPCR assay, the nanoPCR assay was 100-fold more sensitive than a conventional PCR assay.

Characterization of human CD39+ Th17 cells with suppressor activity and modulation in inflammatory bowel disease.

Induced regulatory T-cells (iT-reg) and T helper type 17 (Th17) in the mouse share common CD4 progenitor cells and exhibit overlapping phenotypic and functional features. Here, we show that human Th17 cells endowed with suppressor activity (supTh17) can be derived following exposure of iT-reg populations to Th17 polarizing conditions. In contrast to "pathogenic" Th17, supTh17 display immune suppressive function and express high levels of CD39, an ectonucleotidase that catalyzes the conversion of pro-inflammatory extracellular nucleotides ultimately generating nucleosides.

AMPK inhibition blocks ROS-NFκB signaling and attenuates endotoxemia-induced liver injury.

Background: AMP-activated protein kinase (AMPK) is an important enzyme in regulation of cellular energy homeostasis. We have previously shown that AMPK activation by 5-aminoimidazole-4-carboxamide (AICAR) results in suppression of immune responses, indicating the pivotal role of AMPK in immune regulation. However, the cellular mechanism underpinning AMPK inhibition on immune response remains largely to be elucidated.

Proposing advancement criteria for efficient DMPK triage of new chemical entities.

With the goal of refining our discovery DMPK workflow, we conducted a retrospective analysis on internal Celgene compounds by calculating the physicochemical properties and gathering data from several assays including solubility, rat and human liver S9 stability, Caco-2 permeability, and rat intravenous (iv.) and oral pharmacokinetics. Our analysis identified plasma clearance to be most statistically relevant for prediction of oral exposure.

Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression.

Background: Ceramide is a bioeffector that mediates various cellular processes, including apoptosis. However, the mechanism underlying ceramide function in apoptosis is apparently cell type-dependent and is not well-understood. We aimed at identifying molecular targets of ceramide in metastatic human colon and breast cancer cells, and determining the efficacy of ceramide analog in suppression of colon and breast cancer metastasis.

Characterization of the imprinting signature of mouse embryo fibroblasts by RNA deep sequencing.

Mouse embryo fibroblasts (MEFs) are convenient sources for biochemical studies when cell number in mouse embryos is limiting. To derive the imprinting signature of MEFs and potentially detect novel imprinted genes we performed strand- and allele-specific RNA deep sequencing. We used sequenom allelotyping in embryo and adult organs to verify parental allele-specific expression.

Distribution and bioaccumulation of organochlorine pesticides (OCPs) in food web of Nansi Lake, China.

The concentration of 12 organochlorine pesticides (OCPs) were measured in water, sediment, aquatic plant, and animal (shrimp and fish) of Nansi Lake by gas chromatography equipped with an electron capture detector. The total OCPs concentrations were 65.31-100.

Increased killing of SCCVII squamous cell carcinoma cells after the combination of Pc 4 photodynamic therapy and dasatinib is associated with enhanced caspase-3 activity and ceramide synthase 1 upregulation.

Photodynamic therapy (PDT) is not always effective as an anticancer treatment, therefore, PDT is combined with other anticancer agents for improved efficacy. The combination of dasatinib and PDT with the silicone phthalocyanine photosensitizer Pc 4 was assessed for increased killing of SCCVII mouse squamous cell carcinoma cells, a preclinical model of head and neck squamous cell carcinoma, using apoptotic markers and colony formation as experimental end-points. Because each of these treatments regulates the metabolism of the sphingolipid ceramide, their effects on mRNA levels of ceramide synthase, a ceramide-producing enzyme, and the sphingolipid profile were determined.

Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse.

Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells.

Improving the image quality in computed tomographic pulmonary angiography with dual-energy subtraction: a new application of spectral computed tomography.

Objectives: The objectives of this study were to assess quantitative and subjective image quality in computed tomographic pulmonary angiography using dual-energy subtraction methods compared with those of the monochromatic images using optimal contrast-to-noise ratios and those of the routine polychromatic images and to select the best dual-energy subtraction method.

Materials And Methods: A total of 1 routine polychromatic image, 3 sets of dual-energy subtraction images (DESIs), and 2 sets of monochromatic images with different optimal contrast-to-noise ratios from 30 patients were obtained. The signal intensity and noise were measured; signal-to-noise ratio and contrast-to-noise ratio (CNR) were calculated.

Exploring the site-selective binding of jatrorrhizine to human serum albumin: spectroscopic and molecular modeling approaches.

This paper exploring the site-selective binding of jatrorrhizine to human serum albumin (HSA) under physiological conditions (pH=7.4). The investigation was carried out using fluorescence spectroscopy, UV-vis spectroscopy, and molecular modeling.