Contemporary Business -13/E.

Opening new doors of possibility can be difficult. CONTEMPORARY BUSINESS 13e gives students the business language they need to feel confident in taking the first steps toward becoming successful business majors and successful businesspeople. As with every good business, though, the patterns of innovation and excellence established at the beginning remain steadfast. The goals and standards of Boone & Kurtz, Contemporary Business, remain intact and focused on excellence, as always. We present to you a text and supplement package that will not only move your COURSE FORWARD FASTER but also move your STUDENTS FORWARD FASTER into the new business era

Treatment of Refractory Ventricular Tachycardia with Radiofrequency Ablation and Temporary Mechanical Circulatory Support

Catheter-based radiofrequency ablation has long been recognized as an effective treatment for refractory ventricular tachycardia (VT). A 57-year-old male with severe coronary artery disease underwent percutaneous mechanical circulatory support because of worsening cardiogenic shock after failed revascularization attempts. Despite aggressive medical management, the patient experienced refractory VT episodes, leading to the decision to proceed with radiofrequency catheter ablation. Notably, the Impella 5.5 device (Abiomed) provided critical left ventricular support during the ablation procedure. This case underscores the potential benefits of Impella support during radiofrequency ablation of complex ventricular arrhythmias

AMP peptide targets tight junctions to protect and heal barrier structure and function in models of IBD.

Background: A peptide derived from Antrum Mucosal Protein (AMP)-18 (gastrokine-1) reduces the extent of mucosal erosions and clinical severity in mice with dextran sulfate sodium (DSS)-induced colonic injury. The present study set out to determine if AMP peptide was also therapeutic for immune- and cytokine-mediated mouse models of intestinal injury and inflammatory bowel diseases (IBD) by enhancing and stabilizing tight junctions (TJs). Methods: Therapeutic effects of AMP peptide were examined in interleukin-10 deficient and a T cell adoptive transfer models of colitis in immunodeficient recombinase activating gene-1 knock-out (RAG-1−/−) mice. Mechanisms by which AMP peptide enhances barrier function and structure were studied ex vivo using intestine and colon from mice given lipopolysaccharide (LPS), and in AMP-18 deficient mice given DSS. Results: In interleukin-10 deficient mice given piroxicam, AMP peptide enhanced recovery after weight loss, protected against colon shortening and segmental dilation, and reduced the colitis activity score. In the T cell transfer model, treatment with the peptide protected against colon shortening. In mice given LPS in vivo to induce gut injury, AMP peptide prevented the onset of, and reversed established intestinal hyperpermeability by targeting TJ proteins and perijunctional actin

Coordinate Expression and Trans Presentation of Interleukin (IL)-15Rα and IL-15 Supports Natural Killer Cell and Memory CD8+ T Cell Homeostasis

The high affinity interleukin (IL)-15 receptor, IL-15Rα, is essential for supporting lymphoid homeostasis. To assess whether IL-15Rα's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15Rα– and IL-2/15Rβ–deficient mice. We find that IL-15Rα–competent, IL-2/15Rβ–deficient cells are able to support IL-15Rα–deficient natural killer (NK) and memory CD8+ T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15Rα–mediated presentation of IL-15 in trans is the primary mechanism by which IL-15Rα functions in vivo. Surprisingly, using IL-15– and IL-15Rα–deficient mixed chimera, we also find that IL-15 and IL-15Rα must be expressed by the same cells to present IL-15 in trans, indicating that IL-15Rα is required on a cellular level for the elaboration of IL-15. These studies indicate that IL-15Rα defines homeostatic niches for NK and memory CD8+ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8+ memory T cells

Microsomal triglyceride transfer protein expression in adipocytes: A new component in fat metabolism

AbstractMicrosomal triglyceride transfer protein (MTP) is a carrier of triglyceride essential for the assembly of apolipoprotein (apo)B-containing lipoproteins by the liver and the small intestine. Its role in triglyceride transfer in tissues that do not secrete lipoproteins has not been explored. In particular, MTP would seem to be a candidate for a role in triglyceride metabolism within the adipocyte. To test this hypothesis, we probed adipocytes for the presence of MTP. Immunohistochemical and biochemical studies demonstrate MTP in adipocytes from brown and white fat depots of mice and human, as well as in 3T3-L1 cells. Confocal microscopy revealed MTP throughout 3T3 cells; however, MTP fluorescence was prominent in juxtanuclear areas. In differentiated 3T3 cells MTP fluorescence was very striking around lipid droplets. In vitro lipid transfer assays demonstrated the presence of triglyceride transfer activity within microsomal fractions isolated from rat adipose tissue. In addition, quantitative rtPCR studies showed that MTP expression in mouse white fat depots was approximately 1% of MTP expression in mouse liver. MTP mRNA in differentiated 3T3 cells was approximately 13% of liver expression. Our results provide unequivocal evidence for the presence of MTP in adipocytes and present new possibilities for defining the mechanisms by which triglyceride is stored and/or hydrolyzed and mobilized

[Pemetrexed + Sorafenib] lethality is increased by inhibition of ERBB1/2/3-PI3K-NFκB compensatory survival signaling

In the completed phase I trial NCT01450384 combining the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib it was observed that 20 of 33 patients had prolonged stable disease or tumor regression, with one complete response and multiple partial responses. The pre-clinical studies in this manuscript were designed to determine whether [pemetrexed + sorafenib] –induced cell killing could be rationally enhanced by additional signaling modulators. Multiplex assays performed on tumor material that survived and re-grew after [pemetrexed + sorafenib] exposure showed increased phosphorylation of ERBB1 and of NFκB and IκB; with reduced IκB and elevated G-CSF and KC protein levels. Inhibition of JAK1/2 downstream of the G-CSF/KC receptors did not enhance [pemetrexed + sorafenib] lethality whereas inhibition of ERBB1/2/4 using kinase inhibitory agents or siRNA knock down of ERBB1/2/3 strongly promoted killing. Inhibition of ERBB1/2/4 blocked [pemetrexed + sorafenib] stimulated NFκB activation and SOD2 expression; and expression of IκB S32A S36A significantly enhanced [pemetrexed + sorafenib] lethality. Sorafenib inhibited HSP90 and HSP70 chaperone ATPase activities and reduced the interactions of chaperones with clients including c-MYC, CDC37 and MCL-1. In vivo, a 5 day transient exposure of established mammary tumors to lapatinib or vandetanib significantly enhanced the anti-tumor effect of [pemetrexed + sorafenib], without any apparent normal tissue toxicities. Identical data to that in breast cancer were obtained in NSCLC tumors using the ERBB1/2/4 inhibitor afatinib. Our data argue that the combination of pemetrexed, sorafenib and an ERBB1/2/4 inhibitor should be explored in a new phase I trial in solid tumor patients

Hypothesis Testing and Power Calculations for Taxonomic-Based Human Microbiome Data

This paper presents new biostatistical methods for the analysis of microbiome data based on a fully parametric approach using all the data. The Dirichlet-multinomial distribution allows the analyst to calculate power and sample sizes for experimental design, perform tests of hypotheses (e.g., compare microbiomes across groups), and to estimate parameters describing microbiome properties. The use of a fully parametric model for these data has the benefit over alternative non-parametric approaches such as bootstrapping and permutation testing, in that this model is able to retain more information contained in the data. This paper details the statistical approaches for several tests of hypothesis and power/sample size calculations, and applies them for illustration to taxonomic abundance distribution and rank abundance distribution data using HMP Jumpstart data on 24 subjects for saliva, subgingival, and supragingival samples. Software for running these analyses is available