Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk.

A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut-liver tissue interactions under normal and inflammatory contexts, via an integrative multi-organ platform comprising human liver (hepatocytes and Kupffer cells), and intestinal (enterocytes, goblet cells, and dendritic cells) models. Our results demonstrated long-term (>2 weeks) maintenance of intestinal (e.g., barrier integrity) and hepatic (e.g., albumin) functions in baseline interaction. Gene expression data comparing liver in interaction with gut, versus isolation, revealed modulation of bile acid metabolism. Intestinal FGF19 secretion and associated inhibition of hepatic CYP7A1 expression provided evidence of physiologically relevant gut-liver crosstalk. Moreover, significant non-linear modulation of cytokine responses was observed under inflammatory gut-liver interaction; for example, production of CXCR3 ligands (CXCL9,10,11) was synergistically enhanced. RNA-seq analysis revealed significant upregulation of IFNα/ß/γ signaling during inflammatory gut-liver crosstalk, with these pathways implicated in the synergistic CXCR3 chemokine production. Exacerbated inflammatory response in gut-liver interaction also negatively affected tissue-specific functions (e.g., liver metabolism). These findings illustrate how an integrated multi-tissue platform can generate insights useful for understanding complex pathophysiological processes such as inflammatory organ crosstalk. Biotechnol. Bioeng. 2017;114: 2648-2659. © 2017 Wiley Periodicals, Inc.

Influence of a nontraditional master's degree on graduates' career paths.

Graduates' assessments of the University of Texas at Austin's nontraditional M.S. degree program in pharmacy administration were studied. A survey was constructed to assess the impact of the master's program on career advancement, to examine why pharmacists enrolled in the program, and to determine if the curriculum provided knowledge or developed skills that were practical or beneficial. The survey was mailed in April 1999 to all persons who had completed the program between 1990 and 1998. A total of 56 graduates responded, for a response rate of 90.3%. The three reasons for entering the program most frequently cited as most important were career advancement, personal development, and the desire to change job responsibilities. Thirty-four respondents (60.7%) reported receiving a promotion or changing jobs for a higher position while they were enrolled in the program or after completing it. Of these 34 respondents, 29 (85.3%) attributed their promotion or new job to the master's degree. On average, graduates reported that the knowledge and skills obtained through the program had been useful in their practice. The benefits of the program that were cited most frequently were management skills, competencies in areas of pharmacy business, opportunity to advance career, job satisfaction, and competitive advantage when applying for a job. A nontraditional master's degree program in pharmacy administration had a positive impact on the career paths of graduates.