Promoting High-Quality Cancer Care and Equity Through Disciplinary Diversity in Team Composition.

Disciplinary diversity in team composition is a valuable vehicle for oncology care teams to provide high-quality, person-centered comprehensive care. Such diversity facilitates care that effectively addresses the complex needs (biologic, psychosocial, and spiritual) of the whole person. The concept of professional or disciplinary diversity centers on differences in function, education, and culture, reflecting variety and heterogeneity in the perspectives of team members contributing to care. Thorough understanding of the skills, knowledge, and education related to each team member's professional or lay expertise is critical for members to be able to optimize the team's potential. Furthermore, respect and appreciation for differences and similarities across disciplinary cultures allow team members to create a positive collaboration dynamic that maintains a focus on the care of the person with cancer. We present a case study of one oncology team's provision of care to the patient, a Chinese immigrant woman with breast cancer. The case illuminates the strengths and challenges of disciplinary diversity in team composition in assessing and addressing potential barriers to care. Coordinated sharing of information among the varied team members facilitated understanding and care planning focused on the patient's concerns, needs, and strengths. Importantly, collaboration across the disciplinarily diverse set of team members facilitated high-quality oncology care and promoted equity in access to the full range of care options, including enrollment on a National Cancer Institute-sponsored clinical trial. Further implications of disciplinary diversity in oncology care teams are considered for both clinical practice and research.

The common prophylactic therapy for bowel surgery is ineffective for clearing Bacteroidetes, the primary inducers of systemic inflammation, and causes faster death in response to intestinal barrier damage in mice.

INTRODUCTION AND OBJECTIVE: The role of secreted gut microbial components in the initiation of systemic inflammation and consequences of antibiotic therapies on this inflammatory process are poorly elucidated. We investigate whether peripheral innate cells mount an inflammatory response to gut microbial components, the immune cells that are the primary drivers of systemic inflammation, the bacterial populations that are predominantly responsible, and whether perioperative antibiotics affect these processes. METHOD AND EXPERIMENTAL DESIGN: Conditioned supernatants from gut microbes were used to stimulate murine innate cell types in vitro and in vivo, and proinflammatory responses were characterised. Effects of antibiotic therapies on these responses were investigated using a model of experimental intestinal barrier damage induced by dextran sodium sulfate. RESULTS: Proinflammatory responses in the periphery are generated by components of anaerobes from the Bacteroidetes phylotype and these responses are primarily produced by myeloid dendritic cells. We found that the common prophylactic therapy for sepsis (oral neomycin and metronidazole administered to patients the day prior to surgery) is ineffective for clearing Bacteroidetes from the murine intestine. A point of critical consequence of this result is the increased systemic inflammation and premature death observed in treated mice, and these outcomes appear to be independent of gut bacterial spread in the initial phase of intestinal barrier damage. Importantly, spillage of gut microbial products, rather than dissemination of gut microbes, may underlay the initiation of systemic inflammation leading to death. CONCLUSIONS: Our data further affirm the importance of a balanced gut microflora biodiversity in host immune homeostasis and reinforce the notion that inadequate antibiotic therapy can have detrimental effects on overall immune system.

Phosphatidylcholine synthesis is required for optimal function of Legionella pneumophila virulence determinants.

The function of phosphatidylcholine (PC) in the bacterial cell envelope remains cryptic. We show here that productive interaction of the respiratory pathogen Legionella pneumophila with host cells requires bacterial PC. Synthesis of the lipid in L. pneumophila was shown to occur via either phospholipid N-methyltransferase (PmtA) or phosphatidylcholine synthase (PcsA), but the latter pathway was demonstrated to be of predominant importance. Loss of PC from the cell envelope caused lowered yields of L. pneumophila within macrophages as well as loss of high multiplicity cytotoxicity, while mutants defective in PC synthesis could be complemented either by reintroduction of PcsA or by overproduction of PmtA. The lowered yields and reduced cytotoxicity in mutants with defective PC biosynthesis were due to three related defects. First, there was a poorly functioning Dot/Icm apparatus, which delivers substrates required for intracellular growth into the cytosol of infected cells. Second, there was reduced bacterial binding to macrophages, possibly due to loss of PC or a PC derivative on the bacterium that is recognized by the host cell. Finally, strains lacking PC had low steady-state levels of flagellin protein, a deficit that had been previously associated with the phenotypes of lowered cytotoxicity and poor cellular adhesion.

IcmR-regulated membrane insertion and efflux by the Legionella pneumophila IcmQ protein.

Legionella pneumophila proliferates within alveolar macrophages as a central property of Legionnaires' disease. Intracellular growth involves formation of a replicative phagosome, which requires the bacterial Dot/Icm system, a multiprotein secretion apparatus that translocates proteins from the bacterium across the macrophage plasma membrane. Two components of this system, IcmR and IcmQ, are proposed to exhibit a chaperone/substrate relationship similar to that observed in other protein translocation systems. We report here that IcmQ inserts into lipid membranes and forms pores that allow the efflux of the dye calcein but not Dextran 3000. Both membrane insertion and pore formation were inhibited by IcmR. Trypsin digestion mapping demonstrated that IcmQ is subdivided into two functional domains. The N-terminal region of IcmQ was necessary and sufficient for insertion into lipid membranes and calcein efflux. The C-terminal domain was necessary for efficient association of the protein with lipid bilayers. IcmR was found to bind to the N-terminal portion of the protein thus providing a mechanism for its ability to inhibit IcmQ pore-forming activity. Localization of IcmQ on the surface of the L. pneumophila shortly after infection as well as its pore-forming capacities suggest a role for IcmQ in forming a channel that leads translocated effectors out of the bacterium.