Publications

Type I interferons (IFNs, including IFN-αβ) contribute to the pathogenesis of Mycobacterium tuberculosis strains that induce high IFN-αβ levels. In the current study we examined the role of IFN-αβ during infection with a Mycobacterium africanum strain that induces low IFN-β levels. We infected wild-type and IFN-αβ receptor knockout mice with M. africanum and monitored bacterial growth, lung disease, and survival over 292 days. We found reduced lung bacterial burdens and less severe histopathological findings in the absence of IFN-αβ signaling. We conclude that IFN-αβ is pathogenic during chronic M. africanum infection and that the pathogenic effects may be mediated through poorer control of bacterial growth.

BACKGROUND

Emergency department (ED) clinicians often lack training and resources to conduct advance care planning (ACP) conversations. The use of technology for health education is increasing, yet little is known if it can be used to engage older ED patients in ACP.

OBJECTIVE

To determine the feasibility of using tablets to provide ACP education ( www.prepareforyourcare.org )(PREPARE) to older ED patients.

DESIGN

A feasibility study conducted in late 2014 and early 2015.

SETTING/SUBJECTS

Subjects were recruited from a parent cohort of older adults enrolled in a survey about Geriatric ED care. Inclusion criteria were ≥65 years age and English speaking; exclusions were hearing or vision impairment or if clinically unstable.

MEASUREMENTS

Primary outcome was completion of ≥1 of 5 PREPARE modules. Secondary outcomes were ease of use (10-point scale; 1 = very hard, 10 = very easy) and the reasons for refusal to participate.

RESULTS

Sixty-one subjects were approached; 24 (39%) were interested in viewing PREPARE after the Geriatric ED survey. Mean age was 75 years (standard deviation [SD] 9); 67% were female and 54% were nonwhite. Seventy-one percent of participants completed ≥1 module. Participants rated the website as easy to use for themselves (mean 8.4, SD 2.39) and for others (mean 7.3, SD 2.31). Of the subjects who declined, top reasons cited were fatigue (26%), already feeling prepared (13%), and technology limitations (11%).

CONCLUSION

PREPARE has the potential to engage older adults who are not acutely ill in ACP during their ED visits. Further studies should explore optimal approaches for ED implementation.

Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4 and CD8 T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal TbetCD4 T cells, CD8 T cells, B cells, and CD56CD16 NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes.