Publications

Mitogen-activated protein kinase (MAPK) signaling pathways are dynamic and sensitive regulators of T cell function and differentiation. Altered MAPK signaling has been associated with the inflammatory and autoimmune diseases lupus and arthritis and with some pathogenic viral infections. HIV-1 infection is characterized by chronic immune inflammation, aberrantly heightened CD8(+) T cell activation levels, and altered T cell function. The relationship between MAPK pathway function, HIV-1-induced activation (CD38 and HLA-DR), and exhaustion (Tim-3) markers in circulating CD8(+) T cells remains unknown. Phosphorylation of the MAPK effector proteins ERK and p38 was examined by "phosflow" flow cytometry in 79 recently HIV-1-infected, antiretroviral-treatment-naïve adults and 21 risk-matched HIV-1-negative controls. We identified a subset of CD8(+) T cells refractory to phorbol 12-myristate 13-acetate plus ionomycin-induced ERK1/2 phosphorylation (referred to as p-ERK1/2-refractory cells) that was greatly expanded in HIV-1-infected adults. The CD8(+) p-ERK1/2-refractory cells were highly activated (CD38(+) HLA-DR(+)) but not exhausted (Tim-3 negative), tended to have low CD8 expression, and were enriched in intermediate and late transitional memory states of differentiation (CD45RA(-) CD28(-) CD27(+/-)). Targeting MAPK pathways to restore ERK1/2 signaling may normalize immune inflammation levels and restore CD8(+) T cell function during HIV-1 infection.

Studying the role of the human microbiome as it relates to human health status has revolutionized our view of microbial community contributions to a large number of diseases, particularly chronic inflammatory disorders. The lower gastrointestinal (GI) tract houses trillions of microbial cells representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is not surprising, therefore, that many GI inflammatory diseases, including inflammatory bowel disease (IBD), are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response. Here we review current knowledge in the emerging field of human microbiome research as it relates to IBD, specifically focusing on Crohn's disease (CD) and ulcerative colitis (UC). We discuss bacteriotherapeutic efforts to restore GI microbial assemblage integrity via probiotic supplementation of IBD patients, and speculate on future directions for the field.

BACKGROUND

Whether contraception affects health-related quality of life (HRQoL) is unclear.

STUDY DESIGN

We conducted a cross-sectional analysis of routine intake data collected from women aged 18-50 years, including the RAND-36 (Research and Development Corporation) measure of HRQoL, pregnancy intentions and recent contraceptive use. We used multivariable logistic regression to test the relationship between HRQoL and use of any and specific contraceptives. Physical and mental HRQoLs were dichotomized based on US population averages. Models were adjusted for age, race, marital status, education and pregnancy intentions.

RESULTS

Among the 726 women, those using any form of contraception were more likely to have average or better mental HRQoL than women using no contraception [adjusted odds ratio (aOR)=1.60, 95% confidence interval (CI) 1.01-2.53]. Women using injectable contraception were less likely than those using combined hormonal methods to have average or better physical HRQoL (aOR=0.26, 95% CI 0.09-0.80) and mental HRQoL (aOR=0.24, 95% CI 0.06-0.86).

CONCLUSIONS

Measures of women's HRQoL differ with contraceptive use.