Publications

OBJECTIVE

The objective was to quantify the association of pregnancy context and health-related quality of life (HRQoL).

STUDY DESIGN

English- or Spanish-speaking women, aged 16-44, with pregnancies <24 weeks' gestation were enrolled in this cross-sectional study between June 2014 and June 2015. Participants completed self-assessments of pregnancy "context," including timing, intention, wantedness, desirability, happiness, and planning (measured with the London Measure of Unplanned Pregnancy). HRQoL was measured using the Patient Reported Outcomes Measurement Information System Global Short Form. Associations between measures of pregnancy context and HRQoL scores in the lowest tertile were examined using multivariable logistic regression to adjust for potential confounding variables.

RESULTS

We enrolled 161 participants (mean age=27.2±6.6 years). Only 14% self-identified as White, non-Hispanic; 42% Hispanic; 37% Black, non-Hispanic; and 7% multiracial. Most (79%) participants were unmarried, and 75% were parenting. Mean gestational age was 9±4.6 weeks. In unadjusted models, women reporting mixed feelings about wanting to have a baby, an undesired pregnancy or feeling unhappy about learning of their pregnancy more frequently had low mental and physical HRQoL compared to women reporting wanted, desired, happy pregnancies. Women with an unplanned pregnancy or pregnancy occurring at the wrong time also had lower physical HRQoL than women reporting pregnancies that were planned or happened at the right time. However, after multivariate adjustment, including history of depression, pregnancy contexts were not associated with low mental or physical HRQoL.

CONCLUSIONS

After adjusting for multiple confounders, pregnancy context is not significantly associated with HRQoL.

IMPLICATIONS

The focus on pregnancy intention in public health programs may not sufficiently assess multidimensional aspects of pregnancy context and may not align with patient-centered outcomes such as HRQoL.

Despite clear differences in immune system responses and in the prevalence of autoimmune diseases between males and females, there is little understanding of the processes involved. In this study, we identified a gene signature of immature-like neutrophils, characterized by the overexpression of genes encoding for several granule-containing proteins, which was found at higher levels (up to 3-fold) in young (20-30 y old) but not older (60 to >89 y old) males compared with females. Functional and phenotypic characterization of peripheral blood neutrophils revealed more mature and responsive neutrophils in young females, which also exhibited an elevated capacity in neutrophil extracellular trap formation at baseline and upon microbial or sterile autoimmune stimuli. The expression levels of the immature-like neutrophil signature increased linearly with pregnancy, an immune state of increased susceptibility to certain infections. Using mass cytometry, we also find increased frequencies of immature forms of neutrophils in the blood of women during late pregnancy. Thus, our findings show novel sex differences in innate immunity and identify a common neutrophil signature in males and in pregnant women.

BACKGROUND

We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms.

METHODS

We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE) and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). The streptozotocin (STZ) murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study.

RESULTS

Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold). Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively).

CONCLUSIONS

The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal disease.