Association of Mothers' Perception of Neighborhood Quality and Maternal Resilience with Risk of Preterm Birth.

We examined the associations of mothers' perception of neighborhood quality and maternal resilience with risk of preterm birth and whether maternal resilience moderated the effect of neighborhood quality perception. We analyzed data from 10,758 women with singleton births who participated in 2010-2012 Los Angeles Mommy and Baby surveys. Multilevel logistic regression models assessed the effects of mothers' perception of neighborhood quality and maternal resilience on preterm birth (yes/no), controlling for potential confounders and economic hardship index, a city-level measure of neighborhood quality. Interaction terms were assessed for moderation. Mothers' perception of neighborhood quality and maternal resilience were each uniquely associated with preterm birth, independent of potential confounders (p-values < 0.05). The risk of preterm birth among mothers who perceived their neighborhood as of poor quality was about 30% greater compared to mothers who perceived their neighborhood as of good quality; the risk was 12% greater among mothers with low resilience compared to those with high resilience. Effects of neighborhood quality were not modified by maternal resilience. The findings suggest that mothers' perception of neighborhood quality and resilience are associated with the risk of preterm birth. Further research should explore whether initiatives aimed at improving neighborhood quality and women's self-esteem may improve birth outcomes

GITR signaling potentiates airway hyperresponsiveness by enhancing Th2 cell activity in a mouse model of asthma

<p>Abstract</p> <p>Background</p> <p>Allergic asthma is characterized by airway hyperresponsiveness (AHR) and allergic inflammation of the airways, driven by allergen-specific Th2 cells. The asthma phenotypes and especially AHR are sensitive to the presence and activity of regulatory T (Treg) cells in the lung. Glucocorticoid-induced tumor necrosis factor receptor (GITR) is known to have a co-stimulatory function on effector CD4⁺T cells, rendering these cells insensitive to Treg suppression. However, the effects of GITR signaling on polarized Th1 and Th2 cell effector functions are not well-established. We sought to evaluate the effect of GITR signaling on fully differentiated Th1 and Th2 cells and to determine the effects of GITR activation at the time of allergen provocation on AHR and airway inflammation in a Th2-driven mouse model of asthma.</p> <p>Methods</p> <p>CD4⁺CD25^-cells were polarized <it>in vitro </it>into Th1 and Th2 effector cells, and re-stimulated in the presence of GITR agonistic antibodies to assess the effect on IFNγ and IL-4 production. To evaluate the effects of GITR stimulation on AHR and allergic inflammation in a mouse asthma model, BALB/c mice were sensitized to OVA followed by airway challenges in the presence or absence of GITR agonist antibodies.</p> <p>Results</p> <p>GITR engagement potentiated cytokine release from CD3/CD28-stimulated Th2 but not Th1 cells <it>in vitro</it>. In the mouse asthma model, GITR triggering at the time of challenge induced enhanced airway hyperresponsiveness, serum IgE and <it>ex vivo </it>Th2 cytokine release, but did not increase BAL eosinophilia.</p> <p>Conclusion</p> <p>GITR exerts a differential effect on cytokine release of fully differentiated Th1 and Th2 cells <it>in vitro</it>, potentiating Th2 but not Th1 cytokine production. This effect on Th2 effector functions was also observed <it>in vivo </it>in our mouse model of asthma, resulting in enhanced AHR, serum IgE responses and Th2 cytokine production. This is the first report showing the effects of GITR activation on cytokine production by polarized primary Th1 and Th2 populations and the relevance of this pathway for AHR in mouse models for asthma. Our data provides crucial information on the mode of action of the GITR signaling, a pathway which is currently being considered for therapeutic intervention.</p

Association of Mothers' Perception of Neighborhood Quality and Maternal Resilience with Risk of Preterm Birth.

We examined the associations of mothers' perception of neighborhood quality and maternal resilience with risk of preterm birth and whether maternal resilience moderated the effect of neighborhood quality perception. We analyzed data from 10,758 women with singleton births who participated in 2010-2012 Los Angeles Mommy and Baby surveys. Multilevel logistic regression models assessed the effects of mothers' perception of neighborhood quality and maternal resilience on preterm birth (yes/no), controlling for potential confounders and economic hardship index, a city-level measure of neighborhood quality. Interaction terms were assessed for moderation. Mothers' perception of neighborhood quality and maternal resilience were each uniquely associated with preterm birth, independent of potential confounders (p-values &lt; 0.05). The risk of preterm birth among mothers who perceived their neighborhood as of poor quality was about 30% greater compared to mothers who perceived their neighborhood as of good quality; the risk was 12% greater among mothers with low resilience compared to those with high resilience. Effects of neighborhood quality were not modified by maternal resilience. The findings suggest that mothers' perception of neighborhood quality and resilience are associated with the risk of preterm birth. Further research should explore whether initiatives aimed at improving neighborhood quality and women's self-esteem may improve birth outcomes

Association of Mothers’ Perception of Neighborhood Quality and Maternal Resilience with Risk of Preterm Birth

We examined the associations of mothers’ perception of neighborhood quality and maternal resilience with risk of preterm birth and whether maternal resilience moderated the effect of neighborhood quality perception. We analyzed data from 10,758 women with singleton births who participated in 2010–2012 Los Angeles Mommy and Baby surveys. Multilevel logistic regression models assessed the effects of mothers’ perception of neighborhood quality and maternal resilience on preterm birth (yes/no), controlling for potential confounders and economic hardship index, a city-level measure of neighborhood quality. Interaction terms were assessed for moderation. Mothers’ perception of neighborhood quality and maternal resilience were each uniquely associated with preterm birth, independent of potential confounders (p-values &lt; 0.05). The risk of preterm birth among mothers who perceived their neighborhood as of poor quality was about 30% greater compared to mothers who perceived their neighborhood as of good quality; the risk was 12% greater among mothers with low resilience compared to those with high resilience. Effects of neighborhood quality were not modified by maternal resilience. The findings suggest that mothers’ perception of neighborhood quality and resilience are associated with the risk of preterm birth. Further research should explore whether initiatives aimed at improving neighborhood quality and women’s self-esteem may improve birth outcomes

Glucocorticoid-induced Tumor Necrosis Factor Receptor Negatively Regulates Activation of Human Primary Natural Killer (NK) Cells by Blocking Proliferative Signals and Increasing NK Cell Apoptosis*

Glucocorticoid-induced tumor necrosis factor receptor (GITR), found constitutively expressed on human primary natural killer (NK) cells at low levels was up-regulated upon stimulation by either Toll-like receptor ligand or NK cell growth factor, interleukin (IL)-15. cDNA microarray analysis showed that engagement of GITR primarily suppressed the activation of NF-KB pathway of NK cells and up-regulated anti-inflammatory genes heme oxygenase-1 and IL-10. Further analysis revealed that GITR activation suppressed NK cell proliferation in response to IL-15. GITR activation also suppressed proinflammatory cytokine secretion and increased NK cell apoptosis. GITR activation resulted in blocked phosphorylation of Stat5 and Akt, which may have contributed to the observed antiproliferative effect of GITR on NK cells. Increased apoptosis was independent of the Fas-FasL pathway, but Bcl-XL and phospho-Bad protein expressions were diminished, suggesting involvement of the mitochondrial apoptosis pathway. The results suggest that although GITR is an activation marker for NK cells similar to that for T cells, GITR serves as a negative regulator for NK cell activation. Our studies demonstrate a novel physiological role of GITR on NK cells