Neighborhood Physical Disorder and Adverse Pregnancy Outcomes among Women in Chicago: a Cross-Sectional Analysis of Electronic Health Record Data.

Adverse pregnancy outcomes increase infants' risk for mortality and future health problems. Neighborhood physical disorder may contribute to adverse pregnancy outcomes by increasing maternal chronic stress. Google Street View technology presents a novel method for assessing neighborhood physical disorder but has not been previously examined in the context of birth outcomes. In this cross-sectional study, trained raters used Google's Street View imagery to virtually audit a randomly sampled block within each Chicago census tract (n = 809) for nine indicators of physical disorder. We used an item-response theory model and spatial interpolation to calculate tract-level neighborhood physical disorder scores across Chicago. We linked these data with geocoded electronic health record data from a large, academic women's hospital in Chicago (2015-2017, n = 14,309 births). We used three-level hierarchical Poisson regression to estimate prevalence ratios for the associations of neighborhood physical disorder with preterm birth (overall and spontaneous), small for gestational age (SGA), and hypertensive disorder of pregnancy (HDP). After adjustment for maternal sociodemographics, multiparity, and season of birth, living in a neighborhood with high physical disorder was associated with higher prevalence of PTB, SGA, and HDP (prevalence ratios and 95% confidence intervals 1.21 (1.06, 1.39) for PTB, 1.13 (1.01, 1.37) for SGA, and 1.23 (1.07, 1.42) for HDP). Adjustment for neighborhood poverty and maternal health conditions (e.g., hypertension, diabetes, asthma, substance use) attenuated associations. Results suggest that an adverse neighborhood physical environment may contribute to adverse pregnancy outcomes. However, future work is needed to disentangle the unique contribution of physical disorder from other characteristics of disadvantaged neighborhoods.

Importance of several cysteine residues for the chloride conductance of trout anion exchanger 1 (tAE1).

In this study, we devised a cysteine-focused point mutation analysis of the chloride channel function of trout anion exchanger 1 (tAE1) expressed in X. laevis oocytes. Seven cysteines, belonging to the transmembrane domain of tAE1, were mutated into serines (either individually or in groups) and the effects of these mutations on the chloride conductance of injected oocytes were measured. We showed that three cysteines were essential for the functional expression of tAE1. Namely, mutations C462S, C583S and C588S reduced Cl(-) conductance by 68%, 52% and 83%, respectively, when compared to wild type tAE1. These residual conductances were still inhibited by 0.5 mM niflumic acid. Western blot experiments demonstrated that C462 was involved in protein expression onto the plasma membrane. A mutant devoid of this residue was unable to express onto the plasma membrane, especially if several other cysteines were missing: consequently, the cysteine-less mutant of tAE1 was not functional. C583 and C588 were involved in the channel function of tAE1 as shown by anion substitution experiments proving that selectivity of the mutated pore differs from the wild type one. On the contrary, they were not involved in the Cl(-)/HCO(3)(-) exchange function of tAE1, as demonstrated by intracellular pH measurements. These and several complementary mutations allow us to conclude that a mutant of tAE1 containing the sole C462 can drive a marginal Cl(-) current; however, the minimal configuration necessary to get optimal functional expression of the tAE1 chloride channel is that of a mutant containing unaffected residues C462, C583 and C588.

Molecular mapping of the conductance activity linked to tAE1 expressed in Xenopus oocyte.

It was previously shown that expressed in Xenopus oocyte the trout (tAE1) and the mouse (mAE1) anion exchangers behave differently: both elicit anion exchange activity but only tAE1 induces a transport of organic solutes correlated with an anion conductance. In order to identify the structural domains involved in the induction of tAE1 channel activity, chimeras have been prepared between mouse and trout AE1. As some constructs were not expressed at the plasma membrane, skate exchanger (skAE1) was used instead of mouse exchanger to complete the structure-function analysis. The present paper shows that skAE1, highly similar to mAE1, does not induce a chloride conductance when expressed in Xenopus oocyte. Construct expression analysis showed that only tAE1 transmembrane domain is linked to the anion conductance. More precisely, we identified two regions composed of helices 6, 7 and 8 and putative helices 12 and 13 which are required for this function.