Both Kupffer cells and invariant natural killer T (iNKT) cells suppress neutrophil-dependent liver injury in a mouse model of biliary obstruction. We hypothesize that these roles are interdependent and require iNKT cell-Kupffer cell cross-activation. Female, wild-type and iNKT cell-deficient C57Bl/6 mice were injected with magnetic beads 3 days prior to bile duct ligation (BDL) in order to facilitate subsequent Kupffer cell isolation. On day three post-BDL, the animals were euthanized and the livers dissected. Necrosis was scored; Kupffer cells were isolated and cell surface marker expression (flow cytometry), mRNA expression (qtPCR), nitric oxide (NO.) production (Griess reaction), and protein secretion (cytometric bead-array or ELISAs) were determined. To address the potential role of NO. in suppressing neutrophil accumulation, a group of WT mice received 1400W, a specific inducible nitric oxide synthase (iNOS) inhibitor, prior to BDL. To clarify the mechanisms underlying Kupffer cell-iNKT cell cross-activation, WT animals were administered anti-IFN-γ or anti-lymphocyte function-associated antigen (LFA)-1 antibody prior to BDL. Compared to their WT counterparts, Kupffer cells obtained from BDL iNKT cell-deficient mice expressed lower iNOS mRNA levels, produced less NO., and secreted more neutrophil chemoattractants. Both iNOS inhibition and IFN-γ neutralization increased neutrophil accumulation in the livers of BDL WT mice. Anti-LFA-1 pre-treatment reduced iNKT cell accumulation in these same animals. These data indicate that the LFA-1-dependent cross-activation of iNKT cells and Kupffer cells inhibits neutrophil accumulation and cholestatic liver injury.

To synthesize the empirical research evidence about the association between Medicaid expansion under the Affordable Care Act (ACA) and increasing perinatal care access and utilization among low-income women.DATA SOURCES: We searched MEDLINE through PubMed (1966-present), EMBASE (Ovid), the Cumulative Index to Nursing and Allied Health (1982-present), PAIS Index (ProQuest), Web of Science (1900-present), and the Cochrane Central Register of Controlled Trials. Our review focuses on the association between Medicaid expansion under the ACA and perinatal care access and utilization, which cannot be subjected to randomized controlled trials, therefore ClinicalTrials.gov was not included in our search. METHODS OF STUDY SELECTION:A comprehensive search of the research literature was performed using Covidence. Studies were eligible if they were based on population data and research designs ensuring that the exposure (ie, Medicaid expansion under the ACA) preceded the perinatal care access or utilization outcome, had an appropriate comparison group, presented quantitative data, and examined pregnant or postpartum women. The search in six bibliographic databases returned 1,243 records, with 855 abstracts reviewed, 34 full-text articles screened for eligibility, and nine eligible studies included in the systematic review.

IMPORTANCE Neuraxial labor analgesia is recognized as the most effective method of providing pain relief during labor. Little is known about variation in the rates of neuraxial analgesia across US states. Identifying the presence and extent of variation may provide insights into practice variation and may indicate where access to neuraxial analgesia is inadequate. OBJECTIVE To test the hypothesis that variation exists in neuraxial labor analgesia use among US states. DESIGN, SETTING, AND PARTICIPANTS Retrospective, population-based, cross-sectional analysis using US birth certificate data. Participants were 2 625 950 women who underwent labor in 2015. MAIN OUTCOMES AND MEASURES State-specific prevalence of neuraxial analgesia per 100 women who underwent labor and variability in neuraxial analgesia use among states, assessed using multilevel multivariable regression modeling with the median odds ratio and the intraclass correlation coefficient to evaluate variation by state. RESULTS In the study population of 2 625 950 women, 0.1% (n = 2010) were younger than 15 years, 7.0% (n = 183 546) were between the ages of 15 and 19 years, 23.6% (n = 620 118) were between the ages of 20 and 24 years, 29.6% (n = 777 957) were between the ages of 25 and 29 years, 26.0% (n = 683 656) were between the ages of 30 and 34 years, 11.4% (n = 298 237) were between the ages of 35 and 39 years, 2.2% (n = 57 130) were between the ages of 40 and 44 years, and 0.1% (n = 3296) were between the ages of 45 and 54 years. More than 90% were privately insured or insured with Medicaid. Neuraxial analgesia was used by 73.1% (n = 1 920 368) of women. After adjustment for antepartum, obstetric, and intrapartum factors, Maine had the lowest neuraxial analgesia prevalence (36.6%; 95% CI, 33.2%-40.1%) and Nevada the highest (80.1%; 95% CI, 78.3%-81.7%). The adjusted median odds ratio was 1.5 (95% CI, 1.4-1.6), and the intraclass correlation coefficient was 5.4% (95% CI, 4.0%-7.9%). CONCLUSIONS AND RELEVANCE Results of this study suggest that a small portion of the overall variation in neuraxial analgesia use is explained by US states. Unmeasured patient-level and hospitallevel factors likely account for a large portion of the variation between states. Efforts should be made to understand what the main reasons are for this variation and whether the variation influences maternal or perinatal outcomes.