IMPORTANCE Knowledge of whether serious adverse pregnancy outcomes are associated with increasingly widespread effects of climate change in the US would be crucial for the obstetrical medical community and for women and families across the country.OBJECTIVE To investigate prenatal exposure to fine particulate matter (PM 2.5 ), ozone, and heat, and the association of these factors with preterm birth, low birth weight, and stillbirth. EVIDENCE REVIEWThis systematic review involved a comprehensive search for primary literature in Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, PubMed, ClinicalTrials.gov website, and MEDLINE. Qualifying primary research studies included human participants in US populations that were published in English between January 1, 2007, and April 30, 2019. Included articles analyzed the associations between air pollutants or heat and obstetrical outcomes. Comparative observational cohort studies and cross-sectional studies with comparators were included, without minimum sample size. Additional articles found through reference review were also considered. Articles analyzing other obstetrical outcomes, non-US populations, and reviews were excluded. Two reviewers independently determined study eligibility. The Arskey and O'Malley scoping review framework was used. Data extraction was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. FINDINGS Of the 1851 articles identified, 68 met the inclusion criteria. Overall, 32 798 152 births were analyzed, with a mean (SD) of 565 485 (783 278) births per study. A total of 57 studies (48 of 58[84%] on air pollutants; 9 of 10 [90%] on heat) showed a significant association of air pollutant and heat exposure with birth outcomes. Positive associations were found across all US geographic regions. Exposure to PM 2.5 or ozone was associated with increased risk of preterm birth in 19 of 24 studies (79%) and low birth weight in 25 of 29 studies (86%). The subpopulations at highest risk were persons with asthma and minority groups, especially black mothers. Accurate comparisons of risk were limited by differences in study design, exposure measurement, population demographics, and seasonality. CONCLUSIONS AND RELEVANCEThis review suggests that increasingly common environmental exposures exacerbated by climate change are significantly associated with serious adverse pregnancy outcomes across the US.

clinicaltrials.gov Identifier: NCT02128776.

Blood lead concentrations have decreased dramatically in US children over the past 4 decades, but too many children still live in housing with deteriorated lead-based paint and are at risk for lead exposure with resulting lead-associated cognitive impairment and behavioral problems. Evidence continues to accrue that commonly encountered blood lead concentrations, even those below 5 µg/dL (50 ppb), impair cognition; there is no identified threshold or safe level of lead in blood. From 2007 to 2010, approximately 2.6% of preschool children in the United States had a blood lead concentration ≥5 µg/dL (≥50 ppb), which represents about 535 000 US children 1 to 5 years of age. Evidence-based guidance is available for managing increased lead exposure in children, and reducing sources of lead in the environment, including lead in housing, soil, water, and consumer products, has been shown to be cost-beneficial. Primary prevention should be the focus of policy on childhood lead toxicity.

Linezolid is an oxazolidinone that has activity against most gram-positive bacteria, including in vitro activity against all Nocardia species and strains. We describe 6 clinical cases of nocardiosis that were successfully treated with linezolid. Two patients had underlying X-linked chronic granulomatous disease, and 2 patients were receiving chronic corticosteroid therapy. Four of 6 patients had disseminated disease, and 2 of these 4 patients had multiple brain abscesses. Four patients primarily received monotherapy; for the fifth patient, linezolid was added to a failing multiple-drug regimen, and, for the sixth patient, it was used as part of combination therapy. All 6 patients were successfully treated, although 1 patient had a presumed relapse of central nervous system infection after premature discontinuation of the drug. Linezolid appears to be an effective alternative for the treatment of nocardiosis.

SUMMARY T cells undergo metabolic reprogramming with major changes in cellular energy metabolism during activation. In patients with mitochondrial disease, clinical data were marked by frequent infections and immunodeficiency, prompting us to explore the consequences of oxidative phosphorylation dysfunction in T cells. Since cytochrome c oxidase (COX) is a critical regulator of OXPHOS, we created a mouse model with isolated dysfunction in T cells by targeting a gene, COX10, that produces mitochondrial disease in humans. COX dysfunction resulted in increased apoptosis following activation in vitro and immunodeficiency in vivo. Select T cell effector subsets were particularly affected; this could be traced to their bioenergetic requirements. In summary, the findings presented herein emphasize the role of COX particularly in T cells as a metabolic checkpoint for cell fate decisions following T cell activation, with heterogeneous effects in T cell subsets. In addition, our studies highlight the utility of translational models that recapitulate human mitochondrial disease for understanding immunometabolism.