The specific signals mediating the activation of microglia and astrocytes as a prelude to, or consequence of, CNS inflammation continue to be defined. We investigated TLRs as novel receptors mediating innate immune responses in human glial cells. We find that microglia express mRNA for TLRs 1–9, whereas astrocytes express robust TLR3, low-level TLR 1, 4, 5, and 9, and rare-to-undetectable TLR 2, 6, 7, 8, and 10 mRNA (quantitative real-time PCR). We focused on TLRs 3 and 4, which can signal through both the MyD88-dependent and -independent pathways, and on the MyD88-restricted TLR2. By flow cytometry, we established that microglia strongly express cell surface TLR2; TLR3 is expressed at higher levels intracellularly. Astrocytes express both cell surface and intracellular TLR3. All three TLRs trigger microglial activation upon ligation. TLR3 signaling induces the strongest proinflammatory polarizing response, characterized by secretion of high levels of IL-12, TNF-α, IL-6, CXCL-10, and IL-10, and the expression of IFN-β. CXCL-10 and IL-10 secretion following TLR4 ligation are comparable to that of TLR3; however, other responses were lower or absent. TLR2-mediated responses are dominated by IL-6 and IL-10 secretion. Astrocytes respond to TLR3 ligation, producing IL-6, CXCL-10, and IFN-β, implicating these cells as contributors to proinflammatory responses. Initial TLR-mediated glial activation also regulates consequent TLR expression; while TLR2 and TLR3 are subject to positive feedback, TLR4 is down-regulated in microglia. Astrocytes up-regulate all three TLRs following TLR3 ligation. Our data indicate that activation of innate immune responses in the CNS is not homogeneous but rather tailored according to cell type and environmental signal.

IMPORTANCE Treatment with methadone or buprenorphine is the current standard of care for opioid use disorder. Given the paucity of research identifying which patients will respond best to which medication, both medications should be accessible to all patients so that patients can determine which works best for them. However, given differences in the historical contexts of their initial implementation, access to each of these medications may vary along racial/ethnic lines. OBJECTIVE To examine the extent to which capacity to provide methadone and buprenorphine vary with measures of racial/ethnic segregation. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study included all counties and county-equivalent divisions in the US in 2016. Data on racial/ethnic population distribution were derived from the American Community Survey, and data on locations of facilities providing methadone and buprenorphine were obtained from Substance Abuse and Mental Health Services Administration databases. Data were analyzed from August 22, 2018, to September 11, 2019. EXPOSURES Two county-level measures of racial/ethnic segregation, including dissimilarity (representing the proportion of African American or Hispanic/Latino residents who would need to move census tracts to achieve a uniform spatial distribution of the population by race/ethnicity) and interaction (representing the probability that an African American or Hispanic/Latino resident will interact with a white resident and vice versa, assuming random mixing across census tracts). MAIN OUTCOMES AND MEASURES County-level capacity to provide methadone or buprenorphine, defined as the number of facilities providing a medication per 100 000 population. RESULTS Among 3142 US counties, there were 1698 facilities providing methadone (0.6 facilities per 100 000 population) and 18 868 facilities providing buprenorphine (5.9 facilities per 100 000 population). Each 1% decrease in probability of interaction of an African American resident with a white resident was associated with 0.6 more facilities providing methadone per 100 000 population. Similarly, each 1% decrease in probability of interaction of a Hispanic/Latino resident with a white resident was associated with 0.3 more facilities providing methadone per 100 000 population. Each 1% decrease in the probability of interaction of a white resident with an African American resident was associated with 8.17 more facilities providing buprenorphine per 100 000 population. Similarly, each 1% decrease in the probability of interaction of a white resident with a Hispanic/Latino resident was associated with 1.61 more facilities providing buprenorphine per 100 000 population. CONCLUSIONS AND RELEVANCE These findings suggest that the racial/ethnic composition of a community was associated with which medications residents would likely be able to access when (continued) Key Points Question Does county-level capacity to provide methadone and buprenorphine vary with measures of racial/ethnic segregation? Findings In this cross-sectional s...

This Policy Statement was reaffirmed November 2022. Immigrant children seeking safe haven in the United States, whether arriving unaccompanied or in family units, face a complicated evaluation and legal process from the point of arrival through permanent resettlement in communities. The conditions in which children are detained and the support services that are available to them are of great concern to pediatricians and other advocates for children. In accordance with internationally accepted rights of the child, immigrant and refugee children should be treated with dignity and respect and should not be exposed to conditions that may harm or traumatize them. The Department of Homeland Security facilities do not meet the basic standards for the care of children in residential settings. The recommendations in this statement call for limited exposure of any child to current Department of Homeland Security facilities (ie, Customs and Border Protection and Immigration and Customs Enforcement facilities) and for longitudinal evaluation of the health consequences of detention of immigrant children in the United States. From the moment children are in the custody of the United States, they deserve health care that meets guideline-based standards, treatment that mitigates harm or traumatization, and services that support their health and well-being. This policy statement also provides specific recommendations regarding postrelease services once a child is released into communities across the country, including a coordinated system that facilitates access to a medical home and consistent access to education, child care, interpretation services, and legal services.