ttenuates pain by releasing opioid peptides from the infiltrating macrophages in mice. The opioids were secreted by IL-4 in the intracellular Ca2+-dependent manner and activated local peripheral opioid receptors. These actions represent a novel mode of IL-4 action, since its releasing properties have not been so far reported. Importantly, our findings suggest that the IL-4-opioid system should be targeted in the peripheral damaged tissue, since this can be devoid of central and systemic side effects.Gαs-coupled receptors signaling through cAMP provide a key mechanism for the sensitization of nociceptive sensory neurons, and the cAMP effector Epac has been implicated in the transition from acute to chronic pain. Epac exerts its effects through Rap1 and protein kinase C (PKC). To identify targets of Epac-PKC signaling in sensory neurons of the mouse dorsal root ganglion (DRG), we profiled PKC substrate proteins phosphorylated in response to the activation of Epac with the proinflammatory prostaglandin E2 (PGE2). A prominent Epac-dependent phospho-protein band induced by PGE2 was identified by mass spectrometry as the mitochondrial enzyme pyruvate dehydrogenase (Pdha1). In dissociated DRG from both males and females, the recruitment of Pdha1 to phospho-protein fractions was rapidly induced by PGE2 and prevented by selective inhibition of Epac2. Epac activation increased mitochondrial respiration, consistent with an increase in Pdha1 function mediated by Epac2. Hindpaw injection of PGE2 induced heat hyperalgnt of acute inflammatory hyperalgesia. We describe a mechanism in which Epac2 activation by prostaglandin receptors leads to phosphorylation of pyruvate dehydrogenase and an increase in mitochondrial respiration in peripheral sensory neurons. Although Epac2 activation leads to Pdha1 (pyruvate dehydrogenase) phosphorylation in dissociated neurons from mice of both sexes, induction of this pathway in vivo by hindpaw insult is restricted to males and appears to require intraganglionic prostaglandin synthesis. These findings support a model in which Gs-coupled receptor modulation of mitochondrial function promotes acute nociceptive signaling and inflammatory hyperalgesia.The breast cancer susceptibility protein BRCA1 and its partner BRCA1-associated RING domain protein 1 (BARD1) form an E3-ubiquitin (Ub) ligase complex that acts as a tumor suppressor in mitotic cells. However, the roles of BRCA1-BARD1 in postmitotic cells, such as neurons, remain poorly defined. Here, we report that BRC-1 and BRD-1, the Caenorhabditis elegans orthologs of BRCA1 and BARD1, are required for adult-specific axon regeneration, which is positively regulated by the EGL-30 Gqα-diacylglycerol (DAG) signaling pathway. This pathway is downregulated by DAG kinase (DGK), which converts DAG to phosphatidic acid (PA). We demonstrate that inactivation of DGK-3 suppresses the brc-1 brd-1 defect in axon regeneration, suggesting that BRC-1-BRD-1 inhibits DGK-3 function. Indeed, we show that BRC-1-BRD-1 poly-ubiquitylates DGK-3 in a manner dependent on its E3 ligase activity, causing DGK-3 degradation. Furthermore, we find that axon injury causes the translocation of BRC-1 from the nucleus to the cytoplasm, wherrate that axon injury causes the translocation of BRC-1 from the nucleus to the cytoplasm, where DGK-3 is localized. Thus, this study describes a new role for BRCA1-BARD1 in fully-differentiated neurons.Current data regarding racial and ethnic disparities in health outcomes of newborns requiring care in an NICU reveal significant differences in quality and access to care that disproportionally affects infants of color, particularly African American infants. These inequalities result in an increased infant mortality rate for Black children and higher preterm birth rates, as well as an increase in deaths due to low birth weight and decreased gestational age. Concurrently, there is emerging research exploring the role of diversity and adequate representation among medical providers in patient outcomes in Black communities. In this editorial, we present commentaries from a medical student, a neonatologist, and a parent of former NICU patients to further explore race in the NICU from different perspectives and understand what can be learned from their experiences about these systemic issues and why representation is a critical component of successful change.
  Child sex trafficking is a global health problem, with a prevalence of 4% to 11% among high-risk adolescents. The objective of this study was to confidentially administer a validated screening tool in a pediatric emergency department by using an electronic tablet to identify minors at risk for sex trafficking. Our hypothesis was that this modality of administration would adequately identify high-risk patients.
 
  English- and Spanish-speaking patients from the ages of 12 to 17 years presenting to a large urban pediatric emergency department with high-risk chief complaints were enrolled in a prospective cohort over 13 months. Subjects completed a previously validated 6-item screening tool on an electronic tablet. The screening tool's sensitivity, specificity, and positive and negative predictive values were calculated.  https://www.selleckchem.com/products/ml385.html  Multivariable logistic regression was performed to identify additional risk factors.
 
  A total of 212 subjects were enrolled (72.6% female; median age 15 years; interquartile range 13-16), of which 26 patients were subjected to child sex trafficking (prevalence 12.3%). The sensitivity and specificity of the electronic screening tool were 84.6% (95% confidence interval [CI] 70.8%-98.5%) and 53.2% (95% CI 46.1%-60.4%), respectively. The positive predictive value and negative predictive value were 20.2% (95% CI 12.7%-27.7%) and 96.1% (95% CI 92.4%-99.9%), respectively. A previous suicide attempt and history of child abuse increased the odds of trafficking independent of those who screened positive but did not improve sensitivity of the tool.
 
  A confidentially administered, previously validated, electronic screening tool was used to accurately identify sex trafficking among minors, suggesting that this modality of screening may be useful in busy clinical environments.
 A confidentially administered, previously validated, electronic screening tool was used to accurately identify sex trafficking among minors, suggesting that this modality of screening may be useful in busy clinical environments.