Racial and ethnic disparities of sudden unexpected infant death in large US cities: a descriptive epidemiological study.

BACKGROUND: Sudden unexpected infant death (SUID) accounts for ~ 3400 deaths per year in the USA, and minimal progress has been made in reducing SUID over the past two decades. SUID is the sudden death of an infant that has occurred as a result of accidental suffocation in a sleeping environment, SIDS (sudden infant death syndrome), or from an unknown cause of death. Nationally, non-Hispanic Black (NHB) infants have twice the risk of SUID compared to non-Hispanic White (NHW) infants. In Chicago, this disparity is greatly magnified. To explore whether this disparity is similarly seen in other large cities, we analyzed SUIDs by race and ethnicity for a seven-year period from the 10 most populous US cities. SUID case counts by race and ethnicity were obtained for 2011-2017 from the 10 most populous US cities based on 2010 census data. For each city, we calculated average annual SUID rates (per 1000 live births) by race and ethnicity, allowing calculation of disparity rate ratios. FINDINGS: Nationally, from 2011 through 2017, there were 0.891 SUIDs per 1000 live births, with a rate of 0.847 for NHWs, 1.795 for NHBs, and 0.522 for Hispanics. In most study cities, the NHB and Hispanic SUID rates were higher than the corresponding national rate. Hispanic SUID rates were higher than NHW rates in 9 of the 10 largest cities. In every study city, the NHW SUID rate was lower than the national NHW rate. In Chicago, NHB infants had a SUID rate 12.735 times that of NHW infants. CONCLUSION: With few exceptions, the 10 largest US cities had higher NHB and Hispanic SUID rates, but lower NHW SUID rates, compared to the corresponding rates at the national level. Unlike the national pattern, Hispanic SUID rates were higher than NHW rates in 9 of the 10 largest cities. Prevention is currently hampered by the lack of detailed, accurate, and timely information regarding the circumstances of these tragic deaths. A national SUID surveillance system would allow greater understanding of the factors that lead to this disproportionately distributed and enduring cause of infant death.

Role of signalling molecules in behaviours mediated by the δ opioid receptor agonist SNC80.

BACKGROUND AND PURPOSE: GPCRs exist in multiple conformations that can engage distinct signalling mechanisms which in turn may lead to diverse behavioural outputs. In rodent models, activation of the δ opioid receptor (δ-receptor) has been shown to elicit antihyperalgesia, antidepressant-like effects and convulsions. We recently showed that these δ-receptor-mediated behaviours are differentially regulated by the GTPase-activating protein regulator of G protein signalling 4 (RGS4), which facilitates termination of G protein signalling. To further evaluate the signalling mechanisms underlying δ-receptor-mediated antihyperalgesia, antidepressant-like effects and convulsions, we observed how changes in Gαo or arrestin proteins in vivo affected behaviours elicited by the δ-receptor agonist SNC80 in mice. EXPERIMENTAL APPROACH: Transgenic mice with altered expression of various signalling molecules were used in the current studies. Antihyperalgesia was measured in a nitroglycerin-induced thermal hyperalgesia assay. Antidepressant-like effects were evaluated in the forced swim test. Mice were also observed for convulsive activity following SNC80 treatment. KEY RESULTS: In Gαo RGS-insensitive heterozygous knock-in mice, the potency of SNC80 to produce antihyperalgesia and antidepressant-like effects was enhanced with no change in SNC80-induced convulsions. Conversely, in Gαo heterozygous knockout mice, SNC80-induced antihyperalgesia was abolished while antidepressant-like effects and convulsions were unaltered. No changes in SNC80-induced behaviours were observed in arrestin 3 knockout mice. SNC80-induced convulsions were potentiated in arrestin 2 knockout mice. CONCLUSIONS AND IMPLICATIONS: Taken together, these findings suggest that different signalling molecules may underlie the convulsive effects of the δ-receptor relative to its antihyperalgesic and antidepressant-like effects.

The behavioral effects of a mixed efficacy antinociceptive peptide, VRP26, following chronic administration in mice.

RATIONALE: VRP26 displays mu opioid receptor agonist and delta opioid receptor antagonist activity in vitro, a pharmacological profile purported to produce reduced tolerance, dependence, and rewarding effects. We hypothesized that VRP26 would display reduced adverse effects after chronic administration as compared with the traditional opioid analgesic fentanyl. OBJECTIVE: The aim of this study is to explore the development of tolerance, dependence, and conditioned place preference of VRP26 as compared with the traditional opioid analgesic fentanyl. METHODS: The antinociceptive effects of VRP26 and fentanyl were assessed using the mouse warm water tail withdrawal (WWTW) assay. Measurement of antinociceptive tolerance and physical dependence occurred after 7 days of continuous administration of either fentanyl (0.3 mg/kg/day) or VRP26 (10 mg/kg/day); tolerance was measured by a shift in the antinociceptive dose response curve in the WWTW assay. Physical dependence was determined by observation of withdrawal symptoms after precipitated withdrawal. Rewarding effects were measured by the ability of VRP26 or fentanyl to produce conditioned place preference. RESULTS: Fentanyl produced significant tolerance and dependence, as well as significant conditioned place preference. VRP26 produced neither tolerance nor physical dependence, nor did it produce significant conditioned place preference. CONCLUSIONS: These results suggest that chronic treatment with VRP26 may produce less tolerance or physical dependence than chronic treatment with clinically available mu opioid analgesics such as fentanyl. Additionally, VRP26 produces less rewarding effects than fentanyl. This desirable in vivo profile may be due to the mixed efficacy nature of VRP26 and could provide the framework for safer opioid analgesics.