Background Mechanical ventilation of preterm newborns causes lung injury and is associated with poor neurodevelopmental outcomes. However, the mechanistic links between ventilation-induced lung injury (VILI) and brain injury is not well defined. Since circulating extracellular vesicles (EVs) are known to link distant organs by transferring their cargos, we hypothesized that EVs mediate inflammatory brain injury associated with VILI. Methods Neonatal rats were mechanically ventilated with low (10 mL/kg) or high (25 mL/kg) tidal volume for 1 h on post-natal day 7 followed by recovery for 2 weeks. Exosomes were isolated from the plasma of these rats and adoptively transferred into normal newborn rats. We assessed the effect of mechanical ventilation or exosome transfer on brain inflammation and activation of the pyroptosis pathway by western blot and histology. Results Injurious mechanical ventilation induced similar markers of inflammation and pyroptosis, such as increased IL-1β and activated caspase-1/gasdermin D (GSDMD) in both lung and brain, in addition to inducing microglial activation and cell death in the brain. Isolated EVs were enriched for the exosomal markers CD9 and CD81, suggesting enrichment for exosomes. EVs isolated from neonatal rats with VILI had increased caspase-1 but not GSDMD. Adoptive transfer of these EVs led to neuroinflammation with microglial activation and activation of caspase-1 and GSDMD in the brain similar to that observed in neonatal rats that were mechanically ventilated. Conclusions These findings suggest that circulating EVs can contribute to the brain injury and poor neurodevelopmental outcomes in preterm infants with VILI through activation of GSDMD.

Background Key to the US refugee resettlement effort is the role of non-governmental organizations (NGOs) who receive, place, and provide transitional programs and referrals to new and recently resettled refugees. Yet only one rapid assessment study thus far examined the impact of COVID-19 on service delivery systems of US refugee resettlement agencies. This exploratory study describes the capability and preparedness of US refugee resettlement agencies to provide services and care to clients during the COVID-19 pandemic. Methods Using both telephone interviews and an internet survey, we assessed the impact of COVID-19 on service delivery, agency capacity, and preparedness of 101 US refugee resettlement agencies. Descriptive statistics were used to describe the dataset, while chi-square (χ2) tests were used to examine relationships by resettlement agency size (number of employees in each agency). Results Despite a temporary pause on refugee admissions, restrictive stay-at-home orders, and refugee travel restrictions, the majority of responding US refugee resettlement agencies continued to provide specialized services and care to resettled refugees and other immigrants. Among the more important findings was that agencies that continued to provide refugee services and care onsite in their existing facilities or office rather than moving such services offsite differed by agency size [χ2 (9.494, n = 101), p < 0.05]. Almost all agencies (93.1%) strongly agreed or agreed that staff have timely access to COVID-19 information. Most of the refugee services were provided offsite (n = 72 agencies, some with multiple offices across the US). Conclusions US refugee resettlement agencies continued to perform admirably despite a lack of funding. Future research is underway to obtain a more balanced understanding of the impact of COVID-19 on practice or operations.

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