We recently reported that stressed adipocytes release extracellular vesicles (EVs) that act as “find me” signals to promote macrophage migration and activation. In this study we performed a comprehensive characterization of stressed adipocyte-derived EVs, assessing their antigenic composition, lipidomics, and RNA profiles. Perilipin A was identified as one of the adipose-specific proteins and studied as a potential novel biomarker to detect adipocyte-derived EVs in circulation. Circulating EVs were significantly increased in mice with diet-induced obesity (DIO) and in obese humans with Metabolic Syndrome compared to lean controls. This increase was associated with decreased glucose tolerance in the DIO mice and metabolic dysfunction, elevated insulin and homeostatic model assessment of insulin resistance (HOMA-IR), in the obese humans. EVs from both DIO mice and obese humans were enriched in perilipin A, a central gatekeeper of the adipocyte lipid storehouse and a marker of adipocyte differentiation. In obese humans, circulating levels of EVs enriched in perilipin A were dynamic, decreasing 35% (p<0.05) after a 3-month reduced calorie diet intervention. This translational study provides an extensive characterization of adipocyte-derived EVs. The findings identify perilipin A as a novel biomarker of circulating EVs of adipocyte origin and support the development of circulating perilipin A-positive EVs as indicators of adipose tissue health.

Hemophagocytic lymphohistiocytosis (HLH) is extremely rare in the neonatal period. The incidence of neonatal HLH is not confirmed and may range from 1 in 50,000 to 150,000. The incidence varies based on ethnicity, particularly in populations in which consanguinity is common. HLH is associated with a high fatality rate and poor prognosis, making it important to recognize and diagnose it early. This review will concentrate primarily on the diagnosis and management of neonatal HLH.

Background: The specific etiology of spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) remains elusive. Both can present acutely without antecedent signs and can be difficult to differentiate. Neonatal nucleated red blood cell (NRBC) counts are part of the routine admission and serial CBCs drawn on premature neonates. Elevated NRBC counts could represent relative intrauterine hypoxemia, a possible risk factor for the development of SIP or NEC. Methods: We compared premature neonates with SIP to premature neonates with NEC and controls, matched gestational age (GA) and birth weight (BW). Kruskal-Wallis, Chi-Square, or Fisher's exact tests and univariate and multivariate nominal logistic regression models were used to estimate the association of baseline NRBC. Median times to SIP and NEC were calculated using the Kaplan-Meier method. All analyses were performed with SAS 9.4. Results: Male sex (72.5%), lower GA [Median (Q1, Q3): 25.1 (23.8, 28)], and lower BW [Median (Q1, Q3): 690 g (585, 1072)] had the highest incidence of SIP compared to NEC or controls. Increased baseline NRBC was associated with lower odds of developing NEC compared to controls [Median (Q1, Q3): 9 (5, 29) vs 19 (10, 51); OR (CI) 0.70 (0.55, 0.89), p-value = 0.0033]. Increased baseline NRBC was associated with higher odds of developing SIP compared to NEC [Median (Q1, Q3): 9 (5, 29) vs 19 (10, 51); OR (CI) 1.61 (1.18, 2.20) p-value = 0.0027]. There were no significant differences between intrauterine growth restriction (IUGR), maternal hypertension, chorioamnionitis, multiple births, or depressed APGAR scores in all three groups. NRBC for SIP neonates remained significantly higher at the day of life (DOL) 1-3 compared to other groups [Median (Q1, Q3): 23 (6, 93), p-value = 0.0020]. The percentage of patients with NRBC >4, remained elevated for patients with SIP as late as week three (p = 0.0023). Conclusion: ELBW, male sex, and elevated baseline NRBC were significantly associated with the risk of developing SIP compared to NEC or controls. NRBC remained significantly elevated on DOL 1-3, compared to NEC or controls. Between the groups, there were no significant differences in perinatal stressors.