Small Extracellular Vesicles Harboring PD-L1 in Obstructive Sleep Apnea.

Obstructive sleep apnea syndrome (OSA) has been associated with increased cancer incidence and aggressiveness. One hypothesis to support this association is the implication of immune response, particularly the programmed cell death pathway, formed by the receptor PD-1 and its ligand PD-L1. Recent studies have shown dysregulation of this pathway in severe OSA patients. It has also been shown that small extracellular vesicles (sEVs) carrying PD-L1 induce lymphocyte dysfunction. Thus, the aim of our study was to analyze the expression of PD-L1 on sEVs of OSA patients and to evaluate the role of sEVs on lymphocyte activation and cytotoxicity. Circulating sEVs were isolated from OSA patients and the control group. Lymphocytes were isolated from the control group. Circulating sEVs were characterized by western blot, nanotracking analysis, and flow cytometry and were incubated with lymphocytes. Our results show no differences in the quantity and composition of sEVs in OSA patients and no significant effects of sEVs in OSA patients on lymphocyte activation and cytotoxicity. These results suggest that OSA does not modify PD-L1 expression on sEVs, which does not contribute to dysregulation of cytotoxic lymphocytes.

Eudaimonic Well-Being for Lesbian and Bisexual Women: The Roles of Religion and Social Connectedness.

Understanding how religion and well-being are related for lesbian and bisexual women provides important context for clinical interventions. Current literature in the field diverges on whether the relationship between religious commitment and well-being is positive for those in the queer community. The current study examines whether an independent or interdependent self-construal explains the relationship between religious commitment and eudaimonic well-being (EWB) for lesbian and bisexual women. This empirical study used data from the Multi-Site University Study on Identity and Culture, a research collaboration amongst 30 colleges and universities in the United States. Findings suggest that although self-construal does not mediate the relationship between religious commitment and well-being, there are significant effects between religious commitment and EWB as well as an independent self-construal and EWB. These findings provide a deeper understanding of variables associated with greater well-being and are important for the advancement of research and practice with queer women.

Perceived Discrimination and Risk Behaviors in African American Students: the Potential Moderating Roles of Emotion Regulation and Ethnic Socialization.

Prior research has identified perceived discrimination as being a contributing factor in health and mental health disparities. However, there is little research on the relationship between perceived discrimination and behaviors such as hazardous alcohol and illicit substance use and risky sexual behaviors that put people at risk for negative health consequences including HIV. The current research explores the role that cultural factors may play in a tendency for individuals to engage in unhealthy behaviors or an ability to avoid them. A total of 266 college students who self-identified as Black or African American were surveyed on measures of familial ethnic socialization, perceived discrimination, emotion regulation, substance use, and risky sexual behaviors. Findings indicate that perceived discrimination and emotion regulation-suppression were associated with higher levels of hazardous alcohol use, and that emotion regulation-cognitive reappraisal was associated with lower levels of illicit substance use. Implications for intervention and prevention in African American college students are discussed.

LPS-enriched small extracellular vesicles from metabolic syndrome patients trigger endothelial dysfunction by activation of TLR4.

BACKGROUND: Metabolic syndrome (MetS) is characterized by a cluster of interconnected risk factors -hyperglycemia, dyslipidemia, hypertension and obesity- leading to an increased risk of cardiovascular events. Small extracellular vesicles (sEVs) can be considered as new biomarkers of different pathologies, and they are involved in intercellular communication. Here, we hypothesize that sEVs are implicated in MetS-associated endothelial dysfunction. METHODS: Circulating sEVs of non-MetS (nMetS) subjects and MetS patients were isolated from plasma and characterized. Thereafter, sEV effects on endothelial function were analyzed by measuring nitric oxide (NO) and reactive oxygen species (ROS) production, and mitochondrial dynamic proteins on human endothelial aortic cells (HAoECs). RESULTS: Circulating levels of sEVs positively correlated with anthropometric and biochemical parameters including visceral obesity, glycaemia, insulinemia, and dyslipidemia. Treatment of HAoECs with sEVs from MetS patients decreased NO production through the inhibition of the endothelial NO-synthase activity. Injection of MetS-sEVs into mice impaired endothelium-dependent relaxation induced by acetylcholine. Furthermore, MetS-sEVs increased DHE and MitoSox-associated fluorescence in HAoECs, reflecting enhanced cytosolic and mitochondrial ROS production which was not associated with mitochondrial biogenesis or dynamic changes. MetS patients displayed elevated circulating levels of LPS in plasma, and, at least in part, it was associated to circulating sEVs. Pharmacological inhibition and down-regulation of TLR4, as well as sEV-carried LPS neutralization, results in a substantial decrease of ROS production induced by MetS-sEVs. CONCLUSION: These results evidence sEVs from MetS patients as potential new biomarkers for this syndrome, and TLR4 pathway activation by sEVs provides a link between the endothelial dysfunction and metabolic disturbances described in MetS.

Congenital Cytomegalovirus and Autoimmune Neutropenia: Cause or Coincidence?

BACKGROUND: Congenital cytomegalovirus (CCMV) accounts for high rates of infant morbidity and mortality. Neutropenia is a common finding in CCMV infection, of which the age of presentation overlaps with autoimmune neutropenia (AIN). AIN represents one of the most common forms of chronic neutropenia in childhood. METHODS: A literature search exploring biologic associations between CCMV and AIN was conducted: PubMed (MEDLINE), Ovid and Web of Science. We further describe 2 cases of concurrent CCMV and AIN. Both cases were confirmed with the indirect granulocyte immunofluorescence test and alternative etiologies for neutropenia excluded. RESULTS: Our 2 patients represent confirmed cases of AIN in infants with CCMV. One patient demonstrated neutropenia while undergoing treatment with Valganciclovir, while the other was never treated. With interruption of Valganciclovir in infant A, neutrophil counts (ANC) did not improve and upon resumption of treatment ANC remained static. CONCLUSIONS: Further studies examining a possible biologic link between CCMV and AIN are advocated for. We encourage clinicians to actively consider AIN in the differential diagnosis of all infants with CCMV presenting with neutropenia.