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Mental illness in adolescence is associated with high-risk sexual behaviors including multiple sex partners, infrequent or inconsistent condom use, and nonuse of contraception. Inpatient psychiatric care represents a promising setting to provide sexual health education. This pilot study investigates the feasibility and acceptability of online sexual health education in this group by assessing usability and impact on short-term psychosocial outcomes. We administered online modules on healthy relationships, pregnancy prevention, condom use, and sexually transmitted infection (STI) prevention to youth. We evaluated outcomes using a single group, pre/post-intervention design. One quality improvement session assessed staff acceptability of the programming. Participants included 51 inpatients (mean age = 15.3; 61% female; 57% Hispanic or Latino; 55% heterosexual). Overall, the program was feasible to administer and highly acceptable to youth (84-89% liked the modules, 98-100% found them easy to use, 96-100% found them credible, 91-98% said information would lead to healthier dating relationships, and 78-87% would refer to a friend). Youth who completed modules demonstrated improvement in several outcomes: attitudes and norms towards violence (p p p p p = 0.04), HIV/STI knowledge (p p

Background Despite extensive studies of human immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination, research examining protective correlates of vertical transmission following maternal exposure in pregnancy remain limited. Here, we characterized antibody and cytokine responses in maternal and cord blood following infection or vaccination at various timepoints during gestation. Methods Spike S1 protein-specific binding antibodies and antibodies capable of blocking the interaction between the receptor binding domain (RBD) and the angiotensin converting enzyme 2 (ACE2) were measured in maternal and cord blood by ELISA. Serum concentrations of 74 cytokines/chemokines were measured by multiplex assay. Humoral responses and cytokine levels from matched maternal and fetal cord sera were compared and examined for potential correlations. Results We observed a highly significant correlation between Spike S1-specific antibody titer and RBD-ACE2 blocking antibody activity between maternal and fetal cord serum (p < 2.2e-16, R > 0.90). Blocking antibody activity was significantly higher for mothers infected during the 3rd trimester compared to earlier trimesters; however, vaccinated mothers developed and transferred higher antibody titers with greater RBD-ACE2 blocking antibody activity to their neonates than infected mothers. Furthermore, vaccine-induced Spike S1 IgG transfer ratios (fetal cord/maternal) were significantly higher than those induced by infection (p = 0.002). Multiplex assay showed significantly elevated levels of 33 cytokines/chemokines, mainly pro-inflammatory in infected maternal serum samples, while the paired fetal cord samples exhibited an anti-inflammatory cytokine predominance. Conclusion Our data support selective vertical transmission of potentially protective humoral responses against SARS-CoV-2, especially following vaccination in the 3rd trimester. The anti-inflammatory cytokine predominance in cord blood that persists despite maternal SARS-CoV-2 infection may offset the adverse outcomes of inflammation in pregnancy for the neonate. Disclosures All Authors: No reported disclosures.

Background The pro-inflammatory state associated with obesity leads to B- and T-lymphocyte dysfunction that may lead to an inadequate immune response to natural infection and vaccination. Preliminary studies, conducted outside of the US, involving multiple COVID-19 vaccines indicate that obesity may impact antibody response. The objective of this study was to evaluate the role of inflammatory status as a mediator in the relationship between obesity and COVID-19 vaccine immune response in a predominantly African-American population. Methods This cross-sectional analysis involved 54 participants ≧ 18 years of age who had completed the primary dosing schedule and booster for Novavax’s recombinant COVID-19 vaccine, NVX-CoV2373. Weight, height, and waist circumference (WC) measurements were taken. Medical history including COVID-19 vaccination and known COVID-19 infection were obtained. Blood samples were taken for measurement of c-reactive protein (CRP) and anti-SARS-CoV-2 spike protein IgG levels. Spearman correlation coefficient was used to assess the presence of a relationship between BMI and CRP, WC and CRP, CRP and spike protein IgG, BMI and spike protein IgG, and finally, WC and spike protein IgG. Mediation analysis was used to evaluate the moderating effect of plasma CRP on the relationship between WC and spike protein IgG while adjusting for suspected confounders. Statistical significance was defined as p < .05. Results There was an expected positive relationship between WC and CRP, (ρ = 0.37, p< .05). CRP and spike protein IgG trended towards a weak, negative relationship (ρ= -0.13, p > .05). WC and BMI both trended towards a positive relationship with anti-SARS-CoV-2 spike protein IgG (ρ = 0.29 and 0.15, respectively, p >.05). The mediation analysis showed that WC positively influenced spike protein IgG (p< .05), and this effect was not mediated by CRP. Conclusion Inflammation may be negatively associated with antibody response to COVID-19 vaccines. WC and antibody response may be positively related in NVX-CoV2373 recipients, in spite of chronic low-grade inflammation. Further research is needed to fully characterize the impact of obesity on COVID-19 vaccine immunogenic responses. Disclosures Lilly Immergluck, MD, MS, GSK: Clinical Trial- PI|Merck: Vaccine Trial Site- serve as PI|Moderna: Board Member|Novavax: Part of CoVID-19 Phase 3 Trial through US Covid Prevention Network.

During human pregnancy, proinflammatory responses in the placenta can cause severe fetal complications, including growth restriction, preterm birth, and stillbirth. Villitis of unknown etiology (VUE), an inflammatory condition characterized by the infiltration of maternal CD8+ T cells into the placenta, is hypothesized to be secondary to either a tissue rejection response to the haploidentical fetus or from an undiagnosed infection. In this study, we characterized the global TCR β-chain profile in human T cells isolated from placentae diagnosed with VUE compared with control and infectious villitis–placentae by immunoSEQ. Immunosequencing demonstrated that VUE is driven predominantly by maternal T cell infiltration, which is significantly different from controls and infectious cases; however, these T cell clones show very little overlap between subjects. Mapping TCR clones to common viral epitopes (CMV, EBV, and influenza A) demonstrated that Ag specificity in VUE was equal to controls and significantly lower than CMV-specific clones in infectious villitis. Our data indicate VUE represents an allograft response, not an undetected infection. These observations support the development of screening methods to predict those at risk for VUE and the use of specific immunomodulatory therapies during gestation to improve outcomes in affected fetuses.

The importance of fetal placental macrophages (Hofbauer cell [HCs]) is underscored by their appearance 18 d postconception and maintenance through term; however, how human HCs evolve during healthy pregnancy and how microenvironment and ontogeny impact phenotype and function remain unknown. In this study, we comprehensively classify human HCs ex vivo, interrogate phenotypic plasticity, and characterize antiviral immune responses through gestation. Activated HCs were abundant in early pregnancy and decreased by term; molecular signatures emphasize inflammatory phenotypes early in gestation. Frequency of HCs with regulatory phenotypes remained high through term. Furthermore, term HCs exhibited blunted responses to stimulation, indicating reduced plasticity. IFN-λ1 is a key placental IFN that appeared less protective than IFN-α, suggesting a potential weakness in antiviral immunity. Ligand-specific responses were temporally regulated: we noted an absence of inflammatory mediators and reduced antiviral gene transcription following RIG-I activation at term despite all HCs producing inflammatory mediators following IFN-γ plus LPS stimulation. Collectively, we demonstrate sequential, evolving immunity as part of the natural history of HCs through gestation.

Floodplains of the southeastern United States exhibit high biological productivity, maintained by periodic floodplain inundation as a result of seasonal flooding. To examine the relationship between biological productivity and seasonal flooding following periods of drought, we quantified aquatic macroinvertebrate communities monthly in an inundated floodplain during the annual flood pulse (December-April) in two years, one following a multi-year drought and one following a larger than average flooding event. We predicted that floodplain communities would differ in richness, biomass, and community composition between years and that differences would be driven by discharge at the main stem and organic matter availability. We collected macroinvertebrates from the floodplain of the Altamaha River, an unimpounded 6th order river in the Coastal Plain region of the southeastern US that experiences floodplain connectivity. With invertebrates identified to genus, we elucidated richness, abundance, biomass, community composition, and functional feeding group. Richness was generally higher in the drought year but decreased throughout the flood pulse, while during the flood year richness was lower and increased. Biomass decreased throughout the flood pulse following the drought year and increased during the flood year. There was a high degree of overlap in invertebrate community composition based on abundance data during both years of the study with collector gatherers being the most highly abundant functional feeding group. As climate change impacts (i.e., severe droughts) become more common, it is critical to investigate how aquatic communities are responding to increasingly unpredictable flow conditions in unimpounded and seemingly unaltered rivers.

This article presents a comparative analysis of works of Caribbean art and literature that engage in a mutual project of addressing the paradox of the colonial archive. Trinidadian-Canadian writer M. NourbeSe Philip crafted her long poem Zong! from an eighteenth-century legal document about the murder of 132 enslaved Africans onboard the slave ship of the same name. Exposing the dehumanizing language of historical record from which she nonetheless extracts affective and poetic scraps of human experience, Philip shows the power and necessity of artistic intervention in the colonial archive. The similarities between Philip’s literary strategies and Belle’s artistic interventions in the archive of the Danish (now U.S.) Virgin Islands are striking, and the two illuminate one another. Focusing on Belle’s series entitled Chaney (We Live in the Fragments), the analysis delves into her work with “chaney,” a Creole term for the colonial-era shards of china that wash out of the soil of the Virgin Islands as a reminder of the centuries-long Danish presence there. Belle’s art is both counter-archival and counter-canonical in her direct address to the national Danish institution of the Kongelige Porcelainsfabrik, or Royal Copenhagen Porcelain Factory. Both the poem and the artwork focus on the aesthetic of the fragment, whether in terms of the fragmented nature of the colonial archive with its many blind spots, the fragments of lost narrative that Philip scatters across the page, or the fragments of pottery that Belle transforms into paintings and ceramics that evoke the disjointed nature of Caribbean identity. Framing Zong! and Chaney with the notion of “comparative relativism,” the article draws on literary and art historical methodologies to reveal an important transdisciplinary approach to Caribbean archives and to the creation of cultural memory.

Problem Prenatal exposure to metabolic dysregulation arising from maternal obesity can have negative health consequences in post-natal life. To date, the specific effects of maternal obesity on fetal immunity at a cellular level have not been well characterized. Method of study Using cord blood mononuclear cells (CBMCs) and cord plasma (n = 9/group) isolated from infants born to women with a high body mass index (BMI>25kg/m2 ) compared to women with a normal BMI (18-25kg/m2 ), we evaluated differences in immune cell populations using single-cell mass cytometry (CyTOF). CBMCs were matched according to potentially confounding variables, such as maternal and gestational age, ethnicity, smoking status, and gravidity. Statistical results were adjusted for fetal sex. Data were analyzed by viSNE and FlowSOM softwares in Cytobank™ . Results In newborn CBMCs from women with high BMI, we observed changes in frequency and phenotype of immune cell populations, including significant increases in CD4+ T cells and decreases in myeloid cell populations. IL-12p40 and MDC concentrations were significantly elevated in the high BMI group compared to control. Conclusion This study demonstrates an association between maternal obesity and fetal immunity. Our results warrant following long-term immunologic outcomes and associated clinical risks in children born to women with a high pre-pregnancy BMI.

Jean Rhys’s Wide Sargasso Sea absorbs and has been absorbed by multiple texts. In this joint chapter, we present texts (other than Bronte’s) that influenced Rhys with a focus on the ways in which Wide Sargasso Sea exemplifies a form of influence that can best be understood as encryption, a concept we draw from Abraham and Torok’s conceptualization of the phantom, the unconscious trace of secrets which have been inherited from others and which reside, silently and symptomatically, in the descendent. Rhys’s influences occupy her novel as secrets and include Frances Hodgson Burnett’s The Secret Garden (1911) and Daphne du Maurier’s Rebecca (1938). Beyond looking at intertextuality as such, we focus on the unique mode of literary influence that Rhys models through her encryption of the (violent) secrets of other women’s writing.

This introduction to the volume traces the reception of Wide Sargasso Sea from its publication in 1966 through the various theoretical paradigms used over the decades to articulate its current status as an influence upon other works of literature and the arts, literary criticism and theory. In considering the reasons for the novel’s ability to speak to literary, visual, and critical texts over different time periods, we look at Jean Rhys’s uniquely efficient prose and the geopolitics of her novel. The introduction goes on to provide an overview of the sections and chapters of the volume as a whole.

Zika virus (ZIKV), which emerged in regions endemic to dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission remains unclear. Here, we find that DENV antibodies increase ZIKV infection of placental macrophages (Hofbauer cells [HCs]) from 10% to over 80% and enhance infection of human placental explants. ZIKV-anti-DENV antibody complexes increase viral binding and entry into HCs but also result in blunted type I interferon, pro-inflammatory cytokine, and antiviral responses. Additionally, ZIKV infection of HCs and human placental explants is enhanced in an immunoglobulin G subclass-dependent manner, and targeting FcRn reduces ZIKV replication in human placental explants. Collectively, these findings support a role for pre-existing DENV antibodies in enhancement of ZIKV infection of select placental cell types and indicate that pre-existing immunity to DENV should be considered when addressing ZIKV vertical transmission.

The recent Zika virus (ZIKV) outbreak in Brazil has been directly linked to increased cases of microcephaly in newborns. Current evidence indicates that ZIKV is transmitted vertically from mother to fetus. However, the mechanism of intrauterine transmission and the cell types involved remain unknown. We demonstrate that the contemporary ZIKV strain PRVABC59 (PR 2015) infects and replicates in primary human placental macrophages, called Hofbauer cells, and to a lesser extent in cytotrophoblasts, isolated from villous tissue of full-term placentae. Viral replication coincides with induction of type I interferon (IFN), pro-inflammatory cytokines, and antiviral gene expression, but with minimal cell death. Our results suggest a mechanism for intrauterine transmission in which ZIKV gains access to the fetal compartment by directly infecting placental cells and disrupting the placental barrier.

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infections. When a pregnant woman develops primary HCMV infection in early gestation, the risk of transplacental infection is ~40%. Studies have documented the presence of HCMV in placental macrophages (Hofbauer cells [HCs]) as a consequence of maternal viremia. However, the interplay between HCMV and placental macrophages (HCs) is poorly defined. With written informed consent, placentae were collected from 12 HIV-1/Hep B/HCMV seronegative women (>18 years). HCs were exposed to human HCMV (TB40/E). qPCR, FACS, ELISA, and Western blot analysis determined the expression of activation markers, cytokines, antiviral genes, and host proteins. Here we found that HCs isolated from early gestation (15–23 weeks) placentae are more susceptible to HCMV infection than HCs isolated from term (>39 weeks) placentae. HCMV infection of early gestation HCs led to a significant upregulation of activation markers, along with elevated secretion of proinflammatory cytokines, compared to HCMV-infected term HCs. In early gestation and term HC, HCMV rapidly induces the type I IFN pathway, leading to secretion of IFNs and strong induction of ISGs. However, HCMV diminishes type I IFN-mediated phosphorylation of STAT2, with early gestation HCs exhibiting the greatest level of inhibition. Our findings show that HCMV can subvert type I IFN signaling to support viral growth at the placenta, particularly during early gestation. Studying mechanisms used by viruses to prevent an immune response is of great importance for the development of new strategies to limit the sequelae of viral infections.

Several co-pathogens that pose threats to the fetus during gestation, including human cytomegalovirus (HCMV), may also contribute to mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1). Within endemic settings, associations between maternal HCMV viral load and increased incidence of MTCT of HIV-1 are documented; however, the mechanisms that promote transmission are poorly characterized. Here we demonstrate that HCMV coinfection enhances susceptibility and viral replication of HIV-1 in placental macrophages (Hofbauer cells) in vitro. Consistent with enhanced viral susceptibility, HCMV exposure upregulates CCR5 and CD80 expression on Hofbauer cells. HCMV also significantly induces type I interferon (IFN), proinflammatory cytokines, and antiviral gene expression. Interestingly, we found that HCMV diminishes type I IFN-mediated phosphorylation of STAT2. Collectively, our data suggest that HCMV-induced activation, local inflammation, and antagonism of type I IFN responses in placental Hofbauer cells promote in utero transmission of HIV-1.