Development and preliminary evaluation of a self-guided, internet-based tool for coping with stress and trauma: Life Improvement for Teens (LIFT).

Implementation issues often interfere with delivery of evidence-based interventions for students exposed to trauma. To improve uptake of evidence-based techniques for such students, a partnership of interventionist scientists, research and development experts, and students created a self-paced, confidential, online curriculum. This article describes the program and results of an open trial in 5 schools that serve primarily ethnic minority youth in urban settings. Fifty-one middle and high school students completed surveys before and after the program, as well as within the program, to assess emotional and behavioral symptoms (depressive, anxiety, posttraumatic stress disorder [PTSD] symptoms and behavior) and purported mechanisms of action (coping, cognitions, emotional self-efficacy). Results indicated the program was feasible and acceptable, with moderate satisfaction. Despite low power in this study, we observed changes in several hypothesized mechanisms of action. In addition, we observed promising improvements in PTSD symptoms, emotional problems, and total behavioral difficulties. These findings offer the promise of using a self-help web-based tool to augment and enhance usual school support services. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Violence, Guns, and Suicide in New Orleans: Results from a Qualitative Study of Recent Suicide Decedents.

Many Americans own guns to protect themselves against other people, but there is evidence that both victimization and gun access increase suicide risk. We conducted qualitative interviews with informants of 17 suicide cases in New Orleans of the 60 who died between January 2015 and April 2016 to understand the relationship between past trauma, gun access and storage, and suicide. Nine cases had experienced a past trauma, including three who had recently had a family member killed by homicide. Eight died via firearm; of those, seven owned the guns they used to take their lives and stored them locked (but loaded) at home or in their cars. Preventing community violence and addressing its sequelae may be important for reducing suicides. A multi-pronged strategy consisting of policies, education, and marketing will likely be needed to address the risk of suicide conferred by gun access.

Opportunities to intervene? "Warning signs" for suicide in the days before dying.

To validate warning signs for suicide, researchers interviewed 20 respondents, representing 17 suicides in Orleans Parish, Louisiana, about characteristics of the decedent in the year, month, and days preceding the death. Decedents did exhibit behaviors consistent with existing warning signs, but these were rarely new behaviors present 7 days prior to the suicide but not previously. Research is needed to continue to test warning signs for suicide, and education campaigns that teach warning signs may not be relevant for preventing suicide among those in mental health treatment or involved in the criminal justice system.

The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity.

Although previous studies have investigated the role of IL-27/WSX-1 interactions in the regulation of Th1 responses, little is known about their role in regulating Th2-type responses. Studies presented in this work identify a direct role for IL-27/WSX-1 interactions in the negative regulation of type 2 responses independent of effects on type 1 cytokines. WSX-1-/- mice infected with the gastrointestinal helminth Trichuris muris displayed accelerated expulsion of parasites and the development of exaggerated goblet cell hyperplasia and mastocytosis in the gut due to increased production of Th2 cytokines. Enhanced mast cell activity in the absence of WSX-1 was consistent with the ability of wild-type mast cells to express this receptor. In addition, IL-27 directly suppressed CD4+ T cell proliferation and Th2 cytokine production. Together, these studies identify a novel role for IL-27/WSX-1 in limiting innate and adaptive components of type 2 immunity at mucosal sites.

IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis.

Trichinella spiralis infection elicits a vigorous IgE response and pronounced intestinal and splenic mastocytosis in mice. Since IgE both activates mast cells (MC) and promotes their survival in culture, we examined its role in MC responses and parasite elimination in T. spiralis-infected mice. During primary infection, wild-type but not IgE-deficient (IgE(-/-)) BALB/c mice mounted a strong IgE response peaking 14 days into infection. The splenic mastocytosis observed in BALB/c mice following infection with T. spiralis was significantly diminished in IgE(-/-) mice while eosinophil responses were not diminished in either the blood or jejunum. Similar levels of peripheral blood eosinophilia and jejunal mastocytosis occurred in wild-type and IgE-deficient animals. Despite the normal MC response in the small intestine, serum levels of mouse MC protease-1 also were lower in parasite-infected IgE(-/-) animals and these animals were slower to eliminate the adult worms from the small intestine. The number of T. spiralis larvae present in the skeletal muscle of IgE(-/-) mice 28 days after primary infection was about twice that in BALB/c controls, and the fraction of larvae that was necrotic was reduced in the IgE-deficient animals. An intense deposition of IgE in and around the muscle larvae was observed in wild-type but not in IgE null mice. We conclude that IgE promotes parasite expulsion from the gut following T. spiralis infection and participates in the response to larval stages of the parasite. Furthermore, our observations support a role for IgE in the regulation of MC homeostasis in vivo.

TGF-beta 1 regulates adhesion of mucosal mast cell homologues to laminin-1 through expression of integrin alpha 7.

Mucosal mast cells (MMC) or their precursors migrate through the intestinal lamina propria to reside intraepithelially, where expression of mouse mast cell protease-1 indicates the mature phenotype. Alterations in expression of integrins that govern cell adhesion to the extracellular matrix may regulate this process. As the key cytokine mediating differentiation of mouse mast cell protease-1-expressing MMC homologues in vitro, TGF-beta1 was considered a likely candidate for regulation of the integrins that facilitate intraepithelial migration of MMC. Therefore, we examined adhesion of bone marrow-derived mast cells cultured with and without TGF-beta1 to laminin-1, fibronectin, and vitronectin along with expression of integrins likely to regulate this adhesion. Adhesion of PMA-stimulated cultured mast cells to laminin-1 increased from 5.3 +/- 3.6% (mean +/- SEM) in the absence of TGF-beta1 to 58.7 +/- 4.0% (p < 0.05) when cultured mast cells had differentiated into MMC homologues in the presence of TGF-beta1. Increased adhesion of MMC homologues to laminin-1 was also stimulated by FcepsilonRI cross-linking and the calcium ionophore A23187. Expression of the laminin-binding integrin alpha(7) by MMC homologues grown in the presence of TGF-beta1 was demonstrated by RT-PCR and flow cytometry, and preincubation of MMC homologues with the alpha(7)-neutralizing Ab 6A11 inhibited adhesion to laminin-1 by 98% (p < 0.05), demonstrating a novel role for this molecule in adhesion of a hemopoietic cell to laminin-1.

Chemokine and cytokine expression in murine intestinal epithelium following Nippostrongylus brasiliensis infection.

Infection of mice with the nematode parasite Nippostrongylus brasiliensis results in a well characterized intestinal mastocytosis with intraepithelial migration of mucosal mast cells (MMC). The molecules mediating this response are unknown. We examined expression of several putative mast cell chemoattractants in intestinal epithelium following N. brasiliensis infection. Expression of the chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1alpha), RANTES (regulated on activation normal T-cell expressed and secreted), fractalkine, and thymocyte expressed chemokine (TECK); and the cytokines stem cell factor (SCF) and transforming growth factor beta1 (TGFbeta1), was constitutive and no alteration was detected following infection. MCP-1 expression was also constitutive but at much lower levels and increased expression was detected on days 7 and 14 postinfection. Expression of MCP-1 in whole jejunum was at much higher levels than in epithelium. Constitutive expression of MCP-1, MIP-1alpha and TGFbeta1 was also detected in cultured bone marrow-derived homologues of MMC. In an intestinal epithelial cell line (CMT-93), there was constitutive expression of SCF, TGFalpha1, fractalkine and MCP-1. The results show that, in vivo, epithelium is a potentially important source of mast cell chemoattractants.