Polyvictimization, Emotion Dysregulation, Symptoms of Posttraumatic Stress Disorder, and Behavioral Health Problems among Justice-Involved Youth: a Latent Class Analysis

Among the 90% of adolescents involved in juvenile justice who have experienced traumatic victimization, a sub-group may be at highest risk due to histories of multiple types of interpersonal and non-interpersonal trauma, termed polyvictims. Latent class analyses (LCA) have identified polyvictimized subgroups in several studies of adolescents and adults, but only one study of traumatic victimization has been conducted with justice-involved youth (Ford et al. 2013). The current investigation replicates and extends that study’s findings using LCA to assess a wider range of victimization- and nonvictimization-related adversities and emotion dysregulation, DSM-5 symptom clusters of posttraumatic stress disorder (PTSD), and behavioral health problems, such as substance use, anger, depression, somatic complaints, and suicide ideation. In a sample of juvenile detainees three latent classes were identified: mixed adversity (MA; n = 327), violent environment (VE; n = 337), and polyvictimization (PV; n = 145). In contrast to MA youth, PV youth were more likely to report exposure to all forms of adversity, and in contrast to both MA and VE youth, exposure to maltreatment and family violence, and higher levels of emotion dysregulation, PTSD, and depression/anxiety symptoms, somatic complaints, and suicidality. VE youth (vs. MA youth) were more likely to report exposure to violence and non-interpersonal traumas, and were higher on some forms of emotion dysregulation, PTSD symptoms, anger and substance use. Findings suggest that most justice-involved youth have experienced substantial adversity, with almost one in five identified as a polyvictim having experienced multiple adversities, including impaired caregivers, and evidencing the most severe problems in emotion dysregulation and PTSD, internalizing, and externalizing symptoms

Syndecan-1 Enhances Proliferation, Migration and Metastasis of HT-1080 Cells in Cooperation with Syndecan-2

Syndecans are transmembrane heparan sulphate proteoglycans. Their role in the development of the malignant phenotype is ambiguous and depends upon the particular type of cancer. Nevertheless, syndecans are promising targets in cancer therapy, and it is important to elucidate the mechanisms controlling their various cellular effects. According to earlier studies, both syndecan-1 and syndecan-2 promote malignancy of HT-1080 human fibrosarcoma cells, by increasing the proliferation rate and the metastatic potential and migratory ability, respectively. To better understand their tumour promoter role in this cell line, syndecan expression levels were modulated in HT-1080 cells and the growth rate, chemotaxis and invasion capacity were studied. For in vivo testing, syndecan-1 overexpressing cells were also inoculated into mice. Overexpression of full length or truncated syndecan-1 lacking the entire ectodomain but containing the four juxtamembrane amino acids promoted proliferation and chemotaxis. These effects were accompanied by a marked increase in syndecan-2 protein expression. The pro-migratory and pro-proliferative effects of truncated syndecan-1 were not observable when syndecan-2 was silenced. Antisense silencing of syndecan-2, but not that of syndecan-1, inhibited cell migration. In vivo, both full length and truncated syndecan-1 increased tumour growth and metastatic rate. Based on our in vitro results, we conclude that the tumour promoter role of syndecan-1 observed in HT-1080 cells is independent of its ectodomain; however, in vivo the presence of the ectodomain further increases tumour proliferation. The enhanced migratory ability induced by syndecan-1 overexpression is mediated by syndecan-2. Overexpression of syndecan-1 also leads to activation of IGF1R and increased expression of Ets-1. These changes were not evident when syndecan-2 was overexpressed. These findings suggest the involvement of IGF1R and Ets-1 in the induction of syndecan-2 synthesis and stimulation of proliferation by syndecan-1. This is the first report demonstrating that syndecan-1 enhances malignancy of a mesenchymal tumour cell line, via induction of syndecan-2 expression

PTSD and dissociation symptoms as mediators of the relationship between polyvictimization and psychosocial and behavioral problems among justice-involved adolescents

Polyvictimization (PV) has been shown to be associated with psychosocial and behavioral impairment in community and high risk populations, including youth involved in juvenile justice. However, the mechanisms accounting for these adverse outcomes have not been empirically delineated. Symptoms of posttraumatic stress disorder (PTSD) and dissociation are documented sequelae of PV and are associated with a wide range of behavioral/emotional problems. This study used a cross-sectional research design and bootstrapped multiple mediation analyses with self-report measures completed by a large sample of justice-involved youth (N = 809, ages 12–19 years old, 27% female, 46.5% youth of color) to test the hypothesis that PTSD and dissociation symptoms mediate the relationship between PV and problems with anger, depression/anxiety, alcohol/drug use, and somatic complaints after controlling for the effects of exposure to violence and adversities related to juvenile justice involvement. As hypothesized, PTSD symptoms mediated the relationship of PV with all outcomes except alcohol/drug use problems (which had an unmediated direct association with PV). Partially supporting study hypotheses, dissociation symptoms mediated the relationship between PV and internalizing problems (i.e., depression anxiety; suicide ideation). Implications are discussed for prospective research demarcating the mechanisms linking PV and adverse outcomes in juvenile justice and other high risk populations

Prevention of adjuvant arthritis by cyclosporine in rats

The effect of cyclosporine A during the development phase of adjuvant arthritis was studied in 40 female rats. Five groups of eight animals each received oral cyclosporine, 2.5, 5, 10, 20, or 30 mg/kg daily for 30 days. Also, eight normal and eight diseased rats served as placebo controls. At the time of inoculation of the adjuvant suspension on day 0, measurement of disease parameters (paw swelling and vertebral density) was started concomitantly with beginning of therapy. On completion of the study, the animals were killed, and after measurement of total skeletal and segmental (hind legs and caudal spine plus two caudal vertebrae) calcium, the two assessed vertebrae and both femoral condyles were removed for histomorphometric evaluation (vertebrae) and for estimation of glycosaminoglycan (GAG) content of cartilage. Blood for osteocalcin determinations also was taken at term from control and untreated arthritic rats and from animals that had received 10 mg/kg cyclosporine. Treatment with 2.5 mg/kg was ineffective, but doses between 5 and 20 mg/kg prevented the development of articular and osseous lesions. The 20 mg/kg dose showed no better effect than 10 mg/kg. This was shown by the absence of inflammation and the presence of normal condylar GAG and total mineral content in the areas screened. Untreated animals showed marked reductions in all of these parameters. The 30 mg/kg dose was effective in blocking the GAG loss, but significant reductions in bone density and trabecular volume were seen. There was a close correlation between GAG and bone density values, suggesting a common causal relationship. Circulating osteocalcin was significantly elevated in the untreated animals with adjuvant arthritis.(ABSTRACT TRUNCATED AT 250 WORDS