Impact of peer relationship and exposure to violence on Posttraumatic Stress for children at risk for maltreatment

Post-traumatic Stress (PTS) symptomology includes ruminating thoughts and feelings around trauma, inability to feel and express emotions, and avoidance of things related to the traumatic event (American Psychiatric Association, 2000). Children and youth exposed to child maltreatment (abuse and neglect) are at higher risk of experiencing PTS. Extra-familial support, including peer support can reduce post-traumatic stress among youth (Pina et al., 2008). In the present study, Witnessing, Victimization, and Both Witnessing and Victimization due to Exposure to In-Home Violence and Peer Relationship Quality are evaluated as to their relative impact on PTS for children at risk for child maltreatment. Peer Relationship Quality is also tested as a moderator of the effects of violence exposures on PTS. Data come from the National Survey of Child and Adolescent Well-Being II (NSCAW II). Three waves of assessment were obtained starting in 2008 at 18 month intervals. A subsample of 2,151 children (2,071 children with non-missing values on the predictor, outcome and moderator variables) who were between the ages of 8 and 17 at any of the 3 waves was used. A three process latent linear growth model was estimated to assess PTS, Peer Relationship Quality and Exposure to In-Home Violence. Each of three Exposure to In- Home Violence constructs were assessed separately. Findings suggest that the average PTS at baseline was about 9.18 points (on a 32 point scale) and PTS declines by about 0.58 points every year on average. Additionally, baseline Peer Relationship Quality was predictive of baseline PTS with higher scores on Peer Relationship Quality associated with lower PTS at baseline. Moreover higher Peer Relationship Quality over time was associated with declines in PTS over time. The baseline effect of Exposure to In-Home Violence was positively associated with baseline PTS. So more Exposure to In-Home Violence was related to more post-traumatic stress. Change in witnessing violence at home over time and change in both witnessing and victimization over time were strongly positively associated with change in PTS over time. Peer Relationship Quality did not moderate the association between baseline Exposure to In-home Violence and PTS levels at baseline nor between baseline Exposure to In-Home Violence and change in PTS over time. These findings suggest several possible avenues for intervention for clinicians and help understand the dynamic associations between Exposure to In-Home Violence, Peer Relationship Quality and PTS in the population of children at risk for maltreatment

Final Report: Paths to QUALITY Evaluation

Paths to QUALITY Evaluation—Phase 2 Final Report to the Indiana Office of Early Childhood and Out of School Learning Family and Social Services Administration March, 201

Characterization of BRCA2 R3052Q variant in mice supports its functional impact as a low-risk variant

Pathogenic variants in BRCA2 are known to significantly increase the lifetime risk of developing breast and ovarian cancers. Sequencing-based genetic testing has resulted in the identification of thousands of BRCA2 variants that are considered to be variants of uncertain significance (VUS) because the disease risk associated with them is unknown. One such variant is p.Arg3052Gln, which has conflicting interpretations of pathogenicity in the ClinVar variant database. Arginine at position 3052 in BRCA2 plays an important role in stabilizing its C-terminal DNA binding domain. We have generated a knock-in mouse model expressing this variant to examine its role on growth and survival in vivo. Homozygous as well as hemizygous mutant mice are viable, fertile and exhibit no overt phenotype. While we did not observe any hematopoietic defects in adults, we did observe a marked reduction in the in vitro proliferative ability of fetal liver cells that were also hypersensitive to PARP inhibitor, olaparib. In vitro studies performed on embryonic and adult fibroblasts derived from the mutant mice showed significant reduction in radiation induced RAD51 foci formation as well as increased genomic instability after mitomycin C treatment. We observed mis-localization of a fraction of R3052Q BRCA2 protein to the cytoplasm which may explain the observed in vitro phenotypes. Our findings suggest that BRCA2 R3052Q should be considered as a hypomorphic variant.This research was sponsored by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health

The Association Between Childhood Maltreatment, Substance Use Frequency, and Physical Intimate Partner Violence: A Gene-Environment Study

This dissertation evaluated the complex inter-relatedness between co-occurring childhood maltreatment exposures, physical intimate partner violence (perpetration and victimization), substance use frequency, and molecular genetics for substance use, utilizing appropriate developmental models and theoretical approaches. Three studies were proposed within this dissertation. Data for the three studies come from a national longitudinal panel study: The National Longitudinal Study of Adolescent to Adult Health (Add Health; Harris, 2013). Across studies, latent profile analysis was used to evaluate co-occurring childhood maltreatment exposures based on type and severity of exposures, which resulted in three homogenous sub-groups. The first subgroup was composed of individuals that had high levels of physical abuse exposure and moderate levels of childhood neglect and emotional abuse exposures (high physical abuse sub-group). The second sub-group (high sexual abuse sub-group) included individuals with high severity of sexual abuse exposure and moderate severity of all other childhood maltreatment types (i.e., physical abuse, emotional abuse, and neglect). This second sub-group was, therefore, the most vulnerable in terms of their childhood maltreatment exposure. A final normative sub-group was also found that included a majority of individuals with low severity of childhood maltreatment exposure across types. Additionally, across all three studies, a probabilistic multifaceted genetic risk score (i.e., polygenic risk score) was created to evaluate substance use related genetic risk. The first study evaluated the role of co-occurring childhood maltreatment exposure on substance use development from adolescence to young adulthood while evaluating substance use related genetic moderation. Generalized estimating equations were used to test the proposed model in study 1. Findings suggest that the high physical abuse sub-group was more susceptible to genetic risk and had increases in substance use frequency only at high levels of genetic risk. In contrast, for the high sexual abuse sub-group, childhood maltreatment and environmental exposures were more ubiquitous for substance use development from adolescence to young adulthood. To elaborate, the high sexual abuse sub-group demonstrated increases in substance use from adolescence to young adulthood irrespective of genetic risk. In study 2, substance use frequency in young adulthood was tested as a mechanism between childhood maltreatment sub-groups and subsequent physical intimate partner violence perpetration in adulthood. Once again, genetic moderation for the direct association between childhood maltreatment sub-groups and substance use frequency in young adulthood was tested within the larger mediation model. In study 3, physical partner violence victimization in young adulthood was tested as a mediator of the association between childhood maltreatment sub-groups and substance use frequency in adulthood. In study 3, in addition to the above-mentioned genetic risk score, an additional substance use related dopamine polygenic risk score was also tested. Specifically, in study 3, genetic moderation by both genetic risk scores was tested on 1) the direct pathway from childhood maltreatment sub-groups to substance use frequency in adulthood, and 2) the direct pathway from physical intimate partner violence victimization in young adulthood to substance use frequency in adulthood. In both studies 2 and 3, product of co-efficient method was used to estimate mediation hypothesis, and moderated-mediation models were used to test for genetic moderation within the mediation model. Research aims for studies 2 and 3 were largely not supported. However, supplementary models indicate that substance use frequency may not be a causal mechanism but may be a contextual factor exacerbating the association between childhood maltreatment exposures and physical intimate partner violence perpetration. Implications for findings are discussed in detail

Benefits: Tradition of Use, Experimental Models and Human Studies to Support Health Claims of Botanicals

Making health claims for botanical and plant food supplements (PFS) requires serious investigation and a collection of scientific evidence. The present chapter summarizes different aspects that should be considered for the evaluation of PFS benefits. Well-designed translational in vitro methods combined with human studies provide the best predictive information about their efficacy and safety. In vitro studies should rely on the most predictable cellular model to investigate the molecular mechanisms underlying the biological effect, based on approved standard operating protocols. Studies in the scientific literature generally do not consider the metabolic conversion of PFS and their active principles, as well as the chemical preparation of the extracts. To obtain the highest relevance for health claims, human studies should always describe inclusion criteria, group size, characterization of the intervention material, the control, blinding, duration of intervention and the reporting of study events. Furthermore, suitable use of in vivo validated biomarkers must be combined with large intervention studies to support health benefit of PFS