Associations Among Child Maltreatment, Mental Health, and Police Contact in Adulthood: Findings From a National Canadian Sample.

The purpose of this study was to examine associations between three subtypes of childhood maltreatment (physical abuse, sexual abuse, and exposure to intimate partner violence) and two forms of adult police contact (criminality, victimization) using nationally representative Canadian data. Presence of a mental health disorder was also explored as a potential mediating variable in these associations. The weighted sample included 23,846 adult participants from the 2012 Canadian Community Health Survey-Mental Health. Logistic and multinomial regression analyses examined associations among individual and multiple exposures to subtypes of childhood maltreatment with police contact. The Sobel test was used to assess the mediating effect of mental health disorders. Adjusting for sociodemographic variables, results indicated that all maltreatment subtypes were significantly associated with increased odds of both forms of police contact (adjusted odds ratios ranged from 2.06 to 2.95). Presence of a mental health disorder was a partial mediator in the associations between child maltreatment and both forms of adult police contact (adjusted odds ratios ranged from 1.52 to 2.32). In addition, a dose-response relationship was observed for victimization; as the number of subtypes of maltreatment increased, there was an incremental increase in risk of victimization. Future efforts are needed to prioritize child maltreatment prevention, trauma-informed approaches, mental health awareness, and training in law enforcement.

Dendritic Cells Cause Bone Lesions in a New Mouse Model of Histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disease caused by the clonal accumulation of dendritic Langerhans cells, which is often accompanied by osteolytic lesions. It has been reported that osteoclast-like cells play a major role in the pathogenic bone destruction seen in patients with LCH and these cells are postulated to originate from the fusion of DCs. However, due to the lack of reliable animal models the pathogenesis of LCH is still poorly understood. In this study, we have established a mouse model of histiocytosis- recapitulating human disease for osteolytic lesions seen in LCH patients. At 12 weeks after birth, severe bone lesions were observed in our multisystem histiocytosis (Mushi) model, when CD8α conventional dendritic cells (DCs) are transformed (MuTuDC) and accumulate. Most importantly, our study demonstrates that bone loss in LCH can be accounted for the transdifferentiation of MuTuDCs into functional osteoclasts both in vivo and in vitro. Moreover, we have shown that injected MuTuDCs reverse the osteopetrotic phenotype of oc/oc mice in vivo. In conclusion, our results support a crucial role of DCs in bone lesions in histiocytosis patients. Furthermore, our new model of LCH based on adoptive transfer of MuTuDC lines, leading to bone lesions within 1-2 weeks, will be an important tool for investigating the pathophysiology of this disease and ultimately for evaluating the potential of anti-resorptive drugs for the treatment of bone lesions.

Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes.

While current subunit vaccines successfully induce humoral immune responses, a need exists for vaccine strategies to elicit strong cell-mediated immunity to address diseases such as cancer and chronic viral infection. Polymersomes are stable vesicles composed of self-assembling block copolymers with tunable degradation properties allowing delivery of both hydrophilic (within vesicle interior) or hydrophobic (within vesicle membrane) payload molecules. Here we apply oxidation-sensitive nanoscale polymersomes for both antigen and adjuvant delivery to dendritic cell (DC) endosomes. Calcein-loaded polymersomes were observed to release their payload initially in multiple DC endosomal compartments and subsequently within the cytosol. With either the Toll-like receptor agonists gardiquimod or R848 as payloads within the polymersomes, release resulted in DC activation, as indicated by induction of inflammatory cytokine expression and upregulation of DC maturation surface markers: for example, the ability of gardiquimod to induce IL-6 and IL-12 cytokine expression by DCs was enhanced 10-fold when loaded within polymersomes. With the model antigen ovalbumin as a payload, release resulted in CD8(+) T cell cross-priming by promoting protein antigen cross-presentation through MHC I, as indicated by activation of OT-I CD8(+) T cells. Our results demonstrate that oxidation-sensitive polymersomes can function as a vaccine delivery platform for inducing cell-mediated antigen-specific immune responses.