Folate-Binding Protein Self-Aggregation Drives Agglomeration of Folic Acid Targeted Iron Oxide Nanoparticles.

Folate-conjugated nanomaterials have been widely investigated for drug and imaging-agent delivery. In this work, two folic acid (FA) conjugated iron oxide particles (IOP), a ∼40 nm diameter FA-IOP and a ∼450 nm diameter FA-IOP(FA-SeraMag), were synthesized. Both particles aggregated in the presence of serum folate-binding protein (FBP) at physiological concentration and buffer conditions. Mixing 0.01% w/w FA-conjugated iron oxide particles with FBP-induced agglomeration generated an average hydrodynamic particle diameter of 3800 ± 1100 nm for ∼40 nm FA-IOP and 4030 ± 1100 nm for FA-SeraMag as measured by dynamic light scattering (DLS). The presence of excess human serum albumin (HSA) (600 µM) did not prevent agglomeration of the ∼40 nm FA-IOP; however, it did inhibit agglomeration of FA-SeraMag. Atomic force microscopy measurement provided additional insight into particle morphology with the detection of individual particles in the agglomerate. This behavior is an example of a triggered cascade. A protein structural change is induced by FA binding, and the structural change favors aggregation of the ∼4 nm diameter FBPs on the particle surface; this further triggers the agglomeration of both the ∼40 and ∼450 nm diameter IOPs.

The impact of historical trauma on health outcomes for indigenous populations in the USA and Canada: A systematic review.

Beginning in the mid-1990s, the construct of historical trauma was introduced into the clinical and health science literatures to contextualize, describe, and explain disproportionately high rates of psychological distress and health disparities among Indigenous populations. As a conceptual precursor to racial trauma, Indigenous historical trauma (IHT) is distinguished by its emphasis on ancestral adversity that is intergenerationally transmitted in ways that compromise descendent well-being. In this systematic review of the health impacts of IHT, 32 empirical articles were identified that statistically analyzed the relationship between a measure of IHT and a health outcome for Indigenous samples from the United States and Canada. These articles were categorized based on their specific method for operationalizing IHT, yielding 19 articles that were grouped as historical loss studies, 11 articles that were grouped as residential school ancestry studies, and three articles that were grouped as "other" studies. Articles in all three categories included diverse respondents, disparate designs, varied statistical techniques, and a range of health outcomes. Most reported statistically significant associations between higher indicators of IHT and adverse health outcomes. Analyses were so complex, and findings were so specific, that this groundbreaking literature has yet to cohere into a body of knowledge with clear implications for health policy or professional practice. At the conceptual level, it remains unclear whether IHT is best appreciated for its metaphorical or literal functions. Nevertheless, the enthusiasm surrounding IHT as an explanation for contemporary Indigenous health problems renders it imperative to refine the construct to enable more valid research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).