How Subjective and Objective Factors in Research and Practice May Perpetuate Health Disparities Among Patients With Traumatic Brain Injury.

ABSTRACT: Research shows disparities exist in traumatic brain injury (TBI)-related outcomes and are associated with objective and subjective factors. Objective factors (e.g., age, sex, race/ethnicity, health insurance status, and socioeconomic status) are defined as variables that are frequently measured, not easily modifiable, and not easily influenced by individual perceptions, opinions, or experiences. Conversely, subjective factors (e.g., personal health literacy, cultural competence, patient/family-clinician communication, implicit bias, and trust) are defined as variables that may be less frequently measured, more easily modifiable, and more easily influenced by individual perceptions, opinions, or experiences. The purpose of this analysis and perspective is to provide recommendations for further examination of subjective factors within TBI research and practice, with the overarching goal of reducing TBI-related disparities. Establishing reliable and valid measures of subjective factors is recommended to allow for further examination of the influence of both objective factors and subjective factors in the TBI population. Providers and researchers must also engage in education and training to recognize their biases and how bias influences decision making. The influence of subjective factors in practice and research must also be considered to ensure that knowledge needed to advance health equity is generated and disparities in outcomes for patients with TBI are reduced.

Investigation of insulin loaded self-assembled microtubules for drug release.

Self-assembled microtubules were used to entrap insulin for the preparation of new drug delivery devices. The interactions of insulin with the microtubules were probed by circular dichroism, zeta potential analysis, as well as FTIR spectroscopy. The morphologies of the insulin-loaded tubules were examined by AFM and TEM. We found that insulin loading was both pH- as well as concentration-dependent. The circular dichroism analysis indicated that, at pH range 6-7, the conformation change in the presence of the microtubules was minimal and hence would be the most appropriate conditions for insulin loading. The entrapment efficiency and release of insulin was found to be pH-dependent. Further, the controlled drug release studies indicated that, under acidic conditions, insulin release was extremely slow, and it is likely that the insulin is protected inside the microtubules. Thus, the microtubules may potentially protect the insulin from aggregation and release at lower pH (gastric pH) in ViVo. However, at pH 6.5 (closer to intestinal pH) a sustained release was observed. Such new materials may inhibit the aggregation of peptides under suitable conditions and potentially be used for drug delivery, in particular, for other peptide-based drugs.

Nanoformulation enhances anti-angiogenic efficacy of tunicamycin.

Nanoparticles (<100 nm) evades the immune system's clearing mechanisms long enough to reach the targeted disease tissue efficiently. We have, therefore, hypothesized that nano-formulated Tunicamycin would have a better efficacy and consequently it will be a better candidate for treating solid tumor including breast cancer in the clinic. Tunicamycin, a potent inhibitor of asparagine-linked (N-linked) protein glycosylation has been found earlier (I) inhibits angiogenesis in vitro by arresting cells in G1; (II) in vivo angiogenesis in Matrigel™ implant in nude mice; and (III) prevents the progression of a double- and a triple-negative breast tumor in athymic nude mice by inducing "ER stress" in tumor microvasculature. Tunicamycin could work alone or in combination with radiation/radiotherapy. To evaluate nano-formulated Tunicamycin, we have synthesized Tunicamycin encapsulated in peptide nanotubes, nanotubes bound to gold nanoparticles (Au NPs) conjugated with Tunicamycin, Tunicamycin conjugated with nanotubes, Au NPs bound to tubes and conjugated with Tunicamycin, and Au NPs conjugated with Tunicamycin. Functionalization of the nanoparticles was characterized by transmission electron microscopy (TEM), Fourier Transformed Infrared (FTIR) Spectroscopy, dynamic light scattering, atomic force microscopy (AFM), and absorbance spectroscopy. The 3-(4,5-methylthiazol-2-yl)-2,5-dipheyl-tetrazolium bromide (MTT) assay indicated that nanoparticles (1 µg/mL) inhibited capillary endothelial cells proliferation, i.e., angiogenesis ~50% within one hour of treatment whereas the native Tunicamycin had no effect. The nano-formulated Tunicamycin blocked the cell cycle progression by inhibiting either both cyclin D1 and CDK4, or cyclin D1, or the CDK4 expression as well as the expression of phospho Rb (serine-229/threonine-252). Phosphorylation of p53 at serine-392 was down-regulated but not the total p53. Increased expression of GRP-78/Bip identified "ER stress". Upregulated expression (1.6-5.5 fold) of phopsho-PERK and significant reduction of mannosylphospho dolichol synthase (DPMS) expression supported induction of unfolded protein response (upr) signaling. Down regulated expression of caspase-9 and caspase-3 proposes a non-canonical pathway of cell death during "ER stress" induced by nano-formulated Tunicamycin.

Self-assembled nanofibers from leucine derived amphiphiles as nanoreactors for growth of ZnO nanoparticles.

We report a new method for the green synthesis of ZnO nanoparticles. A new leucine-based diamine amphiphile was synthesized and self-assembled, which in the presence of Zn(2+) ions assembled into nanofibers, that efficiently formed ZnO nanoparticles upon heating in the presence of Zn(CH(3)COO)(2). Further, these ZnO nanoparticles functioned as efficient photocatalysts.