Informing Acceptability and Feasibility of Digital Phenotyping for Personalized HIV Prevention among Marginalized Populations Presenting to the Emergency Department.

For marginalized populations with ongoing HIV epidemics, alternative methods are needed for understanding the complexities of HIV risk and delivering prevention interventions. Due to lack of engagement in ambulatory care, such groups have high utilization of drop-in care. Therefore, emergency departments represent a location with those at highest risk for HIV and in highest need of novel prevention methods. Digital phenotyping via data collected from smartphones and other wearable sensors could provide the innovative vehicle for examining complex HIV risk and assist in delivering personalized prevention interventions. However, there is paucity in exploring if such methods are an option. This study aimed to fill this gap via a cross-sectional psychosocial assessment with a sample of N=85 emergency department patients with HIV risk. Findings demonstrate that although potentially feasible, acceptability of digital phenotyping is questionable. Technology-assisted HIV prevention needs to be designed with the target community and address key ethical considerations.

Rational Molecular Designing of Aggregation-Enhanced Emission (AEE) Active Red-Emitting Iridium(III) Complexes: Effect of Lipophilicity and Nanoparticle Encapsulation on Photodynamic Therapy Efficacy.

Two "aggregation-enhanced emission" (AEE) active cyclometalated phosphorescent iridium(III) complexes, SM2 and SM4, were synthesized to evaluate the influence of lipophilicity on photodynamic therapy efficacy. Compared to SM2, SM4 had a higher logP due to the presence of naphthyl groups. As observed by confocal microscopy, this increased lipophilicity of SM4 significantly enhanced its cellular uptake in breast cancer cells. Both the molecules were found to be noncytotoxic under nonirradiating conditions. However, with light irradiation, SM4 exhibited significant cytotoxicity at a 500 nM dose, whereas SM2 remained noncytotoxic, signifying the influence of lipophilicity on cellular internalization and cytotoxicity. Mechanistically, light-irradiated SM4-treated cancer cells exhibited a significant increase in the intracellular reactive oxygen species (ROS) level. Neutralizing ROS with N-acetylcysteine (NAC) pretreatment partly abolished the cytotoxic ability, indicating ROS as one of the major effectors of cell cytotoxicity. Two nanoparticle (NP) formulations of SM4 were developed to improve the intracellular delivery: a PLGA-based NP and a Soluplus-based micelle. Interestingly, PLGA and Soluplus NP formulations exhibited a 10- and 22-fold increased emission intensity, respectively, compared to SM4. There was also an increase in the excited-state lifetime. Additionally, the Soluplus-based micelles encapsulating SM4 exhibited enhanced cellular uptake and increased cytotoxicity compared to the PLGA NPs encapsulating SM4. Altogether, the current study indicates the importance of rational molecular designing and the significance of a proper delivery vector for improving photodynamic therapy efficacy.

Interleukin-6 Induced Proliferation Is Attenuated by Transforming Growth Factor-ß-Induced Signaling in Human Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is often associated with an inflammatory setting. A plethora of cytokines are secreted in this milieu, actively contributing to the progression of the disease; however, the extent of cytokine interaction and how it contributes to HCC development remains an enigma. In this regard, our analysis of available patient-derived data suggests that cytokines like interleukin-6 (IL-6) and transforming growth factor-beta (TGF-ß) are enriched in HCC. We further analyzed the effect of these cytokines independently or in combination on HCC cells. Importantly, IL-6 was found to induce a STAT-3-dependent proliferation and mediate its pro-proliferative effects through activation and direct interaction with the p65 subunit of NFkB. Alternatively, TGF-ß was found to induce a SMAD-dependent induction of epithelial to mesenchymal transition (EMT) coupled to growth arrest in these cells. Interestingly, the simultaneous addition of IL-6 and TGF-ß failed to profoundly impact EMT markers but resulted in attenuation of IL-6-induced pro-proliferative effects. Analysis of the putative molecular mechanism revealed a decrease in IL-6 receptor (IL-6R) transcript levels, reduced expression of IL-6-induced STAT-3, and its nuclear localization upon addition of TGF-ß along with IL-6. Consequently, a reduced p65 activation was also observed in combination treatment. Importantly, SMAD levels were unperturbed and the cells showed more TGF-ß-like features under combination treatment. Finally, we observed that TGF-ß resulted in enrichment of repressive chromatin mark (H3K27me3) coupled to growth arrest, while IL-6 induced an open chromatin signature (H3K4me3) associated with an enhanced expression of EZH2. Overall, for the first time, we show that TGF-ß attenuates IL-6-induced effects by regulating the receptor level, downstream signaling, and the epigenome. Understanding the complex interactions between these cytokines can be imperative to a better understanding of the disease, and manipulation of cytokine balance can act as a prospective future therapeutic strategy.

Implementation of an expanded point-of-care site inspection checklist in an academic medical center: An eight year experience.

BACKGROUND: We evaluated the effectiveness of an expanded point-of-care (POCT) site inspection checklist over an extended 8-y period. METHODS: A retrospective review of site inspection deficiency reports in a large academic medical center from 2010 to 2017 (year to date). RESULTS: There was a significant decrease in the number of cited deficiencies per site/inspection from 2010 (3.17) to 2017 (0.27) (p<0.001). The percentage of sites without deficiencies steadily increased from 2010 (8.7%) to 2017 (80.7%) (p<0.001). The most common citation was documentation of competency assessment followed by results documentation and annual procedure review. CONCLUSIONS: Regular inspections of sites performing POCT are necessary to maintain regulatory compliance. Over time significant improvements in compliance are achievable.