Eliminating disparities in youth substance use among Native Hawaiian, Micronesian, and sex and gender minorities: A qualitative needs assessment from interviews with public service leaders.

Youth substance use (SU) has been linked to adverse mental health outcomes. For those youth involved in public sector systems of care, reports of SU are consistently high compared to general populations. These public sector services systems of care include mental health, juvenile justice, child welfare, homeless intervention services, as well as SU service systems. In addition, minority and marginalized youth tend to report disproportionately high SU. As an example, in Hawai'i, youth who are Native Hawaiian (NH), Micronesian, or who identify as sexual or gender minorities not only report elevated rates of SU, but are overrepresented in public sectors. In order to reduce youth SU health disparities, access to and quality of the system of care for youth must improve. To inform systems change, this needs assessment study used qualitative methods to engage professionals in Hawai'i working within public sectors that may intersect with youth SU service system of care. Professionals identified several themes which have implications for practice, policy, and research: colonialism and inclusivity at the macro level, the need for policies at the exo level, meso level changes regarding family and community, and stigma and discrimination at the micro level. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Emerging Adulthood Attributes, Discrimination, Mental Health, and Substance Use in a Sample of Asian, Native Hawaiian/Pacific Islander, and White College Students.

Although Asian/Pacific Islanders are considered a single ethnic/racial category in national studies, Native Hawaiians/other Pacific Islanders (NHOPIs) and Asians show marked disparities in health outcomes and risk behaviors, including substance use. Currently, knowledge regarding the psychosocial mechanisms by which NHOPI ethnicity is associated with increased substance use, compared with Asian or White, is limited, especially among emerging adults. The present study tested a model in which the relationship between NHOPI ethnicity and higher substance use (i.e., current tobacco, alcohol, marijuana, and illicit drug use) was hypothesized to be mediated through higher emerging adulthood stress (e.g., feeling "in-between," instability), higher self-reported racial/ethnic discrimination, substance use in one's social networks, and poorer mental health symptomology (i.e., depression, anxiety). Data collected at a single time-point from 2,344 college students (M age = 21.2 [SD = 2.1]; 54% Women; 24% NHOPI, 49% Asian, 27% White) were analyzed by employing structural equation modeling. NHOPI and Asian ethnicity were dummy coded with reference to White, and separate analyses were run for NHOPI and Asian groups, with White as the reference group. Results indicated that the association between NHOPI ethnicity and higher substance use was mediated in two steps, via higher racial/ethnic discrimination and poorer mental health symptomatology. NHOPI ethnicity, but not Asian, was associated with higher identification with emerging adulthood attributes, which in turn was associated with increased substance use. Implications are discussed in the context of reducing health disparities faced by NHOPIs.

A designer bow-tie combination therapeutic platform: An approach to resistant cancer treatment by simultaneous delivery of cytotoxic and anti-inflammatory agents and radiation.

Multimodal therapies are used to treat advanced cancers including castration-resistant prostate cancer to manage the biological characteristics of the tumors like inflammation, bone metastases, and participation of metabolically altered cancer stem cells (CSCs) that have integral roles in disease dissemination and progression. We developed a multifunctional polymer-based self-assembled technology to deliver a predefined stoichiometric combination of a chemotherapy and an anti-inflammatory agent in a stimuli responsive manner, to complement and improve the currently established treatment methods of prostate cancer. We combined clinically applicable fractionated radiation therapy (XRT) to further sensitize the activity of this targeted multifunctional platform towards prostate-specific membrane antigen (PSMA) expressing advanced prostate cancer. After irradiation, our PSMA-targeted self-assembly system could modulate the mitochondrial metabolism, cellular respiration and the overall radiation-induced DNA damage process. We report the synthesis of this advanced multifunctional platform and describe its unique properties that allow the ability to load multiple FDA approved drugs with a predefined stoichiometric ratio for targeted co-delivery of chemotherapeutics and anti-inflammatory agents. The efficacy of this platform was demonstrated using several in vitro and in vivo studies, in a unique bilateral PSMA expressing prostate cancer tumor model, and in patient derived CSCs.

Large-scale production of lentiviral vector in a closed system hollow fiber bioreactor.

Lentiviral vectors are widely used in the field of gene therapy as an effective method for permanent gene delivery. While current methods of producing small scale vector batches for research purposes depend largely on culture flasks, the emergence and popularity of lentiviral vectors in translational, preclinical and clinical research has demanded their production on a much larger scale, a task that can be difficult to manage with the numbers of producer cell culture flasks required for large volumes of vector. To generate a large scale, partially closed system method for the manufacturing of clinical grade lentiviral vector suitable for the generation of induced pluripotent stem cells (iPSCs), we developed a method employing a hollow fiber bioreactor traditionally used for cell expansion. We have demonstrated the growth, transfection, and vector-producing capability of 293T producer cells in this system. Vector particle RNA titers after subsequent vector concentration yielded values comparable to lentiviral iPSC induction vector batches produced using traditional culture methods in 225 cm(2) flasks (T225s) and in 10-layer cell factories (CF10s), while yielding a volume nearly 145 times larger than the yield from a T225 flask and nearly three times larger than the yield from a CF10. Employing a closed system hollow fiber bioreactor for vector production offers the possibility of manufacturing large quantities of gene therapy vector while minimizing reagent usage, equipment footprint, and open system manipulation.