"I'm putting a Band-Aid on a bullet hole the only way I know how:" a qualitative study of barriers and facilitators to opioid misuse and recovery in Nevada.

Nevada, like the rest of the United States, is undergoing substantial challenges with opioid misuse and overdose deaths, further exacerbated by the COVID-19 pandemic. While much of the attention around opioid overdose prevention is centered on treatment and recovery, it is important to understand the factors that influence initiation of use, and the function opioids play in people's everyday lives. We conducted qualitative semi-structured individual interviews using purposive and snowball sampling among 35 people across Nevada with a current or prior history of illegal opioid or nonmedical opioid use. Our study aimed to understand why people start to use drugs, why they continue to use, what motivates them to continue to use or to seek treatment, and why individuals maintain recovery or return to use. We found five significant themes as perceived by the participants: that trauma is a risk factor for drug misuse; that the function of opioids in everyday life is a source of temporary relief but highly disruptive in the longer term; that recovery is most often a complicated and nonlinear process; that there are many barriers to accessing services that are both logistical and psychosocial; and that compassion, hope, and having a sense of purpose are crucial to the recovery process. The experiences of the study participants portray opioid use as a rational choice to escape the emotional ramifications of trauma. However, due to the physiological dependence and physical risk of opioids, drug policies that criminalize addiction, societal stigma, and the barriers to timely access of harm reduction, treatment, and recovery services, opioid users often become trapped in a distressing and dangerous cycle. Lastly, respondents indicated that hope, value, belonging, and purpose are powerful factors in cultivating intrinsic motivation for making positive changes and fostering resilience in the recovery process. Opioid misuse services should help meet basic needs and incorporate holistic approaches to recovery that acknowledge past trauma and the complexity of the recovery process.

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate-induced apoptosis.

Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alters MCF-7 and MDA-MB-231 cell metabolism and promotes proliferation and migration. Since adipocytes are FA-rich, and these FAs are transferred to BrCa cells, we sought to elucidate the FA metabolism of BrCa cells and their response to FA-rich environments. MCF-7 and MDA-MB-231 cells incubated in serum-containing media supplemented with FAs accumulate extracellular FAs as intracellular triacylglycerols (TAG) in a dose-dependent manner, with MDA-MB-231 cells accumulating more TAG. The differences in TAG levels were a consequence of distinct differences in intracellular partitioning of FAs, and not due to differences in the rate of FA uptake. Specifically, MCF-7 cells preferentially partition FAs into mitochondrial oxidation, whereas MDA-MB-231 cells partition FAs into TAG synthesis. These differences in intracellular FA handling underpin differences in the sensitivity to palmitate-induced lipotoxicity, with MDA-MB-231 cells being highly sensitive, whereas MCF-7 cells are partially protected. The attenuation of palmitate-induced lipotoxicity in MCF-7 cells was reversed by inhibition of FA oxidation. Pretreatment of MDA-MB-231 cells with FAs increased TAG synthesis and reduced palmitate-induced apoptosis. Our results provide novel insight into the potential influences of obesity on BrCa biology, highlighting distinct differences in FA metabolism in MCF-7 and MDA-MB-231 cells and how lipid-rich environments modulate these effects.

Sustained User Engagement in Health Information Technology: The Long Road from Implementation to System Optimization of Computerized Physician Order Entry and Clinical Decision Support Systems for Prescribing in Hospitals in England.

OBJECTIVE: To explore and understand approaches to user engagement through investigating the range of ways in which health care workers and organizations accommodated the introduction of computerized physician order entry (CPOE) and computerized decision support (CDS) for hospital prescribing. STUDY SETTING: Six hospitals in England, United Kingdom. STUDY DESIGN: Qualitative case study. DATA COLLECTION: We undertook qualitative semi-structured interviews, non-participant observations of meetings and system use, and collected organizational documents over three time periods from six hospitals. Thematic analysis was initially undertaken within individual cases, followed by cross-case comparisons. FINDINGS: We conducted 173 interviews, conducted 24 observations, and collected 17 documents between 2011 and 2015. We found that perceived individual and safety benefits among different user groups tended to facilitate engagement in some, while other less engaged groups developed resistance and unsanctioned workarounds if systems were perceived to be inadequate. We identified both the opportunity and need for sustained engagement across user groups around system enhancement (e.g., through customizing software) and the development of user competencies and effective use. CONCLUSIONS: There is an urgent need to move away from an episodic view of engagement focused on the preimplementation phase, to more continuous holistic attempts to engage with and respond to end-users.