Preceptor perceptions of contemporary practice skills among new graduates amid community pharmacy transformation.

INTRODUCTION: With community pharmacy transitioning from a fee-for-service model to a value-based care focus, the desired skills of pharmacist graduates is an evolving paradigm. As active stakeholders in community practice, pharmacist preceptors are in a unique position to compare the ever-changing dichotomy between pharmacy practice and training. Examining preceptors' assessments of these essential contemporary practice skills may provide useful insights. METHODS: A survey was emailed to all regional, active college of pharmacy community advanced pharmacy practice experiences preceptors. Participating preceptors were given 30 days to complete the online survey. Weekly reminders were provided. RESULTS: Of the 168 preceptors invited to participate, 42 (25%) completed the survey. Descriptive analysis compared preceptors' perceptions of transformative services vs. their relative implementation in practice. This revealed service areas such as health screenings that were proportionate in their prevalence of offering and perception as contemporary. In contrast, services such as pharmacogenomic testing were more widely perceived as contemporary compared to their low prevalence as an offering. Participants showed broad consensus in the importance of most skills listed in the survey, predominantly indicating these skills were either "very important" or "extremely important." Only a few specific skills areas were identified that showed less consensus, with a minority of respondents specifying that these skills were of less importance. CONCLUSIONS: Preceptor surveys may offer insights on the progression of community practice curricula. Continued monitoring of changes in service parameters over time may reveal trends in practice transformation, identifying service areas being more widely adopted.

Chronic methylphenidate induces increased quinone production and subsequent depletion of the antioxidant glutathione in the striatum.

BACKGROUND: Methylphenidate (Ritalin®) is a psychostimulant used chronically to treat attention deficit hyperactivity disorder. Methylphenidate acts by preventing the reuptake of dopamine and norepinephrine, resulting in an increase in these neurotransmitters in the synaptic cleft. Excess dopamine can be autoxidized to a quinone that may lead to oxidative stress. The antioxidant, glutathione helps to protect the cell against quinones via conjugation reactions; however, depletion of glutathione may result from excess quinone formation. Chronic exposure to methylphenidate appears to sensitize dopaminergic neurons to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We hypothesized that oxidative stress caused by the autooxidation of the excess dopamine renders dopaminergic neurons within the nigrostriatal pathway to be more sensitive to MPTP. METHODS: To test this hypothesis, male mice received chronic low or high doses of MPH and were exposed to saline or MPTP following a 1-week washout. Quinone formation in the striatum was examined via dot blot, and striatal GSH was quantified using a glutathione assay. RESULTS: Indeed, quinone formation increased with increasing doses of methylphenidate. Additionally, methylphenidate dose-dependently resulted in a depletion of glutathione, which was further depleted following MPTP treatment. CONCLUSIONS: Thus, the increased sensitivity of dopamine neurons to MPTP toxicity following chronic methylphenidate exposure may be due to quinone production and subsequent depletion of glutathione.

Neurogenesis within the hippocampus after chronic methylphenidate exposure.

Methylphenidate is a psychostimulant used to treat attention deficit hyperactivity disorder. Neurogenesis occurs throughout adulthood within the dentate gyrus of the hippocampus and can be altered by psychoactive medications; however, the impact of methylphenidate on neurogenesis is not fully understood. We investigated the effects of chronic low (1 mg/kg) and high (10 mg/kg) intraperitoneal doses of methylphenidate on neurogenesis in mouse hippocampus following 28 days and 56 days of treatment. Interestingly, methylphenidate, at both doses, increased neurogenesis. However, if methylphenidate treatment was not continued, the newly generated cells did not survive after 28 days. If treatment was continued, the newly generated neurons survived only in the mice receiving low-dose methylphenidate. To investigate the mechanism for this effect, we examined levels of proteins linked to cell proliferation in the hippocampus, including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), tropomyosin receptor kinase B (TrkB), and beta-catenin. BDNF or GDNF levels were not significantly different between groups. However, hippocampal VEGF, TrkB, and beta-catenin were significantly increased in mice receiving low-dose methylphenidate for 28 days compared to controls. Interestingly, high-dose methylphenidate significantly decreased beta-catenin after 28 days and decreased VEGF, beta-catenin, and TrkB after 56 days compared to controls. Thus, low-dose methylphenidate appears to increase cell proliferation and cell survival in the hippocampus, and these effects may be mediated by increase in VEGF, TrkB, and beta-catenin. While high dose methylphenidate may initially increase neuronal proliferation, newly generated neurons are unable to survive long-term, possibly due to decrease in VEGF, TrkB and beta-catenin.