Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (i.e. quicker and higher peak concentrations). Here, we evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic the clinical drug delivery profile. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60 mg/kg/day; as well as dual-dosages of 4 and 10 mg/kg/day, 20 and 30 mg/kg/day, or 30 and 60 mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Blood was sampled and plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60 mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30 ng/mL), while the 4/10 mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8 ng/mL). Treatment with the higher dual-dosage (HD: 30/60 mg/kg) resulted in hyperactivity, while the lower (LD: 4/10 mg/kg) had no effect. Next, chronic effects of these dual-dosages were assessed on behavior throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle; decreased exploratory behavior; and increased anxiolytic behavior. These findings suggest that this dual-dosage-drinking-paradigm can be used to examine the effects of clinically relevant pharmacokinetic doses of MP, and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes.

Our results suggest that health care professionals should monitor the drinking habits of retired men, as older individuals are particularly susceptible to the adverse effects of heavy alcohol use.

Objective: To document COVID-19 sero-prevalence, prior testing, symptom experiences, and risk factors in a sample of community health center (CHC) workers. Methods: Descriptive statistics and log-binomial regression were used to analyze an electronic employee survey linked with COVID-19 antibody results. The sample included 378 employees who completed the survey; 325 had complete lab data. Results: The sero-positivity rate was 15.4%. One third of sero-positive participants had no previous COVID-19 symptoms or were unsure. Working on-site only and/or with direct patient contact was not associated with sero-positivity. Employees in their 20s were more likely to test positive than employees ages 50+, controlling for sex, race, and region (PR = 2.96; P < 0.05). Conclusions: With CHCs central to COVID-19 response and vaccination efforts, public health messaging should remind CHC workers, especially younger employees, of their risks of community-based exposure.