The time course of processing emotion-laden words during sentence reading: Evidence from eye movements.

While recent research has explored the effect that positive and negative emotion words (e.g., happy or sad) have on the eye-movement record during reading, the current study examined the effect of positive and negative emotion-laden words (e.g., birthday or funeral) on eye movements. Emotion-laden words do not express a state of mind but have emotional associations and connotations. The current results indicated that both positive and negative emotion-laden words have a processing advantage over neutral words, although the relative time-course of processing differs between words of positive and negative valence. Specifically, positive emotion-laden words showed advantages in early, late, and post-target measures, while negative emotion-laden words showed effects only in late and post-target measures.

The Mixed Opioid Receptor Antagonist Naltrexone Mitigates Stimulant-Induced Euphoria: A Double-Blind, Placebo-Controlled Trial of Naltrexone.

OBJECTIVE: Supratherapeutic doses of methylphenidate activate µ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed µ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate (January 2013 to June 2015). Spheroidal Oral Drug Absorption System methylphenidate (SODAS-MPH) was administered twice daily, was titrated to ~1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate-release methylphenidate (IR-MPH). The primary outcome measure was Question 2 (Liking a Drug Effect) on the Drug Rating Questionnaire, Subject version, which was assessed after oral test doses of 60 mg of IR-MPH were administered after the third and sixth weeks of treatment with SODAS-MPH. RESULTS: Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS-MPH and randomized to naltrexone 50 mg/d or placebo. Thirty-one subjects completed through week 3, and 25 completed through week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened-risk titration phase (primary outcome; first 3 weeks) (χ² = 5.07, P = .02) but not the maintenance phase (weeks 4-6) (χ² = 0.22, P = .64) of SODAS-MPH treatment. CONCLUSIONS: Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01673594.

Opiate Antagonists Do Not Interfere With the Clinical Benefits of Stimulants in ADHD: A Double-Blind, Placebo-Controlled Trial of the Mixed Opioid Receptor Antagonist Naltrexone.

OBJECTIVE: Methylphenidate activates µ-opioid receptors, which are linked to euphoria. µ-Opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. This study assessed whether the combination of naltrexone with methylphenidate is well-tolerated while preserving the clinical benefits of stimulants in subjects with attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate from January 2013 to July 2015. Spheroidal Oral Drug Absorption System (SODAS) methylphenidate was administered twice daily, was titrated to approximately 1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with a test dose of immediate-release methylphenidate. The primary outcome measure was the Adult ADHD Investigator Symptom Report Scale (AISRS). RESULTS: Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS methylphenidate and randomly assigned to naltrexone 50 mg or placebo. Thirty-one subjects completed the study through week 3, and 25 completed through week 6. Throughout 6 weeks of blinded naltrexone and open methylphenidate treatment, the coadministration of naltrexone with methylphenidate did not interfere with the clinical effectiveness of methylphenidate for ADHD symptoms. Additionally, the combination of naltrexone and methylphenidate did not produce an increase in adverse events compared with methylphenidate alone. CONCLUSIONS: Our findings provide support for the concept of combining opioid receptor antagonists with stimulants to provide an effective stimulant formulation with less abuse potential. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01673594​.

A scale to measure pharmacy students' self-efficacy in performing medication therapy management services.

OBJECTIVE: To determine whether a college of pharmacy curriculum creates a sense of self-efficacy among students with respect to providing medication therapy management (MTM) services. METHODS: An electronic survey instrument was sent to all pharmacy students to elicit information on their perceived confidence in providing MTM services, and the results were reviewed. RESULTS: Of the 1,160 students targeted, 464 (40%) completed the survey instrument. Responses indicated that overall self-efficacy increased with each successive year of the curriculum that students completed. Fourth-year students completing an advanced pharmacy practice experience (APPE) in medication therapy management (MTM) had significantly higher self-efficacy than did other fourth-year students, whose self-efficacy was similar to that of third-year students. conclusion: In this study population, students' self-efficacy increased with each successive year in pharmacy school, with those who completed an APPE in MTM exhibiting the highest level of self-efficacy. These students may be more likely to pursue MTM opportunities in future careers.

An advanced pharmacy practice experience in a student-staffed medication therapy management call center.

OBJECTIVE: To describe the implementation of an advanced pharmacy practice experience (APPE) in medication therapy management (MTM) designed to contribute to student pharmacists' confidence and abilities in providing MTM. DESIGN: Sixty-four student pharmacists provided MTM services during an APPE in a communication and care center. ASSESSMENT: Students conducted 1,495 comprehensive medication reviews (CMRs) identifying 6,056 medication-related problems. Ninety-eight percent of the students who completed a survey instrument (52 of 53) following the APPE expressed that they had the necessary knowledge and skills to provide MTM services. Most respondents felt that pharmacist participation in providing Medicare MTM could move the profession of pharmacy forward and that pharmacists will have some role in deciding the specific provisions of the Medicare MTM program (92% and 91%, respectively). CONCLUSION: Students completing the MTM APPE received patient-centered experiences that supplemented their confidence, knowledge, and skill in providing MTM services in the future.

Input-dependent induction of oligonucleotide structural motifs for performing molecular logic.

The K(+)-H(+)-triggered structural conversion of multiple nucleic acid helices involving duplexes, triplexes, G-quadruplexes, and i-motifs is studied by gel electrophoresis, circular dichroism, and thermal denaturation. We employ the structural interconversions for perfoming molecular logic operations, as verified by fluorimetry and colorimetry. Short G-rich and C-rich cDNA and RNA single strands are hybridized to produce four A-form and B-form duplexes. Addition of K(+) triggers the unwinding of the duplexes by inducing the folding of G-rich strands into DNA- or RNA G-quadruplex mono- and multimers, respectively. We found a decrease in pH to have different consequences on the resulting structural output, depending on whether the C-rich strand is DNA or RNA: while the protonated C-rich DNA strand folds into at least two isomers of a stable i-motif structure, the protonated C-rich RNA strand binds a DNA/RNA hybrid duplex to form a Y·RY parallel triplex. When using K(+) and H(+) as external stimuli, or inputs, and the induced G-quadruplexes as reporters, these structural interconversions of nucleic acid helices can be employed for performing logic-gate operations. The signaling mode for detecting these conversions relies on complex formation between DNA or RNA G-quadruplexes (G4) and the cofactor hemin. The G4/hemin complexes catalyze the H(2)O(2)-mediated oxidation of peroxidase substrates, resulting in a fluorescence or color change. Depending on the nature of the respective peroxidase substrate, distinct output signals can be generated, allowing one to operate multiple logic gates such as NOR, INH, or AND.