Interactions Between Opioids and Dextroamphetamine on Locomotor Activity: Influence of an Opioid's Relative Efficacy at the Mu Receptor.

Opioids and stimulants are often used in combination for both recreational and non-recreational purposes. High-efficacy mu opioid agonists generally increase the behavioral effects of stimulants, whereas opioid receptor antagonists generally attenuate the behavioral effects of stimulants; however, less is known regarding the interactions between stimulants and opioids possessing low to intermediate efficacy at the mu receptor. The purpose of this study was to examine the role of an opioid's relative efficacy at the mu receptor in altering the behavioral effects of dextro(d-)amphetamine. To this end, opioids possessing a range of relative efficacy at the mu receptor were examined alone and in combination with cumulative doses of d-amphetamine on a test of open-field, locomotor activity in male rats. Levorphanol, buprenorphine, butorphanol, nalbuphine, (-)-pentazocine, (-)-metazocine, (-)-cyclazocine, (-)-NANM, and nalorphine increased the locomotor effects of d-amphetamine in either an additive or greater-than-additive manner according to an effect-additive model. Only the selective, high-efficacy kappa agonist, spiradoline, and the non-selective opioid receptor antagonist, naloxone, failed to increase the effects of d-amphetamine under the conditions examined. These data indicate that opioids possessing a large range of relative efficacy at the mu receptor, including those possessing very low relative efficacy, significantly increase the locomotor effects of d-amphetamine.

Physician and patient determinants of prognostic counseling in idiopathic REM sleep-behavior disorder.

OBJECTIVES/BACKGROUND: Prognostic counseling about the risk for developing overt neurodegenerative disorders for patients with idiopathic REM sleep-behavior disorder (iRBD) and isolated REM sleep without atonia (iRSWA) is difficult, given lack of disease-modifying interventions and uncertainty in accurate prognostication for individuals. We aimed to analyze patient and physician characteristics associated with documented prognostic discussions for patients with iRBD and iRSWA. PATIENTS/METHODS: We retrospectively reviewed the medical records for 138 (112 iRBD and 26 iRSWA) patients seen at the Mayo Clinic between 2012 and 2015. We analyzed physician and patient demographics, initial complaint, and other information discussed during office visits. We then comparatively analyzed the impact of physician and patient characteristics on documented prognostic discussions using Chi Square or Fischer's exact test. RESULTS: Mean iRBD patient age was 65.0 ± 13.0, and mean iRSWA age was 58 ± 15 years. Seventy-eight (69.6%) iRBD and 22 (84.6%) iRSWA patients were men. Sixty-two (55%) iRBD and three (12%) iRSWA patients received prognostic counseling about phenoconversion risk. iRBD was a secondary complaint in 67 (59.8%). Patients over age 60 years and those having iRBD as a chief complaint more frequently received prognostic discussions than those with opposite characteristics (all p < 0.05). Patient sex and antidepressant use were not associated with counseling. Sleep neurologists disclosed prognostic information most frequently, with male more likely than female clinicians to disclose prognoses. CONCLUSIONS: Several patient and physician characteristics appear to influence documented prognostic counseling for iRBD/RSWA patients. Future studies of iRBD/RSWA patients' preferences are needed to clarify ethically appropriate physician-patient communication concerning prognosis.

Comparison between pars plana and anterior endoscopic cyclophotocoagulation for the treatment of glaucoma.

IMPORTANCE: This is the first study to compare the efficacy and safety of endocyclophotocoagulation (ECP) via pars plana (ECP-plus) with ECP via limbus (anterior ECP) for treating glaucoma. BACKGROUND: There is no direct comparison of treatment outcomes between ECP-plus and anterior ECP. DESIGN: Retrospective study. PARTICIPANTS: Fifty-four consecutive patients. METHODS: Fifty-eight eyes from 54 consecutive patients underwent anterior ECP (33 eyes) or ECP-plus (25 eyes) with 2-year follow-up. Linear mixed model was used to analyse the surgical outcomes. MAIN OUTCOME MEASURES: Intraocular Pressure (IOP) was the primary outcome. Secondary outcomes were best-corrected visual acuity, number of glaucoma medications, complications and success rate. RESULTS: Compared to anterior ECP, patients in the ECP-plus group had lower IOP (estimate of effect size [EES] = -3.7 mmHg, P = 0.023) and used fewer number of glaucoma medications (EES = -1.11, P = 0.003), after adjusting for degrees of treatment, preoperative IOP, and presence of combined ECP and phacoemulsification procedure. Patients with ECP-plus achieved a higher success rate at 2 years postoperatively (80% vs 33.3%, P < 0.001). The decrease in IOP between the preoperative and last follow-up visit was greater in the ECP-plus group compared to the anterior ECP group (14.3 mmHg (52%) vs 5.2 mmHg (24%), P = 0.001). There was no significant difference in complication rates between the two groups (28% vs 33%, P = 0.561). CONCLUSIONS AND RELEVANCE: Anterior ECP and ECP-plus have a similar safety profile, and ECP-plus may offer superior IOP control for the management of glaucoma.

The effect of an organ procurement experience on preclinical medical student perceptions of transplant surgery.

Transplant surgery is a predominantly male specialty with high burnout rates. There are currently limited data regarding how programs can attract a diverse applicant pool to the field of transplant surgery. This study evaluated the effect of an Organ Procurement Experience elective on preclinical medical students' perceptions of transplant surgery in a prospective, longitudinal study. Preclinical medical students were anonymously surveyed before and after attending a deceased donor organ procurement. Questions focused on the following themes: Personal Beliefs, Personal/Professional Life, Diversity, and Gender Equality. Responses were rated on a five-point Likert scale. Ninety-nine and 45 students completed pre/post-procurement survey, respectively. Post-procurement responses demonstrated increased education about the field (2.1/5 vs 3.89/5, P < 0.001) and perceptions of the personalities and collegiality between surgeons (3.06/5 vs 3.73/5, P = 0.005). Post-procurement, women were less likely to feel that female transplant surgeons are treated differently (3.98/5 vs. 3.45/5, P < 0.017). Post-procurement, 19% agreed that transplant surgeons have a high quality of life. One percent of respondents felt the current gender distribution in transplant surgery is satisfactory. The Organ Procurement Experience significantly improved preclinical students' perceptions of the field. However, there remains a strong concern about quality of life and gender diversity within the field.

The effects of sex, estrous cycle, and social contact on cocaine and heroin self-administration in rats.

RATIONALE: Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts. OBJECTIVE: The objective of this study was to examine the role of sex and estrous cycle in a rat model during cocaine and heroin self-administration with male-female and female-female social dyads. METHODS: Male and female virgin rats were trained to self-administer cocaine and heroin in operant conditioning chambers that permitted two rats to self-administer concurrently, but prevented physical contact. Experiment 1 examined cocaine self-administration on a progressive ratio schedule in male-female dyads. Experiments 2 and 3 examined heroin self-administration on a fixed ratio schedule in male-female dyads at constant and varying doses, respectively. Experiment 4 examined heroin self-administration in female-female dyads on a fixed ratio schedule. RESULTS: Cocaine-maintained breakpoints increased by ∼17 % in females during estrus, but remained consistent in males. Heroin self-administration decreased by ∼70 % during proestrus in females whether they were isolated, housed with males, or housed with females. Heroin self-administration was lower in males than females under some conditions and was not consistently associated with the responding of females. CONCLUSIONS: Cocaine and heroin self-administration is influenced by the estrous cycle in females when in the presence of a male partner. As a novel finding, these data illustrate that heroin self-administration is reduced in females during proestrus regardless of the social context tested. Finally, these data suggest that drug self-administration in males is only minimally influenced by the hormonal status of a female partner.

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay.

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-s delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures.