This study investigated the acute effects of D 9 -tetrahydrocannabinol (THC) on four behavioral measures of impulsivity in recreational marijuana users. Although impulsive behavior has been studied using several different measures of impulsivity, few studies have utilized more than one of these measures on a single cohort. In this study, 37 healthy men and women participated in three sessions, in which they received capsules containing placebo, 7.5, or 15 mg THC in randomized order under double-blind conditions. Subjects were tested on the following four tasks: the Stop task, which measures the ability to inhibit a prepotent motor response; a Go/no-go task; a Delay discounting task, which measures the value of delayed or uncertain reinforcers; and a time estimation task, which measures alterations in time perception through a time reproduction procedure. Subjects also completed mood questionnaires and general measures of performance. THC produced its expected effects on subjective measures including increases in ARCI euphoria and marijuana scales. THC increased impulsive responding on the Stop task but did not affect performance on either the Go/no-go or Delay or Probability discounting tasks. On the time reproduction task, THC increased estimates of the duration of short intervals while not affecting estimates of longer intervals. There were no significant correlations between the four tasks either before or after drug administration. These results suggest that THC may increase certain forms of impulsive behavior while not affecting other impulsive behaviors. The dissociations between the four measures of impulsivity suggest that impulsivity is an assemblage of distinct components rather than a unitary process.

Background— Acute rejection is a major factor impacting survival in the first 12 months after cardiac transplantation. Transplant monitoring requires invasive techniques. Cardiac magnetic resonance (CMR), noninvasive testing, has been used in monitoring heart transplants. Prolonged T2 relaxation has been related to transplant edema and possibly rejection. We hypothesize that prolonged T2 reflects transplant rejection and that quantitative T2 mapping will concur with the pathological and clinical findings of acute rejection. Methods and Results— Patients were recruited within the first year after transplantation. Biopsies were graded according to the International Society for Heart Lung Transplant system for cellular rejection with immunohistochemistry for humoral rejection. Rejection was also considered if patients presented with signs and symptoms of hemodynamic compromise without biopsy evidence of rejection who subsequently improved with treatment. Patients underwent a novel single-shot T2-prepared steady-state free precession 4-chamber and 3 short axis sequences and regions of interest were drawn overlying T2 maps by 2 independent blinded reviewers. A total of 74 (68 analyzable) CMRs T2 maps in 53 patients were performed. There were 4 cellular, 2 humoral, and 2 hemodynamic rejection cases. The average T2 relaxation time for grade 0R (n=46) and grade 1R (n=17) was 52.5±2.2 and 53.1±3.3 ms (mean±SD), respectively. The average T2 relaxation for grade 2R (n=3) was 59.6±3.1 ms and 3R (n=1) was 60.3 ms (all P value <0.05 compared with controls). The T2 average in humoral rejection cases (n=2) was 59.2±3.3 ms and the hemodynamic rejection (n=2) was 61.1±1.8 ms ( P <0.05 versus controls). The average T2 relaxation time for all-cause rejection versus no rejection is 60.1±2.1 versus 52.8±2.7 ms ( P <0.05). All rejection cases were rescanned 2.5 months after treatment and demonstrated T2 normalization with average of 51.4±1.6 ms. No difference was found in ventricular function between nonrejection and rejection patients, except in ventricular mass 107.8±10.3 versus 127.5±10.4 g ( P < 0.05). Conclusions— Quantitative T2 mapping offers a novel noninvasive tool for transplant monitoring, and these initial findings suggest potential use in characterizing rejections. Given the limited numbers, a larger multi-institution study may help elucidate the benefits of T2 mapping as an adjunctive tool in routine monitoring of cardiac transplants.

In 2008, the National Institutes of Health funded 14 R01 grants to study causal factors that promote and support women's biomedical careers. The Research Partnership on Women in Biomedical Careers, a multi-institutional collaboration of the investigators, is one product of this initiative.A comprehensive framework is needed to address change at many levels-department, institution, academic community, and beyond-and enable gender equity in the development of successful biomedical careers. The authors suggest four distinct but interrelated aspects of culture conducive to gender equity: equal access to resources and opportunities, minimizing unconscious gender bias, enhancing work-life balance, and leadership engagement. They review the collection of eight articles in this issue, which each address one or more of the four dimensions of culture. The articles suggest that improving mentor-mentee fit, coaching grant reviewers on unconscious bias, and providing equal compensation and adequate resources for career development will contribute positively to gender equity in academic medicine.Academic medicine must adopt an integrated perspective on culture for women and acknowledge the multiple facets essential to gender equity. To effect change, culture must be addressed both within and beyond academic health centers (AHCs). Leaders within AHCs must examine their institutions' processes, resources, and assessment for fairness and transparency; mobilize personnel and financial resources to implement evidence-based initiatives; and assign accountability for providing transparent progress assessments. Beyond AHCs, organizations must examine their operations and implement change to ensure parity of funding, research, and leadership opportunities as well as transparency of assessment and accreditation.

No abstract

Divergent selection for heat loss was applied to lines of mice for 15 generations (G) in 3 replicates. Selection resumed at G42 and continued through G51 across all replicates. At the end of G51, differences in heat loss and feed intake per unit of BW were approximately 56 and 34%, respectively, between high heat loss (MH) and low heat loss (ML) lines, as a percentage of the control line (MC) mean. Rates of liver mitochondrial respiration states, degree of coupling, and mitochondrial efficiency were measured in G58 using a Clark-type oxygen electrode to investigate possible causes of underlying variation in maintenance requirements. Body composition, BW, liver weight, feed intake, and residual feed intake (RFI) were also measured or calculated. Results reported here represent data from 197 mature male mice from all replicates. There were no differences in BW (P = 0.91) between the selection lines. Selection had an effect on lean percentage (P = 0.02), with MH mice being leaner. Fat percentage differences between the selection lines tended toward significance (P = 0.13). Livers of MH mice were approximately 13% larger than livers of ML mice (P = 0.01). An effect of selection was observed (P < 0.01) in feed intake per unit BW, with MH mice consuming 29% more feed than ML mice in G58. Differences in state 2 and state 4 respiration rates were significant (P = 0.01), whereas state 3 rates approached significance (P = 0.06). Mitochondria of MH mice respired at a greater rate than mitochondria of ML mice in all states of respiration; ML mice had respiratory control ratios that were, on average, 8% greater than MH mice (P = 0.14). Although this difference only tended toward significance, we suspect a greater degree of coupling of mitochondrial processes exists in ML animals. Mice selected for reduced heat loss had ADP:oxygen ratios that were approximately 20% greater than MH mice (P = 0.03). Therefore, greater mitochondrial efficiency was expressed in the ML animals. Within a line-replicate, there was no correlation between ADP:O and feed intake per unit BW (P = 0.71). In addition, no correlation of ADP:O and RFI existed (P = 0.92). Although the selection lines differed in mitochondrial traits, including overall mitochondrial efficiency (ADP:oxygen), these differences were not a significant underlying cause of variation in feed intake per unit BW or in RFI estimates.

No abstract

Amphetamine is thought to produce its stimulant effects mainly via the dopamine system, but its effects may also be influenced by other systems. Dopamine D1 and D2 receptors exist as heterodimers with adenosine A1 and A(2A) receptors, which modulate their responsiveness, suggesting that responses to amphetamine may also depend on adenosinergic function. We therefore studied the relevance of one adenosine A1 and three adenosine A(2A) receptor gene polymorphisms for the interindividual variability in amphetamine response in 99 healthy volunteers who received placebo or d-amphetamine (10 or 20 mg). The 1976C/T and 2592C/T(ins) polymorphisms of the adenosine receptor gene were associated with increases in anxiety at both doses. This is consistent with recent observations indicating a role for adenosine A(2A) receptor gene polymorphisms in anxiety.

No abstract