Dopamine efflux in the nucleus accumbens during within-session extinction, outcome-dependent, and habit-based instrumental responding for food reward

RATIONALE: Dopamine (DA) activity in the nucleus accumbens (NAc) is related to the general motivational effects of rewarding stimuli. Dickinson and colleagues have shown that initial acquisition of instrumental responding reflects action–outcome relationships based on instrumental incentive learning, which establishes the value of an outcome. Given that the sensitivity of responding to outcome devaluation is not affected by NAc lesions, it is unlikely that incentive learning during the action–outcome phase is mediated by DA activity in the NAc. OBJECTIVES: DA efflux in the NAc after limited and extended training was compared on the assumption that comparable changes would be observed during both action–outcome- and habit-based phases of instrumental responding for food. This study also tested the hypothesis that increase in NAc DA activity is correlated with instrumental responding during extinction maintained by a conditioned stimulus paired with food. METHODS: Rats were trained to lever press for food (random-interval 30 s schedule). On the 5th and 16th day of training, microdialysis samples were collected from the NAc or mediodorsal striatum (a control site for generalized activity) during instrumental responding in extinction and then for food reward, and analyzed for DA content using high performance liquid chromatography. RESULTS: Increase in DA efflux in the NAc accompanied responding for food pellets on both days 5 and 16, with the magnitude of increase significantly enhanced on day 16. DA efflux was also significantly elevated during responding in extinction only on day 16. CONCLUSIONS: These results support a role for NAc DA activity in Pavlovian, but not instrumental, incentive learning

Temporal Dynamics of Hippocampal and Medial Prefrontal Cortex Interactions During the Delay Period of a Working Memory-Guided Foraging Task

Abstract: Connections between the hippocampus (HC) and medial prefrontal cortex (mPFC) are critical for working memory; however, the precise contribution of this pathway is a matter of debate. One suggestion is that it may stabilize retrospective memories of recently encountered task-relevant information. Alternatively, it may be involved in encoding prospective memories, or the internal representation of future goals. To explore these possibilities, simultaneous extracellular recordings were made from mPFC and HC of rats performing the delayed spatial win-shift on a radial maze. Each trial consisted of a training-phase (when 4 randomly chosen arms were open) and test phase (all 8 arms were open but only previously blocked arms contained food) separated by a 60-s delay. Theta power was highest during the delay, and mPFC units were more likely to become entrained to hippocampal theta as the delay progressed. Training and test phase performance were accurately predicted by a linear classifier, and there was a transition in classification for training-phase to test-phase activity patterns throughout the delay on trials where the rats performed well. These data suggest that the HC and mPFC become more strongly synchronized as mPFC circuits preferentially shift from encoding retrospective to prospective informatio

Interpreting short and medium exposure etched-track radon measurements to determine whether an action level could be exceeded

Radon gas is naturally occurring, and can concentrate in the built environment. It is radioactive and high concentration levels within buildings, including homes, have been shown to increase the risk of lung cancer in the occupants. As a result, several methods have been developed to measure radon. The long-term average radon level determines the risk to occupants, but there is always pressure to complete measurements more quickly, particularly when buying and selling the home. For many years, the three-month exposure using etched-track detectors has been the de facto standard, but a decade ago, Phillips et al. (2003), in a DEFRA funded project, evaluated the use of 1-week and 1-month measurements. They found that the measurement methods were accurate, but the challenge lay in the wide variation in radon levels - with diurnal, seasonal, and other patterns due to climatic factors and room use. In the report on this work, and in subsequent papers, the group proposed methodologies for 1-week, 1-month and 3-month measurements and their interpretation. Other work, however, has suggested that 2-week exposures were preferable to 1-week ones. In practice, the radon remediation industry uses a range of exposure times, and further guidance is required to help interpret these results. This paper reviews the data from this study and a subsequent 4-year study of 4 houses, re-analysing the results and extending them to other exposures, particularly for 2-week and 2-month exposures, and provides comprehensive guidance for the use of etched-track detectors, the value and use of Seasonal Correction Factors (SCFs), the uncertainties in short and medium term exposures and the interpretation of results

Selective Effects of D- and L-Govadine in Preclinical Tests of Positive, Negative, and Cognitive Symptoms of Schizophrenia

There is a critical need to develop novel pharmacotherapeutics capable of addressing the positive, negative, and cognitive symptoms of schizophrenia. Building on recent studies with a racemic mixture of the synthetic tetrahydroprotoberberine, D,L-Govadine, we isolated the D- and L-stereoisomers and employed a battery of behavioral, neurochemical, and electrophysiological procedures to assess their individual therapeutic potential. Rodent models predictive of antipsychotic efficacy and those that model positive symptoms were employed and we found that L-Govadine, but not D-Govadine, improved these measures. Pretreatment with either stereoisomer during CS pre-exposure prevented the disruption of latent inhibition by amphetamine. Moreover, pretreatment with either stereoisomer also improved deficits in social interaction in the neonatal ventral hippocampal lesioned rat. Improved cognitive performance in two different prefrontal cortex-dependent tasks was observed with D-, but not L-Govadine, which strongly suggests that the D-steroisomer may be an effective cognitive enhancer. Alterations in dopamine efflux were also assessed and L-Govadine increased dopamine efflux in both the prefrontal cortex and nucleus accumbens. However, D-Govadine only increased dopamine efflux in the prefrontal cortex and not in the nucleus accumbens. Electrophysiological studies confirmed that L-Govadine is a DA-D2 antagonist, whereas D-Govadine shows no appreciable physiological effects at this receptor. Collectively these data show that L-Govadine performs well on measures predictive of antipsychotic efficacy and rodent models of positive symptoms through antagonism of DA-D2 receptors, whereas D-Govadine improves impairments in compromised memory function in delayed response tasks possibly through selective increases in DA efflux in the frontal cortex

The Influence of Physical Activity on Monocyte Phenotype on Circulating Platelet-Monocyte Complexes in Overweight/Obese Persons

Elevated platelet-monocyte complexes (PMC) promote atherosclerosis and are associated with cardiovascular disease. It is unknown whether consistent physical activity (PA) decreases circulating PMCs. Additionally, no one has determined the monocyte phenotype most associated with PMCs. Purposes: 1) to examine the influence of PA on PMCs and their association with inflammatory /prothrombotic markers such as C-reactive protein (CRP), L-selectin (LS), platelet factor 4 (PF4), von Willebrand Factor (vWF), and hemoglobin A1C (HbA1c) and 2) to determine the monocyte phenotype most likely to form PMCs. Methods: Thirty-one overweight/obese subjects (44±5yr, BMI 34.2±5 kg×m2) were divided into two groups: sedentary (SED, n=17) and physically active (PA, n=14) based on physical activity logs. SED participated in \u3c 1 h of formal exercise while PA participated in moderate-high intensity exercise at least 3 h per week. Flow cytometry was used to identify PMCs on the monocyte phenotypes: classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14+CD16++). Platelets were identified using the marker CD42a. Results: Percentage of circulating PMCs and median fluorescence intensity of CD42a (MedFI; marker of platelet density per monocyte) were not different between groups; however, monocyte phenotype significantly impacted PMC percentage and MedFI where the lower the CD16 expression, the greater the adhesion of platelets. Classical monocytes (CD16-) had the highest % of PMC, etc. (Fig 1). HbA1c was greater (p=0.031) and LS (p=0.019) was lower in SED compared to PA (Fig. 2). There were no significant associations between any blood marker and PMC percentage, but PF4 was correlated with percent of CD16 -(r= -0.482, p=0.031) and CD16+(r= 0.473, p=0.035) monocytes. Conclusions: The absence of a separation between groups in VO2max may partially explain the lack of a difference in PMCs between groups. Regarding our second aim, classical monocytes appear to be more involved in PMC formation than do CD16+ monocytes with CD16++ having the lowest percentage of cells with platelets adhered (PMC). This observation may be due to the shedding of adhesion molecules from platelets and monocytes during activation from classical (CD16-) to a more inflammatory state (ie. CD16+)

Increasing biomass in Amazonian forest plots

A previous study by Phillips et al. of changes in the biomass of permanent sample plots in Amazonian forests was used to infer the presence of a regional carbon sink. However, these results generated a vigorous debate about sampling and methodological issues. Therefore we present a new analysis of biomass change in old-growth Amazonian forest plots using updated inventory data. We find that across 59 sites, the above-ground dry biomass in trees that are more than 10 cm in diameter (AGB) has increased since plot establishment by 1.22 ± 0.43 Mg per hectare per year (ha-1 yr-1), where 1 ha = 104 m2), or 0.98 ± 0.38 Mg ha-1 yr-1 if individual plot values are weighted by the number of hectare years of monitoring. This significant increase is neither confounded by spatial or temporal variation in wood specific gravity, nor dependent on the allometric equation used to estimate AGB. The conclusion is also robust to uncertainty about diameter measurements for problematic trees: for 34 plots in western Amazon forests a significant increase in AGB is found even with a conservative assumption of zero growth for all trees where diameter measurements were made using optical methods and/or growth rates needed to be estimated following fieldwork. Overall, our results suggest a slightly greater rate of net stand-level change than was reported by Phillips et al. Considering the spatial and temporal scale of sampling and associated studies showing increases in forest growth and stem turnover, the results presented here suggest that the total biomass of these plots has on average increased and that there has been a regional-scale carbon sink in old-growth Amazonian forests during the previous two decades

Difference in Postoperative Outcomes and Perioperative Resource Utilization Between General Surgeons and Pediatric Surgeons: A Systematic Review

Background: Both general surgeons (GS) and pediatric surgeons (PS) perform a high volume of appendectomies in pediatric patients, but there is a paucity of data on these outcomes based on surgeon training. We performed a systematic review and meta-analysis to compare postoperative outcomes and perioperative resource utilization for pediatric appendectomies.Methods: We searched PubMed to identify articles examining the association between surgeon specialization and outcomes for pediatric patients undergoing appendectomies. Study selection, data extraction, risk of bias assessment, and quality assessment were performed by one reviewer, with another reviewer to resolve discrepancies.Results: We identified 4799 articles, with 98.4% (4724/2799) concordance after initial review. Following resolution of discrepancies, 16 studies met inclusion criteria. Of the studies that reported each outcome, GS and PS demonstrated similar rates of readmission within 30 days (pooled RR 1.61 95% CI 0.66, 2.55) wound infections (pooled RR 1.07, 95% CI .55, 1.60), use of laparoscopic surgery (pooled RR 1.87, 95% CI .21, 3.53), postoperative complications (pooled RR 1.40, 95% CI .83, 1.97), use of preoperative imaging (pooled RR .98,95% CI .90, 1.05), and intra-abdominal abscesses (pooled RR .80, 95% CI .03, 1.58). Patients treated by GS did have a significantly higher risk of negative appendectomies (pooled RR 1.47, 95% CI 1.10, 1.84) when compared to PS.Discussion: This is the first meta-analysis to compare outcomes for pediatric appendectomies performed by GS compared to PS. Patient outcomes and resource utilization were similar among PS and GS, except for negative appendectomies were significantly more likely with GS

Short and long-term radon measurements in domestic premises: reporting results in terms of the HPA action and target levels

In the UK, the Action Level for radon gas in domestic buildings has stood at 200 Bq.m-3 for many years. Some years ago, our group made an extensive study of 7-day, 1-month and 3-month measurements in thirty-four un-remediated dwellings in a high-radon area over a full year. It was shown that one-week exposures were less reliable indicators of the long-term radon level, but that this variability was related to the changes in radon level, due to occupancy, weather changes and other influences. Our analysis reported the confidence limits for each detection period, and recommended a protocol for reporting. Short-term measurements can be reliable indicators in low-radon areas or for new properties, but in high-radon areas, the use of three-month exposures is indicated. In 2010 the UK Health Protection Agency (HPA) recommended the introduction of a lower Target Level of 100 Bq.m-3, with the intention of encouraging those most at risk from radon to consider remediation of their homes, even if the long-term average is between 100 and 200 Bq.m-3. We have reviewed the results of the previous survey in relation to the new Target Level, and report on the limits of confidence established for establishing whether a short-term result is over the target level, and proposes a reporting schem

A critical analysis of climatic influences on indoor radon concentrations: implications for seasonal correction

Although statistically-derived national Seasonal Correction Factors (SCFs) are conventionally used to convert sub-year radon concentration measurements to an annual mean, it has recently been suggested that external temperature could be used to derive local SCFs for short-term domestic measurements. To validate this approach, hitherto unanalysed radon and temperature data from an environmentally-stable location were analysed. Radon concentration and internal temperature were measured over periods totalling 1025 days during an overall period of 1762 days, the greatest continuous sampling period being 334 days, with corresponding meteorological data collected at a weather station 10 km distant. Mean daily, monthly and annual radon concentrations and internal temperatures were calculated. SCFs derived using monthly mean radon concentration, external temperature and internal-external temperature-difference were cross-correlated with each other and with published UK domestic SCF sets. Relatively good correlation exists between SCFs derived from radon concentration and internal-external temperature difference but correlation with external temperature, was markedly poorer. SCFs derived from external temperature correlate very well with published SCF tabulations, confirming that the complexity of deriving SCFs from temperature data may be outweighed by the convenience of using either of the existing domestic SCF tabulations. Mean monthly radon data fitted to a 12-month sinusoid showed reasonable correlation with many of the annual climatic parameter profiles, exceptions being atmospheric pressure, rainfall and internal temperature. Introducing an additional 6-month sinusoid enhanced correlation with these three parameters, the other correlations remaining essentially unchanged. Radon latency of the order of months in moisture-related parameters suggests that the principal driver for radon is total atmospheric moisture content rather than relative humidity