Dopaminergic modulation of rapid reality adaptation in thinking

Dopamine has long held a prominent role in the interpretation of schizophrenia and other psychoses. Clinical studies on confabulation and disorientation, disorders marked by a confusion of reality in thinking, indicated that the ability to keep thinking in phase with reality depends on a process suppressing the interference of upcoming memories that do not refer to ongoing reality. A host of animal studies and a recent clinical study suggested that this suppression might correspond to the phasic inhibition of dopaminergic neurons in response to the absence of expected outcomes. In this study, we tested healthy subjects with a difficult version of a memory paradigm on which confabulating patients had failed. Subjects participated in three test sessions, in which they received in double-blind, randomized fashion L-dopa, risperidone, or placebo. We found that l-dopa, in comparison with risperidone, impaired performance in a highly specific way, which corresponded to the pattern of patients with reality confusion. Specifically, they had an increase of false positive responses, while overall memory performance and reaction times were unaffected. We conclude that dopaminergic transmission influences the ability to rapidly adapt thinking to ongoing reality.

Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients

The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

Terrestrial feeding in aquatic turtles: environment-dependent feeding behavior modulation and the evolution of terrestrial feeding in Emydidae

Evolutionary transitions between aquatic and terrestrial environments are common in vertebrate evolution. These transitions require major changes in most physiological functions, including feeding. Emydid turtles are ancestrally aquatic, with most species naturally feeding only in water, but some terrestrial species can modulate their feeding behavior appropriately for both media. In addition, many aquatic species can be induced to feed terrestrially. A comparison of feeding in both aquatic and terrestrial environments presents an excellent opportunity to investigate the evolution of terrestrial feeding from aquatic feeding, as well as a system within which to develop methods for studying major evolutionary transitions between environments. Individuals from eight species of emydid turtles (six aquatic, two terrestrial) were filmed while feeding underwater and on land. Bite kinematics were analyzed to determine whether aquatic turtles modulated their feeding behavior in a consistent and appropriate manner between environments. Aquatic turtles showed consistent changes between environments, taking longer bites and using more extensive motions of the jaw and hyoid when feeding on land. However, these motions differ from those shown by species that naturally feed in both environments and mostly do not seem to be appropriate for terrestrial feeding. For example, more extensive motions of the hyoid are only effective during underwater suction feeding. Emydids evolving to feed on land probably would have needed to evolve or learn to overcome many, but not all, aspects of the intrinsic emydid response to terrestrial feeding. Studies that investigate major evolutionary transitions must determine what responses to the new environment are shown by naïve individuals in order to fully understand the evolutionary patterns and processes associated with these transitions.

Gender differences of atrial and ventricular remodeling and autonomic tone in nonelite athletes

Veteran endurance athletes have an increased risk of developing atrial fibrillation (AF), with a striking male predominance. We hypothesized that male athletes were more prone to atrial and ventricular remodeling and investigated the signal-averaged P wave and factors that promote the occurrence of AF. Nonelite athletes scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race, were invited. Of the 873 marathon and nonmarathon runners who were willing to participate, 68 female and 70 male athletes were randomly selected. The runners with cardiovascular disease or elevated blood pressure (>140/90 mm Hg) were excluded. Thus, 121 athletes were entered into the final analysis. Their mean age was 42 ± 7 years. No gender differences were found for age, lifetime training hours, or race time. The male athletes had a significantly longer signal-averaged P-wave duration (136 ± 12 vs 122 ± 10 ms; p <0.001). The left atrial volume was larger in the male athletes (56 ± 13 vs 49 ± 10 ml; p = 0.001), while left atrial volume index showed no differences (29 ± 7 vs 30 ± 6 ml/m²; p = 0.332). In male athletes, the left ventricular mass index (107 ± 17 vs 86 ± 16 g/m²; p <0.001) and relative wall thickness (0.44 ± 0.06 vs 0.41 ± 0.07; p = 0.004) were greater. No differences were found in the left ventricular ejection fraction (63 ± 4% vs 66 ± 6%; p = 0.112) and mitral annular tissue Doppler e' velocity (10.9 ± 1.5 vs 10.6 ± 1.5 cm/s; p = 0.187). However, the tissue Doppler a' velocity was higher (8.7 ± 1.2 vs 7.6 ± 1.3 cm/s; p < 0.001) in the male athletes. Male athletes had a higher systolic blood pressure at rest (123 ± 9 vs 110 ± 11 mm Hg; p < 0.001) and at peak exercise (180 ± 15 vs 169 ± 19 mm Hg; p = 0.001). In the frequency domain analysis of heart rate variability, the sympatho-vagal balance, represented by the low/high-frequency power ratio, was significantly greater in male athletes (5.8 ± 2.8 vs 3.9 ± 1.9; p < 0.001). Four athletes (3.3%) had at least one documented episode of paroxysmal AF, all were men (p = 0.042). In conclusion, for a comparable amount of training and performance, male athletes showed a more pronounced atrial remodeling, a concentric type of ventricular remodeling, and an altered diastolic function. A higher blood pressure at rest and during exercise and a higher sympathetic tone might be causal. The altered left atrial substrate might facilitate the occurrence of AF.

Atrial remodeling, autonomic tone, and lifetime training hours in nonelite athletes

Endurance athletes have an increased risk of developing atrial fibrillation (AF) at 40 to 50 years of age. Signal-averaged P-wave analysis has been used for identifying patients at risk for AF. We evaluated the impact of lifetime training hours on signal-averaged P-wave duration and modifying factors. Nonelite men athletes scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race, were invited. Four hundred ninety-two marathon and nonmarathon runners applied for participation, 70 were randomly selected, and 60 entered the final analysis. Subjects were stratified according to their lifetime training hours (average endurance and strength training hours per week × 52 × training years) in low (<1,500 hours), medium (1,500 to 4,500 hours), and high (>4,500 hours) training groups. Mean age was 42 ± 7 years. From low to high training groups signal-averaged P-wave duration increased from 131 ± 6 to 142 ± 13 ms (p = 0.026), and left atrial volume increased from 24.8 ± 4.6 to 33.1 ± 6.2 ml/m(2) (p = 0.001). Parasympathetic tone expressed as root of the mean squared differences of successive normal-to-normal intervals increased from 34 ± 13 to 47 ± 16 ms (p = 0.002), and premature atrial contractions increased from 6.1 ± 7.4 to 10.8 ± 7.7 per 24 hours (p = 0.026). Left ventricular mass increased from 100.7 ± 9.0 to 117.1 ± 18.2 g/m(2) (p = 0.002). Left ventricular systolic and diastolic function and blood pressure at rest were normal in all athletes and showed no differences among training groups. Four athletes (6.7%) had a history of paroxysmal AF, as did 1 athlete in the medium training group and 3 athletes in the high training group (p = 0.252). In conclusion, in nonelite men athletes lifetime training hours are associated with prolongation of signal-averaged P-wave duration and an increase in left atrial volume. The altered left atrial substrate may facilitate occurrence of AF. Increased vagal tone and atrial ectopy may serve as modifying and triggering factors.

Dopaminergic modulation of the human reward system: a placebo-controlled dopamine depletion fMRI study

Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity in 10 healthy volunteers. In addition to blood-oxygen-level-dependent (BOLD) contrast we assessed the effect of dopaminergic depletion on prolactin response, peripheral markers for dopamine and norepinephrine. In the placebo condition we found increased activation in the left caudate and left cingulate gyrus during anticipation of reward. In the α-methylparatyrosine condition there was no significant brain activation during anticipation of reward or loss. In α-methylparatyrosine, anticipation of reward vs. loss increased activation in the right insula, left frontal, right parietal cortices and right cingulate gyrus. Comparing placebo versus α-methylparatyrosine showed increased activation in the left cingulate gyrus during anticipation of reward and the left medial frontal gyrus during anticipation of loss. α-methylparatyrosine reduced levels of dopamine in urine and homovanillic acid in plasma and increased prolactin. No significant effect of α-methylparatyrosine was found on norepinephrine markers. Our findings implicate distinct patterns of BOLD underlying reward processing following dopamine depletion, suggesting a role of dopaminergic neurotransmission for anticipation of monetary reward.

Modulation of chiroptical properties by DNA-guided assembly of fluorenes

The supramolecular organization of fluorene building blocks in a DNA scaffold is described. The molecular assembly into ordered pi-aggregates leads to distinct changes in the electronic properties.

Asymmetric speed modulation of a rotary blood pump affects ventricular unloading

Rotary blood pumps (RBPs) running at a constant speed are routinely used for the mechanical support of the heart in various clinical applications, from short-term use in heart-lung machines to long-term support of a failing heart. Their operating range is delineated by suction and regurgitation events, leaving limited control on the cardiac workload. This study investigates whether different ratios of systolic/diastolic support are advantageous over a constant-speed operation.

Do Central Hypersensitivity and Altered Pain Modulation Predict the Course of Chronic Low Back and Neck Pain?

OBJECTIVES:: Widespread central hypersensitivity and altered conditioned pain modulation (CPM) have been documented in chronic pain conditions. Information on their prognostic values is limited. This study tested the hypothesis that widespread central hypersensitivity (WCH) and altered CPM, assessed during the chronic phase of low back and neck pain, predict poor outcome. METHODS:: A total of 169 consecutive patients with chronic low back or neck pain, referred to the pain clinic during 1 year, were analyzed. Pressure pain tolerance threshold at the second toe and tolerance time during cold pressor test at the hand assessed WCH. CPM was measured by the change in pressure pain tolerance threshold (test stimulus) after cold pressor test (conditioning stimulus). A structured telephone interview was performed 12 to 15 months after testing to record outcome parameters. Linear regression models were used, with average and maximum pain intensity of the last 24 hours at follow-up as endpoints. Multivariable analyses included sex, age, catastrophizing scale, Beck Depression Inventory, pain duration, intake of opioids, and type of pain syndrome. RESULTS:: Statistically significant reductions from baseline to follow-up were observed in pain intensity (P<0.001). No evidence for an association between the measures of WCH or CPM and intensity of chronic pain at follow-up was found. DISCUSSION:: A major predictive value of the measures that we used is unlikely. Future studies adopting other assessment modalities and possibly standardized treatments are needed to further elucidate the prognostic value of WCH and altered CPM in chronic pain.