Effect of Population Heterogenization on the Reproducibility of Mouse Behavior: A Multi-Laboratory Study

In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multi-laboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies.

Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.

Adjacent vertebral failure after vertebroplasty: a biomechanical study of low-modulus PMMA cement

PMMA is the most common bone substitute used for vertebroplasty. An increased fracture rate of the adjacent vertebrae has been observed after vertebroplasty. Decreased failure strength has been noted in a laboratory study of augmented functional spine units (FSUs), where the adjacent, non-augmented vertebral body always failed. This may provide evidence that rigid cement augmentation may facilitate the subsequent collapse of the adjacent vertebrae. The purpose of this study was to evaluate whether the decrease in failure strength of augmented FSUs can be avoided using low-modulus PMMA bone cement. In cadaveric FSUs, overall stiffness, failure strength and stiffness of the two vertebral bodies were determined under compression for both the treated and untreated specimens. Augmentation was performed on the caudal vertebrae with either regular or low-modulus PMMA. Endplate and wedge-shaped fractures occurred in the cranial and caudal vertebrae in the ratios endplate:wedge (cranial:caudal): 3:8 (5:6), 4:7 (7:4) and 10:1 (10:1) for control, low-modulus and regular cement group, respectively. The mean failure strength was 3.3 +/- 1 MPa with low-modulus cement, 2.9 +/- 1.2 MPa with regular cement and 3.6 +/- 1.3 MPa for the control group. Differences between the groups were not significant (p = 0.754 and p = 0.375, respectively, for low-modulus cement vs. control and regular cement vs. control). Overall FSU stiffness was not significantly affected by augmentation. Significant differences were observed for the stiffness differences of the cranial to the caudal vertebral body for the regular PMMA group to the other groups (p < 0.003). The individual vertebral stiffness values clearly showed the stiffening effect of the regular cement and the lesser alteration of the stiffness of the augmented vertebrae using the low-modulus PMMA compared to the control group (p = 0.999). In vitro biomechanical study and biomechanical evaluation of the hypothesis state that the failure strength of augmented functional spine units could be better preserved using low-modulus PMMA in comparison to regular PMMA cement.

Do Zebra Finch Parents Fail to Recognise Their Own Offspring?

Individual recognition systems require the sender to be individually distinctive and the receiver to be able to perceive differences between individuals and react accordingly. Many studies have demonstrated that acoustic signals of almost any species contain individualized information. However, fewer studies have tested experimentally if those signals are used for individual recognition by potential receivers. While laboratory studies using zebra finches have shown that fledglings recognize their parents by their “distance call”, mutual recognition using the same call type has not been demonstrated yet. In a laboratory study with zebra finches, we first quantified between-individual acoustic variation in distance calls of fledglings. In a second step, we tested recognition of fledgling calls by parents using playback experiments. With a discriminant function analysis, we show that individuals are highly distinctive and most measured parameters show very high potential to encode for individuality. The response pattern of zebra finch parents shows that they do react to calls of fledglings, however they do not distinguish between own and unfamiliar offspring, despite individual distinctiveness. This finding is interesting in light of the observation of a high percentage of misdirected feedings in our communal breeding aviaries. Our results demonstrate the importance of adopting a receiver's perspective and suggest that variation in fledgling contact calls might not be used in individual recognition of offspring.

Influence of beveling and ultrasound application on marginal adaptation of box-only Class II (slot) resin composite restorations

A laboratory study was performed to assess the influence of beveling the margins of cavities and the effects on marginal adaptation of the application of ultrasound during setting and initial light curing. After minimal access cavities had been prepared with an 80 microm diamond bur, 80 box-only Class II cavities were prepared mesially and distally in 40 extracted human molars using four different oscillating diamond coated instruments: (A) a U-shaped PCS insert as the non-beveled control (EMS), (B) Bevelshape (Intensiv), (C) SonicSys (KaVo) and (D) SuperPrep (KaVo). In groups B-D, the time taken for additional bevel finishing was measured. The cavities were filled with a hybrid composite material in three increments. Ultrasound was also applied to one cavity per tooth before and during initial light curing (10 seconds). The specimens were subjected to thermomechanical stress in a computer-controlled masticator device. Marginal quality was assessed by scanning electron microscopy and the results were compared statistically. The additional time required for finishing was B > D > C (p < or = 0.05). In all groups, thermomechanical loading resulted in a decrease in marginal quality. Beveling resulted in higher values for "continuous" margins compared with that of the unbeveled controls. The latter showed better marginal quality at the axial walls when ultrasound was used. Beveling seems essential for good marginal adaptation but requires more preparation time. The use of ultrasonic vibrations may improve the marginal quality of unbeveled fillings and warrants further investigation.

Psychoendocrine validation of a short measure for assessment of perceived stress management skills in different non-clinical populations

BACKGROUND: We investigated the psychometric properties of a short questionnaire for combined assessment of different perceived stress management skills in the general population and tested whether scores relate to physiological stress reactivity. METHODS: For psychometric evaluation, we determined the factor structure of the questionnaire and investigated its measurement invariance in the participant groups and over time in three different independent samples representing the general population (total N=332). Reliability was tested by estimating test-retest reliability, internal consistency, and item reliabilities. We examined convergent and criterion validity using selected criterion variables. For endocrine validation, 35 healthy non-smoking and medication-free men in a laboratory study and 35 male and female employees in a workplace study underwent an acute standardized psychosocial stress task. We assessed stress management skills and measured salivary cortisol before and several times up to 60 min (workplace study) and 120 min (laboratory study) after stress. Potential confounders were controlled. RESULTS: The factor structure of the questionnaire consists of five scales reflecting acceptably distinct stress management skills such as cognitive strategies, use of social support, relaxation strategies, anger regulation, and perception of bodily tension. This factor structure was stable across participant groups and over time. Internal consistencies, item reliabilities, and test-retest reliabilities met established statistical requirements. Convergent and criterion validity were also established. In both endocrine validation studies, higher stress management skills were independently associated with lower cortisol stress reactivity (p's<.029). CONCLUSIONS: Our findings suggest that the questionnaire has good psychometric properties and that it relates to subjective psychological and objective physiological stress indicators. Therefore, the instrument seems a suitable measure for differential assessment of stress management skills in the general population.

Grapheme-color synaesthesia is associated with a distinct cognitive style

In this study we investigated whether synaesthesia is associated with a particular cognitive style. Cognitive style refers to preferred modes of information processing, such as a verbal style or a visual style. We reasoned that related to the enriched world of experiences created by synaesthesia, its association with enhanced verbal and visual memory, higher imagery and creativity, synaesthetes might show enhanced preference for a verbal as well as for a visual cognitive style compared to non-synaesthetes. In Study 1 we tested a large convenience sample of 1046 participants, who classified themselves as grapheme-color, sound-color, lexical-gustatory, sequence-space, or as non-synaesthetes. To assess cognitive style, we used the revised verbalizer-visualizer questionnaire (VVQ), which involves three independent cognitive style dimensions (verbal style, visual-spatial style, and vivid imagery style). The most important result was that those who reported grapheme-color synaesthesia showed higher ratings on the verbal and vivid imagery style dimensions, but not on the visual-spatial style dimension. In Study 2 we replicated this finding in a laboratory study involving 24 grapheme-color synaesthetes with objectively confirmed synaesthesia and a closely matched control group. Our results indicate that grapheme-color synaesthetes prefer both a verbal and a specific visual cognitive style. We suggest that this enhanced preference, probably together with the greater ease to switch between a verbal and a vivid visual imagery style, may be related to cognitive advantages associated with grapheme color synaesthesia such as enhanced memory performance and creativity.

Ein neues psychoendokrin-validiertes Verfahren zur Erfassung von Stressbewältigungsfertigkeiten (ISBF)

Background: We previously found good psychometric properties of the Inventory for assessment of stress management skills (German translation: Inventar zur Erfassung von Stressbewältigungsfertigkeiten), ISBF, a short questionnaire for combined assessment of different perceived stress management skills in the general population. Here, we investigate whether stress management skills as measured by ISBF relate to cortisol stress reactivity in two independent studies, a laboratory study (study 1) and a field study (study 2). Methods: 35 healthy non-smoking and medication-free men in study 1 (age mean±SEM:38.0±1.6) and 35 male and female employees in study 2 (age mean±SEM:32.9±1.2) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We assessed stress management skills (ISBF) and measured salivary cortisol before and after stress and several times up to 60 min (study 2) and 120 min (study 1) thereafter. Potential confounders were controlled. Results:. General linear models controlling for potential confounders revealed that in both studies, higher stress management skills (ISBF total score) were independently associated with lower cortisol levels before and after stress (main effects ISBF: p’s<.055) and lower cortisol stress reactivity (interaction ISBF-by-stress: p’s<.029). Post-hoc-testing of ISBF subscales suggest lower cortisol stress reactivity with higher “relaxation abilities” (both studies) and higher scores in the scale “cognitive strategies and problem solving” (study 2). Conclusions: Our findings suggest blunted increases in cortisol following stress with increasing stress management skills as measured by ISBF. This suggests that the ISBF not only relates to subjective psychological but also objective physiological stress indicators which may further underscore the validity of the questionnaire.

Lucid dreaming during NREM sleep: Two case reports

Lucid dreams – dreams in which the dreamer is aware that is dreaming – most frequently occur during REM sleep, yet there is some evidence suggesting that lucid dreaming can occur during NREM sleep as well. By conducting a sleep laboratory study on lucid dreams, we found two possible instances of lucidity during NREM sleep which are reported here. While lucid dreaming during NREM sleep seems to be much rarer and more difficult to achieve, it appears to be possible and is most likely to occur during N1 sleep, somewhat less likely during N2 sleep and yet to be observed during N3 sleep. Future studies should explore induction methods, underlying neural mechanisms and perceptual/dream content differences between REM and NREM lucid dreams. Furthermore, a consensus agreement is needed to define what is meant by lucid dreaming and create a vocabulary that is helpful in clarifying variable psychophysiological states that can support self-reflective awareness.

Infra-Population and -Community Dynamics of the Parasites Nosema apis and Nosema ceranae, and Consequences for Honey Bee (Apis mellifera) Hosts

Nosema spp. fungal gut parasites are among myriad possible explanations for contemporary increased mortality of western honey bees (Apis mellifera, hereafter honey bee) in many regions of the world. Invasive Nosema ceranae is particularly worrisome because some evidence suggests it has greater virulence than its congener N. apis. N. ceranae appears to have recently switched hosts from Asian honey bees (Apis cerana) and now has a nearly global distribution in honey bees, apparently displacing N. apis. We examined parasite reproduction and effects of N. apis, N. ceranae, and mixed Nosema infections on honey bee hosts in laboratory experiments. Both infection intensity and honey bee mortality were significantly greater for N. ceranae than for N. apis or mixed infections; mixed infection resulted in mortality similar to N. apis parasitism and reduced spore intensity, possibly due to inter-specific competition. This is the first long-term laboratory study to demonstrate lethal consequences of N. apis and N. ceranae and mixed Nosema parasitism in honey bees, and suggests that differences in reproduction and intra-host competition may explain apparent heterogeneous exclusion of the historic parasite by the invasive species

Ego depletion after social interference

The present study examines whether social interference (i.e., interference with one’s goal attainment by the bodily presence of others) depletes the limited resource of self-control strength. In an experimental laboratory study (N = 34), half the participants experienced social interference whereas the other half did not experience social interference by two confederates during a dexterity task. Afterwards, we measured participants’ momentary self-control strength applying a Stroop colour-naming task. In line with our prediction, participants’ performance in the Stroop task indicated that social interference reduced self-control strength. We discuss implications for crowding research and crowding in natural settings.

Bryozoan stable carbon and hydrogen isotopes: relationships between the isotopic composition of zooids, statoblasts and lake water

We explored the extent to which δ13C and δD values of freshwater bryozoan statoblasts can provide information about the isotopic composition of zooids, bryozoan food and surrounding water. Bryozoan samples were collected from 23 sites and encompassed ranges of nearly 30‰ for δ13C and 100‰ for δD values. δ13C offsets between zooids and statoblasts generally ranged from −3 to +4.5‰, with larger offsets observed in four samples. However, a laboratory study with Plumatella emarginata and Lophopus crystallinus demonstrated that, in controlled settings, zooids had only 0–1.2‰ higher δ13C values than statoblasts, and 1.7‰ higher values than their food. At our field sites, we observed a strong positive correlation between median δ13C values of zooids and median δ13C values of corresponding statoblasts. We also observed a positive correlation between median δD values of zooids and statoblasts for Plumatella, and a positive correlation between median δD values of statoblasts and δD values of lake water for Plumatella and when all bryozoan taxa were examined together. Our results suggest that isotope measurements on statoblasts collected from flotsam or sediment samples can provide information on the feeding ecology of bryozoans and the H isotopic composition of lake water.

High altitude, a natural research laboratory for the study of cardiovascular physiology and pathophysiology

High altitude constitutes an exciting natural laboratory for medical research. Although initially, the aim of high-altitude research was to understand the adaption of the organism to hypoxia and find treatments for altitude-related diseases, during the past decade or so, the scope of this research has broadened considerably. Two important observations led the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema represents a unique model that allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Second, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we will review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.