BackgroundA dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents.MethodsHere, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants’ anxiety on a behavioral, physiological, and subjective level.ResultsParticipants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants’ with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants’ acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance.ConclusionThese findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-017-0463-6) contains supplementary material, which is available to authorized users.

Background Many trans individuals undergo medical interventions that result in irreversible loss of fertility. Little is known about their desire to have children and attitudes toward fertility preservation options. Aim To study how the desire for children and the use of fertility preservation options varies among trans women and trans men in different transitioning stages in Germany. Methods In this cross-sectional multi-center study, N = 99 trans women and N = 90 trans men were included. Of these, 26 of each sex were just about to start medical treatment. Outcomes Outcome parameter were the prevalence and determinants of a desire to have children in trans persons. Results Before treatment, a desire for children was significantly higher in trans men compared to trans women (P = .016). In contrast, in those who had already started treatment, a current desire to have children was equally present in about one fourth of participants of both genders while the interest in having children in the future was significantly higher in trans women (69.9%) than in trans men (46.9%; P = .034). Although 76.1% of trans women and 76.6% of trans men indicated that they had at least thought about preserving germ cells before starting medical transition, only 9.6% of trans women and 3.1% of trans men had put this idea into practice. Most trans men in both groups indicated that insemination of a female partner with sperm from an unrelated donor was a suitable option to fulfill their child wish, potentially explaining their low interest in preserving their own germ cells. Finally, a logistic regression analysis accounting for potential confounders revealed that overall trans women were more than twice as likely to have a current desire to have children (odds ratio 2.58), and this wish was on average 5.3% lower with each year of increasing age. Clinical Translation A low level of fertility preservation among trans persons is contrasted by a high level of desire for children. This highlights the importance of counseling trans individuals regarding fertility preservation options. Conclusions To our knowledge, this is the first study that addresses desire to have children in a clinical sample of trans women. It is also the first that investigates this issue among trans men who have not started medical treatment, and the first comparison of both genders. A limitation for the generalization of our results is the special legal context in Germany that forbids oocyte donation for reciprocal in vitro fertilization. Reproductive desire is high among trans individuals, but the use of reproductive options is surprisingly low.

Exercise is rewarding, and long-distance runners have described a runner's high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors. We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner's high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.runner's high is described as an ephemeral pleasant phenomenon that may be experienced during long-term running. A popular belief has been that endorphins mediate a runner's high, although neurobiological mechanisms were unclear. In earlier experiments, two prominent systems (the opioid and endocannabinoid systems) were suggested to be involved in a runner's high (1-3). Running increases plasma levels of β-endorphin (an opioid) and anandamide (an endocannabinoid) in mice and men (4, 5). However, unlike the lipophilic anandamide, β-endorphin cannot cross the blood-brain barrier, rendering central effects of peripheral opioids unlikely. In an attempt to disentangle the biomechanism of a runner's high, we were using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, and demonstrated for the first time to our knowledge that a runner's high depends on cannabinoid receptors in mice. Results and DiscussionIn a first step, mice (n = 32) were provided with running wheels for 3 d to start with and to habituate them to wheel running. Mice ran, on average, 5.4 km per day (Fig. 1A). After 2 d with blocked running wheels, half of the mice were assigned into a running (RUN) and the other half to a nonrunning (CON) group, considering matched running distances. Runners (n = 16) were again subjected to a brief period of wheel running (5 h) directly before behavioral testing (day 6) and ran, on average, 6.5 ± 0.7 km (Fig. 1A).When subsequently tested for anxiety-like behavior in the dark-light box test, runners exhibited significantly less anxiety by spending an increased time in the aversive bright area than controls (P = 0.002; Fig. 1B). Runners were also less active and displayed fewer exits from the dark compartment into the lit compartment (RUN, 10.3 ± 0.8 exits; CON, 12.6 ± 0.7 exits; P = 0.040). Next, mice were removed from the dark-light arena and subjected to the hot plate test to study pain sensitivity. Here, runners displayed an increased latency to lick hind paws or jump (first action), suggesting reduced thermal pain sensitivity (P = 0.0...

The data on PES as an incidental finding are too sparse to enable any evidence-based recommendation on the potential indications for hormone testing or its nature and extent. We advise basic neuroendocrinological testing (fasting cortisol, free thyroxine [fT4], estradiol or testosterone, insulin-like growth factor 1 [IGF-1], and prolactin). There is an unexplained discrepancy between the reported high prevalence of pituitary insufficiency among persons with PES and its low prevalence in epidemiologic studies. We suspect that the former may be high because of selection bias in the publications that we reviewed, or else the latter may be erroneously low.

Observations made in April 2013 of the radioxenon isotopes (133)Xe and (131m)Xe at measurement stations in Japan and Russia, belonging to the International Monitoring System for verification of the Comprehensive Nuclear-Test-Ban Treaty, are unique with respect to the measurement history of these stations. Comparison of measured data with calculated isotopic ratios as well as analysis using atmospheric transport modeling indicate that it is likely that the xenon measured was created in the underground nuclear test conducted by North Korea on February 12, 2013, and released 7-8 weeks later. More than one release is required to explain all observations. The (131m)Xe source terms for each release were calculated to 0.7 TBq, corresponding to about 1-10% of the total xenon inventory for a 10 kt explosion, depending on fractionation and release scenario. The observed ratios could not be used to obtain any information regarding the fissile material that was used in the test.

The effects of hormonal therapy on different components of the MS are sex-specific and involve a complex interplay of direct hormonal effects, changes in body composition, and metabolic cytokine secretion.

Persistent feelings of gender dysphoria (GD) are accompanied by distress and body dissatisfaction in most clinically referred adolescents and adults. Transition-related medical interventions (e.g., puberty suppression, hormones, or surgery) may alleviate body dissatisfaction. The aim of the present cross-sectional study was to compare multidimensional body image across clinically referred adolescents and adults undergoing different transition-related medical interventions. Two clinical samples of adolescents (n = 82) and adults (n = 120) referred to specialized departments of four different transgender health services in Germany participated in the study. In total, 202 individuals from the female-to-male (FtM individuals) and male-to-female (MtF individuals) spectrum aged 14-74 years were included at different stages of their transition. Four scales assessing multidimensional aspects of body image (measured by the Body Image Assessment Questionnaire, FBeK) were compared across three groups: sample, gender, and medical interventions (while controlling for age and treatment duration). The results indicated less favorable body image scores compared with the norm in both adolescents and adults with GD. Individuals who had undergone transition-related medical interventions presented a significantly better body image on two of the four scales. Differences according to gender and age were also present. These findings suggest that medical interventions, especially gender-affirming hormones and surgery, are generally beneficial to the body image in individuals with GD. However, not all of the less favorable outcomes in multidimensional body image were positively influenced by the treatment conditions and may thus benefit from additional integrative counseling before and during transition.

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