Observational learning and pain-related fear

Chronic pain is one of the major health problems in Western societies, with a prevalence of 19%. Not only does chronic pain account for enormous health care costs and lost working productivity, it also results in an extensive quality of life reduction. An important predictor in the development as well as the persistence of chronic pain problems is pain-related fear. The Fear-Avoidance Model (FAM) of chronic pain presents a plausible pathway by which people can get caught in a downward spiral of increasing avoidance, disability, and pain. Despite the accumulating research evidence supporting FAM in explaining the interference of pain in daily life, the different pathways to the development of pain-related fear have received scant attention in the pain literature so far. The current project aimed at testing the possibility that pain-related fear can develop via an observational learning pathway, that is through observing others displaying pain behaviour during an encounter with a painful stimulus. For this purpose, a differential fear conditioning paradigm was used in several experimental studies with healthy participants. One of two formerly neutral stimuli (CS+ colour) was associated with painful facial expressions of models presented via video clips, while the other stimulus (CS- colour) was always paired with relaxed expressions of models. Observational learning was predicted to occur when the former stimulus acquired a threat value and elicited defensive responses by the participant, while the latter stimulus preserved its neutral valence. Second, we were interested in the extinction of observationally acquired pain-related fear after direct exposure to the conditioned stimulus. Third, we wanted to investigate the putative moderating effects of observers’ characteristics in order to identify individuals who are at heightened risk of developing pain-related fear through observational learning. We expected pain catastrophizing, trait fear of pain, negative affectivity, intolerance of uncertainty, and dispositional empathy of the observer to facilitate observational learning processes. Results revealed that watching others in pain induced pain-related fear, and caused participants to expect higher pain unpleasantness, pain intensity, and perceived harmfulness regarding the CS+ compared to the CS- stimulus. These beliefs did, however, not always result in changes in behaviour or in changes in psychophysiological responses. Further research is needed to identify the conditions under which these changes do occur. When using a differential cold pressor task (CPT), pain-related fear persisted until the end of the experiment, whereas no differences between CS+ and CS- were found after direct exposure to coloured warm water tasks or cold metal bars. No unequivocal pattern was found across the experiments regarding the possible moderators. The results of this project not only enhance our understanding of the acquisition of pain- related fear, it may also have implications for the development of prevention and cognitive- behavioural management strategies for patients with chronic pain

Metaphor interpretation and use : a window into semantics in schizophrenia

The nature of putative semantic anomalies in schizophrenia is controversial. Metaphor interpretation and use provide a useful methodology with which to probe semantics since metaphors are critical in reasoning processes and in how conceptual knowledge is organized. The first study examined free speech for figurative language. The second study explored whether emotional versus non-emotional metaphorical language interpretation elicits differences in the tendencies to produce idiosyncratic (bizarre) or literal interpretations or use of other metaphors to describe the meaning of a metaphor. The third study examined the interpretation of time metaphors. We expected the time perspective in ambiguous sentences to be differentially influenced by previously presented unambiguous sentences of a specific perspective, either events moving relative to a stationary observer (moving-time) or an observer moving relative to a stationary event (moving-ego). First, we found that patients used a similar amount of figurative language as control participants. Second, we did not find any difference between the groups in terms of idiosyncratic interpretations, although patients did interpret more metaphors literally and controls utilized more figurative language. Third, we did not find evidence of a difference between the groups in terms of time perspectives influencing ambiguous target sentences differentially. As operationalized here, the interpretation and use of metaphors is similar in patients with schizophrenia to that of healthy control participants. To the extent that metaphors recruit semantic processes this area of cognition is generally intact in schizophrenia

Bidirectional Associations Between Sibling Relationships and Parental Support During Adolescence

Sibling relationships and parental support are important for adolescents’ development and well-being, yet both are likely to change during adolescence. Since adolescents participate in both the sibling relationship and the parent–child relationship, we can expect sibling relationships and parental support to be associated with each other. Theoretically, it can be expected that there is either a spillover from one relationship to another (congruence hypothesis) or that one relationship can compensate for the other (compensation hypothesis). However, research examining these associations in adolescence is limited. The present study longitudinally investigated the bidirectional associations between sibling relationships and parental support during adolescence. For five consecutive years, data were collected using self-reports of 428 families, consisting of a father, a mother, and two adolescent siblings. The mean ages of the first-born (52.8% males) and second-born (47.7% males) were 15 and 13 years at T1, respectively. For the second-born siblings, prospective associations were found between sibling relationships and adolescent-reported parental support in early adolescence, with no differences between same-sex and mixed-sex dyads. These associations were not found for first-born siblings or for parents’ reports of support. The findings suggest a spillover from the sibling relationship to adolescent-reported parental support only in early adolescence. Findings and implications are discussed in terms of the congruence/spillover and the compensation hypothesis

Comprehensive overview of the structure and regulation of the glucocorticoid receptor

Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternative RNA splicing and translation initiation of the GR transcript. Additionally, these isoforms are all subject to several transcriptional, post-transcriptional, and post-translational modifications, all of which affect the protein's stability and/or function. In this review, we summarize recent knowledge on the distinct GR isoforms and the processes that generate them. We also review the importance of all known transcriptional, post-transcriptional, and post-translational modifications, including the regulation of GR by microRNAs. Moreover, we discuss the crucial role of the putative GR-bound DNA sequence as an allosteric ligand influencing GR structure and activity. Finally, we describe how the differential composition and distinct regulation at multiple levels of different GR species could account for the wide and diverse effects of glucocorticoids

Enobosarm (GTx-024) modulates adult skeletal muscle mass independently of the androgen receptor in the satellite cell lineage

Androgens increase skeletal muscle mass, but their clinical use is hampered by lack of tissue selectivity and subsequent side-effects. Selective androgen receptor modulators (SARMs) elicit muscle-anabolic effects while only sparingly affecting reproductive tissues. The SARM GTx-024 (enobosarm) is being investigated for cancer cachexia, sarcopenia, and muscle wasting diseases. Here, we investigate the role of muscle androgen receptor (AR) in the anabolic effect of GTx-024. In mice lacking AR in the satellite cell lineage (satARKO), the weight of the androgen-sensitive levator ani muscle was lower, but decreased further upon orchidectomy. GTx-024 was as effective as dihydrotestosterone (DHT) in restoring levator ani weights to sham levels. Expression of the muscle-specific androgen-responsive genes S-adenosylmethionine decarboxylase and myostatin was decreased by orchidectomy and restored by GTx-024 and DHT in control mice, while expression was low and unaffected by androgen status in satARKO. In contrast, insulin-like growth factor IEa expression was not different between satARKO and control muscle, decreased upon castration, and was restored by DHT and GTx-024 in both genotypes. These data indicate that GTx-024 does not selectively modulate AR in the satellite cell lineage and that cells outside this lineage remain androgen-responsive in satARKO muscle. Indeed, residual AR positive cells were present in satARKO muscle, coexpressing the fibroblast-lineage marker vimentin. AR positive, muscle-resident fibroblasts could therefore be involved in the indirect effects of androgens on muscle. In conclusion, both DHT and GTx-024 target AR pathways in the satellite cell lineage, but cells outside this lineage also contribute to the anabolic effects of androgens.status: publishe

Contaminant issues in production and application of biochar

For widespread use of biochar in agriculture and horticulture, it must be ensured that application will neither adversely affect soil and plants, nor exceed legislated contaminant concentrations. The most relevant groups of contaminants in biochar are potentially toxic elements (PTEs), polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOC). In this thesis, the concentrations of these groups of contaminants were analysed in 90 different biochars produced by slow pyrolysis. Subsequently, the concentrations were compared to legislation/guideline threshold values and linked to production conditions. The risk these contaminants pose to plant growth was also assessed, to give recommendations on production of safe biochar. PTEs can neither be formed nor destroyed, which means their presence in biochar is predominantly determined by feedstock type. However, significant levels of Cr, Fe and Ni were introduced into biochar from the furnace steel, whilst PTEs with low boiling points, such as As, Cd and Zn, partially evaporated during pyrolysis. PTEs were not responsible for phytotoxic effects observed for PTE-rich biochars despite biochar’s exceedance of available and total PTE threshold values for soil and soil amendments. Although initial tests were promising, the risk that PTE-rich biochars as amendment for soil and growing media pose, needs further investigation. The PAH concentration in biochar was markedly reduced by increasing carrier gas flow rate, and the type of feedstock also influenced the PAH content. However, there was no clear dependence of pyrolysis temperature on PAH concentrations, which was attributed to PAHs being increasingly formed and evaporated at higher pyrolysis temperatures. Ultimately, condensation of pyrolysis vapours and deposition on biochar was identified as the main risk for biochar contamination with PAHs, as this resulted in elevated concentrations of high-risk, higher molecular weight PAHs. Weaknesses in the pyrolysis unit design, such as cold zones, resulted in elevated concentrations of VOCs, as well as PAHs, in biochar. Comparing concentrations and phytotoxic potential of both compound groups, it was concluded that observed toxic effects were much more likely caused by VOCs in biochars containing both contaminants. Overall, formation of VOCs and PAHs cannot be prevented, but their presence in biochar resulting from retention and deposition can be minimised