Introduction: We aimed to examine susceptibility to dissociation and the impact of dissociation on interoceptive processing in individuals with functional neurological disorder (FND). We hypothesised that dissociative states would be elevated and interoceptive accuracy and awareness impaired at baseline in people with FND, and that such differences would be exacerbated following acute dissociation. Methods: Nineteen adults with FND were compared to 20 healthy controls. A modified heartbeat tracking task measured interoceptive accuracy and awareness (confidence) before and after a validated dissociation induction procedure. An exteroceptive processing control task was included. Mann-Whitney tests and r-values (effect size) were computed for between-group comparisons. Results: The FND group displayed elevated dissociation at baseline (p = 0.001, r = 0.528) compared to controls which increased following dissociation-induction (p < 0.001, r = 0.663). Interoceptive accuracy did not differ between groups at baseline (p = 0.967, r = 0.009); however, the FND group had lower accuracy scores postinduction (p = 0.021, r = 0.379). A negative correlation (trend) between change scores for dissociation and interoceptive accuracy was noted (r s = −0.411, p = 0.057). Confidence ratings on interoceptive and exteroceptive processing tasks were lower in the FND group (p-values < 0.05 or <0.01, r-values 0.331-0.489). Conclusions: Individuals with FND experienced greater susceptibility to dissociation, metacognitive deficits and impaired interoceptive accuracy than controls after acute dissociation.

The skeletal system is generated and maintained by its progenitors, skeletal stem cells (SSCs), across the duration of life. Gradual changes associated with aging result in significant differences in functionality of SSCs. Declines in bone and cartilage production, increase of bone marrow adipose tissue, compositional changes of cellular microenvironments, and subsequent deterioration of external and internal structures culminate in the aged and weakened skeleton. The features and mechanisms of skeletal aging, and of its stem and progenitor cells in particular, are topics of recent investigation. The discovery of functionally homogeneous SSC populations with a defined cell surface phenotype has allowed for closer inspection of aging in terms of its effects on transcriptional regulation, cell function, and identity. Here, we review the aspects of SSC aging on both micro- and macroscopic levels. Up-to-date knowledge of SSC biology and aging is presented, and directions for future research and potential therapies are discussed. The realm of SSC-mediated bone aging remains an important component of global health and a necessary facet in our understanding of human aging.

Fracture healing is highly dependent on an early inflammatory response in which prostaglandin production by cyclo-oxygenases (COX) plays a crucial role. Current patient analgesia regimens favor opioids over Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) since the latter have been implicated in delayed fracture healing. While animal studies broadly support a deleterious role of NSAID treatment to bone-regenerative processes, data for human fracture healing remains contradictory. In this study, we prospectively isolated mouse and human skeletal stem cells (SSCs) from fractures and compared the effect of various NSAIDs on their function. We found that osteochondrogenic differentiation of COX2-expressing mouse SSCs was impaired by NSAID treatment. In contrast, human SSCs (hSSC) downregulated COX2 expression during differentiation and showed impaired osteogenic capacity if COX2 was lentivirally overexpressed. Accordingly, short- and long-term treatment of hSSCs with non-selective and selective COX2 inhibitors did not affect colony forming ability, chondrogenic, and osteogenic differentiation potential in vitro. When hSSCs were transplanted ectopically into NSG mice treated with Indomethacin, graft mineralization was unaltered compared to vehicle injected mice. Thus, our results might contribute to understanding species-specific differences in NSAID sensitivity during fracture healing and support emerging clinical data which conflicts with other earlier observations that NSAID administration for post-operative analgesia for treatment of bone fractures are unsafe for patients.

Objective/aimsInteroceptive differences have been proposed as an aetiological factor in functional neurological disorder (FND) but there is limited supportive evidence. Previous studies are few, have mixed findings and assessed only (objective) interoceptive accuracy, but not (metacognitive) interoceptive awareness. The aim of this study was to explore interoception in FND in greater detail, by assessing interoceptive accuracy and awareness in individuals with a range of FND presentations. As dissociative symptoms (e.g., depersonalisation, derealisation) are common in FND and could influence interoception, we sought to examine the effects of induced acute dissociation on interoception. We hypothesised that interoceptive accuracy/awareness would be impaired at baseline in FND relative to healthy controls, but that the differences would be exacerbated following dissociation induction.MethodsTwenty adults with FND were recruited from online FND support groups. Diagnosis was confirmed by medical documentation from a relevant healthcare professional. The FND group was compared to a group of 20 healthy controls recruited from online community groups. A modified heart-beat tracking task measured interoceptive accuracy (correct detection of heart beats) and awareness (confidence judgements). A control task involved counting visually presented geometric shapes. Both tasks were completed before and after a validated dissociation induction procedure (mirror-gazing).ResultsThe FND group reported elevated dissociation at baseline relative to controls (p<0.01) but this difference was larger following mirror-gazing (p<0.001). Interoceptive accuracy did not differ significantly between groups at baseline; however, the FND group had significantly lower accuracy scores following mirror-gazing (p<0.05). There was no effect of group on shape counting accuracy at either timepoint. Confidence ratings on the interoception and shape counting tasks were significantly lower at both timepoints in the FND group relative to controls (all p-values <0.05 or <0.01).ConclusionsIndividuals with FND reported elevated dissociation both before and after a dissociation induction procedure, although this was exacerbated post-dissociation induction. In contrast, interoceptive accuracy was unimpaired at baseline, but impaired following dissociation induction, relative to controls. The FND group showed reduced metacognitive awareness for detection of bodily states and external (visual) stimuli. Future research should better determine the nature of interoceptive deficits in FND and assess the impact of dissociation on a range of cognitive and affective processes relevant to the disorder.