Leveraging Parent Pain Perspectives to Improve Pain Practices for Children with Medical Complexity.

PURPOSE: Children with medical complexity (MC) must rely on others to notice and address pain. Parents are aware of child pain behaviors and can serve as reliable proxy reporters. Thus, there is a critical need to understand parent perspectives to improve pain practices. DESIGN: Individual interviews were used as a data collection method in this qualitative study. METHODS: Participants were recruited via mail and social media postings. Interviews were audio-recorded and transcribed verbatim. Transcribed documents were imported to NVIVO for qualitative analysis. Conventional and directed approaches to qualitative content analysis were used. RESULTS: From the data analysis, major themes included: pain experiences, confidence in caregivers, parents are partners, proactive communication, and a spontaneous theme, "they can hear us." Emotional pain and challenges identifying the source pain were identified as sub-themes of pain experiences. CONCLUSIONS: Parents in this study shared methods helpful to identifying pain in their children, as well as suggestions for discussing pain with caregivers. Priorities for future research include identifying methods for sharing pain information that are thorough, but do not burden parents or providers. Researchers should also determine how parents and caregivers can partner to identify and address pain in children with MC. Going forward, conversations about pain should be a key part of any admission assessment or first encounter. As pain episodes among children with MC can be complex and may not always be re-created in front of a provider, nurses may advise parents to take photos or videos to share with caregivers.

Riluzole-Triazole Hybrids as Novel Chemical Probes for Neuroprotection in Amyotrophic Lateral Sclerosis.

Despite intense attention from biomedical and chemical researchers, there are few approved treatments for amyotrophic lateral sclerosis (ALS), with only riluzole (Rilutek) and edaravone (Radicava) currently available to patients. Moreover, the mechanistic basis of the activity of these drugs is currently not well-defined, limiting the ability to design new medicines for ALS. This Letter describes the synthesis of triazole-containing riluzole analogues, and their testing in a novel neuroprotective assay. Seven compounds were identified as having neuroprotective activity, with two compounds having similar activity to riluzole.

Neuroprotective effects of phenolic antioxidant tBHQ associate with inhibition of FoxO3a nuclear translocation and activity.

The Forkhead transcription factor, FoxO3a induces genomic death responses in neurones following translocation from the cytosol to the nucleus. Nuclear translocation of FoxO3a is triggered by trophic factor withdrawal, oxidative stress and the stimulation of extrasynaptic NMDA receptors. Receptor activation of phosphatidylinositol 3-kinase (PI3K)-Akt signalling pathways retains FoxO3a in the cytoplasm, thereby inhibiting the transcriptional activation of death-promoting genes. We hypothesized that phenolic antioxidants such as tert-Butylhydroquinone (tBHQ), which is known to stimulate PI3K-Akt signalling, would inhibit FoxO3a translocation and activity. Treatment of cultured cortical neurones with NMDA increased the nuclear localization of FoxO3a, reduced the phosphorylation of FoxO3a, increased caspase activity and up-regulated Fas ligand expression. In contrast the phenolic antioxidant, tBHQ, caused retention of FoxO3a in the cytosol coincident with enhanced PI3K- dependent phosphorylation of FoxO3a. tBHQ-induced nuclear exclusion of FoxO3a was associated with reduced FoxO-mediated transcriptional activity. Exposure of neurones to tBHQ inhibited NMDA-induced nuclear translocation of FoxO3a, prevented NMDA-induced up-regulation of FoxO-mediated transcriptional activity, blocked caspase activation and protected neurones from NMDA-induced excitotoxic death. Collectively, these data suggest that phenolic antioxidants such as tBHQ oppose stress-induced activation of FoxO3a and therefore have potential neuroprotective utility in neurodegeneration.

Regulation of adult neurogenesis by behavior and age in the accessory olfactory bulb.

The vomeronasal system (VNS) participates in the detection and processing of pheromonal information related to social and sexual behaviors. Within the VNS, two different populations of sensory neurons, with a distinct pattern of distribution, line the epithelium of the vomeronasal organ (VNO) and give rise to segregated sensory projections to the accessory olfactory bulb (AOB). Apical sensory neurons in the VNO project to the anterior AOB (aAOB), while basal neurons project to the posterior AOB (pAOB). In the AOB, the largest population of neurons are inhibitory, the granule and periglomerular cells (GCs and PGs) and remarkably, these neurons are continuously born and functionally integrated in the adult brain, underscoring their role on olfactory function. Here we show that behaviors mediated by the VNS differentially regulate adult neurogenesis across the anterior-posterior axis of the AOB. We used immunohistochemical labeling of newly born cells under different behavioral conditions in mice. Using a resident-intruder aggression paradigm, we found that subordinate mice exhibited increased neurogenesis in the aAOB. In addition, in sexually naive adult females exposed to soiled bedding odorized by adult males, the number of newly born cells was significantly increased in the pAOB; however, neurogenesis was not affected in females exposed to female odors. In addition, we found that at two months of age adult neurogenesis was sexually dimorphic, with male mice exhibiting higher levels of newly born cells than females. Interestingly, adult neurogenesis was greatly reduced with age and this decrease correlated with a decrease in progenitor cells proliferation but not with an increase in cell death in the AOB. These results indicate that the physiological regulation of adult neurogenesis in the AOB by behaviors is both sex and age dependent and suggests an important role of newly born neurons in sex dependent behaviors mediated by the VNS.