p-Tyramine is an archetypal member of the endogenous family of monoamines known as trace amines, and is one of the endogenous agonists for trace amine-associated receptor (TAAR)1. While much work has focused on the function of TAAR1, very little is known about the regulation of the endogenous agonists. We have previously reported that p-tyramine readily crosses lipid bilayers and that its release from synaptosomes is non-exocytotic. Such release, however, showed characteristics of modification by one or more transporters. Here we provide the first characterization of such a transporter. Using frontal cortical and striatal synaptosomes we show that p-tyramine passage across synaptosome membranes is not modified by selective inhibition of either the dopamine, noradrenaline or 5-HT transporters. In contrast, inhibition of uptake-2 transporters significantly slowed p-tyramine re-uptake. Using inhibitors of varying selectivity, we identify Organic Cation Transporter 2 (OCT2; SLC22A2) as mediating high affinity uptake of p-tyramine at physiologically relevant concentrations. Further, we confirm the presence of OCT2 protein in synaptosomes. These results provide the first identification of a high affinity neuronal transporter for p-tyramine, and also confirm the recently described localization of OCT2 in pre-synaptic terminals.

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OBJECTIVE Craniosynostosis represents the second most common reason for referral to pediatric neurosurgery. However, the quality of life and neurodevelopmental impact of leaving this physical disorder uncorrected is poorly understood. METHODS This multicenter cross-sectional study identified previously managed nonsyndromic infants (< 24 months of age) with single-suture craniosynostosis at both pediatric neurosurgical centers in Alberta, Canada. The primary variable of interest was the allocated treatment (surgical vs conservative). The primary outcome was the Pediatric Quality of Life Inventory (PedsQL), a validated measure of quality of life examining physical, emotional, social, and school functioning. Treatment decision satisfaction and the reasons for selected management were quantified and collected directly from caregivers. RESULTS One hundred fourteen children met the inclusion criteria: 78% underwent surgery and 22% had conservative treatment. The most common suture affected was sagittal (54%), followed by metopic (33%), coronal (10%), and lambdoid (3%). Caregivers most commonly opted for surgery because of severe appearance (80%). Seventy-six percent and 72% of the caregivers of children with conservative management did so due to concerns of surgical risks and mild appearance, respectively. There was a statistically significant relationship between both the parents’ (p < 0.001) and the surgeon’s (p = 0.001) impression of a severe head shape and surgical management. Parental satisfaction with their child’s appearance as well as satisfaction with their treatment decision did not differ between management types. Regarding quality of life, on univariate analysis, the conservative group had a statistically higher physical summary score (p = 0.01), psychosocial summary score (p = 0.004), and mean total scale score (p = 0.003) compared to the surgical group. However, after adjusting for severity and age at consult, no significant independent associations between management type and any of the PedsQL summary scores were found. CONCLUSIONS Alberta families have a high number of children with craniosynostosis treated with conservative management. Conservatively managed infants were largely minimally affected patients, particularly those with metopic synostosis. The study found no independent association between management type (surgery vs conservative) and quality of life when adjusted for important patient factors.

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Background While diagnosis with a high-grade intracranial tumor is known to be associated with increased psychosocial burden, the burdens associated with meningioma are less well described. This study aimed to investigate the mental health burden in patients with meningiomas who have undergone surgical resection or serial observation, so as to identify and enhance awareness of gaps in care. Methods The Hospital Anxiety and Depression Scale (HADS) was administered to participants. Fisher’s Exact tests were performed to evaluate frequency distributions and t-tests were applied to compare postoperative and non-surgical patients’ HADS scores. Semi-structured interviews were completed on a subset of participants. Thematic analysis of interviews identified emerging themes. Results Thirty patients with intracranial meningiomas met inclusion criteria. The cohort’s mean age was 56.01 years and 66.67% were women (n = 20). Fourteen underwent surgery; sixteen were treated conservatively with observation. The average time since diagnosis of the sample was 37.6 months. Prevalence of mild to severe symptoms of anxiety was 28.6% amongst surgical management patients and 50% for active surveillance patients (p = 0.325). The prevalence of mild to severe symptoms of depression was 7.14% amongst surgical management patients and 6.25% for active surveillance patients (p = 0.533). Emerging themes from eight interviews reveal the influence of resilience, uncertainty and time, social support, interactions with medical experts, and difficulties during recovery on mental health. Conclusion The findings from the present study reveal that patients with meningiomas experience a significant mental health burden, illustrating the need for enhanced patient-centred care focusing on mental health.