Caregiver Burden, Stress, and Relationship Cohesion Among Self-Identified Caregivers of Children with Pediatric Acute-Onset Neuropsychiatric Syndrome.

Objective: Children with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) experience sudden onset neuropsychiatric symptoms after infection or other triggers. Symptoms range from mild to severe, potentially lasting days, weeks, months, or longer. Exacerbation-related functional decline presents in many aspects of daily life, generally accompanied by family stress and caregiver burden. We sought to investigate the relationship between severity of PANS symptoms and caregiver burden/stress and the relationship between severity of PANS symptoms and degree of caregiver/child cohesion. Methods: This cross-sectional online study surveyed caregivers recruited from PANS-related social media support sites. The Pediatric Acute Neuropsychiatric Symptom Scale - Parent Version (PNSS) measured current severity. Caregiver Burden Inventory (CBI) and Caregiver Self-Assessment Questionnaire (CSAQ) assessed caregiver burden/stress. Inclusion of Other in the Self (IOS) scale determined caregiver-perceived current and desired cohesion with their child(ren) with PANS. Results: Of the 216 respondents 79.6% exceeded CBI threshold indicating need for respite in adult care receiver populations. On the CSAQ, 72.9% expressed high distress, 80.5% reported feeling overwhelmed, and 58.1% reported crying spells, meeting cutoffs for support/respite used in adult care receiver populations. Most caregivers reported not having the desired degree of cohesion with their child on the IOS (85.5%). Parents of children with more severe PNSS symptoms fared significantly worse on all measures (CBI: H = 57.83; CSAQ: F = 29.26; IOS: H = 38.04; p < 0.001 for all). Content analysis of comments revealed five themes: (1) severe caregiver and/or family emotional distress and trauma; (2) caregivers wondering what happened to their child; (3) lack of awareness and support among health and education professionals; (4) relationship strain with family, friends, and significant others; and (5) financial and/or legal struggles because of their child's diagnosis. Conclusion: There is strong need for support and respite for children with PANS and their families. Long-term effects including posttraumatic stress symptoms among family members should be studied.

Characterizing On-Chip Angiogenesis Induction in a Microphysiological System as a Functional Measure of Mesenchymal Stromal Cell Bioactivity.

Mesenchymal stromal cells (MSCs) continue to be proposed for clinical investigation to treat myriad diseases given their purported potential to stimulate endogenous regenerative processes, such as angiogenesis. However, MSC functional heterogeneity has hindered clinical success and still poses a substantial manufacturing challenge from a product quality control perspective. Here, a quantitative bioassay based on an enhanced-throughput is described, microphysiological system (MPS) to measure the specific bioactivity of MSCs to stimulate angiogenesis as a potential measure of MSC potency. Using this novel bioassay, MSCs derived from multiple donors at different passages are co-cultured with human umbilical vein endothelial cells and exhibit significant heterogeneity in angiogenic potency between donors and cell passage. Depending on donor source and cellular passage number, MSCs varied in their ability to stimulate tip cell dominant or stalk cell dominant phenotypes in angiogenic sprout morphology which correlated with expression levels of hepatocyte growth factor (HGF). These findings suggest that MSC angiogenic bioactivity may be considered as a possible potency attribute in MSC quality control strategies. Development of a reliable and functionally relevant potency assay for measuring clinically relevant potency attributes of MSCs will help to improve consistency in quality and thereby, accelerate clinical development of these cell-based products.

Modeling immunity in microphysiological systems.

There is a need for better predictive models of the human immune system to evaluate safety and efficacy of immunomodulatory drugs and biologics for successful product development and regulatory approvals. Current in vitro models, which are often tested in two-dimensional (2D) tissue culture polystyrene, and preclinical animal models fail to fully recapitulate the function and physiology of the human immune system. Microphysiological systems (MPSs) that can model key microenvironment cues of the human immune system, as well as of specific organs and tissues, may be able to recapitulate specific features of the in vivo inflammatory response. This minireview provides an overview of MPS for modeling lymphatic tissues, immunity at tissue interfaces, inflammatory diseases, and the inflammatory tumor microenvironment in vitro and ex vivo. Broadly, these systems have utility in modeling how certain immunotherapies function in vivo, how dysfunctional immune responses can propagate diseases, and how our immune system can combat pathogens.