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Aim: Parents and carers of children with developmental and epileptic encephalopathies (DEEs) experience high rates of mental health disorders including depression and posttraumatic stress disorder. Physical activity is an evidence-based strategy which may help to improve the wellbeing of this population., Method: We delivered a 4-week physical activity group program via a private Facebook group for carers of children with DEEs and their nominated support person. The facilitators provided education and motivation on different weekly topics (e.g. goal setting, overcoming barriers to exercise) and encouraged social support between participants. All participants were provided with a physical activity tracker (Fitbit). The primary outcome was feasibility and secondary outcomes included psychological distress, quality of life, physical activity levels, and PTSD symptoms., Results: N=20 (parents and support partners) were recruited. All participants remained in the program for the full duration and 85% completed the post assessment questionnaires. High acceptability was observed in the qualitative interviews and exploratory analysis of pre-post outcomes found significant improvements in psychological distress and quality of life (ps < 0.01), while changes in physical activity levels and PTSD symptoms were non-significant., Conclusion: A mental health informed physical activity program delivered via Facebook is feasible for carers of children with DEEs and may help improve wellbeing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gene expression studies and gene therapy require efficient gene delivery into cells. Different technologies by viral and non-viral mechanisms have been used for gene delivery into cells. Small gene vectors transfer across the cell membrane with a relatively high efficiency, but not large genes or entire loci spanning several kilobases, which do not remain intact following introduction. Previously, we developed an efficient delivery system based on herpes virus simplex type 1 (HSV-1) amplicons to transfer large fragments of DNA incorporated in human artificial chromosome (HAC) vectors into the nucleus of human cells. The HSV-1 amplicon lacks the signals for cleavage and replication of its own genome, yet each amplicon has the capacity to incorporate up to 150 kb of exogenous DNA. In this study, we investigated whether the capacity of gene delivery could be increased by simultaneously introducing multiple HSV-1 modified amplicons carrying a gene expressing HAC vector into cells with the aim of generating a single artificial chromosome containing the desired genes. Following co-transduction of two HSV-1 HAC amplicons, artificial chromosomes were successfully generated containing the introduced genes, which were appropriately expressed in different human cell types., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous studies by us and others have demonstrated the expression of acetylcholine receptors on epithelial cells in the thymus of myasthenia gravis (MG) and control subjects. In the present experiments, we used a reverse transcription-polymerase chain reaction (RT-PCR) to analyze the profile of the two major isoforms of the alpha chain of these receptors (AChRalpha), P3A- and P3A+, in thymus tissue obtained from MG and control subjects and a human thymic epithelial cell line (TEC9). In addition, using a semiquantitative RT-PCR, we compared the amounts of P3A- and P3A+ mRNA expressed in thymic tissue obtained from these two sources and determined if their expression in TEC9 is modulated by cytokines. We found that mRNAs encoding P3A- and P3A+ are expressed at approximately a 5:1 ratio in both MG and control thymus tissue. This contrasts with skeletal muscle where mRNAs encoding these isoforms are expressed equally. A pattern of preferential P3A- vs P3A+ mRNA expression was also observed in TEC9. We observed 2.8-fold greater expression of both isoforms in MG than in control thymus. Expression of both isoforms in TEC9 was enhanced significantly by treatment with interferon-gamma whereas IL-1alpha, IL-4, and IL-6 had no effect. Thus, there is differential regulation of AChRalpha variants in thymus and TEC relative to muscle and interferon-gamma represents a novel regulator of AChRalpha mRNA expression. MG thymus is distinguished by increased expression of both isoforms of this autoantigen, a finding that may reflect enhancement of transcription by local microenvironmental factors., (Copyright 1999 Academic Press.)