Objective: To evaluate the association between physical activity (PA) and multiple sclerosis (MS) disease activity, depression, and fatigue in a cohort of children with MS and monophasic acquired demyelinating syndrome (mono-ADS).Methods: In this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, we administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. Quantitative MRI analysis was performed to obtain whole brain and T2 lesion volume in a subset of participants (n 5 60). Conclusions: Children with MS are less physically active than children with mono-ADS. Reasons for this are unclear, but may be related to ongoing disease activity, perceived limitations, or symptoms such as depression or fatigue. Children with MS reporting higher levels of strenuous PA had lower T2 lesion volumes and lower relapse rates, suggesting a potential protective effect of strenuous PA in this population. Further longitudinal studies are needed to establish the relationship of PA to MS symptoms and disease activity in this population. Neurology ® 2015;85:1663-1669 GLOSSARY ARR 5 annualized relapse rate; CES-DC 5 Center for Epidemiological Studies Depression Scale for Children; EDSS 5 Expanded Disability Status Scale; GLTEQ 5 Godin Leisure-Time Exercise Questionnaire; HCS 5 health contribution score; IQR 5 interquartile range; MET 5 metabolic equivalent; mono-ADS 5 monophasic acquired demyelinating syndrome; MS 5 multiple sclerosis; NIHPD 5 NIH-funded MRI Study of Normal Brain Development; PA 5 physical activity; PedsQL MFS 5 PedsQL Multidimensional Fatigue Scale; TBV 5 total brain volume.Up to three-quarters of children with multiple sclerosis (MS) have depression, fatigue, or cognitive impairment.1,2 Children with MS experience more active disease than adults with MS, as demonstrated by increased lesion burden on MRI, 3 relapse frequency, 4 and irreversible motor disability occurring in young adulthood. 5 Little is known about behavioral approaches for managing these problems in pediatric MS, but multicomponent interventions involving physical activity (PA) have improved cognition, mathematics, and reading, 6,7 and exercise interventions have improved depression, 8 executive function, and cognition, 9 in healthy children and individuals with chronic illnesses.Several studies support relationships between PA and outcomes in adult MS. Studies have documented lower PA levels in patients with MS than healthy controls 10,11 ; the level of premorbid PA predicts the trajectory of disability scores 12 ; and an association has been demonstrated between

No abstract

SUMMARYIndividual cell shape changes are essential for epithelial morphogenesis. A transcriptional network for epithelial cell shape change is emerging in Drosophila, but this area remains largely unexplored in vertebrates. The distinction is important as so far, key downstream effectors of cell shape change in Drosophila appear not to be conserved. Rather, Shroom3 has emerged as a central effector of epithelial morphogenesis in vertebrates, driving both actin-and microtubule-based cell shape changes. To date, the morphogenetic role of Shroom3 has been explored only in the neural epithelium, so the broad expression of this gene raises two important questions: what are the requirements for Shroom3 in non-neural tissues and what factors control Shroom3 transcription? Here, we show in Xenopus that Shroom3 is essential for cell shape changes and morphogenesis in the developing vertebrate gut and that Shroom3 transcription in the gut requires the Pitx1 transcription factor. Moreover, we show that Pitx proteins directly activate Shroom3 transcription, and we identify Pitx-responsive regulatory elements in the genomic DNA upstream of Shroom3. Finally, we show that ectopic expression of Pitx proteins is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change. These data demonstrate new breadth to the requirements for Shroom3 in morphogenesis, and they also provide a cell-biological basis for the role of Pitx transcription factors in morphogenesis. More generally, these results provide a foundation for deciphering the transcriptional network that underlies epithelial cell shape change in developing vertebrates.

Rates of non-adherence varied by information source. Better self-reported physical functioning was the strongest predictor of adherence. Parental involvement in adherence was associated with worse PedsQL School Functioning and lower MS Self-Efficacy-measured confidence in controlling MS.

No abstract

ABBREVIATIONS IVIGIntravenous immunoglobulin MOG Myelin oligodendrocyte glycoproteinThe aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population.Myelin oligodendrocyte glycoprotein (MOG) antibodies are seen in the serum of 25% to 58% of children who present with a first acquired demyelinating syndrome, 1-5 and may also be seen in adults presenting with acute neuroinflammation (4-15%). 3,5-7 Twenty-five per cent to almost 75% will continue to have high titers of MOG antibodies after presenting acutely, 8 with considerable risk of relapse. 9 In one adult-based cohort of 252 patients in the UK with elevated MOG antibodies, 36% had relapses within a median duration of 16 months. 8 Steroids, intravenous immunoglobulin (IVIG), and plasma exchange 10 may be beneficial in reducing symptomatology at the time of an acute event, but are unlikely to decrease the risk of relapse.There is variable support in the literature for the relevance of persistent MOG antibody status for predicting recurrent disease. 11,12 However, prevention of recurrence in the face of repeated neuroinflammatory events prevent future disability. Given the potential for irreversible neurological disability, 13 and the robust response of other antibody-mediated conditions to B-cell suppression with rituximab therapy, 14 we used a standardized treatment protocol using rituximab in children with recurrent central nervous system (CNS) inflammatory disease and persistent MOG antibody positivity 12 weeks or more af...

Purpose To report the results of a randomized controlled trial using an electronic monitoring device (EM) plus a motivational interviewing (MI) intervention to enhance adherence to disease-modifying therapies (DMT) in pediatric MS. Methods Fifty-two youth with MS (16.03 ± 2.2 years) were randomized to receive either MI (n = 25) (target intervention) or a MS medication video (n = 27) (attention control). Primary endpoint was change in adherence. Secondary outcomes included changes in quality of life, well-being and self-efficacy. Random effects modeling and Cohen’s effect size computation evaluated intervention impact. Results Longitudinal random effect models revealed that the MI group decreased their EM adherence (GroupxTime interaction = −0.19), while increasing frequency of parental DMT reminder (26.01)/administration (11.69). We found decreased EM use in the MI group at 6 months (Cohen’s d = −0.61), but increased pharmacy refill adherence (d = 0.23). Parental reminders about medication increased in MI subjects vs controls (d = 0.59 at 3 months; d = 0.70 at 6 months). We found increases in self-reported adherence (d = 0.21) at 3 but not 6 months, fewer barriers to adherence at three (d = −0.58) and six months (d = −0.31), better physical (d = 0.23 at 3 months; d = 0.45 at 6 months), emotional (d = 0.25 at 3 months) and self-efficacy function (d = 0.55 at 3 months; 0.48 at 6 months), but worse well-being, including self-acceptance (d = −0.53 at 6 months) and environmental mastery (d = −0.42 at 3 and 6 months) in intervention as compared to control patients. Conclusions Participants receiving MI + EM experienced worsening on objective measures of adherence and increased parental involvement, but improved on some self- and parent-reported measures. MI participants reported improvements in quality of life and self-efficacy, but worsened well-being.

To date, there is limited published data on same-sex male couples and single men using assisted reproduction treatment to build their families. The objective of this retrospective study was to better understand treatment considerations and outcomes for this population when using assisted reproduction treatment. A total of 37 same-sex male couples and eight single men (seven homosexual and one heterosexual) who attended the CReATe Fertility Centre for assisted reproduction services were studied. There was a 21-fold increase in the number of same-sex male couples and single men undergoing assisted reproduction treatment since 2003. The mean age was 46years (24-58). Twenty-eight couples (76%) chose to use spermatozoa from both partners to fertilize their donated oocytes. Most men (32 same-sex male couples and seven single men; 87%) obtained oocytes from an anonymous donor, whereas five couples and one single man (13%) had a known donor. Anonymous donors who were open to be contacted by the child after the age of 18 were selected by 67% of patients. Of all 25 deliveries, eight (32%) were sets of twins. All of the twins were half genetic siblings.