Objective. To examine the effectiveness of high-intensity aerobic training compared with low-intensity training in terms of energy cost of locomotion, peak oxygen uptake, peak power, and self-reported physical function in children with juvenile idiopathic arthritis (JIA). Methods. Eighty children with JIA, ages 8 -16 years, were enrolled in a randomized, single-blind controlled trial. Both groups participated in a 12-week, 3-times-weekly training program consisting of high-intensity aerobics in the experimental group and qigong in the control group. Subjects underwent exercise testing measuring submaximal oxygen uptake at 3 km/hour (VO 2submax ) as the primary outcome, maximal oxygen uptake, and peak power at the beginning and end of the program. Physical function was measured using the Child Health Assessment Questionnaire (C-HAQ). Results. The exercise program was well tolerated in both groups. There was no difference in VO 2submax or any other exercise testing measures between the groups through the study period and no indication of improvement. Both groups showed significant improvements in C-HAQ with no difference between the groups. Adherence was higher in the control group than the experimental group. Conclusion. Our findings suggest that activity programs with or without an aerobic training component are safe and may result in an important improvement in physical function. The intensity of aerobic training did not seem to provide any additional benefits, but higher adherence in the qigong program may suggest that less intensive regimens are easier for children with JIA to comply with, and provide a degree of benefit equivalent to more intensive programs.

Although the prevalence rates of sleep disorders at different stages of childhood and adolescence have been well established, little is known about the developmental course of general sleep problems. This also holds true for the bidirectional relationship between sleep problems and emotional as well as behavioral difficulties. This longitudinal study investigated the general pattern and the latent trajectory classes of general sleep problems from a large community sample aged 5–14 years. In addition, this study examined the predictive value of emotional/behavioral difficulties (i.e., anxiety/depression, attention problems, and aggressive behavior) on sleep problems latent trajectory classes, and vice-versa. Participants (N = 1993) were drawn from a birth cohort of Western Australian children born between 1989 and 1991 who were followed until 14 years of age. Sleep problems were assessed at ages 5, 8, 10, and 14, respectively, whereas anxiety/depression, attention problems, and aggressive behavior were assessed at ages 5 and 17 years. Latent growth curve modeling revealed a decline in an overall pattern of sleep problems during the observed 10-year period. Anxiety/depression was the only baseline factor that predicted the longitudinal course of sleep problems from ages 5 to 14 years, with anxious and depressed participants showing faster decreasing patterns of sleep problems over time than those without anxiety or depression. Growth mixture modeling identified two classes of sleep problem trajectories: Normal Sleepers (89.4%) and Troubled Sleepers (10.6%). Gender was randomly distributed between these groups. Childhood attention problems, aggressive behavior, and the interaction between gender and anxiety/depression were significantly predictive of membership in the group of Troubled Sleepers. Group membership in Troubled Sleepers was associated with higher probability of having attention problems and aggressive behavior in mid-adolescence. Boys and girls with behavioral difficulties, and girls with emotional difficulties were at increased risk of having sleep problems during later childhood and adolescence. Developmental trajectories of sleep problems were also predictive of behavioral difficulties in later life. Findings from this study provide empirical evidence for the heterogeneity of sleep problems and their development, and emphasize the importance of understanding sleep problems and their relationship to children and adolescents’ mental health.

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Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology. Genetic ALS may also be amenable to investigating earlier intervention given the possibility of identifying clinically presymptomatic, at-risk individuals with causative genetic variants. There is increasing evidence for a presymptomatic phase of ALS, with biomarker data from the Pre-Symptomatic Familial ALS (Pre-fALS) study showing that an elevation in blood neurofilament light chain (NfL) precedes phenoconversion to clinically manifest disease. Tofersen is an investigational antisense oligonucleotide designed to reduce synthesis of superoxide dismutase 1 (SOD1) protein through degradation of SOD1 mRNA. Informed by Pre-fALS and the tofersen clinical development program, the ATLAS study (NCT04856982) is designed to evaluate the impact of initiating tofersen in presymptomatic carriers of SOD1 variants associated with high or complete penetrance and rapid disease progression who also have biomarker evidence of disease activity (elevated plasma NfL). The ATLAS study will investigate whether tofersen can delay the emergence of clinically manifest ALS. To our knowledge, ATLAS is the first interventional trial in presymptomatic ALS and has the potential to yield important insights into the design and conduct of presymptomatic trials, identification, and monitoring of at-risk individuals, and future treatment paradigms in ALS.

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