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Background: Rates of mental health problems among youth are high and rising, whereas treatment seeking in this population remains low. Technology-delivered interventions (TDIs) appear to be promising avenues for broadening the reach of evidence-based interventions for youth well-being. However, to date, meta-analytic reviews on youth samples have primarily been limited to computer and internet interventions, whereas meta-analytic evidence on mobile TDIs (mTDIs), largely comprising mobile apps for smartphones and tablets, have primarily focused on adult samples., Objective: This study aimed to evaluate the effectiveness of mTDIs for a broad range of well-being outcomes in unselected, at-risk, and clinical samples of youth., Methods: The systematic review used 5 major search strategies to identify 80 studies evaluating 83 wellness- and mental health-focused mTDIs for 19,748 youth (mean age 2.93-26.25 years). We conducted a 3-level meta-analysis on the full sample and a subsample of the 38 highest-quality studies., Results: Analyses demonstrated significant benefits of mTDIs for youth both at posttest (g=0.27) and follow-up (range 1.21-43.14 weeks; g=0.26) for a variety of psychosocial outcomes, including general well-being and distress, symptoms of diverse psychological disorders, psychosocial strategies and skills, and health-related symptoms and behaviors. Effects were significantly moderated by the type of comparison group (strongest for no intervention, followed by inert placebo or information-only, and only marginal for clinical comparison) but only among the higher-quality studies. With respect to youth characteristics, neither gender nor pre-existing mental health risk level (not selected for risk, at-risk, or clinical) moderated effect sizes; however, effects increased with the age of youth in the higher-quality studies. In terms of intervention features, mTDIs in these research studies were effective regardless of whether they included various technological features (eg, tailoring, social elements, or gamification) or support features (eg, orientation, reminders, or coaching), although the use of mTDIs in a research context likely differs in important ways from their use when taken up through self-motivation, parent direction, peer suggestion, or clinician referral. Only mTDIs with a clear prescription for frequent use (ie, at least once per week) showed significant effects, although this effect was evident only in the higher-quality subsample. Moderation analyses did not detect statistically significant differences in effect sizes based on the prescribed duration of mTDI use (weeks or sessions), and reporting issues in primary studies limited the analysis of completed duration, thereby calling for improved methodology, assessment, and reporting to clarify true effects., Conclusions: Overall, this study's findings demonstrate that youth can experience broad and durable benefits of mTDIs, delivered in a variety of ways, and suggest directions for future research and development of mTDIs for youth, particularly in more naturalistic and ecologically valid settings., (©Colleen S Conley, Elizabeth B Raposa, Kate Bartolotta, Sarah E Broner, Maya Hareli, Nicola Forbes, Kirsten M Christensen, Mark Assink. Originally published in JMIR Mental Health (https://mental.jmir.org), 29.07.2022.)

Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction in NARS1 mRNA expression as well as in NARS1 enzyme levels and activity in both individual fibroblasts and induced neural progenitor cells (iNPCs). Molecular modeling of the recessive c.1633C>T (p.Arg545Cys) variant shows weaker spatial positioning and tRNA selectivity. We conclude that de novo and bi-allelic mutations in NARS1 are a significant cause of neurodevelopmental disease, where the mechanism for de novo variants could be toxic gain-of-function and for recessive variants, partial loss-of-function., (Copyright © 2020. Published by Elsevier Inc.)

Statewide newborn screening for Pompe disease began in Illinois in 2015. As of 30 September 2019, a total of 684,290 infants had been screened and 395 infants (0.06%) were screen positive. A total of 29 cases of Pompe disease were identified (3 infantile, 26 late-onset). While many of the remainder were found to have normal alpha-glucosidase activity on the follow-up testing (234 of 395), other findings included 62 carriers, 39 infants with pseudodeficiency, and eight infants who could not be given a definitive diagnosis due to inconclusive follow-up testing., Competing Interests: Conflicts of InterestB.K.B. has received consulting fees and/or honoraria from Sanofi Genzyme, Biomarin, Shire (a Takeda company), Ultragenyx, Moderna, Horizon, Alexion, Chiesi, Denali, JCR Pharma, Aeglea, and Agios. She has conducted contracted research for Sanofi Genzyme, Biomarin, Shire, Alexion, Ultragenyx, and Sangamo and Homology Medicines. J.C. has also received grant support for research from: Sanofi Genzyme, Shire, Amicus, BioMarin, and Protalix. Dorothy K. Grange conducts contracted research for Biomarin and Shire (a Takeda company). The following authors declare no conflict of interest: K.B., S.R.B., K.M.C., J.F., D.G., R.H., L.H., G.E.H., H.S., R.S., and P.S., (© 2020 by the authors.)

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic condition characterized by ocular, cutaneous, and central nervous system anomalies. Key clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas. Seizures, spasticity, and intellectual disability can be present, although affected individuals without seizures and with normal intellect have also been reported. Given the patchy and asymmetric nature of the malformations, ECCL has been hypothesized to be due to a post-zygotic, mosaic mutation. Despite phenotypic overlap with several other disorders associated with mutations in the RAS-MAPK and PI3K-AKT pathways, the molecular etiology of ECCL remains unknown. Using exome sequencing of DNA from multiple affected tissues from five unrelated individuals with ECCL, we identified two mosaic mutations, c.1638C>A (p.Asn546Lys) and c.1966A>G (p.Lys656Glu) within the tyrosine kinase domain of FGFR1, in two affected individuals each. These two residues are the most commonly mutated residues in FGFR1 in human cancers and are associated primarily with CNS tumors. Targeted resequencing of FGFR1 in multiple tissues from an independent cohort of individuals with ECCL identified one additional individual with a c.1638C>A (p.Asn546Lys) mutation in FGFR1. Functional studies of ECCL fibroblast cell lines show increased levels of phosphorylated FGFRs and phosphorylated FRS2, a direct substrate of FGFR1, as well as constitutive activation of RAS-MAPK signaling. In addition to identifying the molecular etiology of ECCL, our results support the emerging overlap between mosaic developmental disorders and tumorigenesis., (Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Purpose: Fabry disease is a pan-ethnic, progressive, X-linked genetic disorder that commonly presents in childhood and is caused by deficient activity of the lysosomal enzyme alpha-galactosidaseA (α-gal A). Symptoms of Fabry disease in the pediatric population are well described for patients over five years of age; however, data are limited for infancy and early childhood. The purpose of this article is to delineate the age of detection for specific Fabry symptoms in early childhood., Methods: A systematic retrospective analysis of PubMed indexed, peer-reviewed publications and case reports in the pediatric Fabry population was performed to review symptoms in patients reported before 5 years of age., Results: The most frequently reported symptom in all age groups under 5 years was acroparesthesias/neuropathic pain, reported in 9 children, ranging in age from 2.0-4.0 years. Also notable is the frequency of gastrointestinal issues reported in 6 children aged 1.0-4.1 years of age., Conclusion: This article finds clear evidence that symptoms can occur in early childhood, before age 5 years. Given early presenting symptoms and the ability to monitor these disease hallmarks, a timely referral to a medical geneticist or other specialty clinician experienced in managing children with Fabry disease is strongly indicated.

Introduction: Using data from the 2004 Texas Behavioral Risk Factor Surveillance System, we investigated whether the physical activity behaviors of people with disabilities are related to their perceptions of the characteristics of the built environment and whether this relationship differs from that of people without disabilities., Methods: The research questions were, "Are perceived neighborhood characteristics and reported use of community facilities associated with reported leisure-time physical activity for adults aged 18 to 64 years with disabilities?"; "Are perceived neighborhood characteristics and reported use of community facilities associated with reported moderate to vigorous physical activity for adults with disabilities?"; and "To what extent do perceived neighborhood characteristics, reported use of community facilities, reported leisure-time physical activity, and reported moderate to vigorous physical activity differ between adults with disabilities and without disabilities?" We used logistic regression to analyze the responses., Results: People with disabilities were less likely to engage in leisure-time physical activity and meet recommendations for physical activity than people without disabilities. Participation of people with disabilities in leisure-time physical activity had significant correlations with positive perceptions of neighbors, physical activity, trails, parks, playgrounds, or sports fields, and with their use of private or membership-only recreation facilities. The presence of sidewalks was significantly related to whether people with disabilities met recommended levels of physical activity., Conclusion: Although people with disabilities engaged in less leisure-time physical activity and physical activity than people without disabilities, perceptions of the built environment and use of community facilities similarly affected people with and without disabilities.

Purpose: To investigate the potential influence of additional copy number variants in patients with 15q24 rearrangements and the possible underlying mechanisms for these rearrangements., Methods: Oligonucleotide-based chromosomal microarray analyses were performed, and the results were subsequently confirmed by fluorescence in situ hybridization analyses. Long-range polymerase chain reaction amplification and DNA sequencing analysis were used for breakpoint junction sequencing., Results: We describe a 15-year-old boy with cognitive impairment and dysmorphic features with deletions in 15q24 and 3q21, a 2-month-old female infant with growth deficiency, heterotaxy, cardiovascular malformations, intestinal atresia, and duplications in 15q24 and 16q22, and a 3.5-year-old boy with developmental delay, microcephaly, and dysmorphic features, with duplications in 15q24 and 2q36.3q37.1. Breakpoint sequencing for the 15q24 deletion in the first patient revealed microhomology and suggested the underlying mechanism of either nonhomologous end joining or fork stalling and template switching/microhomology-mediated break-induced replication., Conclusions: The three described patients with 15q24 rearrangements have copy number variants at other loci and exhibit additional clinical features with a more severe phenotype than that observed in previously reported patients with isolated 15q24 rearrangements, suggesting that the genomic mutational load may contribute to the phenotypic severity and variability in patients with 15q24 rearrangements.

The partitioning behavior of the polycyclic aromatic hydrocarbon (PAH) compounds naphthalene and phenanthrene with the temperate green seaweed Acrosiphonia coalita was characterized. The uptake and partitioning experiments were designed to prevent PAH volatilization, and the PAH concentration was measured in both the seawater liquid medium and in the algal biomass. Axenic microplantlets of A. coalita were used in all experiments to eliminate the possibility of microbial PAH biotransformation. Gas chromatography/mass spectrometry analysis did not reveal any putative metabolites of phenanthrene oxidative biotransformation in either the seawater medium or the algal biomass, but did show that dissolved organic matter from algal biomass constituents were in the liquid medium. The algal biomass grew by 30% over the 114h duration of the partitioning experiments, suggesting PAH compounds did not harm the organism. Both living and heat-killed microplantlets partitioned PAH compounds into the biomass. Naphthalene and phenanthrene reversibly partitioned into the lipid fraction of the algal biomass with equilibrium partitioning constants of 0.130+/-0.007 and 1.58+/-0.03Lg(-1) dry cell mass, respectively, which scaled proportionally to their octanol-water partitioning constants. The PAH material balance for the partitioning process closed between 86% and 100% for naphthalene adsorption and phenanthrene desorption, but closed at 52% for phenanthrene adsorption. To account for the loss, it was proposed that phenanthrene interacted with dissolved organic matter released by the living algal biomass. This study has provided fundamental information needed to assess how seaweeds can play a role in the bioaccumulation and bioremediation of PAH compounds in the marine environment.

We report on a case of cloverleaf skull deformity in a patient with hypochondroplasia, a disorder which has not been previously associated with this anomaly. Hypochondroplasia is a bone dysplasia caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Cloverleaf skull is a trilobar skull deformity which is etiologically and genetically heterogeneous and occurs in association with a number of disorders which result from mutations in the fibroblast growth factor receptor genes. Our patient demonstrated one of the common FGFR3 mutations identified in hypochondroplasia, a C-to-A change at nucleotide 1620 (C1620A) in the tyrosine kinase domain. The occurrence of a cloverleaf skull deformity appears to represent an example of variable expressivity in hypochondroplasia and suggests that additional factors other than a specific mutation can modify the phenotype in this disorder. In addition, identification of another FGFR mutation associated with cloverleaf skull further illustrates the genetic heterogeneity of this anomaly.

Using 6 years of observational and experimental data, we examined the hypothesis that water and nutrient stress increase the susceptibility of pinyon pine (Pinus edulis) to the stem- and cone-boring moth (Dioryctria albovittella). At two geographic levels, a local scale of 550 km 2 and a regional scale of 10,000 km 2 , moth herbivory was strongly correlated with an edaphic stress gradient. At a local scale, from the cinder soils of Sunset Crater to nearby sandy-loam soils, nine of ten soil macro- and micronutrients, and soil water content were lowest in cinder-dominated soils. Herbivore damage was six times greater on trees growing in the most water and nutrient deficient site at Sunset Crater compared to sites with well-developed soils. Percentage silt-clay content of soil, which was highly positively correlated with soil nutrient and soil moisture at a local scale, accounted for 56% of the variation in herbivory at a regional scale among 22 sites. Within and across sites, increased stem resin flow was positively associated with reduced moth attack. On the basis of moth distribution across a stress gradient, we predicted that pinyons growing in highly stressful environments would show increased resistance to herbivores if supplemented with water and/or nutrients. We conducted a 6-year experiment at a high-stress site where individual trees received water only, fertilizer only, and water + fertilizer. Relative to control trees, stem growth and resin flow increased in all three treatments, but only significantly in the water + fertilizer treatment. Although there was no significant difference in herbivore damage among these three treatments, there was an overall reduction in herbivore damage on all treatment trees combined, compared to control trees. This experiment suggests that release from stress leads to increased resistance to insect attack and is consistent with our observational data. While other studies have predicted that short-term stress will result in herbivore outbreaks, our studies extend this prediction to chronically stressed host populations. Finally, while flush-feeders are not predicted to respond positively to stressed host plants, we found a positive association between herbivore attack and stressed pinyon populations.

We examined the abundances of three common insect herbivores on pure and hybrid pinyon pines along a 250-km transect in west-central Arizona, United States. Using six morphological traits, we developed a hybrid index to classify trees as pure Pinus californiarum, hybrid, or pure Pinus edulis. The insects (the stem-boring moth, Dioryctria albovittella, the scale insect, Matsucoccus acalyptus, and several species of pitch moths that produce wounds on the trunk and branches) exhibited different distributional patterns across tree types. Stem-boring moths were significantly more abundant on trees at "hybrid" sites compared to trees at "pure" sites. In addition, within hybrid sites, hybrids supported significantly more moth larvae than pure trees of either species. These two patterns support the hybrid susceptibility hypothesis in which hybrid breakdown results in increased susceptibility to herbivory. In contrast to stem-borers, there were significantly more pitch moth wounds on trees at pure P. californiarum sites than at hybrid and pure P. edulis sites. Within the hybrid zone, pitch moth abundance was equal on pure P. californiarum and hybrids, and both were significantly greater than on pure P. edulis. These within-site comparisons support the dominance hypothesis where hybrid resistance differs from one tree species, but not the other. Scale insects exhibited the most restricted distribution; over the 250 km transect they were found only in the hybrid zone. This supports the hybrid susceptibility and/or the stress hypothesis (i.e., species at the edge of their range suffer greater stress and are more susceptible to herbivory). We summed the mean numbers of these three common herbivores across sites and found that hybrid sites supported 2.1 and 3.9 times more herbivores than pure P. californiarum and P. edulis sites, respectively. Furthermore, tree mortality was on average, 35 times greater within the hybrid zone compared to pure zones of each species and was associated with the cumulative abundance of herbivores (r 2 =0.646). Regardless of whether this mortality is due to insect infestation, stress or a combination of both, these results suggest that hybrid zones are important arenas of natural selection.

Arizona's Sunset Crater began erupting in 1064 AD and for the next 200 years buried over 2,000 km 2 in ash, cinders, and lava. Soil analyses indicate that pinyon pines (Pinus edulis) currently colonizing the cinder fields are faced with a highly stressful environment. Many of these pinyons suffer chronic, intense insect herbivory that reduces plant growth and eliminates female cone production. In contrast, herbivory among pinyons growing in neighboring sandy-loam soils is minimal. Furthermore, numerous trees within the heavily infested cinder field population suffer relatively low herbivory and maintain normal growth and reproduction. We used four polymorphic enzymes to examine the relationship between herbivore attack, environmental stress and genotypes of the adjacent cinder field, and sandy-loam soil pinyon populations. Our results demonstrate that 1) resistant trees display significant genetic differences and are more heterozygous for two enzymes associated with herbivory than susceptible trees; and 2) the cinder-soil pinyons exhibit significant genetic differences and are more heterozygous for an enzyme associated with environmental stress than the neighboring sandy-loam soil pinyons. We conclude that heterozygosity of specific or closely linked loci may facilitate pinyon resistance to herbivory and environmental stress, and that strong selection across narrow geographic boundaries resulted in rapid genetic differentiation of pinyon populations., (© 1991 The Society for the Study of Evolution.)

The influences of Colorado pinyon pine (Pinus edulis) cone crop size, cone and seed weight, cone length, number of seeds per cone, number of viable seeds, and percent viable seeds on the foraging behavior of avian seed dispersal agents were examined in field and laboratory settings. In the field, there was a significant positive relationship between cone number per tree and both the absolute number of cones and the percentage of the cone crop from which seeds were harvested. Cone weight and the number of viable seeds were also significantly related to seed harvest intensity. Laboratory experiments examined the relationship between crop size and cone characters on seed harvest by 18 Clark's Nutcrackers (Nucifraga columbiana). Nutcrackers were offered a choice of two tree types: one with 20 cones attached, and another with 10 cones attached. Significantly more birds chose to remove seeds first from the tree with 20 cones than the tree with 10 cones. In timed trials, they also harvested seeds from significantly more cones on the tree with the higher cone density. In the laboratory, cones chosen for seed removal by the nutcrackers had significantly more viable seeds, more seeds, and were longer compared to cones that were not chosen. Such discriminatory foraging behavior may increase avian foraging efficiency and result in differential reproductive success of pinyon pines. This behavior may therefore influence the evolution of pinyon pine reproductive traits.

The pilot study of Newman Taylor et al (1976) in which, by adding bromocriptine to the full medical treatment, they improved the symptoms of three out of four asthmatic patients, prompted us to carry out this study. Bromocriptine is a dopaminergic agonist that is used in acromegalic patients, as well as an inhibitor of prolactin in doses of 5 to 20 mg a day. We decided to use 15 mg a day, which is usually without major side effects.