Brief Report: Assessment of Intervention Effects on In Vivo Peer Interactions in Adolescents with Autism Spectrum Disorder (ASD)

This study aimed to evaluate the effectiveness of a randomized controlled trial of a social skills intervention, the Program for the Education and Enrichment of Relational Skills (PEERS: Laugeson et al. in J Autism Dev Disord 39(4): 596–606, 2009), by coding digitally recorded social interactions between adolescent participants with ASD and a typically developing adolescent confederate. Adolescent participants engaged in a 10-min peer interaction at pre- and post-treatment. Interactions were coded using the Contextual Assessment of Social Skills (Ratto et al. in J Autism Dev Disord 41(9): 1277–1286, 2010). Participants who completed PEERS demonstrated significantly improved vocal expressiveness, as well as a trend toward improved overall quality of rapport, whereas participants in the waitlist group exhibited worse performance on these domains. The degree of this change was related to knowledge gained in PEERS

Unveiling the catalytic mechanism of a processive metalloaminopeptidase

Funding: C.M.C. is funded by the Wellcome Trust (210486/Z/18/Z and [204821/Z/16/Z] to the University of StAndrews). M.C.S.is funded by a PhD studentship from the University of St Andrews. B.E.B. acknowledges equipment funding by BBSRC (BB/R013780/1).Intracellular leucine aminopeptidases (PepA) are metalloproteases from the family M17. These enzymes catalyze peptide bond cleavage, removing N-terminal residues from peptide and protein substrates, with consequences for protein homeostasis and quality control. While general mechanistic studies using model substrates have been conducted on PepA enzymes from various organisms, specific information about their substrate preferences and promiscuity, choice of metal, activation mechanisms, and the steps that limit steady-state turnover remain unexplored. Here, we dissected the catalytic and chemical mechanisms of PaPepA: a leucine aminopeptidase from Pseudomonas aeruginosa. Cleavage assays using peptides and small-molecule substrate mimics allowed us to propose a mechanism for catalysis. Steady-state and pre-steady-state kinetics, pH rate profiles, solvent kinetic isotope effects, and biophysical techniques were used to evaluate metal binding and activation. This revealed that metal binding to a tight affinity site is insufficient for enzyme activity; binding to a weaker affinity site is essential for catalysis. Progress curves for peptide hydrolysis and crystal structures of free and inhibitor-bound PaPepA revealed that PaPepA cleaves peptide substrates in a processive manner. We propose three distinct modes for activity regulation: tight packing of PaPepA in a hexameric assembly controls substrate length and reaction processivity; the product leucine acts as an inhibitor, and the high concentration of metal ions required for activation limits catalytic turnover. Our work uncovers catalysis by a metalloaminopeptidase, revealing the intricacies of metal activation and substrate selection. This will pave the way for a deeper understanding of metalloenzymes and processive peptidases/proteases.Publisher PDFPeer reviewe

Frequency and duration of vigorous physical activity bouts are associated with adolescent boys’ bone mineral status: A cross-sectional study

Purpose: Vigorous physical activity (VPA) has been proven to promote osteogenesis in adolescents; however the specifics of the optimal pattern of frequency and duration of VPA are unknown. The main goal of the present study was to analyze the associations of different length of VPA bouts with bone health. Methods: 180 healthy male adolescents (11–13 years) had their bone mineral content and density assessed by dual-energy X-ray absorptiometry scans at the whole body, femoral neck (FN) and lumbar spine and their physical activity measured by an accelerometer during one week. Results: VPA was the intensity with the strongest associations with bone mineral parameters especially at the FN. Subjects whose longest VPA bout was 5 min or above had higher FN bone mineral density (BMD) than those who did not complete any 5-min bout and these differences were greater with participants who reached 15 consecutive minutes of VPA (>15': 0.977 ± 0.020 g/cm2; 5'-15': 0.907 ± 0.009 g/cm2; <5': 0.876 ± 0.009 g/cm2; all p < 0.05). When comparing the relevance of VPA bouts and volume of physical activity, the group with low volume and having a VPA bout had better FN BMD compared to the group with high volume but no VPA bout. Additionally, the group with both high volume and VPA bout showed better FN BMD than the rest of the groups. Conclusions: VPA may be the most effective activity intensity to improve bone mineral density and content of adolescent boys, with greater benefits if VPA periods either long or frequent

Vigorous physical activity patterns affect bone growth during early puberty in boys

Summary: This study aims to analyze the impact of participation in vigorous physical activity as it can promote a healthy bone development. Adolescents who increased their participation in vigorous physical activity showed higher improvements in bone parameters compared to those who did not, which highlights the relevance of vigorous physical activity engagement. Introduction: The main purpose of the study was to analyze the effects of different patterns of vigorous physical activity (VPA) on bone development. Methods: One-week accelerometry registers and dual-energy X-ray absorptiometry scans at the whole body, hip, and lumbar spine of 140 healthy male adolescents (11–13 years, at baseline) were performed twice with a 1-year interval between measurements. Four patterns of VPA evolution (“low–low, ” “low–high, ” “high–low, ” and “high–high”) and three patterns of bone growth (“optimal, ” “mean, ” and “reduced”) were defined according to the median participation in VPA and a cluster analysis of the longitudinal changes in BMC and BMD in all sites measured, respectively. Bone mineral parameters were adjusted for skeletal age and body weight prior to statistical comparison among groups. Results: Participants in the “low–high” group had greater adjusted BMD increases at both the femoral neck and lumbar spine when compared to the “low–low” group (estimated mean (95% CI) 0.066 (0.047–0.085) vs. 0.034 (0.021–0.047) g/cm2 and 0.074 (0.054–0.093) vs. 0.049 (0.035–0.062) g/cm2 respectively, both p &lt; 0.05). Femoral neck BMD adjusted increase was also different between the “high–high” and the “high–low” groups (0.053 (0.041–0.066) vs. 0.030 (0.011–0.049) g/cm2, p &lt; 0.05). Additionally, a higher percentage of “optimal” growth was found in the “low–high” group than in the “low–low” and “high–low” categories (36.3, 12.5 and 13.6% respectively, p &lt; 0.05). Conclusions: Engaging in VPA as well as maintaining high levels of VPA during puberty is associated with greater gains in bone mass, which can have an impact in future bone health

Safety of an intravenous formulation of lamotrigine

AbstractPurposeIntravenous (IV) formulations are useful when treating patients where oral administration is not possible and to study certain pharmacokinetic parameters such as bioavailability. We developed a stable-labeled IV formulation of lamotrigine (LTG) for studying pharmacokinetics in epilepsy patients.MethodsStable-labeled IV LTG was given to 20 persons with epilepsy (6 men; 14 women) with a mean age of 34.8 years (SD 11.7). A 50mg dose of LTG (stable labeled) was given intravenously and replaced 50mg of the regular morning oral dose of LTG (unlabeled, commercially available formulation).ResultsNo significant changes in blood pressure, heart rate, or adverse events including rash were attributed to administration of a 50-mg dose of the intravenous LTG formulation.ConclusionOur results show that LTG base that is complexed with 2-hydroxypropyl-β-cyclodextrin and stable-labeled can be given safely as a tracer replacement dose

Insect herbivores should follow plants escaping their relatives

Neighboring plants within a local community may be separated by many millions of years of evolutionary history, potentially reducing enemy pressure by insect herbivores. However, it is not known how the evolutionary isolation of a plant affects the fitness of an insect herbivore living on such a plant, especially the herbivore's enemy pressure. Here, we suggest that evolutionary isolation of host plants may operate similarly as spatial isolation and reduce the enemy pressure per insect herbivore. We investigated the effect of the phylogenetic isolation of host trees on the pressure exerted by specialist and generalist enemies (parasitoids and birds) on ectophagous Lepidoptera and galling Hymenoptera. We found that the phylogenetic isolation of host trees decreases pressure by specialist enemies on these insect herbivores. In Lepidoptera, decreasing enemy pressure resulted from the density dependence of enemy attack, a mechanism often observed in herbivores. In contrast, in galling Hymenoptera, enemy pressure declined with the phylogenetic isolation of host trees per se, as well as with the parallel decline in leaf damage by non-galling insects. Our results suggest that plants that leave their phylogenetic ancestral neighborhood can trigger, partly through simple density-dependency, an enemy release and fitness increase of the few insect herbivores that succeed in tracking these plants

The effects of spatial legacies following shifting management practices and fire on boreal forest age structure

Forest age structure and its spatial arrangement are important elements of sustainable forestry because of their effects on biodiversity and timber availability. Forest management objectives that include specific forest age structure may not be easily attained due to constraints imposed by the legacies of historical management and natural disturbance. We used a spatially explicit stochastic model to explore the synergetic effects of forest management and fire on boreal forest age structure. Specifically, we examined (1) the duration of spatial legacies of different management practices in the boreal forest, (2) how multiple shifts in management practices affect legacy duration and the spatial trajectories of forest age structure, and (3) how fire influences legacy duration and pattern development in combination with harvesting. Results based on 30 replicates of 500 years for each scenario indicate that (1) spatial legacies persist over 200 years and the rate at which legacies are overcome depends on whether new management targets are in synchrony with existing spatial pattern; (2) age specific goals were met faster after multiple management shifts due to the similar spatial scale of the preceding management types; (3) because large fires can erase the spatial pattern created by smaller disturbances, scenarios with fire had shorter lags than scenarios without fire. These results suggest that forest management goals can be accelerated by applying management at a similar spatial scale as existing spatial patterns. Also, management planning should include careful consideration of historical management as well as current and likely future disturbances

Geographical trends in the yolk carotenoid composition of the pied flycatcher (Ficedula hypoleuca)

Carotenoids in the egg yolks of birds are considered to be important antioxidants and immune stimulants during the rapid growth of embryos. Yolk carotenoid composition is strongly affected by the carotenoid composition of the female’s diet at the time of egg formation. Spatial and temporal differences in carotenoid availability may thus be reflected in yolk concentrations. To assess whether yolk carotenoid concentrations or carotenoid profiles show any large-scale geographical trends or differences among habitats, we collected yolk samples from 16 European populations of the pied flycatcher, Ficedula hypoleuca. We found that the concentrations and proportions of lutein and some other xanthophylls in the egg yolks decreased from Central Europe northwards. The most southern population (which is also the one found at the highest altitude) also showed relatively low carotenoid levels. Concentrations of β-carotene and zeaxanthin did not show any obvious geographical gradients. Egg yolks also contained proportionally more lutein and other xanthophylls in deciduous than in mixed or coniferous habitats. We suggest that latitudinal gradients in lutein and xanthophylls reflect the lower availability of lutein-rich food items in the northern F. hypoleuca populations and in montane southern populations, which start egg-laying earlier relative to tree phenology than the Central European populations. Similarly, among-habitat variation is likely to reflect the better availability of lutein-rich food in deciduous forests. Our study is the first to indicate that the concentration and profile of yolk carotenoids may show large-scale spatial variation among populations in different parts of the species’ geographical range. Further studies are needed to test the fitness effects of this geographical variation

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)