31 research outputs found
Temperament and Sensory Features of Children with Autism
This study sought to characterize temperament traits in a sample of children with autism spectrum disorder (ASD), ages 3–7 years old, and to determine the potential association between temperament and sensory features in ASD. Individual differences in sensory processing may form the basis for aspects of temperament and personality, and aberrations in sensory processing may inform why some temperamental traits are characteristic of specific clinical populations
Two Antagonistic MALT1 Auto-Cleavage Mechanisms Reveal a Role for TRAF6 to Unleash MALT1 Activation.
The paracaspase MALT1 has arginine-directed proteolytic activity triggered by engagement of immune receptors. Recruitment of MALT1 into activation complexes is required for MALT1 proteolytic function. Here, co-expression of MALT1 in HEK293 cells, either with activated CARD11 and BCL10 or with TRAF6, was used to explore the mechanism of MALT1 activation at the molecular level. This work identified a prominent self-cleavage site of MALT1 isoform A (MALT1A) at R781 (R770 in MALT1B) and revealed that TRAF6 can activate MALT1 independently of the CBM. Intramolecular cleavage at R781/R770 removes a C-terminal TRAF6-binding site in both MALT1 isoforms, leaving MALT1B devoid of the two key interaction sites with TRAF6. A previously identified auto-proteolysis site of MALT1 at R149 leads to deletion of the death-domain, thereby abolishing interaction with BCL10. By using MALT1 isoforms and cleaved fragments thereof, as well as TRAF6 WT and mutant forms, this work shows that TRAF6 induces N-terminal auto-proteolytic cleavage of MALT1 at R149 and accelerates MALT1 protein turnover. The MALT1 fragment generated by N-terminal self-cleavage at R149 was labile and displayed enhanced signaling properties that required an intact K644 residue, previously shown to be a site for mono-ubiquitination of MALT1. Conversely, C-terminal self-cleavage at R781/R770 hampered the ability for self-cleavage at R149 and stabilized MALT1 by hindering interaction with TRAF6. C-terminal self-cleavage had limited impact on MALT1A but severely reduced MALT1B proteolytic and signaling functions. It also abrogated NF-κB activation by N-terminally cleaved MALT1A. Altogether, this study provides further insights into mechanisms that regulate the scaffolding and activation cycle of MALT1. It also emphasizes the reduced functional capacity of MALT1B as compared to MALT1A
Differential Associations Between Sensory Response Patterns and Language, Social, and Communication Measures in Children With Autism or Other Developmental Disabilities
Examine patterns of sensory responsiveness (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) as factors that may account for variability in social-communicative symptoms of autism and variability in language, social, and communication skill development in children with autism or other developmental disabilities
Psychometric Validation of the Sensory Experiences Questionnaire
We evaluated the psychometric properties of the Sensory Experiences Questionnaire (Version 1; Baranek, David, Poe, Stone, & Watson 2006), a brief caregiver questionnaire for young children with autismand developmental delays used to identify sensory processing patterns in the context of daily activities
Congenital human toxoplasmosis caused by non-clonal Toxoplasma gondii genotypes in Argentina
Toxoplasmosis, a worldwide distributed zoonosis, can be transmitted congenitally affecting fetuses and developing variable clinical signs. Different Toxoplasma gondii genotypes and infective dose are related factors with different clinical manifestations. Several studies indicate that atypical strains could produce more severe clinical manifestations compared to typical strains. Umbilical cord blood (n = 37) and placenta (n = 19) were collected at birth from women with acute T. gondii infection and processed for isolation by mice bioassay. Six isolates were obtained and identified as TgHm14-4Arg, TgHm15-02Arg, TgHm16-01Arg, TgHm16-02Arg, TgHm17-01Arg and TgHm17-02Arg. Three genotypes described previously on Toxo-DB were identified: #138 identified in chickens from Brazil, #182 isolated from eared doves from Brazil, #14 from wallaby kangaroos and chickens from Argentina, chickens from Brazil, Colombia, Chile and Venezuela, cats and dogs from Brazil and Colombia and also coyotes from USA indicating worldwide distribution of these genotypes. Two new allele combinations were obtained showing high genotypes diversity in Argentina. Four of the isolates (TgHm14-4Arg, TgHm15-02Arg, TgHm16-01Arg, TgHm16-02Arg) and two of them (TgHm17-01Arg, TgHm17-02Arg) produced chronic and acute infections in mice, respectively. Until now, seven T. gondii isolates have been obtained from humans in Argentina, and all were atypical or non-clonal genotypes. The identification of atypical strains causing congenital toxoplasmosis and circulating in our region, make important to perform the serological screenings according Argentine Consensus of Toxoplasmosis and to apply and monitoring treatments earlier in pregnancy. To achieve this aim, it is necessary to inform general population about T. gondii infection, diagnostics and control measures. These results should serve to generate awareness about congenital toxoplasmosis in South America.Facultad de Ciencias Veterinaria
Nicotine preloading for smoking cessation: the Preloading RCT
Background: Nicotine preloading means using nicotine replacement therapy prior to a quit date while
smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after
quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and
heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with
no cost-effectiveness data.
Objectives: To assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS
setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness
of preloading.
Design: Open-label randomised controlled trial with examination of mediation and a cost-effectiveness
analysis.
Setting: NHS smoking cessation clinics.
Participants: People seeking help to stop smoking. Interventions: Nicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support.
Randomisation was stratified by centre and concealed from investigators.
Main outcome measures: The primary outcome was 6-month prolonged abstinence assessed using the
Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs)
were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of
varenicline (Champix®; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness
analysis took a health-service perspective. The within-trial analysis assessed health-service costs during
the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case
was based on multiple imputation for missing cost data. We modelled long-term health outcomes of
smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection
from Tobacco (EQUIPT) model.
Results: In total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the
control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people
discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically
validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129
(14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI)
–0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62; p = 0.081]. Adjusted for use
of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73; p = 0.028). Secondary abstinence
outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03).
Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the
control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated
the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up
for preloading relative to control was £710 (95% CI –£13,674 to £23,205), but preloading was dominant
at 12 months and in the long term, with an 80% probability that it is cost saving.
Limitations: The open-label design could partially account for the mediation results. Outcome assessment
could not be blinded but was biochemically verified.
Conclusions: Use of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can
increase the proportion of people who stop successfully, but its benefit is undermined because it reduces
the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading
appears to improve health and reduce health-service costs in the long term. Future work should determine
how to ensure that people using nicotine preloading opt to use varenicline as cessation medication.
Trial registration: Current Controlled Trials ISRCTN33031001.NIHR Health Technology Assessment programm
Carrot psyllid (Trioza apicalis) winter habitats - insights in shelter plant preference and migratory capacity
The carrot psyllid (Trioza apicalis) is a serious pest in carrot-growing areas in northern and parts of central Europe. The psyllids overwinter as adults on conifers and during summer feed and lay eggs on carrot plants (Daucus carota ssp. sativus), thereby destroying the crop. To investigate the migratory capabilities and preferences for different shelter plant species of the carrot psyllid, we made an inventory study of its winter habitats in three carrot-growing regions in southern Sweden. Norway spruce (Picea abies) was the preferred conifer over Scots pine (Pinus sylvestris) and juniper (Juniperus communis). We found psyllids on trees up to 1 km from the carrot fields, which was the largest distance sampled. The regression of catch numbers over distance was non-significant, however all samples containing more than seven psyllids were collected within 250m distance from the fields. There was no obvious pattern between catch directions and the prevailing wind directions of the preceding migratory period. Our study did not show any differences between males and females with respect to migration or shelter species preferences