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

The Structure of Ca2+ Sensor Case16 Reveals the Mechanism of Reaction to Low Ca2+ Concentrations

Here we report the first crystal structure of a high-contrast genetically encoded circularly permuted green fluorescent protein (cpGFP)-based Ca2+ sensor, Case16, in the presence of a low Ca2+ concentration. The structure reveals the positioning of the chromophore within Case16 at the first stage of the Ca2+-dependent response when only two out of four Ca2+-binding pockets of calmodulin (CaM) are occupied with Ca2+ ions. In such a “half Ca2+-bound state”, Case16 is characterized by an incomplete interaction between its CaM-/M13-domains. We also report the crystal structure of the related Ca2+ sensor Case12 at saturating Ca2+ concentration. Based on this structure, we postulate that cpGFP-based Ca2+ sensors can form non-functional homodimers where the CaM-domain of one sensor molecule binds symmetrically to the M13-peptide of the partner sensor molecule. Case12 and Case16 behavior upon addition of high concentrations of free CaM or M13-peptide reveals that the latter effectively blocks the fluorescent response of the sensor. We speculate that the demonstrated intermolecular interaction with endogenous substrates and homodimerization can impede proper functioning of this type of Ca2+ sensors in living cells

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

Argentine Consensus of congenital toxoplasmosis

La transmisión vertical de la infección por Toxoplasma gondii ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. El diagnóstico de la infección materna y la del re cién nacido se logra con el conjunto de pruebas serológicas, hallazgos clínicos y ecográficos. El reconocimiento temprano de la infección materna permite un tratamiento que reduce la tasa de transmisión y el riesgo de daño en el producto de la concepción. El objetivo de este consenso de expertos fue revisar la literatura científica para actualizar las recomendaciones de práctica clínica respecto de la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita en nuestro país.Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diag nosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage. The aim of this expert consensus was to review the scientific literature which would enable an update of the clinical practice guideline of prevention, diagnosis and treatment of congenital toxoplasmosis in our country.Fil: Durlach, Ricardo A.. Asociación Argentina de Zoonosis; ArgentinaFil: Freuler, Cristina. Hospital Aleman; ArgentinaFil: Messina, Matías. Hospital Aleman; Argentina. Asociación Argentina de Zoonosis; ArgentinaFil: Freilij, Hector León. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Gonzalez Ayala, Silvia Elena. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Venturini, María Cecilia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Epizootiología y Salud Pública. Laboratorio de Inmunoparasitología; ArgentinaFil: Kaufer, Federico. Hospital Aleman; ArgentinaFil: García, Fabiana. Centro de Estudios Infectológicos Dr. Daniel Stamboulia; ArgentinaFil: Ceriotto, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Pardini, Lais Luján. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Epizootiología y Salud Pública. Laboratorio de Inmunoparasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Nadal, Mónica Zaida. Hospital Materno Infantil Ramon Sarda ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Ortiz de Zárate, Marcela. Hospital Materno Infantil Ramon Sarda ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Schneider, Vanessa. Hospital Aleman; ArgentinaFil: Mayer Wolf, Micaela. Hospital Aleman; ArgentinaFil: Jacob, Néstor. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich.; ArgentinaFil: Abuin, Juan Carlos. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Fiameni, Facundo. Hospital Aleman; ArgentinaFil: Salomon, Cristina del Carmen. Universidad del Aconcagua. Facultad de Ciencias Médicas; ArgentinaFil: Ledesma, Bibiana. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; ArgentinaFil: Guarnera, Eduardo. Asociación Argentina de Zoonosis; Argentin

Argentine Consensus of congenital toxoplasmosis

La transmisión vertical de la infección por Toxoplasma gondii ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. El diagnóstico de la infección materna y la del re cién nacido se logra con el conjunto de pruebas serológicas, hallazgos clínicos y ecográficos. El reconocimiento temprano de la infección materna permite un tratamiento que reduce la tasa de transmisión y el riesgo de daño en el producto de la concepción. El objetivo de este consenso de expertos fue revisar la literatura científica para actualizar las recomendaciones de práctica clínica respecto de la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita en nuestro país.Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diag nosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage. The aim of this expert consensus was to review the scientific literature which would enable an update of the clinical practice guideline of prevention, diagnosis and treatment of congenital toxoplasmosis in our country.Fil: Durlach, Ricardo A.. Asociación Argentina de Zoonosis; ArgentinaFil: Freuler, Cristina. Hospital Aleman; ArgentinaFil: Messina, Matías. Hospital Aleman; Argentina. Asociación Argentina de Zoonosis; ArgentinaFil: Freilij, Hector León. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Gonzalez Ayala, Silvia Elena. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Venturini, María Cecilia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Epizootiología y Salud Pública. Laboratorio de Inmunoparasitología; ArgentinaFil: Kaufer, Federico. Hospital Aleman; ArgentinaFil: García, Fabiana. Centro de Estudios Infectológicos Dr. Daniel Stamboulia; ArgentinaFil: Ceriotto, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Pardini, Lais Luján. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Epizootiología y Salud Pública. Laboratorio de Inmunoparasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Nadal, Mónica Zaida. Hospital Materno Infantil Ramon Sarda ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Ortiz de Zárate, Marcela. Hospital Materno Infantil Ramon Sarda ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Schneider, Vanessa. Hospital Aleman; ArgentinaFil: Mayer Wolf, Micaela. Hospital Aleman; ArgentinaFil: Jacob, Néstor. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich.; ArgentinaFil: Abuin, Juan Carlos. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Fiameni, Facundo. Hospital Aleman; ArgentinaFil: Salomon, Cristina del Carmen. Universidad del Aconcagua. Facultad de Ciencias Médicas; ArgentinaFil: Ledesma, Bibiana. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; ArgentinaFil: Guarnera, Eduardo. Asociación Argentina de Zoonosis; Argentin

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