Pubmed du 19/04/20

dimanche 19 avril 2020

1. High Polygenic Risk Scores Associated with Autism Spectrum Disorder. Am J Med Genet A. 2020 ; 182(5) : 949-50.

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2. Abdelzaher LA, Hussein OA, Ashry IEM. The Novel Potential Therapeutic Utility of Montelukast in Alleviating Autistic Behavior Induced by Early Postnatal Administration of Thimerosal in Mice. Cellular and molecular neurobiology. 2020.

BACKGROUND AND AIM : Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined. METHODOLOGY : Newborn mice were randomly distributed into three groups : (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 mug Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (alpha7nAChRs), nuclear factor kappa B p65 (NF-kappaB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well. RESULTS : THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through alpha7nAChRs upregulation, NF-kappaB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation. CONCLUSION : Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of alpha7nAChRs that inhibited NF-kappaB activation and significant suppression of neuronal injury and the associated apoptosis.

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3. Donhauser J. Hormonal contraceptives and autism epidemics. Med Hypotheses. 2020 ; 141 : 109729.

This paper defends the hypothesis of a potential causal link between increased usage of hormonal contraceptives (HCs) and significant rises in instances of Autism Spectrum Disorders (ASDs) worldwide. It develops a background theory that supports this hypothesis through analysis of : observed correlations between increased usage of HCs and increased instances of ASDs ; consistent evidence from independent studies linking "birth spacing" intervals and ASD-risk ; evidence from studies on the effects of HCs on folate and B12 absorption ; and hypotheses concerning disruptions to mechanisms of delivery of folate and B12 during periods of in utero brain development. The proposed theory is then defended through discussion of how it may explain numerous puzzling correlations with increased instances of ASDs documented in certain demographics.

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4. Kamp-Becker I, Stroth S, Stehr T. [Autism spectrum disorder in childhood and adults : diagnosis and differential diagnoses]. Der Nervenarzt. 2020.

Autistic disorders are summarized in DSM5 under the term autism spectrum disorder (ASD) and are severe, lifelong, pervasive neurodevelopmental disorders. Core features manifested even in childhood are impairments in social interaction and communication as well as restricted and repetitive behavior. The intensity of symptoms, language and cognitive impairments vary but the majority of affected individuals have below average intelligence and 80% have at least one comorbid disorder. The diverse pathology and heterogeneity in phenotypes are caused by a complex genetic etiology, which is associated with a reduced synaptic plasticity of neural networks. The disorder is associated with a clearly reduced quality of life as well as a high familial burden. The differential diagnostics have a high relevance and the diagnosis should be carried out by specialized institutions. Behavioral therapeutic interventions are indicated.

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5. Khayatzadeh-Mahani A, Wittevrongel K, Petermann L, Graham ID, Zwicker JD. Stakeholders’ engagement in co-producing policy-relevant knowledge to facilitate employment for persons with developmental disabilities. Health research policy and systems. 2020 ; 18(1) : 39.

BACKGROUND : Persons with developmental disabilities (PWDD) face a number of individual, environmental and societal barriers when seeking employment. Integrated knowledge translation (IKT) involves ongoing and dynamic interactions between researchers and stakeholders for the purpose of engaging in mutually beneficial research to address these types of multi-faceted barriers. There is a knowledge gap in the IKT literature on effective stakeholder engagement strategies outside of the dissemination stage to inform policy. In this paper, we report on a number of engagement strategies employed over a 2-year period to engage a wide range of stakeholders in different stages of an IKT project that aimed to investigate the ’wicked’ problem of employment for PWDD. METHOD : Our engagement plan included multiple linked strategies and was designed to ensure the meaningful engagement of, and knowledge co-production with, stakeholders. We held two participatory consensus-building stakeholder policy dialogue events to co-produce knowledge utilising the nominal group technique and the modified Delphi technique. A total of 31 and 49 stakeholders engaged in the first and second events, respectively, from six key stakeholder groups. Focused engagement strategies were employed to build on the stakeholder dialogues for knowledge mobilisation and included a focus group attended only by PWDD, a stakeholder workshop attended only by policy/decision-makers, a webinar attended by human resources professionals and employers, and a current affairs panel attended by the general public. RESULTS : Our findings suggest that the level of engagement for each stakeholder group varies depending on the goal and need of the project. Our stakeholder dialogue findings highlight the inherent challenges in co-framing and knowledge co-production through the meaningful engagement of multiple stakeholders who hold different ideas and interests. Focused outreach is needed to foster relationships and trust for meaningful engagement. CONCLUSIONS : In addition to providing guidance on how to implement adaptable meaningful engagement strategies, these findings contribute to discussions on how IKT projects are planned and funded. More studies to explore effective mechanisms for engaging a wide range of stakeholders in IKT research are needed. More evidence of successful engagement strategies employed by researchers to achieve meaningful knowledge co-production is also key to advancing the discipline.

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6. Moliadze V, Brodski-Guerniero A, Schuetz M, Siemann J, Lyzhko E, Schlitt S, Kitzerow J, Langer A, Kaiser J, Naumer MJ, Wibral M, Chan J, Freitag CM, Siniatchkin M. Significance of Beta-Band Oscillations in Autism Spectrum Disorders During Motor Response Inhibition Tasks : A MEG Study. Brain topography. 2020.

In Autism Spectrum Disorders (ASD), impaired response inhibition and lack of adaptation are hypothesized to underlie core ASD symptoms, such as social communication and repetitive, stereotyped behavior. Thus, the aim of the present study was to compare neural correlates of inhibition, post-error adaptation, and reaction time variability in ASD and neuro-typical control (NTC) participants by investigating possible differences in error-related changes of oscillatory MEG activity. Twelve male NTC (mean age 20.3 +/- 3.7) and fourteen male patients with ASD (mean age 17.8 +/- 2.9) were included in the analysis. Subjects with ASD showed increased error-related reaction time variability. MEG analysis revealed decreased beta power in the ASD group in comparison to the NTC group over the centro-parietal channels in both, the pre-stimulus and post-response interval. In the ASD group, mean centro-parietal beta power negatively correlated with dimensional autism symptoms. In both groups, false alarms were followed by an early increase in temporo-frontal theta to alpha power ; and by a later decrease in alpha to beta power at central and posterior sensors. Single trial correlations were additionally studied in the ASD group, who showed a positive correlation of pre-stimulus beta power with post-response theta, alpha, and beta power, particularly after hit trials. On a broader scale, the results deliver important insights into top-down control deficits that may relate to core symptoms observed in ASD.

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