Autism spectrum disorder (ASD) may arise from increased ratio of excitatory to inhibitory neurotransmission in the brain. Many pharmacological treatments have been tested in ASD, but only limited ...success has been achieved. Here we report that BTBR T+Itpr3tf/J (BTBR) mice, a model of idiopathic autism, have reduced spontaneous GABAergic neurotransmission. Treatment with low nonsedating/nonanxiolytic doses of benzodiazepines, which increase inhibitory neurotransmission through positive allosteric modulation of postsynaptic GABAA receptors, improved deficits in social interaction, repetitive behavior, and spatial learning. Moreover, negative allosteric modulation of GABAA receptors impaired social behavior in C57BL/6J and 129SvJ wild-type mice, suggesting that reduced inhibitory neurotransmission may contribute to social and cognitive deficits. The dramatic behavioral improvement after low-dose benzodiazepine treatment was subunit specific—the α2,3-subunit-selective positive allosteric modulator L-838,417 was effective, but the α1-subunit-selective drug zolpidem exacerbated social deficits. Impaired GABAergic neurotransmission may contribute to ASD, and α2,3-subunit-selective positive GABAA receptor modulation may be an effective treatment.
•BTBR mice have reduced spontaneous GABAergic inhibitory transmission•Nonsedating doses of benzodiazepines improved autism-related deficits in BTBR mice•Impairment of GABAergic transmission reduced social interaction in wild-type mice•Behavioral rescue by low-dose benzodiazepine is GABAA receptor α2,3-subunit specific
Han et al. study the impact of manipulating inhibitory neurotransmission on social behaviors in mice. Their data indicate that impaired GABAergic signaling may contribute to social and cognitive deficits, suggesting that GABAA receptor modulation might have potential for treatment of autism.
The Health Belief Model (HBM) posits that messages will achieve optimal behavior change if they successfully target perceived barriers, benefits, self-efficacy, and threat. While the model seems to ...be an ideal explanatory framework for communication research, theoretical limitations have limited its use in the field. Notably, variable ordering is currently undefined in the HBM. Thus, it is unclear whether constructs mediate relationships comparably (parallel mediation), in sequence (serial mediation), or in tandem with a moderator (moderated mediation). To investigate variable ordering, adults (N = 1,377) completed a survey in the aftermath of an 8-month flu vaccine campaign grounded in the HBM. Exposure to the campaign was positively related to vaccination behavior. Statistical evaluation supported a model where the indirect effect of exposure on behavior through perceived barriers and threat was moderated by self-efficacy (moderated mediation). Perceived barriers and benefits also formed a serial mediation chain. The results indicate that variable ordering in the Health Belief Model may be complex, may help to explain conflicting results of the past, and may be a good focus for future research.
Difficulties associated with Autism Spectrum Disorders can cause considerable impact on personal, familial, social, educational and occupational functioning. Living with a child who has an Autism ...Spectrum Disorder can therefore pose a challenge to family members, including typically developing siblings. However, it is only in recent years that the experience of typically developing siblings has become a focal point. A systematic review using keywords across six databases was undertaken to summarise qualitative studies that focused on the experience of being a sibling of a child with an Autism Spectrum Disorder. Fifteen studies met inclusion criteria and a thematic synthesis was completed. The synthesis found that having a sibling who has an Autism Spectrum Disorder can impact typically developing sibling’s self-identity and personal development in a number of ways. Similarly, interactions with the sibling who has Autism Spectrum Disorders and with other individuals can evoke a myriad of experiences that can both benefit and challenge typically developing siblings. The ability of typically developing siblings to cope with adverse experiences needs to remain a focus. This synthesis concludes that further research is needed to identify which methods are the most effective in supporting typically developing siblings of children with Autism Spectrum Disorders.
In order to profile the lipidome for untargeted lipidomics applications, analysis by ultra-high performance liquid chromatography – high resolution mass spectrometry (UHPLC-HRMS) typically requires ...the extraction of lipid content from sample matrices using matrix-specific conditions. The Folch, Bligh-Dyer, and Matyash extraction methods, while promising approaches, were originally tailored to specific matrices (brain tissue, fish muscle, and E. coli, respectively). Each of these methods have specific solvent ratios that must be adhered to achieve optimal extraction. Thus, the sample-to-solvent ratios for these methods should be optimized for the sample matrix of interest prior to employment. This study evaluated the appropriate sample-to-extraction solvent ratios for human plasma-based lipidomics studies. An advantage of employing biphasic lipid extractions is the ability to investigate both the aqueous and organic layers for increased analyte coverage in untargeted studies. Therefore, this work also evaluated the multi-omic capability of each lipid extraction method for plasma in an effort to provide a workflow capable of increasing analyte coverage in a single extraction, thus providing a more complete understanding of complex biological systems. In plasma, a decrease in sample-to-solvent ratios from 1:4, 1:10, 1:20, to 1:100 (v/v) resulted in a gradual increase in the peak area of a diverse range of metabolite (aqueous layer) and lipid (organic layer) species for each extraction method up to the 1:20(v/v) sample-to-solvent ratio. The Bligh-Dyer and Folch methods yielded the highest peak areas at every plasma sample-to-solvent ratios for both metabolite and lipid species. Depending on the lipid class of interest, the Folch or Bligh-Dyer method is best suited for analysis of human plasma at a 1:20 (v/v) sample to total solvent ratio.
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•Evaluated sample-to-solvent ratios for plasma lipid extractions.•Evaluated the applicability of plasma multi-omic analysis for the Bligh-Dyer, Folch, and Matyash lipid extraction methods.•Plasma sample-to-solvent ratios of 1:20 (v/v) are ideal for multi-omics analysis with the Folch and Bligh-Dyer methods.•The Folch and Bligh-Dyer (aqueous layer from the 1:20 (v/v) ratio) yielded similar results to an 80% methanol extraction.
Background
Studies have identified that food allergy (FA) in children is related to poorer caregiver quality of life (QoL). However, it is unclear which interventions are most effective at improving ...outcomes for caregivers of children with FA. This review aimed to identify and determine the efficacy, acceptability and quality of interventions for caregivers of children with FA.
Methods
A systematic search of four databases was conducted to identify studies evaluating any intervention that targeted well‐being and support of caregivers of children with FA. Studies were not excluded based on design and were rated for quality using the Mixed Methods Appraisal Tool (MMAT) and the Cochrane risk of bias tool for randomized controlled trials (RCTs).
Results
Fifteen studies met the inclusion criteria: eight studies used a pre‐test/post‐test design, four studies used a post‐test design, two studies used an RCT design, and one study used a case‐control design. Seven studies were educational interventions, five were psychological interventions, and three involved peer/professional support. All interventions had high participant acceptability; some evidence for cognitive behavioural interventions in supporting mothers was observed. Educational interventions tended to be associated with improvements in FA knowledge. With the exception of three studies, most studies were assessed as poor or moderate in terms of quality.
Conclusion
There is a paucity of high‐quality research evaluating interventions to improve outcomes in parents of children with FA. Limited evidence suggests that cognitive behavioural interventions could benefit some mothers, but this has not been tested in other populations. Future research should use methodologically sound designs with validated outcome measures.
The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered ...terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.
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