The Broader Autism Phenotype in Mothers is Associated with Increased Discordance Between Maternal-Reported and Clinician-Observed Instruments that Measure Child Autism Spectrum Disorder

Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician-observed instruments. Sometimes, results between these instruments disagree. The broader autism phenotype (BAP) in parent-reporters may be associated with discordance. Study to Explore Early Development data (N = 712) were used to address whether mothers with BAP and children with ASD or non-ASD developmental disabilities were more likely than mothers without BAP to ‘over-’ or ‘under-report’ child ASD on ASD screeners or interviews compared with clinician observation or overall impression. Maternal BAP was associated with a child meeting thresholds on a maternal-reported screener or maternal interview when clinician ASD instruments or impressions did not (risk ratios: 1.30 to 2.85). Evidence suggests acknowledging and accounting for reporting discordances may be important when diagnosing ASD

Associations between parental broader autism phenotype and child autism spectrum disorder phenotype in the Study to Explore Early Development

The autism spectrum disorder phenotype varies by social and communication ability and co-occurring developmental, behavioral, and medical conditions. Etiology is also diverse, with myriad potential genetic origins and environmental risk factors. Examining the influence of parental broader autism phenotype—a set of sub-clinical characteristics of autism spectrum disorder—on child autism spectrum disorder phenotypes may help reduce heterogeneity in potential genetic predisposition for autism spectrum disorder. We assessed the associations between parental broader autism phenotype and child phenotype among children of age 30–68 months enrolled in the Study to Explore Early Development (N = 707). Child autism spectrum disorder phenotype was defined by a replication of latent classes derived from multiple developmental and behavioral measures: Mild Language Delay with Cognitive Rigidity, Mild Language and Motor Delay with Dysregulation (e.g. anxiety/depression), General Developmental Delay, and Significant Developmental Delay with Repetitive Motor Behaviors. Scores on the Social Responsiveness Scale-Adult measured parent broader autism phenotype. Broader autism phenotype in at least one parent was associated with a child having increased odds of being classified as mild language and motor delay with dysregulation compared to significant developmental delay with repetitive motor behaviors (odds ratio: 2.44; 95% confidence interval: 1.16, 5.09). Children of parents with broader autism phenotype were more likely to have a phenotype qualitatively similar to broader autism phenotype presentation; this may have implications for etiologic research

Binocular Rivalry in Children on the Autism Spectrum

When different images are presented to the eyes, the brain is faced with ambiguity, causing perceptual bistability: visual perception continuously alternates between the monocular images, a phenomenon called binocular rivalry. Many models of rivalry suggest that its temporal dynamics depend on mutual inhibition among neurons representing competing images. These models predict that rivalry should be different in autism, which has been proposed to present an atypical ratio of excitation and inhibition [the E/I imbalance hypothesis; Rubenstein & Merzenich, 2003]. In line with this prediction, some recent studies have provided evidence for atypical binocular rivalry dynamics in autistic adults. In this study, we examined if these findings generalize to autistic children. We developed a child-friendly binocular rivalry paradigm, which included two types of stimuli, low- and high-complexity, and compared rivalry dynamics in groups of autistic and age- and intellectual ability-matched typical children. Unexpectedly, the two groups of children presented the same number of perceptual transitions and the same mean phase durations (times perceiving one of the two stimuli). Yet autistic children reported mixed percepts for a shorter proportion of time (a difference which was in the opposite direction to previous adult studies), while elevated autistic symptomatology was associated with shorter mixed perception periods. Rivalry in the two groups was affected similarly by stimulus type, and consistent with previous findings. Our results suggest that rivalry dynamics are differentially affected in adults and developing autistic children and could be accounted for by hierarchical models of binocular rivalry, including both inhibition and top-down influences

An investigation of the effects of walking frame height and width on walking stability

Background Walking aids are designed for structural support during walking, however, surprisingly self-reported use of a walking aid (“Yes, I use one.”) has been identified as a risk factor for falling. Adjustment and design of walking aids may affect their usefulness in facilitating a stable walking pattern. We previously identified that increased body weight transfer onto a walking frame (‘device loading’) is associated with increased user stability. Research Question We asked: “Could adjustment of walking frame height to a lower height than clinically recommended serve as a mechanism to facilitate device loading and thereby increase stability? And: “Do ultra-narrow frames have an adverse effect on stability as compared to standard-width frames? Methods Ten older adults that were users of front-wheeled walking frames walked with walking frames of 1)‘standard width, standard height’, 2)‘standard width, low height’, 3)‘narrow width, standard height’. Smart Walker technology was used to record forces acting on the walking frame and inside the user’s shoes, and cameras recorded relative position of the user’s feet in relation to the frame’s feet. Stability of the user-frame system and device loading (percent body weight transferred onto the frame) were calculated. A general linear mixed effects model was used for statistical analysis. Results A lower height setting did not increase device loading and stability, therefore adjusting the height to a lower setting proved to be an unsuccessful mechanism to increase stability. However, device loading was positively correlated with stability for all frame conditions (p<0.05). Finally, stability was reduced when walking with the ultra-narrow, as compared to standard-width, frame (p=0.002). Significance To increase stability in fall-prone users, active encouragement to transfer body weight onto the walking frame is needed. Considering the adverse effects of ultra-narrow frames on stability, such frames should be prescribed and used with caution

The proinsulin C-peptide—a multirole model

The C-peptide links the insulin A and B chains in proinsulin, providing thereby a means to promote their efficient folding and assembly in the endoplasmic reticulum during insulin biosynthesis. It then facilitates the intracellular transport, sorting, and proteolytic processing of proinsulin into biologically active insulin in the maturing secretory granules of the β cells. These manifold functions impose significant constraints on the C-peptide structure that are conserved in evolution. After cleavage of proinsulin, the intact C-peptide is stored with insulin in the soluble phase of the secretory granules and is subsequently released in equimolar amounts with insulin, providing a useful independent indicator of insulin secretion. This brief review highlights many aspects of its roles in biosynthesis, as a prelude to consideration of its possible additional role(s) as a physiologically active peptide after its release with insulin into the circulation in vivo

Association between risk factors for injurious falls and new benzodiazepine prescribing in elderly persons

<p>Abstract</p> <p>Background</p> <p>Benzodiazepines are frequently prescribed to elderly patients' despite concerns about adverse effects leading to injurious falls. Previous studies have not investigated the extent to which patients with pre-existing risk factors for falls are prescribed benzodiazepines. The objective of this study is to assess if some of the risk factors for falls are associated with new benzodiazepine prescriptions in elderly persons.</p> <p>Methods</p> <p>Using provincial administrative databases, elderly Quebec residents were screened in 1989 for benzodiazepine use and non-users were followed for up to 5 years. Logistic regression models were used to evaluate potential predictors of new benzodiazepine use among patient baseline characteristics.</p> <p>Results</p> <p>In the 252,811 elderly patients who had no benzodiazepine prescription during the baseline year (1989), 174,444 (69%) never filled a benzodiazepine prescription and 78,367 (31%) filled at least one benzodiazepine prescription. In the adjusted analysis, several risk factors for falls were associated with statistically significant increases in the risk of receiving a new benzodiazepine prescription including the number of prescribing physicians seen at baseline (OR: 1.12; 95% CI 1.11–1.13), being female (OR: 1.20; 95% CI 1.18–1.22) or a diagnosis of arthritis (OR: 1.11; 95% CI 1.09–1.14), depression (OR: 1.42; 95% CI 1.35–1.49) or alcohol abuse (OR: 1.24; 95% CI 1.05–1.46). The strongest predictor for starting a benzodiazepine was the use of other medications, particularly anti-depressants (OR: 1.85; 95% CI 1.75–1.95).</p> <p>Conclusion</p> <p>Patients with pre-existing conditions that increase the risk of injurious falls are significantly more likely to receive a new prescription for a benzodiazepine. The strength of the association between previous medication use and new benzodiazepine prescriptions highlights an important medication safety issue.</p