494 research outputs found

    Abnormalities in visual processing lead to hypersociability and evaluation of trust:An ERP study of Williams syndrome

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    Accurate assessment of trustworthiness is fundamental to successful and adaptive social behavior. Initially, people assess trustworthiness from facial appearance alone. These assessments then inform critical approach or avoid decisions. Individuals with Williams syndrome (WS) exhibit a heightened social drive, especially toward strangers. This study investigated the temporal dynamics of facial trustworthiness evaluation in neurotypic adults (TD) and individuals with WS. We examined whether differences in neural activity during trustworthiness evaluation may explain increased approach motivation in WS compared to TD individuals. Event-related potentials were recorded while participants appraised faces previously rated as trustworthy or untrustworthy. TD participants showed increased sensitivity to untrustworthy faces within the first 65–90 ms, indexed by the negative-going rise of the P1 onset (oP1). The amplitude of the oP1 difference to untrustworthy minus trustworthy faces was correlated with lower approachability scores. In contrast, participants with WS showed increased N170 amplitudes to trustworthy faces. The N170 difference to low–high-trust faces was correlated with low approachability in TD and high approachability in WS. The findings suggest that hypersociability associated with WS may arise from abnormalities in the timing and organization of early visual brain activity during trustworthiness evaluation. More generally, the study provides support for the hypothesis that impairments in low-level perceptual processes can have a cascading effect on social cognition.</p

    Health engagement: a systematic review of tools modifiable for use with vulnerable pregnant women

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    Objective To examine available health engagement tools suitable to, or modifiable for, vulnerable pregnant populations.Design Systematic review.Eligibility criteria Original studies of tool development and validation related to health engagement, with abstract available in English, published between 2000 and 2022, sampling people receiving outpatient healthcare including pregnant women.Data sources CINAHL Complete, Medline, EMBASE and PubMed were searched in April 2022.Risk of bias Study quality was independently assessed by two reviewers using an adapted COSMIN risk of bias quality appraisal checklist. Tools were also mapped against the Synergistic Health Engagement model, which centres on women’s buy-in to maternity care.Included studies Nineteen studies were included from Canada, Germany, Italy, the Netherlands, Sweden, the UK and the USA. Four tools were used with pregnant populations, two tools with vulnerable non-pregnant populations, six tools measured patient–provider relationship, four measured patient activation, and three tools measured both relationship and activation.Results Tools that measured engagement in maternity care assessed some of the following constructs: communication or information sharing, woman-centred care, health guidance, shared decision-making, sufficient time, availability, provider attributes, discriminatory or respectful care. None of the maternity engagement tools assessed the key construct of buy-in. While non-maternity health engagement tools measured some elements of buy-in (self-care, feeling hopeful about treatment), other elements (disclosing risks to healthcare providers and acting on health advice), which are significant for vulnerable populations, were rarely measured.Conclusions and implications Health engagement is hypothesised as the mechanism by which midwifery-led care reduces the risk of perinatal morbidity for vulnerable women. To test this hypothesis, a new assessment tool is required that addresses all the relevant constructs of the Synergistic Health Engagement model, developed for and psychometrically assessed in the target group.PROSPERO registration number CRD42020214102

    Development of the N400 for Word Learning in the First 2 Years of Life: A Systematic Review

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    The N400 ERP component is a direct neural index of word meaning. Studies show that the N400 component is already present in early infancy, albeit often delayed. Many researchers capitalize on this finding, using the N400 component to better understand how early language acquisition unfolds. However, variability in how researchers quantify the N400 makes it difficult to set clear predictions or build theory. Not much is known about how the N400 component develops in the first 2 years of life in terms of its latency and topographical distributions, nor do we know how task parameters affect its appearance. In the current paper we carry out a systematic review, comparing over 30 studies that report the N400 component as a proxy of semantic processing elicited in infants between 0 and 24 months old who listened to linguistic stimuli. Our main finding is that there is large heterogeneity across semantic-priming studies in reported characteristics of the N400, both with respect to latency and to distributions. With age, the onset of the N400 insignificantly decreases, while its offset slightly increases. We also examined whether the N400 appears different for recently-acquired novel words vs. existing words: both situations reveal heterogeneity across studies. Finally, we inspected whether the N400 was modulated differently with studies using a between-subject design. In infants with more proficient language skills the N400 was more often present or showed itself here with earlier latency, compared to their peers; but no consistent patterns were observed for distribution characteristics of the N400. One limitation of the current review is that we compared studies that widely differed in choice of EEG recordings, pre-processing steps and quantification of the N400, all of which could affect the characteristics of the infant N400. The field is still missing research that systematically tests development of the N400 using the same paradigm across infancy

    Book Reviews

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    Book Reviews

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    Intelligence in Williams Syndrome Is Related to STX1A, Which Encodes a Component of the Presynaptic SNARE Complex

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    Although genetics is the most significant known determinant of human intelligence, specific gene contributions remain largely unknown. To accelerate understanding in this area, we have taken a new approach by studying the relationship between quantitative gene expression and intelligence in a cohort of 65 patients with Williams Syndrome (WS), a neurodevelopmental disorder caused by a 1.5 Mb deletion on chromosome 7q11.23. We find that variation in the transcript levels of the brain gene STX1A correlates significantly with intelligence in WS patients measured by principal component analysis (PCA) of standardized WAIS-R subtests, r  = 0.40 (Pearson correlation, Bonferroni corrected p-value  = 0.007), accounting for 15.6% of the cognitive variation. These results suggest that syntaxin 1A, a neuronal regulator of presynaptic vesicle release, may play a role in WS and be a component of the cellular pathway determining human intelligence

    A preliminary study of orbitofrontal activation and hypersociability in Williams Syndrome

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    Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. Methods: We performed an event-related functional magnetic resonance imaging study while individuals with WS and typically developing controls (TD) matched positive and negative emotional faces. WS compared to TD showed reduced right amygdala activation during presentation of negative faces, as in the previous literature. In addition, WS showed a unique pattern of right orbitofrontal cortex activation. While TD showed medial orbitofrontal cortex activation in response to positive, and lateral orbitofrontal cortex activation to negative, WS showed the opposite pattern. In light of the general notion of a medial/lateral gradient of reward/punishment processing in the orbitofrontal cortex, these findings provide an additional biological explanation for, or correlate of positive attribution bias and hypersociability in WS

    Discovery of sarolaner:A novel, Orally administered, broad-spectrum, Isoxazoline ectoparasiticide for dogs

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    AbstractThe novel isoxazoline ectoparasiticide, sarolaner, was identified during a lead optimization program for an orally-active compound with efficacy against fleas and ticks on dogs. The aim of the discovery program was to identify a novel isoxazoline specifically for use in companion animals, beginning with de novo synthesis in the Zoetis research laboratories. The sarolaner molecule has unique structural features important for its potency and pharmacokinetic (PK) properties, including spiroazetidine and sulfone moieties. The flea and tick activity resides in the chirally pure S-enantiomer, which was purified to alleviate potential off-target effects from the inactive enantiomer. The mechanism of action was established in electrophysiology assays using CHO-K1 cell lines stably expressing cat flea (Ctenocephalides felis) RDL (resistance-to-dieldrin) genes for assessment of GABA-gated chloride channel (GABACls) pharmacology. As expected, sarolaner inhibited GABA-elicited currents at both susceptible (CfRDL-A285) and resistant (CfRDL-S285) flea GABACls with similar potency. Initial whole organism screening was conducted in vitro using a blood feeding assay against C. felis. Compounds which demonstrated robust activity in the flea feed assay were subsequently tested in an in vitro ingestion assay against the soft tick, Ornithodoros turicata. Efficacious compounds which were confirmed safe in rodents at doses up to 30mg/kg were progressed to safety, PK and efficacy studies in dogs. In vitro sarolaner demonstrated an LC80 of 0.3μg/mL against C. felis and an LC100 of 0.003μg/mL against O. turicata. In a head-to-head comparative in vitro assay with both afoxolaner and fluralaner, sarolaner demonstrated superior flea and tick potency. In exploratory safety studies in dogs, sarolaner demonstrated safety in dogs≥8 weeks of age upon repeated monthly dosing at up to 20mg/kg. Sarolaner was rapidly and well absorbed following oral dosing. Time to maximum plasma concentration occurred within the first day post-dose. Bioavailability for sarolaner was calculated at >85% and the compound was highly protein bound (>99.9%). The half-life for sarolaner was calculated at 11–12 days. Sarolaner plasma concentrations indicated dose proportionality over the range 1.25–5mg/kg, and these same doses provided robust efficacy (>99%) for ≥35days against both fleas (C. felis) and multiple species of ticks (Rhipicephalus sanguineus, Ixodes ricinus and Dermacentor reticulatus) after oral administration to dogs. As a result of these exploratory investigations, sarolaner was progressed for development as an oral monthly dose for treatment and control of fleas and ticks on dogs
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