Lactic acid bacterial surface display of scytovirin inhibitors for anti-ebolavirus infection.

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, this approach is also simple and cost-effective and can be easily applied in the regions of Ebola outbreaks in the developing countries.

A case example of community-based supervision to overcome barriers and support the implementation of exposure therapy.

Supervision in community mental health (CMH) settings is critically important for supporting clinical competency and optimizing clinical outcomes. However, CMH supervision is hindered by numerous administrative and fiscal challenges, which makes aligning supervision practices with gold-standard recommendations notoriously difficult. This article describes a case example of one multicomponent supervision approach within a CMH clinic used to support the delivery of exposure therapy ("exposure") to youth with publicly funded insurance. We first review current recommendations for supervision and highlight the primary barriers to the use of these supervisory practices in CMH settings. We then present three low-burden supervisory approaches used to supplement traditional individual supervision. Each strategy presented aims to mitigate known barriers and maximize alignment with gold-standard supervision practices for exposure while being sustainable within a community setting. Finally, we review the strengths and limitations of each supervision strategy. The multicomponent strategies presented represent a creative approach to CMH supervision that maximizes the limited resources and infrastructure in CMH settings to support the delivery of gold-standard supervision. We conclude by offering insights into how these strategies could support supervision for a broader range of evidence-based practices (EBPs) and make recommendations for future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ligand-based design of peptide entry inhibitors targeting the endosomal receptor binding site of filoviruses.

Filoviruses enter cells through macropinocytosis and trafficking into the endosomes in which they bind to the receptor Niemann-Pick C1 protein (NPC1) for membrane fusion and entry into the cytoplasm. The endosomal receptor-binding is critical step for filovirus entry. Designing inhibitors to block receptor binding will prevent viral entry. Using available binding structural information from the co-crystal structures of the viral GP with the receptor NPC1 or with monoclonal antibodies, we have conducted structure-based design of peptide inhibitors to target the receptor binding site (RBS). The designed peptides were tested for their inhibition activity against pseudo-typed or replication-competent viruses in a cell-based assay. The results indicate that these peptides exhibited strong activities against both Ebola and Marburg virus infection. It is expected that these peptides can be further developed for therapeutic use to treat filovirus infection and combat the outbreaks.

Gross motor impairment and its relation to social skills in autism spectrum disorder: A systematic review and two meta-analyses.

Gross motor ability is associated with profound differences in how children experience and interact with their social world. A rapidly growing literature on motor development in autism spectrum disorder (ASD) indicates that autistic individuals exhibit impairment in gross motor skills. However, due to substantial heterogeneity across studies, it remains unclear which gross motor skills are impaired in ASD, when and for whom these differences emerge, and whether motor and social impairments are related. The present article addressed these questions by synthesizing research on gross motor skills in ASD in two separate meta-analyses. The first examined gross motor deficits in ASD compared to neurotypical (NT) controls, aggregating data from 114 studies representing 6,423 autistic and 2,941 NT individuals. Results demonstrated a significant overall deficit in gross motor skills in ASD (Hedges' g = -1.04) that was robust to methodological and phenotypic variation and was significant at every level of the tested moderators. However, moderation analyses revealed that this deficit was most pronounced for object control skills (i.e., ball skills), clinical assessment measures, and movements of the upper extremities or the whole body. The second meta-analysis investigated whether gross motor and social skills are related in ASD, synthesizing data from 21 studies representing 654 autistic individuals. Findings revealed a modest but significant overall correlation between gross motor and social skills in ASD (r = 0.27). Collectively, results support the conclusion that motor deficits are tied to the core symptoms of ASD. Further research is needed to test the causality and directionality of this relationship. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Motor Skill Differences in Autism Spectrum Disorder: a Clinically Focused Review.

PURPOSE OF REVIEW: This review synthesizes recent, clinically relevant findings on the scope, significance, and centrality of motor skill differences in autism spectrum disorder (ASD). RECENT FINDINGS: Motor challenges in ASD are pervasive, clinically meaningful, and highly underrecognized, with up to 87% of the autistic population affected but only a small percentage receiving motor-focused clinical care. Across development, motor differences are associated with both core autism symptoms and broader functioning, though the precise nature of those associations and the specificity of motor profiles to ASD remain unestablished. Findings suggest that motor difficulties in ASD are quantifiable and treatable, and that detection and intervention efforts targeting motor function may also positively influence social communication. Recent evidence supports a need for explicit recognition of motor impairment within the diagnostic framework of ASD as a clinical specifier. Motor differences in ASD warrant greater clinical attention and routine incorporation into screening, evaluation, and treatment planning.

Face Processing and Social Functioning in Pediatric Brain Tumor Survivors.

OBJECTIVE: Pediatric brain tumor survivors (PBTS) experience deficits in social functioning. Facial expression and identity recognition are key components of social information processing and are widely studied as an index of social difficulties in youth with autism spectrum disorder (ASD) and other neurodevelopmental conditions. This study evaluated facial expression and identity recognition among PBTS, youth with ASD, and typically developing (TD) youth, and the associations between these face processing skills and social impairments. METHODS: PBTS (N = 54; ages 7-16) who completed treatment at least 2 years prior were matched with TD (N = 43) youth and youth with ASD (N = 55) based on sex and IQ. Parents completed a measure of social impairments and youth completed a measure of facial expression and identity recognition. RESULTS: Groups significantly differed on social impairments (p < .001), with youth with ASD scoring highest followed by PBTS and lastly TD youth. Youth with ASD performed significantly worse on the two measures of facial processing, while TD youth and PBTS were not statistically different. The association of facial expression recognition and social impairments was moderated by group, such that PBTS with higher levels of social impairment performed worse on the expression task compared to TD and ASD groups (p < .01, η2 = 0.07). CONCLUSIONS: Variability in face processing may be uniquely important to the social challenges of PBTS compared to other neurodevelopmental populations. Future directions include prospectively examining associations between facial expression recognition and social difficulties in PBTS and face processing training as an intervention for PBTS.

Identification of filovirus entry inhibitors targeting the endosomal receptor NPC1 binding site.

Filoviruses, mainly consisting of Ebola viruses (EBOV) and Marburg viruses (MARV), are enveloped negative-strand RNA viruses which can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. The filovirus infection is mediated by the interaction of viral envelope glycoprotein (GP) and the human endosomal receptor Niemann-Pick C1 (NPC1). Blocking this interaction will prevent the infection. Therefore, we utilized an In silico screening approach to conduct virtual compound screening against the NPC1 receptor-binding site (RBS). Twenty-six top-hit compounds were purchased and evaluated by in vitro cell based inhibition assays against pseudotyped or replication-competent filoviruses. Two classes (A and U) of compounds were identified to have potent inhibitory activity against both Ebola and Marburg viruses. The IC50 values are in the lower level of micromolar concentrations. One compound (compd-A) was found to have a sub-micromolar IC50 value (0.86 µM) against pseudotyped Marburg virus. The cytotoxicity assay (MTT) indicates that compd-A has a moderate cytotoxicity level but the compd-U has much less toxicity and the CC50 value was about 100 µM. Structure-activity relationship (SAR) study has found some analogs of compd-A and -U have reduced the toxicity and enhanced the inhibitory activity. In conclusion, this work has identified several qualified lead-compounds for further drug development against filovirus infection.

Bayesian regression-based developmental norms for the Benton Facial Recognition Test in males and females.

Face identity recognition is important for social interaction and is impaired in a range of clinical disorders, including several neurodevelopmental disorders. The Benton Facial Recognition Test (BFRT; Benton & Van Allen, 1968), a widely used assessment of identity recognition, is the only standardized test of face identity perception, as opposed to face memory, that has been normed on children and adolescents. However, the existing norms for the BFRT are suboptimal, with several ages not represented and no established time limit (which can lead to inflated scores by allowing individuals with prosopagnosia to use feature matching). Here we address these issues with a large normative dataset of children and adolescents (ages 5-17, N = 398) and adults (ages 18-55; N = 120) who completed a time-limited version of the BFRT. Using Bayesian regression, we demonstrate that face identity perception increases asymptotically from childhood through adulthood, and provide continuous norms based on age and sex that can be used to calculate standard scores. We show that our time limit of 16 seconds per item yields scores comparable to the existing norms without time limits from the non-prosopagnostic samples. We also find that females (N = 156) score significantly higher than males (N = 362), supporting the existence of a female superiority effect for face identification. Overall, these results provide more robust norms for the BFRT and promote future research on face identity perception in developmental populations.

What's in a name? A preliminary event-related potential study of response to name in preschool children with and without autism spectrum disorder.

The ability to selectively respond to one's own name is important for social and language development, and is disrupted in atypically developing populations (e.g., autism spectrum disorder). Research with typically developing samples using event-related potentials (ERPs) has demonstrated that the subject's own name (SON) is differentiated from other stimuli at both early sensory and later cognitive stages of auditory processing. While neural indices of response to name have been researched extensively in adults, no such studies have been conducted with typically developing preschool children or children with autism spectrum disorder (ASD). The present study investigated ERP response to name in a sample of typically developing (TD) preschoolers (n = 19; mean age = 4.3 years) as well as a small, exploratory comparison group of preschoolers with ASD (n = 13; mean age = 4.4 years). TD preschoolers exhibited significantly greater negativity to SON over frontal regions than to an unfamiliar nonsense name, consistent with the adult SON negativity component. This component was present whether the name was spoken by a parent or an unfamiliar adult, suggesting that it reflects SON-specific processing rather than broad self-relevant information processing. Comparing preschoolers with ASD to the TD children revealed a significant SON negativity component across both groups. The amplitude of the SON negativity response was significantly correlated with social variables in the ASD group, though these correlations did not survive correction for multiple comparisons. This study is the first to demonstrate the presence of the SON component in preschool children with and without ASD.