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LAY ABSTRACT: Expert recommendations for toddlers who are likely to develop autism include caregivers being actively involved in the services children receive. However, many services available in the community may not follow these recommendations. Evidence suggests that an intervention named Project ImPACT for Toddlers demonstrates positive parent and child outcomes for families in the community. Project ImPACT for Toddlers was designed specifically for toddlers by a group of parents, clinicians, researchers, and funders. It teaches parents of young children strategies to support their child's development in daily routines. This study reports the perspectives of early intervention providers who learned to use Project ImPACT for Toddlers on whether the intervention was a good fit for their practice and easy to use. The study also examines how many agencies are using Project ImPACT for Toddlers and how many families have received the intervention in the community. The goal of the study is to inform the continued use of Project ImPACT for Toddlers in the community and support offering the intervention in other regions. Participants include 38 community providers who participated in a training study of Project ImPACT for Toddlers and completed a survey and semi-structured interview after approximately 3 months of using Project ImPACT for Toddlers with families. Participants perceived the training model as acceptable and appropriate, and identified the group-based model of training, comprehensive materials, and agency support as strengths of the approach. Survey findings complemented the results from the interviews. Data indicate an increasing number of agencies and families accessing Project ImPACT for Toddlers. Efforts to expand evidence-based intervention in early intervention should continue to build upon the model used for Project ImPACT for Toddlers.

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Females with autism have unique socialization profiles, but less is known about sex/gender differences in the context of socialization interventions. This study utilized a combination of behavioral and survey measures to examine sex/gender differences in 32 autistic adolescents (10 females, 22 males) before and after participation in the 20-week START socialization program. At intake, males self-reported superior social skills use while parents endorsed that females demonstrated superior social competencies. While males and females both experienced socialization improvements post-trial, females experienced greater increases in self-reported social competency and the proportion of questions they asked during peer conversations. These preliminary findings on differential intervention response may help inform future social skill intervention efforts for the needs of females on the spectrum.

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The symptoms of autism spectrum disorder are conceptualized to alter the quality of parent-children interactions, exposure to social learning exchanges, and ultimately the course of child development. There is evidence that modifying the procedures of Pivotal Response Treatment (PRT) to explicitly target social motivation enhances child engagement and parent-child synchrony in moment-by-moment exchanges. However, it is unclear if these within session improvements ultimately yield favorable developmental outcomes over time. The current investigation presents feasibility, utility, and preliminary efficacy data of a pilot randomized clinical trial (RCT) of a Pivotal Response Intervention for Social Motivation (PRISM) model. Data on participant factors, treatment protocol acceptability, and outcome variance and effect size are highly favorable and support the pursuit of a future, large scale RCT.

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Lyme disease is a complex tick-borne zoonosis that poses an escalating public health threat in several parts of the world, despite sophisticated healthcare infrastructure and decades of effort to address the problem. Concepts like the true burden of the illness, from incidence rates to longstanding consequences of infection, and optimal case management, also remain shrouded in controversy. At the heart of this multidisciplinary issue are the causative spirochetal pathogens belonging to the Borrelia Lyme complex. Their unusual physiology and versatile lifestyle have challenged microbiologists, and may also hold the key to unlocking mysteries of the disease. The goal of this review is therefore to integrate established and emerging concepts of Borrelia biology and pathogenesis, and position them in the broader context of biomedical research and clinical practice. We begin by considering the conventions around diagnosing and characterizing Lyme disease that have served as a conceptual framework for the discipline. We then explore virulence from the perspective of both host (genetic and environmental predispositions) and pathogen (serotypes, dissemination, and immune modulation), as well as considering antimicrobial strategies (lab methodology, resistance, persistence, and clinical application), and borrelial adaptations of hypothesized medical significance (phenotypic plasticity or pleomorphy).

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There has been a significant increase in the development of interventions to improve the social competence and success of adolescents with autism spectrum disorder. The current investigation used direct observation and coding of social conversations as a rigorous method to further assess the efficacy of the Social Tools And Rules for Teens socialization intervention for adolescents with autism spectrum disorder in the context of a randomized controlled trial. A total of 35 adolescents with high-functioning autism spectrum disorder were randomized to either a treatment or waitlist control group. The 20-week group intervention took place once a week for 90 min per session. Brief video-recorded conversations between participants and unfamiliar, untrained peers were recorded at pre- and post-time points and coded for selected social behaviors (i.e. questions asked, positive facial expressions, and mutual engagement). Results revealed a significant Group × Time treatment effect for both questions asked and positive facial expressions. The findings support that the Social Tools And Rules for Teens intervention can positively impact specific, observable social behaviors through systematic coding of live social conversations within the context of a randomized controlled trial. This investigation is one of the first randomized controlled trials of a group socialization intervention to use systematic coding of live social conversations to assess social competence improvements.

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Adolescents with ASD face numerous personal and contextual barriers that impede the development of social motivation and core competencies, warranting the need for targeted intervention. A randomized controlled trial was conducted with 40 adolescents to evaluate the merits of a multi-component socialization intervention that places emphasis on experiential learning. This investigation evaluated the impact of the 20-week START program on the social functioning of adolescents with ASD. Significant Group × Time differences between START and waitlist control groups were found across multiple measures. Secondary analyses of the entire program cohort also yielded significant improvement trends across all measures. These findings may be an important step in identifying optimal strategies to target the complex factors limiting optimal social development in ASD.

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G-quadruplexes represent a class of noncanonical nucleic acid structures implicated in transcriptional regulation, cellular function, and disease. An understanding of the forces involved in stabilization and destabilization of the G-quadruplex conformation relative to the duplex or single-stranded conformation is a key to elucidating the biological role of G-quadruplex-based genomic switches and the quest for therapeutic means for controlled induction or suppression of a G-quadruplex at selected genomic loci. Solute-solvent interactions provide a ubiquitous and, in many cases, the determining thermodynamic force in maintaining and modulating the stability of nucleic acids. These interactions involve water as well as water-soluble cosolvents that may be present in the solution or in the crowded environment in the cell. We present here the first quantitative investigation of the effect of urea, a destabilizing cosolvent, on the conformational preferences of a G-quadruplex formed by the telomeric d[A(G3T2A)3G3] sequence (Tel22). At 20 mM NaCl and room temperature, Tel22 undergoes a two-state urea-induced unfolding transition. An increase in salt mitigates the deleterious effect of urea on Tel22. The urea m-value of Tel22 normalized per change in solvent-accessible surface area, ΔSA, is similar to those for other DNA and RNA structures while being several-fold larger than that of proteins. Our results suggest that urea can be employed as an analytical tool in thermodynamic characterizations of G-quadruplexes in a manner similar to the use of urea in protein studies. We emphasize the need for further studies involving a larger selection of G-quadruplexes varying in sequence, topology (parallel, antiparallel, hybrid), and molecularity (monomolecular, bimolecular, tetramolecular) to outline the advantages and the limits of the use of urea in G-quadruplex studies. A deeper understanding of the effect of solvent and cosolvents on the differential stability of the G-quadruplex and duplex conformations is a step toward elucidation of the modulating influence of different types of cosolvents on duplex-G-quadruplex molecular switches triggering genomic events.

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Experiential learning is an essential process in the development of core social competencies. Unfortunately, adolescents with autism spectrum disorders often do not possess the prerequisite skillset and motivation to sustain the level of social immersion needed to benefit from this learning process. These persisting social vulnerabilities can limit their long-term relational success and associated quality of life, creating a need for comprehensive social programming. This paper describes a multi-component socialization intervention that simultaneously targets motivational, conceptual, and skill deficits using a hybrid experiential/didactic treatment approach. Evidence of social competence improvements was noted in survey and live conversational measures, indicating that the START program may hold promise as a method for improving the social success of participating adolescents with ASD.

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Tuberous sclerosis complex is an autosomal dominant genetic disorder that confers a high risk for neurodevelopmental disorders, such as autism spectrum disorder and intellectual disability. Studies have demonstrated specific delays in visual reception skills that may predict the development of autism spectrum disorder and intellectual disability. Based on evidence for alterations in the retinogeniculate pathway in animal models of tuberous sclerosis complex, we asked whether children with tuberous sclerosis complex demonstrate alterations in early visual processing that may undermine the development of higher-level visual behaviors. Pattern-reversal visual evoked potentials were recorded in infants with tuberous sclerosis complex (n = 16) and typically developing infants (n = 18) at 12 months of age. Infants with tuberous sclerosis complex demonstrated remarkably intact visual evoked potentials even within the context of intellectual disability and epilepsy. Infants with tuberous sclerosis complex show intact visual cortical processing, suggesting that delays in visually mediated behaviors in tuberous sclerosis complex may not be rooted in early visual processing deficits.

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OBJECTIVE: We performed a longitudinal cohort study of infants with tuberous sclerosis complex (TSC), with the overarching goal of defining early clinical, behavioral, and biological markers of autism spectrum disorder (ASD) in this high-risk population. METHODS: Infants with TSC and typically developing controls were recruited as early as 3 months of age and followed longitudinally until 36 months of age. Data gathered at each time point included detailed seizure history, developmental testing using the Mullen Scales of Early Learning, and social-communication assessments using the Autism Observation Scale for Infants. At 18 to 36 months, a diagnostic evaluation for ASD was performed using the Autism Diagnostic Observation Schedule. RESULTS: Infants with TSC demonstrated delays confined to nonverbal abilities, particularly in the visual domain, which then generalized to more global delays by age 9 months. Twenty-two of 40 infants with TSC were diagnosed with ASD. Both 12-month cognitive ability and developmental trajectories over the second and third years of life differentiated the groups. By 12 months of age, the ASD group demonstrated significantly greater cognitive delays and a significant decline in nonverbal IQ from 12 to 36 months. CONCLUSIONS: This prospective study characterizes early developmental markers of ASD in infants with TSC. The early delay in visual reception and fine motor ability in the TSC group as a whole, coupled with the decline in nonverbal ability in infants diagnosed with ASD, suggests a domain-specific pathway to ASD that can inform more targeted interventions for these high-risk infants.

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