Behavioral,cognitive, and adaptive development in infants with autism spectrum disorder in the first 2?years of life

Background

To delineate the early progression of autism spectrum disorder (ASD) symptoms, this study investigated developmental characteristics of infants at high familial risk for ASD (HR), and infants at low risk (LR).

Methods

Participants included 210 HR and 98 LR infants across 4 sites with comparable behavioral data at age 6, 12, and 24 months assessed in the domains of cognitive development (Mullen Scales of Early Learning), adaptive skills (Vineland Adaptive Behavioral Scales), and early behavioral features of ASD (Autism Observation Scale for Infants). Participants evaluated according to the DSM-IV-TR criteria at 24 months and categorized as ASD-positive or ASD-negative were further stratified by empirically derived cutoff scores using the Autism Diagnostic Observation Schedule yielding four groups: HR-ASD-High, HR-ASD-Moderate (HR-ASD-Mod), HR-ASD-Negative (HR-Neg), and LR-ASD-Negative (LR-Neg).

Results

The four groups demonstrated different developmental trajectories that became increasingly distinct from 6 to 24 months across all domains. At 6 months, the HR-ASD-High group demonstrated less advanced Gross Motor and Visual Reception skills compared with the LR-Neg group. By 12 months, the HR-ASD-High group demonstrated increased behavioral features of ASD and decreased cognitive and adaptive functioning compared to the HR-Neg and LR-Neg groups. By 24 months, both the HR-ASD-High and HR-ASD-Moderate groups demonstrated differences from the LR- and HR-Neg groups in all domains.

Conclusions

These findings reveal atypical sensorimotor development at 6 months of age which is associated with ASD at 24 months in the most severely affected group of infants. Sensorimotor differences precede the unfolding of cognitive and adaptive deficits and behavioral features of autism across the 6- to 24-month interval. The less severely affected group demonstrates later symptom onset, in the second year of life, with initial differences in the social-communication domain.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9117-6) contains supplementary material, which is available to authorized users.     

Structural analysis of the inactive state of the Escherichia coli DNA polymerase clamp-loader complex

Clamp-loader complexes are heteropentameric AAA+ ATPases that load sliding clamps onto DNA. The structure of the nucleotide-free Escherichia coli clamp loader had been determined previously and led to the proposal that the clamp-loader cycles between an inactive state, in which the ATPase domains form a closed ring, and an active state that opens up to form a "C" shape. The crystal structure was interpreted as being closer to the active state than the inactive state. The crystal structure of a nucleotide-bound eukaryotic clamp loader [replication factor C (RFC)] revealed a different and more tightly packed spiral organization of the ATPase domains, raising questions about the significance of the conformation seen earlier for the bacterial clamp loader. We describe crystal structures of the E. coli clamp-loader complex bound to the ATP analog ATPgammaS (at a resolution of 3.5 A) and ADP (at a resolution of 4.1 A). These structures are similar to that of the nucleotide-free clamp-loader complex. Only two of the three functional ATP-binding sites are occupied by ATPgammaS or ADP in these structures, and the bound nucleotides make no interfacial contacts in the complex. These results, along with data from isothermal titration calorimetry, molecular dynamics simulations, and comparison with the RFC structure, suggest that the more open form of the E. coli clamp loader described earlier and in the present work corresponds to a stable inactive state of the clamp loader in which the ATPase domains are prevented from engaging the clamp in the highly cooperative manner seen in the fully ATP-loaded RFC-clamp structure.     

Efficacy of Human Chorion Membrane Allograft for Recession Coverage: A Case Series

Background : Membranes of human placentas have been used in the field of medicine for skin grafts, treatment of burns, and ulcerated skin conditions with great success. The use of placenta allografts in dentistry is a more recent development, with the first commercial product being made available in 2008. The unique inherent biologic properties in placenta allografts enhance wound healing and may propagate regeneration. Methods: Ten healthy adult patients presenting with 21 Miller Class I gingival recession (GR) defects (isolated or adjacent multiple) were surgically treated with a modified coronally advanced flap and chorion membrane for root coverage. Clinical parameters measured at baseline, 3 months, and 6 months were probing depth, clinical attachment level, GR height, width of keratinized gingiva, and assessment of gingival biotype. Statistical analysis was performed to compare the treatment outcomes at the follow‐up intervals. Results: The results showed statistically significant (P <0.001) improvements in all clinical parameters at the 3‐ and 6‐month follow‐ups. The mean percentage of root coverage at the end of 6 months was 89.92% ± 15.59%, and 14 of 21 treated GR defects showed 100% root coverage. The gingival biotype also showed a thick biotype in nine sites that had an initial thin biotype. Conclusions: Fetal membranes possess distinctive properties that can be harnessed to promote periodontal healing. The chorion membrane covered by a modified coronally advanced flap is a new approach that has shown promising results in terms of root coverage, increased width of keratinized tissue, and thickness of the gingival biotype.