Development of a new tool for predicting the behavior of individuals with intellectual disability in the dental office: A pilot study.

BACKGROUND: The dental treatment of individuals with intellectual disability can represent a considerable professional challenge. OBJECTIVE: To develop a model for predicting the behavior of patients with intellectual disability in the dental office. METHODS: The study group comprised 250 patients with Down syndrome (DS), autism spectrum disorder (ASD), cerebral palsy (CP), idiopathic cognitive impairment or rare disorders. We collected their demographic, medical, social and behavioral information and identified potential predictors (chi-squared test). We developed stratified models (Akaike information criterion) to anticipate the patients'behavior during intraoral examinations and to discern whether the dental treatment should be performed under general anesthesia. These models were validated in a new study group consisting of 80 patients. Goodness of fit was quantified with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC). We developed a mathematical algorithm for executing the models and developed software for its practical implementation (PREdictors of BEhavior in Dentistry, "PREBED"). RESULTS: For patients with DS, ASD and CP, the model predicting the need for physical restraint during examination achieved a PPV of 0.90, 0.85 and 1.00, respectively, and an NPV of 0.66, 0.76 and 1.00, respectively. The model predicting the need for performing treatment under general anesthesia achieved a PPV of 0.63, 1.00 and 1.00, respectively, and an NPV of 1.00, 1.00 and 0.73, respectively. However, when validating the stratified models, the percentage of poorly classified individuals (false negatives + false positives) ranged from 24% to 46.6%. CONCLUSIONS: The results of the PREBED tool open the door to establishing new models implementing other potentially predictive variables.

Restoring Shank3 in the rostral brainstem of shank3ab-/- zebrafish autism models rescues sensory deficits.

People with Phelan-McDermid Syndrome, caused by mutations in the SHANK3 gene, commonly exhibit reduced responses to sensory stimuli; yet the changes in brain-wide activity that link these symptoms to mutations in the shank3 gene remain unknown. Here we quantify movement in response to sudden darkness in larvae of two shank3 zebrafish mutant models and show that both models exhibit dampened responses to this stimulus. Using brain-wide activity mapping, we find that shank3-/- light-sensing brain regions show normal levels of activity while sensorimotor integration and motor regions are less active. Specifically restoring Shank3 function in a sensorimotor nucleus of the rostral brainstem enables the shank3-/- model to respond like wild-type. In sum, we find that reduced sensory responsiveness in shank3-/- models is associated with reduced activity in sensory processing brain regions and can be rescued by restoring Shank3 function in the rostral brainstem. These studies highlight the importance of Shank3 function in the rostral brainstem for integrating sensory inputs to generate behavioral adaptations to changing sensory stimuli.

Allenes and Derivatives in Gold(I)- and Platinum(II)-Catalyzed Formal Cycloadditions.

Cycloaddition reactions, by involving the formation of at least two bonds and one cycle in a single operation, represent one of the more practical ways to assemble carbo- and heterocyclic structures from simple acyclic precursors. Especially appealing are formal cycloadditions promoted by transition metals, owing to the ability of these reagents to open mechanisms that are not accessible using classical chemistry. Therefore, along the years, a great variety of annulations based on first-, and particularly second-row transition metals have been discovered. Most of these reactions involve inner sphere mechanisms, with the metal participating via standard oxidative addition or reductive elimination processes. Curiously, metals of the third row like platinum and, especially, gold remained largely unexplored, likely because of the belief that they were inert and expensive. However, from the beginning of this century, many groups realized that these metals can open very interesting mechanistic scenarios and promote novel types of transformations. In particular, the π-acidic, carbophilic behavior of gold(I) complexes, together with the possibility of tuning their reactivity using designed ligands, has triggered important activity in the field. Many gold-catalyzed transformations involved addition or cycloisomerization processes, but during recent years, there have been also important advances in the development of formal cycloaddition reactions. While many of these reactions rely on the activation of alkynes, there has been an increasing number of reports that exploit the peculiar reactivities of allenes and derivatives. In this Account, we present recent efforts on the development of platinum- and gold-catalyzed formal cycloadditions of allenes. For the sake of simplicity, we only include annulations initiated by a direct metal-promoted activation of the allene moiety. Thus, alternative Pt- or Au-catalyzed reactions wherein the allene does not interact with the metal catalyst are not covered. Upon activation by the metals, allenes generate allyl-cation alkenylmetal species that can behave as 1,2- or 1,3-carbon dipoles in cycloaddition processes. Especially relevant is the reactivity of allenamides. The presence of the amide substituent provides for the generation of gold intermediates with a good balance of reactivity and stability, which can therefore react with the corresponding partners in a controlled manner. Moreover, despite the difficulties associated with the transfer of stereochemical information from chiral linear gold(I) complexes, a variety of enantioselective gold-catalyzed annulations have been discovered. This Account is organized considering the number of atoms engaged in the annulation process, and when possible, we present the results in a chronological order.

Gold(I)-Catalyzed Enantioselective Annulations between Allenes and Alkene-Tethered Oxime Ethers: A Straight Entry to Highly Substituted Piperidines and aza-Bridged Medium-Sized Carbocycles.

Piperidine scaffolds are present in a wide range of bioactive natural products and are therefore considered as highly valuable, privileged synthetic targets. In this manuscript, we describe a gold-catalyzed annulation strategy that allows a straightforward assembly of piperidines and piperidine-containing aza-bridged products from readily available alkene-tethered oxime ethers (or esters) and N-allenamides. Importantly, we demonstrate the advantages of using oxime derivatives over imines, something pertinent to the whole area of gold catalysis, and provide relevant mechanistic experiments that shed light into the factors affecting the annulation processes. Moreover, we also describe preliminary experiments demonstrating the viability of enantioselective versions of the above reactions.

Gold(i)-catalyzed [2 + 2 + 2] cycloaddition of allenamides, alkenes and aldehydes: a straightforward approach to tetrahydropyrans.

Allenamides participate as two-carbon components in an intermolecular [2 + 2 + 2] cycloaddition with alkenes and aldehydes when treated with catalytic amounts of a phosphite gold complex. The reaction is highly regio- and chemoselective, and works with different types of alkenes, including styrenes, enol ethers or enamides, as well as with aromatic and aliphatic aldehydes. Accordingly, different types of 2,6-disubstituted tetrahydropyrans can be stereoselectively assembled in a single step from commercial or very accessible starting materials.