Sleep in Children with Autism Spectrum Disorder: A Narrative Review and Systematic Update.

Purpose of Review: Sleep problems are a common comorbidity for children with autism spectrum disorder (ASD), and research in this area has a relatively long history. Within this review, we first outline historic patterns in the field of sleep and ASD. Second, we conducted a systematic update and coded these studies based on their alignment with historic patterns. Research on ASD and sleep over the past two decades has primarily focused on four principal areas: (1) documenting the prevalence and types of sleep problems; (2) sleep problem treatment options and efficacy; (3) how sleep problems are associated with other behavioral, contextual, or biological elements; and (4) the impact of child sleep problems on families and care providers. The systematic update in this paper includes empirical studies published between 2018 and 2021 with terms for sleep and ASD within the title, keywords, or abstract. Recent Findings: In sum, 60 studies fit the inclusion/exclusion criteria and most fit within the historic patterns noted above. Notable differences included more global representation in study samples, studies on the impacts of COVID-19, and a growing body of work on sleep problems as an early marker of ASD. The majority of studies focus on correlates of sleep problems noting less optimal behavioral, contextual, and biological elements are associated with sleep problems across development for children with ASD. Summary: Recommendations for future directions include continued expansion of global and age representation across samples, a shift toward more treatment and implementation science, and studies that inform our mechanistic understanding of how sleep and ASD are connected. Supplementary Information: The online version contains supplementary material available at 10.1007/s40675-022-00234-5.

In Vitro and Cellular Probes to Study PARP Enzyme Target Engagement.

Poly(ADP-ribose) polymerase (PARP) enzymes use nicotinamide adenine dinucleotide (NAD+) to modify up to seven different amino acids with a single mono(ADP-ribose) unit (MARylation deposited by PARP monoenzymes) or branched poly(ADP-ribose) polymers (PARylation deposited by PARP polyenzymes). To enable the development of tool compounds for PARP monoenzymes and polyenzymes, we have developed active site probes for use in in vitro and cellular biophysical assays to characterize active site-directed inhibitors that compete for NAD+ binding. These assays are agnostic of the protein substrate for each PARP, overcoming a general lack of knowledge around the substrates for these enzymes. The in vitro assays use less enzyme than previously described activity assays, enabling discrimination of inhibitor potencies in the single-digit nanomolar range, and the cell-based assays can differentiate compounds with sub-nanomolar potencies and measure inhibitor residence time in live cells.

Validation of edible taste strips for assessing PROP taste perception.

A novel delivery method is described that incorporates taste stimuli into edible strips for determining n-propylthiouracil (PROP) taster status. Edible strips that contained 400 or 600 nanomoles of PROP were prepared for psychophysical studies. Using these strips, we measured taste intensity, taste hedonics, and taste quality responses in a sample of healthy volunteers (n = 118). Participants were also asked to assess a single NaCl strip, a quinine strip, 3 NaCl solutions, and 3 PROP solutions. All psychophysical data were subsequently analyzed as a function of TAS2R38 genotype. The use of PROP strips for distinguishing between individuals with at least 1 PAV allele and individuals with other genotypes was assessed and compared with the use of PROP solutions for making this same distinction. For the 2 PROP strips and PROP solutions, individuals who expressed at least 1 PAV allele could perceive the bitter taste of PROP. Individuals who expressed 2 AVI alleles responded similarly to 400 nanomole PROP strips and blank strips. Furthermore, individuals with 2 AVI alleles responded to 0.032 and 0.32 mM PROP solutions at intensities that were similar to water, though intensity ratings to 3.2 mM PROP solution exceeded water. In general, those with at least 1 PAV allele rated the bitter taste of PROP as unpleasant in both delivery methods (strips or solutions). Psychophysical data from PROP strips and solutions were consistent with TAS2R38 genotype. These results support the validity of edible taste strips as a method for assessing PROP taste perception in humans.

Validation of edible taste strips for identifying PROP taste recognition thresholds.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to validate the use of edible taste strips for measuring taste recognition thresholds for the bitter-tasting compound 6-n-propylthiouracil (PROP). STUDY DESIGN: Taste recognition thresholds for PROP were obtained by two separate methods. Thresholds were also identified in subjects whose airflow through the nose was blocked. Threshold values were then compared to genotype analysis of the TAS2R38 taste receptor, which is the major determinant for the detection of PROP. METHODS: Edible taste strips were used to examine taste recognition thresholds for PROP. Thresholds were determined by the method of ascending limits and by the method of reversals. Single nucleotide polymorphism analysis of the TAS2R38 gene was used to identify PROP taster status. RESULTS: Taste recognition thresholds for PROP formed two distributions. Thresholds for one group varied from 4 to 219 nmol and represented PROP tasters. The second group could not detect the bitter taste of PROP at ≤800 nmol and represented PROP nontasters. The method of ascending limits and the method of reversals yielded similar threshold results. The expression of a PAV allele permitted detection of PROP, but AVI homozygotes could not detect the bitter taste of PROP. CONCLUSIONS: Edible taste strips were successfully used to detect PROP thresholds at values equal to or lower than those obtained in previous studies using PROP solutions or PROP-impregnated filter papers. This study provides validity evidence for the use of edible taste strips for identifying PROP in the human population.

A test for measuring gustatory function.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to determine the usefulness of edible taste strips for measuring human gustatory function. STUDY DESIGN: The physical properties of edible taste strips were examined to determine their potential for delivering threshold and suprathreshold amounts of taste stimuli to the oral cavity. Taste strips were then assayed by fluorescence to analyze the uniformity and distribution of bitter tastant in the strips. Finally, taste recognition thresholds for sweet taste were examined to determine whether or not taste strips could detect recognition thresholds that were equal to or better than those obtained from aqueous tests. METHODS: Edible strips were prepared from pullulan-hydroxypropyl methylcellulose solutions that were dried to a thin film. The maximal amount of a tastant that could be incorporated in a 2.54 cm2 taste strip was identified by including representative taste stimuli for each class of tastant (sweet, sour, salty, bitter, and umami) during strip formation. Distribution of the bitter tastant quinine hydrochloride in taste strips was assayed by fluorescence emission spectroscopy. The efficacy of taste strips for evaluating human gustatory function was examined by using a single series ascending method of limits protocol. Sucrose taste recognition threshold data from edible strips was then compared with results that were obtained from a standard "sip and spit" recognition threshold test. RESULTS: Edible films that formed from a pullulan-hydroxypropyl methylcellulose polymer mixture can be used to prepare clear, thin strips that have essentially no background taste and leave no physical presence after release of tastant. Edible taste strips could uniformly incorporate up to 5% of their composition as tastant. Taste recognition thresholds for sweet taste were over one order of magnitude lower with edible taste strips when compared with an aqueous taste test. CONCLUSION: Edible taste strips are a highly sensitive method for examining taste recognition thresholds in humans. This new means of presenting taste stimuli should have widespread applications for examining human taste function in the laboratory, in the clinic, or at remote locations.