Pediatric Media Guidance for Parents of Children on the Autism Spectrum: A Thematic Analysis.

Very little is known about pediatric media guidance, or the one-on-onse advice that medical and clinical professionals (MCPs) communicate to parents about their children's recreational media and technology (RMT) use. One population that stands to benefit from a closer examination is children on the autism spectrum due to their behavior and communication challenges. We surveyed one group of pediatric autism MCPs, applied behavioral analysis (ABA) providers (N = 234), due to their proximity to families and conducted an applied thematic analysis of RMT advice they deliver. Providers reported primarily suggesting that caregivers employ restrictive parental mediation with their autistic child, that RMT should primarily be limited to use as a reward or reinforcement, and that parents should set time limits. Our findings offer new insights into the intersections of health communication theory and practice, while highlighting the need for greater research into RMT guidance for children with and without disabilities.

The Caenorhabditis elegans proteasome subunit RPN-12 is required for hermaphrodite germline sex determination and oocyte quality.

BACKGROUND: The proteasome is a multi-subunit complex and a major proteolytic machinery in cells. Most subunits are essential for proteasome function, and depletion of individual subunits normally results in lethality. RPN-12/Rpn12/PSMD8 is a lid subunit of the 19S regulatory particle (RP) of the 26S proteasome. Studies in Caenorhabditis elegans demonstrated that RNAi depletion of RPN-12 does not result in lethality. RPN-12 has not been well studied in higher eukaryotes. In this study, we investigate the biological significance of RPN-12 in C. elegans. RESULTS: We found that the null mutant rpn-12(av93) did not cause major impairment of the proteolytic activity of the proteasome. Most rpn-12(av93) hermaphrodites lack sperm leading to feminization of the germ line that can be partially rescued by mating to males. The lack of sperm phenotype can be suppressed by downregulation of TRA-1, a player in the hermaphrodite germline sex determination pathway. Also, rpn-12(av93) animals show significant nuclear accumulation of the meiotic kinase WEE-1.3, a protein predominantly localized to the perinuclear region. Interestingly, chemical inhibition of the proteasome did not cause nuclear accumulation of WEE-1.3. CONCLUSIONS: RPN-12 plays a previously unknown role in oogenesis and the germline sex determination pathway in C. elegans hermaphrodites.

The effect of cue type on directive-following in children with moderate to severe autism spectrum disorder.

For this study, 11 children with moderate to severe autism spectrum disorder (ASD) were given directives containing prepositions in three cue conditions: (a) spoken alone, (b) a short video clip along with spoken cues, and (c) a sequence of three graphic symbols accompanied by spoken cues. Participants followed directives significantly more accurately with the video clip than with spoken cues only, and significantly more accurately with spoken cues only relative to the sequence of graphic symbols. Results suggest that the short video clip along with spoken cues may be an optimal mode for enhancing learners' ability to follow directives containing prepositions. In addition, results reveal three statistically significant correlations between participants' preexisting skills and directive-following accuracy: a positive correlation between spoken preposition preassessment total score and accuracy in the spoken-alone condition; a positive correlation between spoken noun preassessment total score and accuracy in the video-clip condition; and a positive correlation between ASD severity and the need for repetition in the video-clip condition. Results also suggested that, for children with more severe ASD symptoms, the video clips require repetitions so that the relationships illustrated within it can gain more semantic salience. Implications for clinical practice and future research are discussed.

Physician Mediation Theory and Pediatric Media Guidance in the Digital Age: A Survey of Autism Medical and Clinical Professionals.

Research on physician mediation suggests that physicians actively discuss media use (e.g., seeking online health information) with their patients. This theory has been limited though with respect to incorporating key behavioral determinants, varied forms of mediation, and samples beyond primary care physicians (MDs). A survey of 335 U.S.-based medical and clinical professionals (MCPs) treating pediatric clients on the autism spectrum (e.g., pediatricians, speech-language pathologists) examined how they advise caregivers about managing their child's recreational media and technology use, also known as media guidance. Results indicate the frequency of these discussions varies by MCP type. Hierarchical regression analyses show, as hypothesized, that additional behavioral and contextual determinants not previously considered (i.e., perceived norms, self-efficacy, information sources and child factors) are significantly associated with positive, negative and redirective mediation practices. Results expand existing theory and justify extending physician mediation research beyond MDs. Implications for clinical practice and health communication research are discussed.

Providing visual directives via a smart watch to a student with Autism Spectrum Disorder: an intervention note.

Smart watches are discreet and wearable tools that may be repurposed to improve directive-following for individuals with autism spectrum disorder (ASD). Specifically, a mentor can transmit just-in-time (JIT) visual supports (e.g., video clips, photographs, text) that depict an upcoming directive to a learner's smart watch to prompt the learner as needed from a distance. Using a single-case multiple probe design across settings, this investigation evaluated the effectiveness of providing text-based prompts on an Apple Watch 1 to a child with ASD within a school setting. A mentor transmitted 2-step written directives via text message to the participant's Apple Watch. The participant was instructed to attend to, read, and follow directives received on the watch. Results demonstrated that the intervention improved directive-following as well as increased the instructor's distance from the learner. It is proposed that JIT supports sent to a learner's smart watch may reduce the obtrusiveness of traditional prompting while also maintaining the naturalness of ongoing social or academic interactions. Clinical limitations and implications are discussed.

Health Literacy and Health Outcomes in Persons Living with HIV Disease: A Systematic Review.

Low health literacy is associated with challenges for those living with HIV including medication non-adherence and poorer health outcomes. The aim of this study was to systematically review the literature on health literacy and health outcomes in persons living with HIV. The extended guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, as well as A Measurement Tool to Assess Systematic Reviews (AMSTAR) checklist were utilized to guide the approach to the review. A variety of electronic databases including PubMed, CINAHL, PsychInfo, and Cochrane Library were searched. Additional literature available on U.S. government websites was also included in the search. Search terms were used in a variety of combinations and included HIV, health literacy, adherence, and health outcomes. Forty-eight studies were identified that addressed health literacy and health outcomes in HIV. Although several studies in this review did not provide robust results of statistical significance linking health literacy with health outcomes, all of the studies addressed the key significance of health literacy within the scope of living with HIV disease. The relationship between health literacy and the identified health outcomes requires further research and explication.

Novel functions for the RNA-binding protein ETR-1 in Caenorhabditis elegans reproduction and engulfment of germline apoptotic cell corpses.

RNA-binding proteins (RBPs) are essential regulators of gene expression that act through a variety of mechanisms to ensure the proper post-transcriptional regulation of their target RNAs. RBPs in multiple species have been identified as playing crucial roles during development and as having important functions in various adult organ systems, including the heart, nervous, muscle, and reproductive systems. ETR-1, a highly conserved ELAV-Type RNA-binding protein belonging to the CELF/Bruno protein family, has been previously reported to be involved in C. elegans muscle development. Animals depleted of ETR-1 have been previously characterized as arresting at the two-fold stage of embryogenesis. In this study, we show that ETR-1 is expressed in the hermaphrodite somatic gonad and germ line, and that reduction of ETR-1 via RNA interference (RNAi) results in reduced hermaphrodite fecundity. Detailed characterization of this fertility defect indicates that ETR-1 is required in both the somatic tissue and the germ line to ensure wild-type reproductive levels. Additionally, the ability of ETR-1 depletion to suppress the published WEE-1.3-depletion infertility phenotype is dependent on ETR-1 being reduced in the soma. Within the germline of etr-1(RNAi) hermaphrodite animals, we observe a decrease in average oocyte size and an increase in the number of germline apoptotic cell corpses as evident by an increased number of CED-1::GFP and acridine orange positive apoptotic germ cells. Transmission Electron Microscopy (TEM) studies confirm the significant increase in apoptotic cells in ETR-1-depleted animals, and reveal a failure of the somatic gonadal sheath cells to properly engulf dying germ cells in etr-1(RNAi) animals. Through investigation of an established engulfment pathway in C. elegans, we demonstrate that co-depletion of CED-1 and ETR-1 suppresses both the reduced fecundity and the increase in the number of apoptotic cell corpses observed in etr-1(RNAi) animals. Combined, this data identifies a novel role for ETR-1 in hermaphrodite gametogenesis and in the process of engulfment of germline apoptotic cell corpses.

The effectiveness of aided augmented input techniques for persons with developmental disabilities: a systematic review.

When working with individuals with little or no functional speech, clinicians often recommend that communication partners use the client's augmentative and alternative communication (AAC) device when speaking to the client. This is broadly known as "augmented input" and is thought to enhance the client's learning of language form and content. The purpose of this systematic review was to determine the effects of augmented input on communication outcomes in persons with developmental disabilities and persons with childhood apraxia of speech who use aided AAC. Nineteen studies met the inclusion criteria. Each included study was reviewed in terms of participant characteristics, terminology used, symbol format, augmented input characteristics, outcomes measured, effectiveness, and study quality. Results indicate that augmented input can improve single-word vocabulary skills and expression of multi-symbol utterances; however, comprehension beyond the single word level has not been explored. Additionally, it is difficult to form conclusions about the effect of augmented input on specific diagnostic populations. Directions for future research are posited.

Andy Golden: Mentorship through the Years.

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Proteasomal subunit depletions differentially affect germline integrity in C. elegans.

The 26S proteasome is a multi-subunit protein complex that is canonically known for its ability to degrade proteins in cells and maintain protein homeostasis. Non-canonical or non-proteolytic roles of proteasomal subunits exist but remain less well studied. We provide characterization of germline-specific functions of different 19S proteasome regulatory particle (RP) subunits in C. elegans using RNAi specifically from the L4 stage and through generation of endogenously tagged 19S RP lid subunit strains. We show functions for the 19S RP in regulation of proliferation and maintenance of integrity of mitotic zone nuclei, in polymerization of the synaptonemal complex (SC) onto meiotic chromosomes and in the timing of SC subunit redistribution to the short arm of the bivalent, and in turnover of XND-1 proteins at late pachytene. Furthermore, we report that certain 19S RP subunits are required for proper germ line localization of WEE-1.3, a major meiotic kinase. Additionally, endogenous fluorescent labeling revealed that the two isoforms of the essential 19S RP proteasome subunit RPN-6.1 are expressed in a tissue-specific manner in the hermaphrodite. Also, we demonstrate that the 19S RP subunits RPN-6.1 and RPN-7 are crucial for the nuclear localization of the lid subunits RPN-8 and RPN-9 in oocytes, further supporting the ability to utilize the C. elegans germ line as a model to study proteasome assembly real-time. Collectively, our data support the premise that certain 19S RP proteasome subunits are playing tissue-specific roles, especially in the germ line. We propose C. elegans as a versatile multicellular model to study the diverse proteolytic and non-proteolytic roles that proteasome subunits play in vivo.

The increasing proportion of adult discharges at children's hospitals, 2004-2019.

Significant medical advances now enable individuals with pediatric illnesses to survive into adulthood. Finding medical homes for these individuals often remains challenging. We utilized the Pediatric Health Information System to measure the variation in and growth of admissions to children's hospitals, stratified by age and payor from 2004 to 2019. We identified 8,097,081 patient encounters from 30 hospitals. Compared to children, adults discharged at children's hospitals are more likely to have a complex chronic condition, have a higher median cost, and have a longer median length of stay. Hospital-level adult discharges ranged from 1.9% to 10.1% (median 4.1%; interquartile range: 2.8%-5.4%). Significantly higher increases were seen in each adult age subgroup (18-20, 21-25, and >25 years old) compared to the pediatric age group (p < .001). The number of adults discharged from children's hospitals is increasing faster than children, impacting children's hospitals and the populations they serve.

Student Attitudes Contribute to the Effectiveness of a Genomics CURE.

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student's epistemic beliefs to achieving positive learning outcomes.

Enantioselective α-arylation of aldehydes via the productive merger of iodonium salts and organocatalysis.

The enantioselective α-arylation of aldehydes has been accomplished using diaryliodonium salts and a combination of copper and organic catalysts. These mild catalytic conditions provide a new strategy for the enantioselective construction and retention of enolizable α-formyl benzylic stereocenters, a valuable synthon for the production of medicinal agents. As one example, this new asymmetric protocol has been applied to the rapid synthesis of (S)-ketoprofen, a commercially successful oral and topical analgesic.

Comparison of N- and C-terminally endogenously GFP-tagged WEE-1.3 strains in C. elegans.

We have generated a WEE-1.3 strain in C. elegans wherewe have endogenously tagged the C-terminus with GFP. In this publication we demonstrate that this new strain exhibits the same expression localization pattern as the WEE-1.3 antibody and N-terminally endogenously GFP-tagged WEE-1.3 strain that have been previously published. We also show for the first time that endogenously tagging WEE-1.3 at either termini does not affect the reproductive function of the worms.

An intrinsically disordered nascent protein interacts with specific regions of the ribosomal surface near the exit tunnel.

The influence of the ribosome on nascent chains is poorly understood, especially in the case of proteins devoid of signal or arrest sequences. Here, we provide explicit evidence for the interaction of specific ribosomal proteins with ribosome-bound nascent chains (RNCs). We target RNCs pertaining to the intrinsically disordered protein PIR and a number of mutants bearing a variable net charge. All the constructs analyzed in this work lack N-terminal signal sequences. By a combination chemical crosslinking and Western-blotting, we find that all RNCs interact with ribosomal protein L23 and that longer nascent chains also weakly interact with L29. The interacting proteins are spatially clustered on a specific region of the large ribosomal subunit, close to the exit tunnel. Based on chain-length-dependence and mutational studies, we find that the interactions with L23 persist despite drastic variations in RNC sequence. Importantly, we also find that the interactions are highly Mg+2-concentration-dependent. This work is significant because it unravels a novel role of the ribosome, which is shown to engage with the nascent protein chain even in the absence of signal or arrest sequences.

In-gel SOD assay reveals SOD-2 is the single active, water-soluble SOD enzyme in C. elegans.

The nematode C. elegans has a contingent of five sod genes, one of the largest among aerobic organisms. Earlier studies revealed each of the five sod genes is capable of making perfectly active SOD proteins in heterologous expression systems therefore none appears to be a pseudogene. Yet deletion of the entire contingent of sod genes fails to impose any effect on the survival of C. elegans except these animals appear more sensitive to extraneously applied oxidative stress conditions. We asked how many of the five sod genes are actually making active SOD enzymes in C. elegans through the usage of in-gel SOD activity analysis and by using KCN as a selective inhibitor against Cu-ZnSOD enzyme(s). Here we provide evidence that out of the five SOD proteins only the mitochondrial SOD is active in the water-soluble fraction of C. elegans extracts albeit at an apparently much lower activity than the multiple active SODs in D. melanogaster and E. coli. We had no opportunity to test the activity of Sod-4a isoform which is possibly a membrane-bound form of SOD. The mutant analysis further confirmed that among the two mitochondrial SOD proteins, SOD-2 is the only naturally active SOD in C. elegans.

The productive merger of iodonium salts and organocatalysis: a non-photolytic approach to the enantioselective alpha-trifluoromethylation of aldehydes.

An enantioselective organocatalytic alpha-trifluoromethylation of aldehydes has been accomplished using a commercially available, electrophilic trifluoromethyl source. The merging of Lewis acid and organocatalysis provides a new strategy for the enantioselective construction of trifluoromethyl stereogenicity, an important chiral synthon for pharmaceutical, materials, and agrochemical applications. This mild and operationally simple protocol allows rapid access to enantioenriched alpha-trifluoromethylated aldehydes through a nonphotolytic pathway.