Cornelia de Lange syndrome and the Cohesin complex: Abstracts from the 9th Biennial Scientific and Educational Virtual Symposium 2020.

Cornelia de Lange syndrome (CdLS) is a spectrum disorder due to variants in genes of the cohesin protein complex. The following abstracts are from the Cornelia de Lange Syndrome Scientific and Educational Symposium held virtually in October 2020. Aspects of behavior, including autistic features, impulsivity, adaptive skills, executive function, and anxiety are described. Applied behavioral analysis is a promising approach for autism, and an N-acetylcysteine trial is proposed. Children below 6 years with CdLS have an increased number of and further travel to medical providers, with insurance type comprising a significant barrier. Speech, language, and feeding abilities fall significantly below expectations for age in CdLS. Augmentative alternative communication can yield potential barriers as well as interesting benefits. Developmentally, studies in animal models further elucidate the mechanisms and roles of cohesin: link with mediator transcriptional complex; facilitation of enhancer-promoter communication; regulation of gene expression; allocation of cells to germ layers; and repair of spontaneous DNA damage in placental cells. Genome and RNA sequencing can help identify the molecular cause in the 20% of individuals with suspected CdLS and negative testing. The phenotypes in individuals with variants in the SMC1A gene are distinct, and that with intractable seizures has been further evaluated. AMA CME credits provided by GBMC, Baltimore, MD. All studies approved by an ethics committee.

Cornelia de Lange syndrome and molecular implications of the cohesin complex: Abstracts from the 7th biennial scientific and educational symposium 2016.

Cornelia de Lange Syndrome (CdLS) is due to mutations in the genes for the structural and regulatory proteins that make up the cohesin complex, and is considered a cohesinopathy disorder or, more recently, a transcriptomopathy. New phenotypes have been recognized in this expanding field. There are multiple clinical issues facing individuals with all forms of CdLS, particularly in the neurodevelopmental system, but also gastrointestinal, cardiac, and musculoskeletal. Aspects of developmental and cell biology have found common endpoints in the biology of the cohesin complex, with improved understanding of the mechanisms, easier diagnostic tests, and the possibility of potential therapeutics, all major clinical implications for the individual with CdLS. The following abstracts are the presentations from the 7th Cornelia de Lange Syndrome Scientific and Educational Symposium, June 22-23, 2016, in Orlando, FL, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting. In addition to the scientific and clinical discussions, there were talks related to practical aspects of behavior including autism, transitions, communication, access to medical care, and databases. At the end of the symposium, a panel was held, which included several parents, affected individuals and genetic counselors, and discussed the greatest challenges in life and how this information can assist in guiding future research. The Research Committee of the CdLS Foundation organizes this meeting, reviews, and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board and publications. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD.

Clinical, developmental and molecular update on Cornelia de Lange syndrome and the cohesin complex: abstracts from the 2014 Scientific and Educational Symposium.

Cornelia de Lange Syndrome (CdLS) is the most common example of disorders of the cohesin complex, or cohesinopathies. There are a myriad of clinical issues facing individuals with CdLS, particularly in the neurodevelopmental system, which also have implications for the parents and caretakers, involved professionals, therapists, and schools. Basic research in developmental and cell biology on cohesin is showing significant progress, with improved understanding of the mechanisms and the possibility of potential therapeutics. The following abstracts are presentations from the 6th Cornelia de Lange Syndrome Scientific and Educational Symposium, which took place on June 25-26, 2014, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting in Costa Mesa, CA. The Research Committee of the CdLS Foundation organizes the meeting, reviews and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board. In addition to the scientific and clinical discussions, there were educationally focused talks related to practical aspects of behavior and development. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD.

A Systematic Review of Tablet-Based Interactive Distraction as a Preoperative Anxiolytic in Pediatric Patients Undergoing Same-Day Procedures.

Evidence shows tablet-based interactive distraction (TBID) is effective as a preoperative anxiolytic in pediatric patients. TBID involves age-appropriate video games that have been preloaded onto a tablet (TAB) and subsequently given to a pediatric patient before the administration of anesthesia. The purpose of this study is to provide a comprehensive analysis of previous studies that have investigated the use of TBID to minimize preoperative anxiety. The literature criteria for this systematic review included randomized controlled trials and prospective studies that used TBID as a method to reduce preoperative anxiety in pediatric patients aged 1-12 years. Data extraction concentrated on the patient population to which the TABs were introduced, the method of TAB administration, how anxiety was evaluated, who completed the evaluations, and the results of each publication. This chosen data set is to systematically understand if TBID is effective and to identify the most practical ways to implement TBID. Collected data from the selected publications were entered into a table. For this systematic review, 27 publications from 2006 to 2023 were screened for eligibility. These studies were selected using a combination of MeSH terms and a Title-Abstract filter in PubMed, Embase, and Scopus. These data represented 475 total patients (T) and 249 patients who implemented TAB use. The other 226 patients were used as various control groups. The outcome of each study is summarized and placed into a table. This study is expected to provide an overall assessment of the effectiveness of TBID and proposed guidelines for clinicians to incorporate TAB use into preoperative protocols. The time to give the TAB to the children impacts its efficiency. This review accentuates the effectiveness of utilizing TBID to mitigate preoperative anxiety in pediatric patients based on a comprehensive analysis of multiple prior studies conducted in diverse healthcare settings, including pediatric hospitals and surgical centers. TAB use demonstrated an effective reduction in perioperative anxiety, emergence of delirium, and time to discharge, increasing parental satisfaction compared to midazolam. These results are likely replicable across a broader range of clinical settings, provided the intervention parameters, such as the timing of TAB introduction and the personalization of content to patient interests, are carefully adapted to each situation. The anxiety evaluations of patients using TBID varied based on the evaluator. Therefore, future research should analyze if perceived anxiety in patients using TABs is consistent or not among the evaluators. The impact of this TBID review has the potential to set a new benchmark for managing pediatric preoperative anxiety, with significant implications for healthcare quality and patient satisfaction.

Assessing the Agreement of Light Microscopic Evaluation of Oral Lichen Planus Lesions With Associated Direct Immunofluorescence Evaluation.

Aim/objective: Assess agreement between light microscopy and direct immunofluorescence (DIF) for histopathologic evaluation of oral lichen planus (OLP). Methods: Records evaluated included 60 OLP, 16 lichenoid mucositis (LM), and 56 non-OLP/non-LM cases. Cases had both light microscopic and DIF evaluations. Histopathologic parameters of OLP included: (1) hydropic degeneration of the basal cell layer, (2) band-like lymphocytic infiltrate immediately subjacent to the epithelium, and (3) presence of Civatte bodies. Two calibrated examiners independently assessed light microscopic features. Examiners reviewed cases with discordant diagnoses to determine a consensus diagnosis. Intra-rater reliability (IRR), sensitivity, specificity, positive, and negative predictive values (PPV and NPV) were determined. Results: Of 132 patients, 72.7% were female, average age 61.9 (SD = 13.8). Most common sites were gingiva (37.9%), buccal mucosa (37.1%), and tongue (7.6%). IRR was 0.74 (95% CI: 0.40, 1.00) for the consensus diagnosis and 0.73 (95% CI: 0.39, 1.00) and 0.34 (95% CI: -0.03, 0.72) for the 2 examiners. Comparing consensus and definitive diagnoses: sensitivity of light microscopy: 0.32 (95% CI: 0.20, 0.45); specificity: 0.88 (95% CI: 0.78, 0.94); PPV: 0.68 (95% CI: 0.48, 0.84), and NPV: 0.61 (95% CI: 0.51, 0.70). Conclusion: Light microscopy alone is not a viable alternative to adjunctive DIF for diagnosis of OLP lesions.

Risk of HIV Viral Rebound in the Era of Universal Treatment in a Multicenter Sample of Persons With HIV in Primary Care.

Background: Antiretroviral therapy (ART) is recommended for people with HIV (PWH), irrespective of CD4 cell count, to improve their health and reduce the risk of transmission to sexual partners through long-term viral suppression. We identified risk factors for viral rebound among patients with a period of stable viral suppression to inform counseling and monitoring. Methods: We conducted a multisite, retrospective study of PWH with a 2-year period of sustained viral suppression in the United States using the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We used multivariable logistic regression to identify characteristics independently associated with any viral rebound (viral load [VL] ≥200 copies/mL) and sustained viral rebound (VL ≥200 copies/mL followed by a VL that was also ≥200 copies/mL within 6 months), within 2 years of follow-up. Results: Among 3496 eligible patients with a 2-year period of sustained viral suppression, most (90%) continued to have viral suppression over 2 additional years; 10% experienced viral rebound, and 4% experienced sustained viral rebound. In multivariable analyses, Black race, current smoking, integrase strand transfer inhibitor use, and 5- to 9-year duration of ART were positively associated, and being age ≥50 years was negatively associated, with any viral rebound. Only current smoking and 5- to 9-year (vs 2- to 4-year) duration of ART were positively associated, and being age ≥60 years was negatively associated, with sustained viral rebound. Conclusions: Most people retained in clinical care and with HIV viral suppression on ART will have persistent viral suppression. However, some patients may benefit from additional treatment adherence support.

Wastewater sequencing reveals community and variant dynamics of the collective human virome.

Wastewater is a discarded human by-product, but its analysis may help us understand the health of populations. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels while bypassing the difficulties and pit falls of individual testing. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. Here, we conduct a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Critical to detection is the use of a viral probe capture set targeting thousands of viral species or variants. Over 450 distinct pathogenic viruses from 28 viral families are observed, most of which have never been detected in such samples. Sequencing reads of established pathogens and emerging viruses correlate to clinical data sets of SARS-CoV-2, influenza virus, and monkeypox viruses, outlining the public health utility of this approach. Viral communities are tightly organized by space and time. Finally, the most abundant human viruses yield sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.

Incidental Hepatic Granulomata as the Initial Presentation of Crohn's Disease in a Pediatric Patient.

We describe a 9-year-old girl who presented with abdominal pain, found incidentally to have multiple liver granulomata. Extensive autoimmune and infectious workup was negative. The patient had esophagogastroduodenoscopy and colonoscopy, confirming the diagnosis of Crohn's disease. Hepatic granulomata are a rare complication of Crohn's disease and are often secondary to pharmacotherapy or infection in immunosuppressed patients. This case, to our knowledge, is the first reported case of a pediatric patient diagnosed with Crohn's disease after initially presenting with hepatic granulomata as an extraintestinal manifestation of the disease.

Infections of Deep Neck Spaces.

Identifying infections of the deep neck spaces and understanding how they spread can be a diagnostic challenge that is complicated by complex anatomy and far-reaching clinical implications. Deep neck infections have the potential to quickly spread throughout the neck and chest, leading to widespread disease that can be rapidly fatal and resistant to treatment. This article provides a foundation for evaluating deep neck infections through a review of essential anatomy and a discussion of important diseases that interact with these spaces.

Functional MRI connectivity of children with autism and low verbal and cognitive performance.

Background: Functional neuroimaging research in autism spectrum disorder has reported patterns of decreased long-range, within-network, and interhemispheric connectivity. Research has also reported increased corticostriatal connectivity and between-network connectivity for default and attentional networks. Past studies have excluded individuals with autism and low verbal and cognitive performance (LVCP), so connectivity in individuals more significantly affected with autism has not yet been studied. This represents a critical gap in our understanding of brain function across the autism spectrum. Methods: Using behavioral support procedures adapted from Nordahl, et al. (J Neurodev Disord 8:20-20, 2016), we completed non-sedated structural and functional MRI scans of 56 children ages 7-17, including LVCP children (n = 17, mean IQ = 54), children with autism and higher performance (HVCP, n = 20, mean IQ = 106), and neurotypical children (NT, n = 19, mean IQ = 111). Preparation included detailed intake questionnaires, video modeling, behavioral and anxiety reduction techniques, active noise-canceling headphones, and in-scan presentation of the Inscapes movie paradigm from Vanderwal et al. (Neuroimage 122:222-32, 2015). A high temporal resolution multiband echoplanar fMRI protocol analyzed motion-free time series data, extracted from concatenated volumes to mitigate the influence of motion artifact. All participants had > 200 volumes of motion-free fMRI scanning. Analyses were corrected for multiple comparisons. Results: LVCP showed decreased within-network connectivity in default, salience, auditory, and frontoparietal networks (LVCP < HVCP) and decreased interhemispheric connectivity (LVCP < HVCP=NT). Between-network connectivity was higher for LVCP than NT between default and dorsal attention and frontoparietal networks. Lower IQ was associated with decreased connectivity within the default network and increased connectivity between default and dorsal attention networks. Conclusions: This study demonstrates that with moderate levels of support, including readily available techniques, information about brain similarities and differences in LVCP individuals can be further studied. This initial study suggested decreased network segmentation and integration in LVCP individuals. Further imaging studies of LVCP individuals with larger samples will add to understanding of origins and effects of autism on brain function and behavior.

Managing Student Behavior in Dual Immersion Classrooms: A Study of Class-Wide Function-Related Intervention Teams.

Classroom management in dual immersion classrooms includes unique challenges. The teacher must instruct and correct in the L2 language, in which students are beginning learners, and effective classroom management strategies appropriate to the L2 context. Class-Wide Function-Related Intervention Teams (CW-FIT) is a positive classroom management program that teaches social skills and uses group contingencies to improve behavior. The present study examined the ability of French immersion teachers to implement CW-FIT in the L2, including the effects of CW-FIT on teacher praise and reprimand rates and as well as on students' classroom behavior. Social validity was also assessed. A single-subject multiple baseline design with embedded reversals was used to evaluate impact in second-, third-, and fourth-grade dual immersion classrooms. Results indicated that dual immersion teachers were able to implement CW-FIT in L2 with fidelity. The intervention significantly increased teacher praise and improved classroom on-task behavior. Changes in teacher reprimand rates were inconsistent. Students and teachers reported CW-FIT to be socially valid.

A Pilot Study of a Behavioral Parent Training in the Republic of Macedonia.

Parenting children with autism in countries with limited professional and financial resources can be overwhelming. Parent training led by non-governmental organizations may help alleviate some of these burdens. The present pilot study was conducted in the Republic of Macedonia, a country located in Southeastern Europe. The purpose of the study was to evaluate a parent training model for disseminating evidence-based practices through didactic and pyramidal training strategies. Results indicated that children improved on a number of different behaviors and results provide some evidence that parenting confidence and distress improved.

Relationship between brain stem volume and aggression in children diagnosed with autism spectrum disorder.

BACKGROUND: Aggressive behaviors are common in individuals diagnosed with autism spectrum disorder (ASD) and may be phenotypic indicators of different subtypes within ASD. In current research literature for non-ASD samples, aggression has been linked to several brain structures associated with emotion and behavioral control. However, few if any studies exist investigating brain volume differences in individuals with ASD who have comorbid aggression as indicated by standardized diagnostic and behavioral measures. METHOD: We examined neuroimaging data from individuals rigorously diagnosed with ASD versus typically developing (TD) controls. We began with data from brain volume regions of interest (ROI) taken from previous literature on aggression including the brainstem, amygdala, orbitofrontal cortex, anterior cingulate cortex, and dorsolateral prefrontal cortex. We defined aggression status using the Irritability subscale of the Aberrant Behavior Checklist and used lasso logistic regression to select among these predictor variables. Brainstem volume was the only variable shown to be a predictor of aggression status. RESULTS: We found that smaller brainstem volumes are associated with higher odds of being in the high aggression group. CONCLUSIONS: Understanding brain differences in individuals with ASD who engage in aggressive behavior from those with ASD who do not can inform treatment approaches. Future research should investigate brainstem structure and function in ASD to identify possible mechanisms related to arousal and aggression.

Teaching multi-step math skills to adults with disabilities via video prompting.

The purpose of this study was to evaluate the effectiveness of teaching multi-step math skills to nine adults with disabilities in an 18-21 post-high school transition program using a video prompting intervention package. The dependent variable was the percentage of steps completed correctly. The independent variable was the video prompting intervention, which involved several multi-step math calculation skills: (a) calculating a tip (15%), (b) calculating item unit prices, and (c) adjusting a recipe for more or fewer people. Results indicated a functional relationship between the video prompting interventions and prompting package and the percentage of steps completed correctly. 8 out of the 9 adults showed significant gains immediately after receiving the video prompting intervention.

Class-Wide Function-Related Intervention Teams "CW-FIT" Efficacy Trial Outcomes.

The purpose of the study was to determine the efficacy of the Class-wide Function-related Intervention Teams (CW-FIT) program for improving students' on-task behavior, and increasing teacher recognition of appropriate behavior. The intervention is a group contingency classroom management program consisting of teaching and reinforcing appropriate behaviors (i.e., getting the teacher's attention, following directions, and ignoring inappropriate behaviors of peers). Seventeen elementary schools, the majority in urban and culturally diverse communities, participated in a randomized trial with 86 teachers (classrooms) assigned to CW-FIT, and 73 teachers (classrooms) assigned to the comparison group. Class-wide student on-task behavior improved over baseline levels in the intervention classes. Teachers were able to implement the intervention with high fidelity overall, as observed in adherence to 96% of the fidelity criteria on average. Teacher praise and attention to appropriate behaviors increased, and reprimands decreased. These effects were replicated in new classrooms each of the 4 years of the study, and for all years combined.

The effects of goal setting, contingent reward, and instruction on writing skills.

Writing is one of the primary skills that children learn in school. Interventions that address performance deficits and skill deficits have been shown to improve aspects of elementary school children's writing. This study demonstrates performance-based interventions (goal setting, feedback, and contingent reward) and a skill-based intervention (instruction) on the writing skills of a 10-year-old child. Results indicated that the performance intervention increased the number of correctly spelled words, and the combination of performance and instructional intervention increased the number of complete sentences.

Effects of naturalistic instruction on phonological awareness skills of children with intellectual and developmental disabilities.

This study evaluated the effects of an intervention for teaching phonological awareness skills to kindergarten-age children with intellectual and developmental disabilities. The intervention employed a combined multiple treatment and multiple baseline design, embedded in playtime and implemented under naturally occurring conditions. Six children in a special education kindergarten class were taught syllable segmentation, first sound identification, and phoneme segmenting. Results indicated that all children made gains on each skill. Results are discussed in light of current research on phonological awareness intervention for young children with intellectual and developmental disabilities.