Menke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles.

CREB-binding protein (CBP, encoded by CREBBP) and its paralog E1A-associated protein (p300, encoded by EP300) are involved in histone acetylation and transcriptional regulation. Variants that produce a null allele or disrupt the catalytic domain of either protein cause Rubinstein-Taybi syndrome (RSTS), while pathogenic missense and in-frame indel variants in parts of exons 30 and 31 cause phenotypes recently described as Menke-Hennekam syndrome (MKHK). To distinguish MKHK subtypes and define their characteristics, molecular and extended clinical data on 82 individuals (54 unpublished) with variants affecting CBP (n = 71) or p300 (n = 11) (NP_004371.2 residues 1,705-1,875 and NP_001420.2 residues 1,668-1,833, respectively) were summarized. Additionally, genome-wide DNA methylation profiles were assessed in DNA extracted from whole peripheral blood from 54 individuals. Most variants clustered closely around the zinc-binding residues of two zinc-finger domains (ZZ and TAZ2) and within the first α helix of the fourth intrinsically disordered linker (ID4) of CBP/p300. Domain-specific methylation profiles were discerned for the ZZ domain in CBP/p300 (found in nine out of 10 tested individuals) and TAZ2 domain in CBP (in 14 out of 20), while a domain-specific diagnostic episignature was refined for the ID4 domain in CBP/p300 (in 21 out of 21). Phenotypes including intellectual disability of varying degree and distinct physical features were defined for each of the regions. These findings demonstrate existence of at least three MKHK subtypes, which are domain specific (MKHK-ZZ, MKHK-TAZ2, and MKHK-ID4) rather than gene specific (CREBBP/EP300). DNA methylation episignatures enable stratification of molecular pathophysiologic entities within a gene or across a family of paralogous genes.

Turn that music down! Affective musical bursts cause an auditory dominance in children recognizing bodily emotions.

Previous work has shown that different sensory channels are prioritized across the life course, with children preferentially responding to auditory information. The aim of the current study was to investigate whether the mechanism that drives this auditory dominance in children occurs at the level of encoding (overshadowing) or when the information is integrated to form a response (response competition). Given that response competition is dependent on a modality integration attempt, a combination of stimuli that could not be integrated was used so that if children's auditory dominance persisted, this would provide evidence for the overshadowing over the response competition mechanism. Younger children (≤7 years), older children (8-11 years), and adults (18+ years) were asked to recognize the emotion (happy or fearful) in either nonvocal auditory musical emotional bursts or human visual bodily expressions of emotion in three conditions: unimodal, congruent bimodal, and incongruent bimodal. We found that children performed significantly worse at recognizing emotional bodies when they heard (and were told to ignore) musical emotional bursts. This provides the first evidence for auditory dominance in both younger and older children when presented with modally incongruent emotional stimuli. The continued presence of auditory dominance, despite the lack of modality integration, was taken as supportive evidence for the overshadowing explanation. These findings are discussed in relation to educational considerations, and future sensory dominance investigations and models are proposed.

Evaluating psychiatric readmissions in the emergency department of a large public hospital.

INTRODUCTION: Hospital emergency departments (EDs) around the country are being challenged by an ever-increasing volume of patients seeking psychiatric services. This manuscript describes a study performed to identify internal and external factors contributing to repeated psychiatric patient admissions to the hospital main ED. METHODS: Data from ED visits of patients who were admitted to the Parkland Memorial Hospital ED (the community hospital for Dallas County, TX, USA) with a psychiatric complaint more than once within a 30-day period were evaluated (n=202). A 50-item readmission survey was used to collect information on demographic and clinical factors associated with 30-day readmission, as well as to identify quality improvement opportunities by assessing related moderating factors. An analysis of acute readmission visits (occurring within 3 days of previous discharge) was also performed. RESULTS: Patients readmitted to the ED commonly present with a combination of acute psychiatric symptoms, substance use (especially in the case of acute readmission), and violent or suicidal behavior. The vast majority of cases reviewed found that readmitted patients had difficulties coordinating care outside the ED. A number of moderating factors were identified and targeted for quality improvement including additional support for filling prescriptions, transportation, communication with family and outside providers, drug and alcohol treatment, intensive case management, and housing. CONCLUSION: Many of the resources necessary to reduce psychiatric patient visits to hospital EDs are available within the community. There is no formal method of integrating and insuring the continuity of community services that may reduce the demand for psychiatric and related services in the ED. While agreements between community service providers may be challenging and require considerable vigilance to maintain equitable agreements between parties, this route of improving efficiency may be the only available method, given the current and projected patient care needs.

Analyzing the contribution of community change to population health outcomes in an adolescent pregnancy prevention initiative.

Few evaluations of community initiatives have established a link between intermediate outcomes, such as community or systems change, and more distant population-level health outcomes (e.g., estimated rates of employment or adolescent pregnancy). This article describes an analysis of the contribution of community changes facilitated by a community health initiative to prevent adolescent pregnancy to the population-level outcome of birth rates for teens. The authors examine a hypothesis that this link might be expected when community changes are of greater amount, intensity, duration, and exposure. The results showed reductions in birth rates in Target Area A, where there was a greater concentration of community changes and a slight increase where there were far fewer changes. This report provides a method for describing empirically the contribution of environmental change to more distant population-level outcomes.