Skeletal abnormalities in mice with Dnmt3a missense mutations.

Overgrowth and intellectual disability disorders in humans are typified by length/height and/or head circumference ≥ 2 standard deviations above the mean as well as intellectual disability and behavioral comorbidities, including autism and anxiety. Tatton-Brown-Rahman Syndrome is one type of overgrowth and intellectual disability disorder caused by heterozygous missense mutations in the DNA methyltransferase 3A (DNMT3A) gene. Numerous DNMT3A mutations have been identified in Tatton-Brown-Rahman Syndrome patients and may be associated with varying phenotype severities of clinical presentation.

Non-CG DNA methylation and MeCP2 stabilize repeated tuning of long genes that distinguish closely related neuron types.

The extraordinary diversity of neuron types in the mammalian brain is delineated at the highest resolution by subtle gene expression differences that may require specialized molecular mechanisms to be maintained. Neurons uniquely express the longest genes in the genome and utilize neuron-enriched non-CG DNA methylation (mCA) together with the Rett syndrome protein, MeCP2, to control gene expression, but the function of these unique gene structures and machinery in regulating finely resolved neuron type-specific gene programs has not been explored. Here, we employ epigenomic and spatial transcriptomic analyses to discover a major role for mCA and MeCP2 in maintaining neuron type-specific gene programs at the finest scale of cellular resolution.

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits.

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3a mouse mimicking a mutation with mild to moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation.

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits.

Phenotypic heterogeneity is a common feature of monogenic neurodevelopmental disorders that can arise from differential severity of missense variants underlying disease, but how distinct alleles impact molecular mechanisms to drive variable disease presentation is not well understood. Here, we investigate missense mutations in the DNA methyltransferase DNMT3A associated with variable overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity in neurodevelopmental disease. We generate a DNMT3A P900L/+ mouse model mimicking a disease mutation with mild-to-moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation.

Implications of full compliance with the computed tomography scanning recommendations of the National Institute for Clinical Excellence and Scottish Intercollegiate Guidelines Network guidelines for the management of head injury.

A prospective study was conducted to examine clinical practices in the management of head-injured patients preinception and postinception of the Scottish Intercollegiate Guidelines Network guidelines. Comparison was made between the Scottish Intercollegiate Guidelines Network and National Institute for Clinical Excellence guidelines on their indications for computed tomography scanning. Information was available on 2827 adult patients.

Laryngoscopic views during rapid sequence intubation in the emergency department.

Objectives: Our objective was to document and compare the views obtained at laryngoscopy during emergency department (ED) rapid sequence intubation (RSI) by anesthetists and emergency physicians of varying seniority and experience.

Methods: Data were prospectively collected on every intubation attempt in 7 urban Scottish EDs for 2 calendar years, commencing Jan. 11, 1999.

Scottish urban versus rural trauma outcome study.

Background: Outcome following trauma and health care access are important components of health care planning. Resources are limited and quality information is required. We set the objective of comparing the outcomes for patients suffering significant trauma in urban and rural environments in Scotland.

Eleven years of liver trauma: the Scottish experience.

The aim of this population based study was to assess the incidence, mechanisms, management, and outcome of patients who sustained hepatic trauma in Scotland (population 5 million) over the period 1992-2002. The Scottish Trauma Audit Group database was searched for details of any patient with liver trauma. Data on identified patients were analyzed for demographic information, mechanisms of injury, associated injuries, hemodynamic stability on presentation, management, and outcome.

Rapid sequence intubation of trauma patients in Scotland.

Background: Endotracheal intubation remains the gold standard for trauma airway management. Rapid sequence intubation (RSI) has traditionally been performed by anesthesiologists but increasingly, emergency physicians are also undertaking RSI. We aimed to compare success and complication rates for trauma intubations for the two specialties.

Patients with a head injury who "talk and die" in the 1990s.

Background: Patients who "talk and die" after head injury may represent a group who suffer delayed and therefore potentially preventable complications after injury. We have compared the clinical and pathologic features of patients who talk and die with those who "talk and live" after head injury.

Methods: Data collected prospectively by the Scottish Trauma Audit Group were used to identify patients with a head injury and classify them according to verbal response at admission to hospital.