Reported exposures to respirable crystalline silica during construction tasks and guidance for harmonizing future research.

Airborne respirable crystalline silica (RCS) has been a widely recognized hazard in the United States for nearly 100 years, yet it continues to pose a risk to construction tradespersons, among others. RCS exposures vary widely depending on site conditions and tools and materials used. The proper use of engineering, administrative, and personal protective equipment (PPE) controls can effectively reduce exposure to RCS. Historically, others have reviewed available RCS exposure data among construction trades and reported that there were considerable data gaps and variability that needed to be addressed. This current assessment aimed to synthesize available peer-reviewed exposure studies to determine potential RCS exposures during the use of common construction materials and evaluate to what extent data gaps and variability persist. Twenty-eight studies were identified that reported RCS exposure during construction tasks. After conversion to the unit of µg/m3, reported measurements from samples collected for varying durations ranged from 6.0 to 75,500 µg/m3 for work with concrete, 80 to 4,240 µg/m3 for work with brick, <59 to 10,900 µg/m3 for work with mortar, 90 to 44,370 µg/m3 for work with engineered stone, and 70 to 380 µg/m3 for work with roof tile. To better facilitate pooling data across studies, future researchers should report their sample duration, clarify how time-weighted average (TWA) exposure data are calculated, report the silica content of the material being manipulated, and specify whether samples were collected while the task was performed in isolation or on a worksite where other silica-containing materials were also actively handled. When reporting results as respirable quartz, it is important to note whether any other polymorphic forms of silica were detected. It is ultimately the employer's responsibility to train employees and monitor and control RCS exposures on construction worksites. To do this effectively, it is important to have a clear understanding of the tasks, materials, and site conditions where intervention is most urgently needed.

Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy.

De novo mutations of the voltage-gated sodium channel gene SCN8A have recently been recognized as a cause of epileptic encephalopathy, which is characterized by refractory seizures with developmental delay and cognitive disability. We previously described the heterozygous SCN8A missense mutation p.Asn1768Asp in a child with epileptic encephalopathy that included seizures, ataxia, and sudden unexpected death in epilepsy (SUDEP). The mutation results in increased persistent sodium current and hyperactivity of transfected neurons. We have characterized a knock-in mouse model expressing this dominant gain-of-function mutation to investigate the pathology of the altered channel in vivo. The mutant channel protein is stable in vivo. Heterozygous Scn8a(N1768D/+) mice exhibit seizures and SUDEP, confirming the causality of the de novo mutation in the proband. Using video/EEG analysis, we detect ictal discharges that coincide with convulsive seizures and myoclonic jerks. Prior to seizure onset, heterozygous mutants are not defective in motor learning or fear conditioning, but do exhibit mild impairment of motor coordination and social discrimination. Homozygous mutant mice exhibit earlier seizure onset than heterozygotes and more rapid progression to death. Analysis of the intermediate phenotype of functionally hemizygous Scn8a(N1768D/-) mice indicates that severity is increased by a double dose of mutant protein and reduced by the presence of wild-type protein. Scn8a(N1768D) mutant mice provide a model of epileptic encephalopathy that will be valuable for studying the in vivo effects of hyperactive Nav1.6 and the response to therapeutic interventions.