Preventable tragedies: findings from the #NotAnAccident index of unintentional shootings by children.

BACKGROUND: Between 2015 and 2021, 3,498 Americans died from unintentional gun injuries, including 713 children 17 years and younger. Roughly 30 million American children live in homes with firearms, many of which are loaded and unlocked. This study assesses the scope of unintentional shootings by children 17 and younger in the US and the relationship between these shootings and state-level secure storage laws. METHODS: Demographic and injury data of both perpetrators and victims of unintentional shootings by children 17 and younger in the US from 1/1/2015-12/31/2021 were extracted from the #NotAnAccident Index. The #NotAnAccident Index contains media-report data, which is systematically flagged through Google Alerts. We describe characteristics of incidents and examine incident rates over time. The association between state-level secure storage laws and rates of unintentional shootings by children is assessed in multivariate negative binomial regression models. RESULTS: 2,448 unintentional shootings by children resulted in 926 deaths and 1,603 nonfatal gun injuries over a period of seven years. Most perpetrators (81%) and victims (76%) were male. The mean age was 10.0 (SD 5.5) for shooters and 10.9 (SD 8.1) for victims. Children were as likely to shoot themselves (49%) as they were to shoot others (47%). The majority of victims were under 18 years old (91%). Shootings most often occurred in or around homes (71%) and with handguns (53%). From March to December 2020, coinciding with the COVID-19 pandemic, incidents increased 24% over the same period in 2019, which was driven largely by an increase among shooters ages 0-5. Depending on the type of law, rates of unintentional shootings by children were 24% to 72% lower in states with secure storage laws, compared to states without such laws. CONCLUSIONS: Unintentional shootings by children are on the rise, particularly among children 0-5 years old, but are preventable tragedies. Our results show that secure firearm storage policies are strongly correlated with lower rates of unintentional shootings by children. Firearm storage policies, practices, and education efforts are needed to ensure guns are kept secured and inaccessible to children.

Whole-exome sequencing of a family with local anesthetic resistance.

BACKGROUND: Local anesthetics (LA) work by blocking sodium conductance through voltage-gated sodium channels. Complete local anesthetic resistance is infrequent, and the cause is unknown. Genetic variation in sodium channels is a potential mechanism for local anesthetic resistance. A patient with a history of inadequate loss of sensation following LA administration underwent an ultrasound-guided brachial plexus nerve block with a complete failure of the block. We hypothesized that LA resistance is due to a variant form of voltage-gated sodium channel. METHODS: Whole-Exome Sequencing. The patient and her immediate family provided consent for exome sequencing, and they were screened with a questionnaire to identify family members with a history of LA resistance. Exome sequencing results for four individuals were referenced to the 1000 Genomes Project and the NHLBI ESP to identify variants associated with local anesthetic resistance present in less than 1% of the general population and located in functional regions of the genome. RESULTS: Exome sequencing of the four family members identified one genetic variant in the voltage-gated sodium channel shared by the three individuals with LA resistance but not present in the unaffected family member. Specifically, we noted the A572D mutation in the SCN5A gene encoding for Nav1.5. CONCLUSIONS: We identified a genetic variant that is associated with LA resistance in the gene encoding for Nav1.5. We also demonstrate that Nav1.5 is present in human peripheral nerves to support the plausibility that an abnormal form of the Nav1.5 protein could be responsible for the observed local anesthetic resistance.

Progranulin mutations in primary progressive aphasia: the PPA1 and PPA3 families.

BACKGROUND: Primary progressive aphasia (PPA) is a language-based dementia characterized by fluent or nonfluent language disorder as its principal feature. OBJECTIVE: To describe progranulin gene mutations in 2 families with PPA. DESIGN: Report of affected families. SETTING: Academic research. PATIENTS: Two families, PPA1 and PPA3, were studied. Genomic DNA was isolated from 3 of 4 siblings in PPA1, from all 3 siblings in PPA3, and from more than 200 control subjects. MAIN OUTCOME MEASURES: All 12 coding exons of the progranulin gene and the 5" and 3" untranslated regions were amplified by polymerase chain reaction and were sequenced in both directions using relevant primers. RESULTS: Both affected members of PPA1 for whom DNA was available and both affected sisters of PPA3 had a progranulin gene mutation not found in the unaffected siblings or in the controls. The mutations likely cause a null allele and a reduction in the level of functional progranulin protein. Both affected members of PPA1 with autopsies had frontotemporal lobar degeneration with tau-negative ubiquinated inclusions. CONCLUSIONS: To our knowledge, these are the only known families in which affected members display phenotypical homogeneity for PPA in the initial stages of the disease. In both families, the disease segregated with progranulin gene mutations. Whether progranulin dysfunction also extends to sporadic PPA and how it affects the initial anatomical specificity of neurodegeneration remain to be determined.