No abstract

Employer-sponsored wellness programs have proliferated in the United States since the 1990 s. Projections have estimated that the corporate wellness industry could exceed $12 billion US sometime in 2020 (Roberts & Fowler, 2017; Wolfe, 2018). In 2018, 82% of large firms and 53% of small employers in the United States offered a wellness program, with key health and wellness components, including nutrition, physical activity, stress reduction, and preventive services (Song & Baicker, 2019). Despite the high prevalence of employer-sponsored wellness programs (Roberts & Fowler, 2017),

Prophylaxis of posttraumatic epilepsy will require a detailed knowledge of the epileptogenic pathophysiological processes that follow brain injury. Results from studies of experimental models and human epilepsy highlight alterations in GABAergic interneurons and formation of excessive new excitatory synaptic connectivity as prominent targets for prophylactic therapies. Promising laboratory results suggest that it will be possible to experimentally modify these aberrant processes and interfere with epileptogenesis. However, a number of key issues must be addressed before these results can be used to frame clinical antiepileptogenic therapy.

Background In current care, patients’ personal and self-reported family histories are primarily used to determine whether genetic testing for hereditary endocrine tumor syndromes (ETS) is indicated. Population genomic screening for other conditions has increased ascertainment of individuals with pathogenic/likely pathogenic (P/LP) variants, leading to improved management and earlier diagnoses. It is unknown whether such benefits occur when screening broader populations for P/LP ETS variants. This manuscript assesses clinical utility outcomes of a large, unselected, healthcare-based genomic screening program by describing personal and family history of syndrome-related features, risk management behaviors after result disclosure, and rates of relevant post-disclosure diagnoses in patient-participants with P/LP ETS variants. Methods Observational study of individuals informed of a P/LP variant in MEN1, RET, SDHAF2, SDHB, SDHC, SDHD, or VHL through Geisinger’s MyCode Community Health Initiative between June 2016 and October 2019. Electronic health records (EHRs) of participants were evaluated for a report of pre-disclosure personal and self-reported family histories and post-disclosure risk management and diagnoses. Results P/LP variants in genes of interest were identified in 199 of 130,490 (1 in 656) adult Geisinger MyCode patient-participants, 80 of which were disclosed during the study period. Eighty-one percent (n = 65) did not have prior evidence of the result in their EHR and, because they were identified via MyCode, were included in further analyses. Five participants identified via MyCode (8%) had a personal history of syndrome-related features; 16 (25%) had a positive self-reported family history. Time from result disclosure to EHR review was a median of 0.7 years. Post-disclosure, 36 (55.4%) completed a recommended risk management behavior; 11 (17%) were diagnosed with a syndrome-related neoplasm after completing a risk management intervention. Conclusions Broader screening for pathogenic/likely pathogenic variants associated with endocrine tumor syndromes enables detection of at-risk individuals, leads to the uptake of risk management, and facilitates relevant diagnoses. Further research will be necessary to continue to determine the clinical utility of screening diverse, unselected populations for such variants.

Lysophosphatidic acid (LPA) levels increase in the cerebrospinal fluid and blood within 24 hours after traumatic brain injury (TBI), indicating it may be a biomarker for subsequent cellular pathology. However, no data exist that document this association after TBI. We, therefore, acquired matrix-assisted laser desorption ionization imaging mass spectrometry data of LPA, major LPA metabolites, and hemoglobin from adult rat brains at 1 and 3 hours after controlled cortical impact injury. Data were semiquantitatively assessed by signal intensity analysis normalized to naïve rat brains acquired concurrently. Gray and white matter pathology was assessed on adjacent sections using immunohistochemistry for cell death, axonal injury, and intracellular LPA, to determine the spatiotemporal patterning of LPA corresponding to pathology. The results revealed significant increases in LPA and LPA precursors at 1 hour after injury and robust enhancement in LPA diffusively throughout the brain at 3 hours after injury. Voxel-wise analysis of LPA by matrix-assisted laser desorption ionization and β-amyloid precursor protein by immunohistochemistry in adjacent sections showed significant association, raising the possibility that LPA is linked to secondary axonal injury. Total LPA and metabolites were also present in remotely injured areas, including cerebellum and brain stem, and in particular thalamus, where intracellular LPA is associated with cell death. LPA may be a useful biomarker of cellular pathology after TBI.