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Objectives This cross‐sectional study examined the association between adverse childhood experiences (ACEs) and history of frequent headaches (including migraine) among children 3‐17 years old using data from the 2016 and 2017 U.S. National Survey of Children’s Health (NSCH). Background ACEs include abuse (physical, emotional, or sexual), parental divorce, death, mental illness, or addiction, and are linked to higher morbidity and mortality in adulthood. A relationship between ACEs and headaches exists among adults, but studies examining the relationship among children are lacking. To our knowledge, no studies have examined the link among children using NSCH data. Methods The NSCH is a nationally representative survey of U.S. children’s physical and emotional well‐being aimed at understanding their health needs. Parental‐reported information was collected on child history of headaches and 9 ACEs for the selected child. The survey collected information on 71,881 children in 2016 and 2017 out of which 61,565 were eligible for the study (age ≥3 years and not missing data on history headaches). Children with missing values for headache, ACEs, or covariates (n = 58,958) were excluded from the final analysis. We used multivariable logistic regression with survey weighting and adjusted for demographics and comorbidities (anxiety, depression, epilepsy, and brain injury) to examine the association between ACEs and headaches overall and stratified by gender. We further assessed the independent relationship between each ACE and headaches. Results In the current study, out of 61,656 children, 26,884 (48.6%) experienced at least 1 ACE and 3426 (6.5%) experienced 4+ ACEs. Overall, compared with children with no ACEs, the adjusted odds of headache were 1.34 times higher among children with 1 reported ACE (95% CI: 1.07, 1.68), 2.15 times higher among children with 2 ACEs (95% CI: 1.66, 2.80), 1.89 times higher among children with 3 ACEs (95% CI: 1.40, 2.53), and 3.40 times higher among children with 4+ ACEs (95% CI: 2.61, 4.43). Females with 3 and 4+ ACEs were somewhat more likely to report headaches compared to males with the same number of ACEs. Individually, no ACE was independently associated with history of headaches except for difficulty due to family’s income (aOR = 2.46, 95% CI: 1.98, 3.06). Conclusion Experiencing one or more ACEs vs none was associated with higher risk of headaches in children, and difficulty due to family’s income was the only ACE independently associated with headaches. Our findings support results of other studies on ACEs and headache in young adults and suggest that adverse ACE‐related health outcomes begin earlier than previously recognized. Additionally, struggling due to low income may represent a constellation of chronic stressors that independently contribute to poor health outcomes in childhood as compared to other individual ACEs. Future research should examine the importance of specific ACE clusters and stressors during childhood.

Tegobuvir (TGV) is a novel non-nucleoside inhibitor (NNI) of HCV RNA replication with demonstrated antiviral activity in patients with genotype 1 chronic HCV infection. The mechanism of action of TGV has not been clearly defined despite the identification of resistance mutations mapping to the NS5B polymerase region. TGV does not inhibit NS5B enzymatic activity in biochemical assays in vitro, suggesting a more complex antiviral mechanism with cellular components. Here, we demonstrate that TGV exerts anti-HCV activity utilizing a unique chemical activation and subsequent direct interaction with the NS5B protein. Treatment of HCV subgenomic replicon cells with TGV results in a modified form of NS5B with a distinctly altered mobility on a SDS-PAGE gel. Further analysis reveals that the aberrantly migrating NS5B species contains the inhibitor molecule. Formation of this complex does not require the presence of any other HCV proteins. The intensity of the aberrantly migrating NS5B species is strongly dependent on cellular glutathione levels as well as CYP 1A activity. Furthermore analysis of NS5B protein purified from a heterologous expression system treated with TGV by mass spectrometry suggests that TGV undergoes a CYP- mediated intracellular activation step and the resulting metabolite, after forming a glutathione conjugate, directly and specifically interacts with NS5B. Taken together, these data demonstrate that upon metabolic activation TGV is a specific, covalent inhibitor of the HCV NS5B polymerase and is mechanistically distinct from other classes of the non-nucleoside inhibitors (NNI) of the viral polymerase.

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Background: Women are more likely to develop post-traumatic stress disorder (PTSD) than men. Limited research exists evaluating the risk of hypertensive disorders of pregnancy (HDP) among military women with PTSD. Methods:We conducted a retrospective cohort study using US Department of Defense (DoD) data comprised of all active-duty women giving birth to their first, liveborn singleton infant using DoD-sponsored health insurance from 1 January 2004 to 31 December 2008 (n = 34 176). Birth hospitalisation records, maternal mental health visits, and Post-Deployment Health Assessment (PDHA) and Reassessment (PDHRA) screenings were included. The HDP outcome (yes vs no) was defined using ICD-9-CM codes in the maternal birth hospitalisation record. Women fit into one of four PTSD exposure categories (confirmed, probable, possible, none).Confirmed cases had a PTSD ICD-9-CM diagnosis code. Probable/possible cases were classified using PDHA screening items. We used multiple log-linear regression to assess PTSD (confirmed, any vs none) and the risk of HDP overall, and then explored effect modification by military service and demographic variables. We assessed the risk of HDP among deployed mothers with PTSD (confirmed, probable/ possible vs none) who completed a PDHA, and explored effect modification by race/ ethnicity. We also assessed risk of HDP with differing PTSD lead times.Results: Overall, PTSD was not associated with HDP except among mothers whose PTSD was diagnosed ≥1 year prior to conception (RR 1.42, 95% CI 1.06, 1.90). Conclusions:Post-traumatic stress disorder preceding conception by at least a year appeared to confer an increased risk of HDP, but further research is needed using more thorough PTSD assessment. K E Y W O R D S deployment, hypertensive disorders of pregnancy, military, post-traumatic stress disorder | 239 NASH et Al.