Advertising Exposure and Use of E-Cigarettes Among Female Current and Former Tobacco Users of Childbearing Age

Objective: The study examined the relationship between exposure to e‐cigarette advertising and e‐cigarette use by pregnancy status, including use of flavored e‐cigarette products, among women of childbearing age. Design: A cross‐sectional, correlational design was used. Subjects: Female current or former tobacco users in Central and Eastern Kentucky, 18–45 years old (N = 194, 52% pregnant). Measures: Demographics, pregnancy status, cigarette and e‐cigarette use, and exposure to e‐cigarette advertising. Results: Younger age, white non‐Hispanic race, and greater exposure to e‐cigarette advertising were associated with a higher likelihood of ever using e‐cigarettes (p \u3c .05 for each variable). Pregnancy was not associated with ever use (p = .11). Younger age was associated with use of flavored e‐cigarettes (p = .0027). Among e‐cigarette users, those who used flavored products were more likely to have seen advertisements or information about e‐cigarettes on social media, compared to those who used unflavored e‐cigarettes only (p = .016). Conclusion: There is a link between advertising exposure and ever use of e‐cigarettes. Pregnancy status is not significantly associated with ever use. Use of flavored e‐cigarettes is associated with younger age. E‐cigarette users with greater exposure to advertising on social media were more likely to use flavored products

Solving the molecular structure of hybrid human-porcine factor VIII through X-ray crystallization

Factor VIII (fVIII) is a protein that is involved in the coagulation cascade, a collection of reactions that is activated by injury and leads to the formation of blood clots. Deficiencies in fVIII lead to the bleeding disorder hemophilia A, a condition that occurs in 1 in 5000 births. The current treatment for hemophilia A is inefficient and costly; however, there is potential through the use of recombinant hybrid human-porcine fVIII. Hybrid fVIII shows up to 12-fold higher coagulant activity than human fVIII, and can retain its activity even in the presence of inhibitory antibodies. The primary objective of our study is to determine the molecular structure of full-length hybrid human-porcine fVIII through X- ray crystallography. This allows us to see how the protein functions on a molecular level, along with the details of its interactions with binding partners. Thus far we have produced crystals of fVIII in complex with IgG antibodies 3E6 FAB and G99 FAB, along with the TIL’E’ domain of binding partner von Willebrand factor. These crystals have exhibited limited diffraction, and we are working towards optimizing crystals to increase the resolution of the diffraction pattern. The structure of hybrid fVIII has not yet been studied in detail, and this information could demonstrate its viability, bringing us one step closer to a long-term, effective, and economical treatment of hemophilia

Associations of Demographic Factors and Tobacco Use With Progesterone and Estradiol During Pregnancy

Objective: To evaluate the association of biochemically validated prenatal tobacco use with serum progesterone and estradiol in the second trimester of pregnancy, controlling for demographic and personal factors. Study design: This secondary analysis of a multicenter longitudinal study included 114 women with singleton pregnancies. Multiple regression analysis assessed whether prenatal tobacco use was related to hormone levels during the second trimester, controlling for covariates (age, body mass index, and race or ethnicity, with gestational age added to subsequent models). Result: In the initial regressions, tobacco users had significantly lower progesterone level compared with nonsmokers (p = .037), while estradiol was unrelated to prenatal tobacco use. Women with greater body mass index also had significantly lower progesterone (p = .028), but body mass index was unrelated to estradiol. With gestational age as an additional covariate, prenatal tobacco use was no longer a significant predictor of progesterone, but both body mass index and gestational age were significant (F = 10.6, p \u3c .001, R2 = 0.35). For estradiol, the overall regression of estradiol on age, body mass index, and race or ethnicity was not significant (F = 1.2, p = .31). With gestational age added to the model, the overall model was significant (F = 7.2, p \u3c .001, R2 = 0.27). Conclusion: This study provides additional evidence that prenatal tobacco use may influence lower serum progesterone during the second trimester. This is of particular concern given the link between depressed progesterone activity and risk for preterm birth

Comparison of Serum and Cervical Cytokine Levels Throughout Pregnancy Between Preterm and Term Births

Objective: To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births. Study Design: This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study (N ¼ 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester). Results: For the CVF values of IL-6, IL-8, IL-10, TNF-α, and CRP, and serum MMP-8, those who delivered preterm had significantly higher values than the full-term group regardless of trimester. For the serum values of IL-1β, IL-6, and TNF-α, those delivering preterm had significantly lower values than those delivering full-term regardless of trimester. For IL-1β in CVF, the cytokine was significantly higher in the PTB group for second and third trimesters only, relative to the full-term group. Conclusion: For each CVF cytokine that differed by birth status, values were higher for PTB than term, averaged over trimester. Numerous cytokine profiles varied across trimesters in women delivering term versus preterm in both CVF and serum

Comparison of Serum and Cervical Cytokine Levels Throughout Pregnancy Between Preterm and Term Births

Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births. Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study (N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester). Results For the CVF values of IL-6, IL-8, IL-10, TNF-α, and CRP, and serum MMP-8, those who delivered preterm had significantly higher values than the full-term group regardless of trimester. For the serum values of IL-1β, IL-6, and TNF-α, those delivering preterm had significantly lower values than those delivering full-term regardless of trimester. For IL-1β in CVF, the cytokine was significantly higher in the PTB group for second and third trimesters only, relative to the full-term group. Conclusion For each CVF cytokine that differed by birth status, values were higher for PTB than term, averaged over trimester. Numerous cytokine profiles varied across trimesters in women delivering term versus preterm in both CVF and serum

Effects of a College-Mentored Physical Activity Program for Elementary Students

Health risks of a sedentary lifestyle for children, defined as being less than 5,000 steps per day, include unfavorable indicators of body composition and cardio-metabolic risk. Results of school-based physical activity interventions to increase physical activity levels have been mixed. However, mentorship programs have shown promise. Previous mentorship programs have relied on peer-to-peer mentorships, with participants being of a similar age group. College mentors present an alternative and low-cost resource that may also provide positive results, yet have been largely ignored in research studies to date. PURPOSE: The purpose of this study was to investigate the impact of a novel, individualized college-mentored physical activity program on physical activity levels among older elementary school students. METHODS: Fifth grade students (n = 12) were paired one-to-one with local college mentors for 30 minute bi-weekly running sessions on the elementary school campus for six weeks. Multiple assessments from activity trackers were compared on intervention versus non-intervention days using paired-samples t-tests. RESULTS: Significant increases in steps (t(11) = 8.056; p ≤ .001) and moderate-to-vigorous activity (t(11) = 5.202; p ≤ .001) were seen on intervention days, as compared to non-intervention days. The average increase in step count on intervention days (6,381) versus non-intervention days (3,158) also resulted in students being elevated out of a sedentary classification. CONCLUSION: Individualized mentoring from college students significantly increased multiple assessments of physical activity, including minutes of moderate-to-vigorous activity and number of steps taken. Perhaps most notably, the mentored physical activity program promoted students from a sedentary to active lifestyle on intervention days as determined by step count. This novel high-impact and low-cost approach should be further developed for future school-based physical activity programs and research

CATMoS: Collaborative Acute Toxicity Modeling Suite.

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50≤50mg/kg)], and nontoxic chemicals (LD50>2,000mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495

Structural Studies of Blood Coagulation Factor VIII in Complexes in Circulation

Hemophilia A is a bleeding disorder caused by the loss of factor VIII (fVIII) function. When vascular injury occurs, this plasma glycoprotein functions as a cofactor for the serine protease factor IXa and facilitates blood coagulation by nucleating the assembly of a membrane-bound protease complex on the surface of activated platelets. This complex proteolytically activates fX to fXa, which subsequently converts prothrombin to thrombin, ultimately aiding in the formation of a fibrin clot. Common and effective treatment for hemophilia A is replacement therapy with either plasma-derived or recombinant fVIII. These fVIII products are effective, but limited by price and availability. Recently, a hybrid human-porcine fVIII was developed using a novel lentiviral-driven recombinant protein manufacturing platform, resulting in 16- to 160-fold greater yield of therapeutic protein. This could contribute to the production of future clinical hemophilia A therapeutics and facilitate the treatment of a larger proportion of patients with hemophilia A. For structural studies of the engineered fVIII, protein crystallography was utilized. A promising approach in protein crystallization is to select a high affinity binding partner, such as an antibody to fVIII. Following complex formation, crystallization trials have been performed. A binding partner (the antibody) can potentially reduce the conformational freedom of fVIII and additionally aid in the formation of well-ordered crystals for improved X-ray diffraction