786 research outputs found

    Adverse childhood experiences and prescription drug use in a cohort study of adult HMO patients

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    <p>Abstract</p> <p>Background</p> <p>Prescription drugs account for approximately 11% of national health expenditures. Prior research on adverse childhood experiences (ACEs), which include common forms of child maltreatment and related traumatic stressors, has linked them to numerous health problems. However, data about the relationship of these experiences to prescription drug use are scarce.</p> <p>Method</p> <p>We used the ACE Score (an integer count of 8 different categories of ACEs) as a measure of cumulative exposure to traumatic stress during childhood. We prospectively assessed the relationship of the Score to prescription drug use in a cohort of 15,033 adult HMO patients (mean follow-up: 6.1 years) and assessed mediation of this relationship by documented ACE-related health and social problems.</p> <p>Results</p> <p>Nearly 1.2 million prescriptions were recorded; prescriptions rates increased in a graded fashion as the ACE Score increased (p for trend < 0.0001). Compared to persons with an ACE Score of 0, persons with a Score ≥ 5 had rates increased by 40%; graded relationships were seen for all age groups (18–44, 45–64, and 65–89 years) (p for trend < 0.01). Graded relationships were observed for the risk of being in the upper decile of number of classes of drugs used; persons with scores of ≥ 5 had this risk increased 2-fold. Adjustment for ACE-related health problems reduced the strength of the associations by more than 60%.</p> <p>Conclusion</p> <p>ACEs substantially increase the number of prescriptions and classes of drugs used for as long as 7 or 8 decades after their occurrence. The increases in prescription drug use were largely mediated by documented ACE-related health and social problems.</p

    Differentiated transplant derived airway epithelial cell cytokine secretion is not regulated by cyclosporine

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    <p>Abstract</p> <p>Background</p> <p>While lung transplantation is an increasingly utilized therapy for advanced lung diseases, chronic rejection in the form of Bronchiolitis Obliterans Syndrome (BOS) continues to result in significant allograft dysfunction and patient mortality. Despite correlation of clinical events with eventual development of BOS, the causative pathophysiology remains unknown. Airway epithelial cells within the region of inflammation and fibrosis associated with BOS may have a participatory role.</p> <p>Methods</p> <p>Transplant derived airway epithelial cells differentiated in air liquid interface culture were treated with IL-1β and/or cyclosporine, after which secretion of cytokines and growth factor and gene expression for markers of epithelial to mesenchymal transition were analyzed.</p> <p>Results</p> <p>Secretion of IL-6, IL-8, and TNF-α, but not TGF-β1, was increased by IL-1β stimulation. In contrast to previous studies using epithelial cells grown in submersion culture, treatment of differentiated cells in ALI culture with cyclosporine did not elicit cytokine or growth factor secretion, and did not alter IL-6, IL-8, or TNF-α production in response to IL-1β treatment. Neither IL-1β nor cyclosporine elicited expression of markers of the epithelial to mesenchymal transition E-cadherin, EDN-fibronectin, and α-smooth muscle actin.</p> <p>Conclusion</p> <p>Transplant derived differentiated airway epithelial cell IL-6, IL-8, and TNF-α secretion is not regulated by cyclosporine <it>in vitro</it>; these cells thus may participate in local inflammatory responses in the setting of immunosuppression. Further, treatment with IL-1β did not elicit gene expression of markers of epithelial to mesenchymal transition. These data present a model of differentiated airway epithelial cells that may be useful in understanding epithelial participation in airway inflammation and allograft rejection in lung transplantation.</p

    Influence of a Conductive Material and Different Anaerobic Inocula on Biochemical Methane Potential of Substrates from Alcoholic Beverage Production

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    The impact of a conductive material as powdered activated carbon (PAC) on the biochemical methane potential of whisky pot ale (PA) and brewery spent yeast (SY) was investigated. The test was carried out with three different types of anaerobic inocula: manure inoculum (MI), sewage sludge (SS) and granular sludge (GR). Brewery spent yeast produced partial (in sewage and granular sludge) and total (in manure inoculum) methanogenesis inhibition due to the toxicity of some of its constituents (hops extract). The inhibition was overcome by the supplementation of PAC, that improved significantly the anaerobic digestion process for SY, allowing to reach biochemical methane potential values between 657-699 L CH4 kg-1 VS and it reduced redox potential from 369 to 398 mV. The activated carbon did not improve the methane yields from whisky PA since microorganisms did not have difficulties to process this substrate; in fact, the redox potential slightly increased from 355 to 330 mV

    Plasma membrane receptor mediated MAPK signaling pathways are activated in human uterine cervix at parturition

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    BACKGROUND: Cervical ripening resembles an inflammatory reaction. Estrogens induce leukocyte migration into tissue and factors promoting cervical remodeling and labor, although the mechanisms are only partially known. The aim of this study was to investigate whether plasma membrane receptor mediated pathways, known to be activated by estrogens and proinflammatory compounds, are involved in cervical ripening before labor. METHODS: The expression and distribution of mitogen activated protein kinases (MAPK), which transduce extracellular signals into intracellular responses through phosphorylation, and their intracellular targets transcription factors c-Jun and c-Fos proteins (AP-1) were analysed in cervical biopsies from term pregnant women (TP), immediately after parturition (PP), and from non-pregnant women (NP). Immunohistochemistry and RT-PCR techniques were used. RESULTS: Cell-specific alterations in the immunostaining pattern for MAPK were observed. The expressions of activated, phosphorylated MAPK forms pERK1/2, pJNK and p38MAPK were significantly increased in cervical stroma until TP and pERK1/2 expression was significantly enhanced in PP group. c-Jun was significantly increased in cervical stroma and smooth muscle in TP as compared to NP group. c-Fos was significantly increased in stroma, squamous epithelium and glandular epithelium in PP as compared to TP group. CONCLUSION: We report, for the first time, cell-specific activation of pMAPKs and their targets transcription factors c-Fos and c-Jun (AP-1) proteins in human uterine cervix until term pregnancy, and immediately after parturition. These results suggest a role for MAPK activation in cervical ripening before labor

    Multilingualism and the Brexit referendum

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    This chapter argues that the (lack of) foreign language skills has contributed to the outcome of the Brexit referendum. Theory suggests that speaking foreign languages reduces perceptions of cultural distance and contributes to the formation of transnational identities. Research also shows a link between language skills and European identity (Kuhn 2015; Díez Medrano 2018). Did Britons’ relative lack of foreign language skills play a role in the Brexit decision? Using matching methods and data from the referendum wave of the British Election Study, it is possible to estimate the effect of foreign language skills on the referendum vote. The results suggest that a significant effect of foreign language skills remains, even when taking into account education, age, gender, income, and region, party preference, and personality differences

    Persistence of Pathogens with Short Infectious Periods in Seasonal Tick Populations: The Relative Importance of Three Transmission Routes

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    BACKGROUND: The flaviviruses causing tick-borne encephalitis (TBE) persist at low but consistent levels in tick populations, despite short infectious periods in their mammalian hosts and transmission periods constrained by distinctly seasonal tick life cycles. In addition to systemic and vertical transmission, cofeeding transmission has been proposed as an important route for the persistence of TBE-causing viruses. Because cofeeding transmission requires ticks to feed simultaneously, the timing of tick activity may be critical to pathogen persistence. Existing models of tick-borne diseases do not incorporate all transmission routes and tick seasonality. Our aim is to evaluate the influence of seasonality on the relative importance of different transmission routes by using a comprehensive mathematical model. METHODOLOGY/PRINCIPAL FINDINGS: We developed a stage-structured population model that includes tick seasonality and evaluated the relative importance of the transmission routes for pathogens with short infectious periods, in particular Powassan virus (POWV) and the related "deer tick virus," emergent encephalitis-causing flaviviruses in North America. We used the next generation matrix method to calculate the basic reproductive ratio and performed elasticity analyses. We confirmed that cofeeding transmission is critically important for such pathogens to persist in seasonal tick populations over the reasonable range of parameter values. At higher but still plausible rates of vertical transmission, our model suggests that vertical transmission can strongly enhance pathogen prevalence when it operates in combination with cofeeding transmission. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the consistent prevalence of POWV observed in tick populations could be maintained by a combination of low vertical, intermediate cofeeding and high systemic transmission rates. When vertical transmission is weak, nymphal ticks support integral parts of the transmission cycle that are critical for maintaining the pathogen. We also extended the model to pathogens that cause chronic infections in hosts and found that cofeeding transmission could contribute to elevating prevalence even in these systems. Therefore, the common assumption that cofeeding transmission is not relevant in models of chronic host infection, such as Lyme disease, could lead to underestimating pathogen prevalence
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