Influence of Multiple Traumatic Event Types on Mental Health Outcomes: Does Count Matter?

The experience of potentially traumatizing events (PTEs) may be associated with conflicting outcomes: individuals may experience greater psychological distress (dose-response theory), or individuals may become more resilient against repeated PTEs (stress-inoculation theory). With limited empirical data comparing these theories, we examined the relationships between the count of lifetime PTE types and psychological outcomes [posttraumatic stress disorder (PTSD), depression, impaired distress tolerance] using linear and quadratic regressions. A linear relationship would support the dose-response theory, and a quadratic relationship would support the stress-inoculation theory. We also explored whether there was a threshold number of PTE types fostering resiliency before an increase of distressing outcomes. The sample included 123 (68.30% female) treatment-seeking patients at a community mental health center participating in a larger study (Contractor et al. in Psychiatry Research, 252, 252215–252222, 2017). Linear regression results indicated number of PTE types significantly predicted increasing PTSD and depression severity and distress tolerance difficulties. Quadratic regression model results were not significant. ROC analyses indicated exposure to at least 3.5 PTE types predicted PTSD with moderate accuracy. In conclusion, the dose-response theory was supported, with results indicating there may be a threshold count of lifetime PTE types (\u3e 3) influencing traumatic stress outcomes

The Challenges of Place, Capacity, and Systems Change: The Story of Yes we can!

· Yes we can!, a comprehensive community initiative (CCI) funded by the W. K. Kellogg Foundation, was designed to improve educational and economic outcomes within the foundation’s hometown of Battle Creek, Mich. Since 2002, Yes we can! has supported five core strategies designed to trigger the systems changes needed to reduce educational and economic inequities in Battle Creek. · Yes we can! has achieved some important wins to date; for example, more residents are involved, more neighborhoods have stronger neighborhood associations, and more organizations are engaging residents in their decision-making processes. However, the scale of wins remains small, and the targeted systemic changes have not yet emerged. · Some common CCI design elements featured in Yes we can! may have inadvertently bounded its success: a) community building efforts targeted small-scale places, restricting the scale and scope of wins; b) demands for current work competed with building capacities for future work; and c) local partners who were implementing their individual grants struggled to maintain a focus on the larger vision and collective work

Investigation of the Cellular and Molecular Mechanisms of Radiation-induced Bystander Effects

The overall aim of this study was to investigate the cellular and molecular mechanisms involved in radiation-induced bystander effects in HaCaT cells, predominantly at low-doses of irradiation. They do not follow the original dose-response theory and exhibit a unique cascade of signalling events, which are under intense investigation for radiation risk purposes. An in vitro system was first used to observe the bystander effect, comparing two cell viability assays while measuring apoptotic cell death in these known reporter HaCaT cells and established the most sensitive assay for bystander responses Downstream bystander signalling events were then investigated through gene expression studies of apoptotic genes over a complex time-course with different low doses to reveal very specific changes in bystander responses. The expression pattern profile revealed novel unique bystander-induced apoptotic signalling pathways in different low doses of irradiation. Proteomic methods using 2D gel electrophoresis and mass spectroscopy further revealed novel proteins which were significantly over or under–expressed in the bystander reporter cells but using an ex-vivo fish model. These results revealed an induction of protection of the cells in response to oxidative stress and modulation of cell death processes. The data generated in this thesis has led to the proposal of two distinct and comparative signalling pathways of a cellular radiation induced bystander response for 0.05 Gy and 0.5 Gy ionising radiation. These novel pathways have expanded our knowledge in the cellular and molecular mechanisms which occur when a cell receives a bystander signal and may have future clinical considerations and implications for patients undergoing radiotherapy treatment plans

Evaluation of toxic effects of several carboxylic acids on bacterial growth by toxicodynamic modelling

<p>Abstract</p> <p>Background</p> <p>Effects of organic acids on microbial fermentation are commonly tested in investigations about metabolic behaviour of bacteria. However, they typically provide only descriptive information without modelling the influence of acid concentrations on bacterial kinetics.</p> <p>Results</p> <p>We developed and applied a mathematical model (secondary model) to capture the toxicological effects of those chemicals on kinetic parameters that define the growth of bacteria in batch cultures. Thus, dose-response kinetics were performed with different bacteria (<it>Leuconostoc mesenteroides</it>, <it>Carnobacterium pisicola</it>, <it>Escherichia coli</it>, <it>Bacillus subtilis </it>and <it>Listonella anguillarum</it>) exposed at increasing concentrations of individual carboxylic acids (formic, acetic, propionic, butyric and lactic). In all bioassays the acids affected the maximum bacterial load (<it>X_m</it>) and the maximum growth rate (<it>v_m</it>) but only in specific cases the lag phase (λ) was modified. Significance of the parameters was always high and in all fermentations the toxicodynamic equation was statistically consistent and had good predictability. The differences between D and L-lactic acid effects were significant for the growth of <it>E. coli</it>, <it>L. mesenteroides </it>and <it>C. piscicola</it>. In addition, a global parameter (<it>EC</it>_50,τ) was used to compare toxic effects and provided a realistic characterization of antimicrobial agents using a single value.</p> <p>Conclusions</p> <p>The effect of several organic acids on the growth of different bacteria was accurately studied and perfectly characterized by a bivariate equation which combines the basis of dose-response theory with microbial growth kinetics (secondary model). The toxicity of carboxylic acids was lower with the increase of the molecular weight of these chemicals.</p

The Emergence of the Dose–Response Concept in Biology and Medicine

A historical assessment of the origin of the dose–response in modern toxicology and its integration as a central concept in biology and medicine is presented. This article provides an overview of how the threshold, linear and biphasic (i.e., hormetic) dose–response models emerged in the late 19th and early 20th centuries and competed for acceptance and dominance. Particular attention is directed to the hormetic model for which a general description and evaluation is provided, including its historical basis, and how it was marginalized by the medical and pharmacology communities in the early decades of the 20th century

The Maturing of Hormesis as a Credible Dose-Response Model

Hormesis is a dose-response phenomenon that has received little recognition, credibility and acceptance as evidenced by its absence from major toxicological/risk assessment texts, governmental regulatory dose-response modeling for risk assessment, and non-visibility in major professional toxicological society national meetings. This paper traces the historical evolution of the hormetic dose-response hypothesis, why this model is not only credible but also more common than the widely accepted threshold model in direct comparative evaluation, and how the toxicological community made a critical error in rejecting hormesis, a rejection sustained over 70 years

Mathematical models of cytotoxic effects in endpoint tumor cell line assays: Critical assessment of the application of a single parametric value as a standard criterion to quantify the dose-response effects and new unexplored proposal formats

The development of convenient tools for describing and quantifying the effects of standard and novel therapeutic agents is essential for the research community, to perform more precise evaluations. Although mathematical models and quantification criteria have been exchanged in the last decade between different fields of study, there are relevant methodologies that lack proper mathematical descriptions and standard criteria to quantify their responses. Therefore, part of the relevant information that can be drawn from the experimental results obtained and the quantification of its statistical reliability are lost. Despite its relevance, there is not a standard form for the in vitro endpoint tumor cell lines' assays (TCLA) that enables the evaluation of the cytotoxic dose-response effects of anti-tumor drugs. The analysis of all the specific problems associated with the diverse nature of the available TCLA used is unfeasible. However, since most TCLA share the main objectives and similar operative requirements, we have chosen the sulforhodamine B (SRB) colorimetric assay for cytotoxicity screening of tumor cell lines as an experimental case study. In this work, the common biological and practical non-linear dose-response mathematical models are tested against experimental data and, following several statistical analyses, the model based on the Weibull distribution was confirmed as the convenient approximation to test the cytotoxic effectiveness of anti-tumor compounds. Then, the advantages and disadvantages of all the different parametric criteria derived from the model, which enable the quantification of the dose-response drug-effects, are extensively discussed. Therefore, model and standard criteria for easily performing the comparisons between different compounds are established. The advantages include a simple application, provision of parametric estimations that characterize the response as standard criteria, economization of experimental effort and enabling rigorous comparisons among the effects of different compounds and experimental approaches. In all experimental data fitted, the calculated parameters were always statistically significant, the equations proved to be consistent and the correlation coefficient of determination was, in most of the cases, higher than 0.98.The authors are grateful to the Foundation for Science and Technology (FCT) of Portugal and FEDER for financial support to CIMO (UID/AGR/00690/2013); and to the Xunta de Galicia for financial support for the post-doctoral research of M. A. Prieto.info:eu-repo/semantics/publishedVersio

Relations Between Adverse Childhood Experiences and Current Maladaptive Beliefs in a College Sample

Cumulative childhood trauma has been associated with both symptoms of post-traumatic stress disorder and depression. However, few studies have examined these relations with normative young adult populations nor have they explored the relation between childhood adversities and cognitive distortions as an outcome variable. The current study aimed to: 1) replicate and extend research on the relations between cumulative adversity, using a broad measure of adverse childhood experiences (ACEs; Felitti et al., 1998), which assesses both maltreatment (e.g., physical, sexual, emotional abuse and neglect) and exposure to elements of household dysfunction (e.g., caregiver substance use, witnessing maternal abuse), and mental health outcomes (i.e., symptoms of PTSD and depression) with a relatively high-functioning young adult sample of female college students, and 2) examine if the dose-response relation frequently found between ACEs and negative distress outcomes also existed with cognitive distortions, a common post-traumatic response and target of trauma-specific treatments that is rarely examined as an outcome variable. Participants (N = 252) were female undergraduate university students who were primarily white and reported a range of traumatic experiences. I hypothesized that increases in number of types of ACEs would be positively related to increases in post-traumatic stress and depressive symptoms, as well as the three domains of maladaptive cognitions on a measure of global beliefs, the Posttraumatic Maladaptive Beliefs Scale (PMBS; Vogt et al., 2012). Controlling for adverse experiences since age 18, results of hierarchical regression analyses supported the hypotheses and indicated greater endorsement of ACEs was positively related to increases in post-traumatic stress and depressive symptoms, as well as increases in all three domains of the PMBS: Threat of Harm, Reliability & Trustworthiness of Others, and Self-Worth & Judgment