Increasing Access: Building Working Solutions

Outlines the problem of access to basic healthcare services in the U.S. Cites local efforts to enroll people into existing insurance programs and reduce other roadblocks to care, and offers a comprehensive framework for addressing these issues

Community Voices: Lessons for National Health Policy

Highlights successful models that were designed to improve access to health care for vulnerable populations, describes ways that government can support local communities, and emphasizes the need for fundamental reform of the U.S. healthcare system

Community-Based Health Plans for the Uninsured: Expanding Access, Enhancing Dignity

Highlights community-based initiatives in Albuquerque, New Mexico; Ingham County, Michigan; El Paso, Texas; Alameda County, California; and North Carolina that have developed health plans for uninsured individuals and families

Reaching Out: Successful Efforts to Provide Children and Families With Health Care

Interweaves personal stories and policy recommendations to offer an inventory of ideas and resources to improve enrollment rates and help more people access essential health care

\u3ci\u3eIn Vitro\u3c/i\u3e Gene Regulatory Networks Predict In Vivo Function of Liver

Background: Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed. Results: Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo. Conclusions: The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cyle related genes could be key machanism for TNT induced liver toxicity

Measuring Metacognition in Cancer: Validation of the Metacognitions Questionnaire 30 (MCQ-30)

Objective The Metacognitions Questionnaire 30 assesses metacognitive beliefs and processes which are central to the metacognitive model of emotional disorder. As recent studies have begun to explore the utility of this model for understanding emotional distress after cancer diagnosis, it is important also to assess the validity of the Metacognitions Questionnaire 30 for use in cancer populations. Methods 229 patients with primary breast or prostate cancer completed the Metacognitions Questionnaire 30 and the Hospital Anxiety and Depression Scale pre-treatment and again 12 months later. The structure and validity of the Metacognitions Questionnaire 30 were assessed using factor analyses and structural equation modelling. Results Confirmatory and exploratory factor analyses provided evidence supporting the validity of the previously published 5-factor structure of the Metacognitions Questionnaire 30. Specifically, both pre-treatment and 12 months later, this solution provided the best fit to the data and all items loaded on their expected factors. Structural equation modelling indicated that two dimensions of metacognition (positive and negative beliefs about worry) were significantly associated with anxiety and depression as predicted, providing further evidence of validity. Conclusions These findings provide initial evidence that the Metacognitions Questionnaire 30 is a valid measure for use in cancer populations

Medicaid Expansion and Postoperative Mortality in Women with Gynecologic Cancer: A Difference-in-Difference Analysis

BACKGROUND: The association between Medicaid expansion and postoperative mortality after surgery for gynecologic cancer is unknown. Our objective was to compare 30- and 90-day postoperative mortality after gynecologic cancer surgery before and after 2014 in states that did and did not expand Medicaid. METHODS: We searched the National Cancer Database for women aged 40-64 years old between 2010 and 2016 who underwent surgery for a primary gynecologic malignancy. We used pre/post and quasi-experimental difference-in-difference (DID) multivariable logistic regressions to evaluate mortality pre-2014 (2010-2013) and post-2014 (2014-2016) for states that did and did not expand Medicaid in January 2014. We completed univariable logistic regressions for covariates of interest. RESULTS: Among 169,731 women, 30-day postoperative mortality in expansion states after 2014 significantly decreased for endometrial cancer (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.26-0.67) and ovarian cancer (OR 0.67, 95% CI 0.46-0.99) and increased for cervical cancer (OR 3.82, 95% CI 1.12-13.01). Compared with non-expansion states, expansion states had improved 30-day postoperative mortality for endometrial cancer after 2014 (DID OR 0.54, 95% CI 0.31-0.96). Univariable analysis demonstrated improved 30-day postoperative mortality for Black women with endometrial cancer in expansion states (DID OR 0.22, 95% CI 0.05-0.95). There was improved 90-day postoperative mortality for endometrial cancer in expansion states (OR 0.66, 95% CI 0.50-0.85), and improved 90-day postoperative mortality for Midwestern women with ovarian cancer in expansion states on univariable analysis (DID OR 0.48, 95% CI 0.26-0.91). CONCLUSIONS: State Medicaid legislation was associated with improved postoperative survival in women with endometrial cancer and subgroups of women with endometrial and ovarian cancer

The evolution of drug-activated nuclear receptors: one ancestral gene diverged into two xenosensor genes in mammals

BACKGROUND: Drugs and other xenobiotics alter gene expression of cytochromes P450 (CYP) by activating the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in mammals. In non-mammalian species, only one xenosensor gene has been found. Using chicken as a model organism, the aim of our study was to elucidate whether non-mammalian species only have one or two xenosensors like mammals. RESULTS: To explore the evolutionary aspect of this divergence, we tried to identify additional xenobiotic sensing nuclear receptors in chicken using various experimental approaches. However, none of those revealed novel candidates. Ablation of chicken xenobiotic receptor (CXR) function by RNAi or dominant-negative alleles drastically reduced drug-induction in a chicken hepatoma cell line. Subsequently, we functionally and structurally characterized CXR and compared our results to PXR and CAR. Despite the high similarity in their amino acid sequence, PXR and CAR have very distinct modes of activation. Some aspects of CXR function, e.g. direct ligand activation and high promiscuity are very reminiscent of PXR. On the other hand, cellular localization studies revealed common characteristics of CXR and CAR in terms of cytoplasmic-nuclear distribution. Finally, CXR has unique properties regarding its regulation in comparison to PXR and CAR. CONCLUSION: Our finding thus strongly suggest that CXR constitutes an ancestral gene which has evolved into PXR and CAR in mammals. Future studies should elucidate the reason for this divergence in mammalian versus non-mammalian species

A new approach to construct pathway connected networks and its application in dose responsive gene expression profiles of rat liver regulated by 2,4DNT

<p>Abstract</p> <p>Background</p> <p>Military and industrial activities have lead to reported release of 2,4-dinitrotoluene (2,4DNT) into soil, groundwater or surface water. It has been reported that 2,4DNT can induce toxic effects on humans and other organisms. However the mechanism of 2,4DNT induced toxicity is still unclear. Although a series of methods for gene network construction have been developed, few instances of applying such technology to generate pathway connected networks have been reported.</p> <p>Results</p> <p>Microarray analyses were conducted using liver tissue of rats collected 24h after exposure to a single oral gavage with one of five concentrations of 2,4DNT. We observed a strong dose response of differentially expressed genes after 2,4DNT treatment. The most affected pathways included: long term depression, breast cancer regulation by stathmin1, WNT Signaling; and PI3K signaling pathways. In addition, we propose a new approach to construct pathway connected networks regulated by 2,4DNT. We also observed clear dose response pathway networks regulated by 2,4DNT.</p> <p>Conclusions</p> <p>We developed a new method for constructing pathway connected networks. This new method was successfully applied to microarray data from liver tissue of 2,4DNT exposed animals and resulted in the identification of unique dose responsive biomarkers in regards to affected pathways.</p

Use of traditional knowledge by the United States Bureau of Ocean Energy Management to support resource management

Professionals who collect and use traditional knowledge to support resource management decisions often are preoccupied with concerns over how and if traditional knowledge should be integrated with science. To move beyond the integration dilemma, we treat traditional knowledge and science as distinct and complementary knowledge systems. We focus on applying traditional knowledge within the decision-making process. We present succinct examples of how the Bureau of Ocean Energy Management has used traditional knowledge in decision making in the North Slope Borough, Alaska: 1) using traditional knowledge in designing, planning, and conducting scientific research; 2) applying information from both knowledge systems at the earliest opportunity in the process; 3) using traditional knowledge in environmental impacts assessment; 4) consulting with indigenous leaders at key decision points; and 5) applying traditional knowledge at a programmatic decision level. Clearly articulating, early in the process, how best to use traditional knowledge and science can allow for more complete and inclusive use of available and pertinent information