Adenosine induced pulmonary fibrosis and the contribution of the adenosine A2B receptor to the induction of osteopontin in a mouse model of pulmonary fibrosis

Pulmonary fibrosis is a devastating and lethal lung disease with no current cure. Research into cellular signaling pathways able to modulate aspects of pulmonary inflammation and fibrosis will aid in the development of effective therapies for its treatment. Our laboratory has generated a transgenic/knockout mouse with systemic elevations in adenosine due to the partial lack of its metabolic enzyme, adenosine deaminase (ADA). These mice spontaneously develop progressive lung inflammation and severe pulmonary fibrosis suggesting that aberrant adenosine signaling is influencing the development and/or progression of the disease in these animals. These mice also show marked increases in the pro-fibrotic mediator, osteopontin (OPN), which are reversed through ADA therapy that serves to lower lung adenosine levels and ameliorate aspects of the disease. OPN is known to be regulated by intracellular signaling pathways that can be accessed through adenosine receptors, particularly the low affinity A2BR receptor, suggesting that adenosine receptor signaling may be responsible for the induction of OPN in our model. In-vitro, adenosine and the broad spectrum adenosine receptor agonist, NECA, were able to induce a 2.5-fold increase in OPN transcripts in primary alveolar macrophages. This induction was blocked through antagonism of the A2BR receptor pharmacologically, and through the deletion of the receptor subtype in these cells genetically, supporting the hypothesis that the A2BR receptor was responsible for the induction of OPN in our model. These findings demonstrate for the first time that adenosine signaling is an important modulator of pulmonary fibrosis in ADA-deficient mice and that this is in part due to signaling through the A2BR receptor which leads to the induction of the pro-fibrotic molecule, otseopontin. ^

The response of Texas public health agencies and workers to the emergency preparedness initiatives after 9/11

The purpose of this research was to better understand the impact of the terrorist attacks in 2001 on public health, particularly for Texas public health. This study employed mixed methods to examine changes to public health culture within Texas local public health agencies, important attitudes of public health workers toward responding to a disaster, and the funding policies that might ensure our investment in public health emergency preparedness is protected. ^ A qualitative analysis of interviews conducted with a large sample of public health officials in Texas found that all the constituent parts of a peculiar culture for public health preparedness existed that spanned the state's local health departments regardless of size, or funding level. The new preparedness culture in Texas had the hallmarks necessary for a robust public health preparedness and emergency response system. ^ The willingness of public health workers, necessary to make these kinds of changes and mount a disaster response was examined in one of Texas' most experienced disaster response teams—the public health workers for the City of Houston. A hypothesized latent variable model showed that willingness mediated all other factors in the model (self-efficacy, knowledge, barriers, and risk perception) for self-reported likelihood of reporting to work for a disaster. The RMSEA for the final model was 0.042 with a confidence interval of 0.036—0.049 and the chi-squared difference test was P=0.08, indicating a well-fitted model that suggests willingness is an important factor for consideration by preparedness planners and researchers alike. ^ Finally, with disasters on the rise and federal funding for preparedness dwindling, a review of states' policies for the distribution of these funds and their advantages and disadvantages were examined through a review of current literature and public documents, and a survey of state-level public health officials, emergency management professionals and researchers. Although the base plus per-capita method is the most common, it is not necessarily perceived to be the most effective. No clear "optimal" method emerged from the study, but recommendations for a strategic combination of three methods were made that has the potential to maximize the benefits of each method, while minimizing the weaknesses.^

Policy analysis of shifting to the state-run Texas women's health program

During the 82nd Texas legislature, state leaders passed a provision stating that healthcare providers, who perform, promote, or affiliate with providers who perform or promote elective abortion services may not be eligible to participate in the Texas Medicaid Women's Health Program (WHP). The federal government reacted to this new provision by vowing to eliminate its 90% share of program support on the grounds that the provision violated a patient's freedom to choose a provider; a right protected by the Social Security Act. Texas leaders stated that the Women's Health Program would continue without federal support, financed exclusively with state funds.^ The following policy analysis compares the projected impact of the current Medicaid Women's Health Program to the proposed state-run program using the criteria-alternative matrix framework. The criteria used to evaluate the program alternatives include population affected, unintended pregnancy and abortion impact, impact on cervical cancer rate, and state-level government expenditures. Each criterion was defined by selected measures. The population affected was measured by the number of women served in the programs. Government expenditures were measured in terms of payments for program costs, Medicaid delivery costs, and cervical cancer diagnostic costs. Unintended pregnancy impact was measured by the number of projected unplanned pregnancies and abortions under each alternative. The impact on cervical cancer was projected in terms of the number of new cervical cancer cases under each alternative. Differences in the projections with respect to each criterion were compared to assess the impact of shifting to the state-only policy.^ After examining program alternatives, it is highly recommended that Texas retain the Medicaid WHP. If the state does decide to move forward with the state-run WHP, it is recommended that the program run at its previous capacity. Furthermore, for the purpose of addressing the relatively high cervical cancer incidence rate in Texas, incorporating HPV vaccination coverage for women ages 18-26 as part of the Women's Health Program is recommended.^

Attitudes and other barriers to the utilization of clinical research findings by American physicians: A systematic review

Background: The Institute of Medicine estimates that only a maximum of 25% of clinical research findings are incorporated into practice by physicians. To improve clinical practice, efforts have been made to promote evidence-based medicine and the use of clinical guidelines. Despite these efforts, the gap between research and clinical practice remains wide.^ Objective: To systematically review the literature describing the factors which influence the use of clinical research recommendations by American physicians.^ Hypothesis: Barriers exist in the application of clinical research into clinical practice, and are multifactorial. The establishment of the Clinical and Translational Awards (CTSA; special federal grants awarded to selected institutions to support clinical and translational research) has reduced the effect of these barriers and improved the process of clinical research translation into practice among American physicians.^ Aims: Identify barriers and facilitators of the use of research findings in clinical practice by American physicians. Contrast studies published six years before and after the creation of the CTSA.^ Methods: The sources of data include published literature from Medline, PubMed and PsycINFO. Selected studies must be qualitative, a survey of American clinicians, based on evidence-based medicine practice, clinical guidelines or treatment pathways. Systematic reviews and reports were excluded, as well as studies with less than 100 respondents.^ Results: In total, 1036 abstracts were reviewed; 115 full text potential articles were identified and reviewed, and a total of 31 studies met all criteria for inclusion in the final review.^ Conclusions: The barriers against the application of clinical research findings, in the forms of clinical guidelines, evidence-based medicine guides and clinical pathways, can be divided broadly into physician barriers, practice/system barriers and patient barriers. Physician barriers are the most common barriers, especially the lack of familiarity with guidelines and the lack of time. Of the factors which improve the use of research based guidelines, physician factors such as younger age, lower duration of clinical practice, specialty training, and practice in large group Health Maintenance Organization (HMO) settings with fewer patients seen were the most commonly cited.^