Defining the Ail Ligand-Binding Surface: Hydrophobic Residues in Two Extracellular Loops Mediate Cell and Extracellular Matrix Binding To Facilitate Yop Delivery.

Yersinia pestis, the causative agent of plague, binds host cells to deliver cytotoxic Yop proteins into the cytoplasm that prevent phagocytosis and generation of proinflammatory cytokines. Ail is an eight-stranded ß-barrel outer membrane protein with four extracellular loops that mediates cell binding and resistance to human serum. Following the deletion of each of the four extracellular loops that potentially interact with host cells, the Ail-Δloop 2 and Ail-Δloop 3 mutant proteins had no cell-binding activity while Ail-Δloop 4 maintained cell binding (the Ail-Δloop 1 protein was unstable). Using the codon mutagenesis scheme SWIM (selection without isolation of mutants), we identified individual residues in loops 1, 2, and 3 that contribute to host cell binding. While several residues contributed to the binding of host cells and purified fibronectin and laminin, as well as Yop delivery, three mutations, F80A (loop 2), S128A (loop 3), and F130A (loop 3), produced particularly severe defects in cell binding. Combining these mutations led to an even greater reduction in cell binding and severely impaired Yop delivery with only a slight defect in serum resistance. These findings demonstrate that Y. pestis Ail uses multiple extracellular loops to interact with substrates important for adhesion via polyvalent hydrophobic interactions.

The Quality and Safety Educators Academy: fulfilling an unmet need for faculty development.

Educating physician trainees in the principles of quality improvement (QI) and patient safety (PS) is a national imperative. Few faculty are trained in these disciplines, and few teaching institutions have the resources and infrastructure to develop faculty as instructors of these skills. The authors designed a 3-day, in-person academy to provide medical educators with the knowledge and tools to integrate QI and PS concepts into their training programs. The curriculum provided instruction in quality and safety, curriculum development and assessment, change management, and professional development while fostering peer networking, mentorship, and professional development. This article describes the characteristics, experiences, and needs of a cross-sectional group of faculty interested in acquiring skills to help them succeed as quality and safety educators. It also describes the guiding principles, curriculum blueprint, program evaluation, and lessons learned from this experience which could be applied to future faculty development programs in quality and safety education.

Ail proteins of Yersinia pestis and Y. pseudotuberculosis have different cell binding and invasion activities.

The Yersinia pestis adhesin Ail mediates host cell binding and facilitates delivery of cytotoxic Yop proteins. Ail from Y. pestis and Y. pseudotuberculosis is identical except for one or two amino acids at positions 43 and 126 depending on the Y. pseudotuberculosis strain. Ail from Y. pseudotuberculosis strain YPIII has been reported to lack host cell binding ability, thus we sought to determine which amino acid difference(s) are responsible for the difference in cell adhesion. Y. pseudotuberculosis YPIII Ail expressed in Escherichia coli bound host cells, albeit at ~50% the capacity of Y. pestis Ail. Y. pestis Ail single mutants, Ail-E43D and Ail-F126V, both have decreased adhesion and invasion in E. coli when compared to wild-type Y. pestis Ail. Y. pseudotuberculosis YPIII Ail also had decreased binding to the Ail substrate fibronectin, relative to Y. pestis Ail in E. coli. When expressed in Y. pestis, there was a 30-50% decrease in adhesion and invasion depending on the substitution. Ail-mediated Yop delivery by both Y. pestis Ail and Y. pseudotuberculosis Ail were similar when expressed in Y. pestis, with only Ail-F126V giving a statistically significant reduction in Yop delivery of 25%. In contrast to results in E. coli and Y. pestis, expression of Ail in Y. pseudotuberculosis led to no measurable adhesion or invasion, suggesting the longer LPS of Y. pseudotuberculosis interferes with Ail cell-binding activity. Thus, host context affects the binding activities of Ail and both Y. pestis and Y. pseudotuberculosis Ail can mediate cell binding, cell invasion and facilitate Yop delivery.

Appropriate use of screening and diagnostic tests to foster high-value, cost-conscious care.

Unsustainable rising health care costs in the United States have made reducing costs while maintaining high-quality health care a national priority. The overuse of some screening and diagnostic tests is an important component of unnecessary health care costs. More judicious use of such tests will improve quality and reflect responsible awareness of costs. Efforts to control expenditures should focus not only on benefits, harms, and costs but on the value of diagnostic tests-meaning an assessment of whether a test provides health benefits that are worth its costs or harms. To begin to identify ways that practicing clinicians can contribute to the delivery of high-value, cost-conscious health care, the American College of Physicians convened a workgroup of physicians to identify, using a consensus-based process, common clinical situations in which screening and diagnostic tests are used in ways that do not reflect high-value care. The intent of this exercise is to promote thoughtful discussions about these tests and other health care interventions to promote high-value, cost-conscious care.

The Medical Education Commission Report 2008-2009: Louisiana GME plan is tracking U.S. averages.

Graduate medical education (GME) in Louisiana has evolved into the present status, the sum of institutions providing medical education, as in each of the states and the country as a whole. Louisiana reflects the United States (U.S.) averages in practically every GME parameter and measurement with relatively small variations. The record suggests that GME in Louisiana is moving forward in desirable growth and improvement. In 2005, Hurricanes Katrina and Rita produced major setbacks for GME in Louisiana. Now, the signs of recovery are robust and GME is getting back on track. Today, the health care delivery system is under scrutiny to be reformed, creating a difficult situation for all physicians and others in the medical fields and health care industry. The widely accepted reality of the growing shortage of all types of physicians may be worse by many reform proposals. This Medical Education Commission (MEC) report will provide data and comment on medical students, GME trends, and projections as background and guidance for the Louisiana plan for recovery and reform.

The medical education commission report 2007: GME is recovering from Katrina.

Before Hurricane Katrina, graduate medical education (GME) in Louisiana was growing slowly but steadily, similarly to the United States (US) average. Katrina's destructive force disrupted practically every aspect of GME, resulting in early quantitative rearrangement by geographic location and the heroic efforts to rescue programs across the state. This report provides evidence that the numbers have stabilized and are getting back on track. This year's successful match leads the way, with numbers of entering residents nearing pre-Katrina levels. Total GME gained some ground. National trends are noted, as primary care specialties are less in the national match, even as a national effort to increase the supply of physicians is underway. Institutional and state efforts to restore and increase GME are key to the long-term solution for physician recruitment in Louisiana, especially when a growing physician shortage is on the horizon.

Leadership in graduate medical education: eleven steps instrumental in recovering residency programs after a disaster.

BACKGROUND: A disaster such as Hurricane Katrina can result in extensive devastation to graduate medical education programs. While clinical services largely determine the recovery of each residency program, program director leadership is important. METHODS: A qualitative survey of program directors was conducted to determine the leadership lessons most instrumental after a disaster. RESULTS: Gaining control, establishing communication, designing a vision for the recovery, maintaining physical accessibility, and identifying leaders within the program were identified as critical leadership attributes associated with a residency program's recovery. Understanding the logistics and finances of resident placement was also important. CONCLUSIONS: Preparing for a disaster is the best approach, but where a disaster policy is incomplete or inadequate, it will be the leadership skills of the program's director that will define the success of failure of the residency program.

The effects of ethanol ingestion on the accuracy of pulmonary diffusing capacity measurement.

BACKGROUND: Erroneous diffusing capacity of the lung for carbon monoxide (Dlco) values as measured by spectrophotometry were observed at our facility in ethanol-intoxicated subjects. An atypical methane curve tracing was noted in these subjects. STUDY OBJECTIVES: We hypothesized that ethanol intoxication interferes with Dlco measurements obtained using methane and designed a study to assess the blood ethanol level at which this occurs. STUDY DESIGN: Dlco and breath ethanol levels were measured at baseline and after escalating doses of ethanol in seven healthy subjects. SETTING: Pulmonary function testing laboratory of a university hospital. PARTICIPANTS: Seven healthy volunteers. INTERVENTIONS: Dlco measurement at baseline and after escalating doses of ethanol. MEASUREMENTS AND RESULTS: We found no significant change in measured Dlco values for a wide range of blood ethanol levels (from 0.006 to 0.12 mg/dL). However, subsequently, an abnormal methane curve and Dlco were again observed in an intoxicated subject whose ethanol blood level was 0.22 mg/dL. CONCLUSIONS: We conclude that interference between breath ethanol level and Dlco measurement exists only for blood ethanol levels well above the legal limit for intoxication. Based on our observations, we suggest that ethanol intoxication should be suspected when an abnormal Dlco measurement occurs along with an abnormal methane curve tracing. If intoxication is confirmed, precautions should be taken and referral for treatment of possible ethanol dependence should be offered.