Faculty Bibliography

Crazy Heart [Motion Picture] -- Alcoholic hepatitis (inflammation of the liver due to the toxic effects of alcohol) occurs in 35% of heavy drinkers, and cirrhosis (scarring of the liver) in 10% to 20%

Nerve growth factor (NGF) is initially synthesized as a precursor, proNGF, that is cleaved to release its C-terminal mature form. Recent studies suggested that proNGF is not an inactive precursor but acts as a signaling ligand distinct from its mature counterpart. proNGF and mature NGF initiate opposing biological responses by utilizing both distinct and shared receptor components. In this study, we carried out structural and biochemical characterization of proNGF interactions with p75NTR and sortilin. We crystallized proNGF complexed to p75NTR and present the structure at 3.75-A resolution. The structure reveals a 2:2 symmetric binding mode, as compared with the asymmetric structure of a previously reported crystal structure of mature NGF complexed to p75NTR and the 2:2 symmetric complex of neurotrophin-3 (NT-3) and p75NTR. Here, we discuss the possible origins and implications of the different stoichiometries. In the proNGF-p75NTR complex, the pro regions of proNGF are mostly disordered and two hairpin loops (loop 2) at the top of the NGF dimer have undergone conformational changes in comparison with mature NT structures, suggesting possible interactions with the propeptide. We further explored the binding characteristics of proNGF to sortilin using surface plasmon resonance and cell-based assays and determined that calcium ions promote the formation of a stable ternary complex of proNGF-sortilin-p75NTR. These results, together with those of previous structural and mechanistic studies of NT-receptor interactions, suggest the potential for distinct signaling activities through p75NTR mediated by different NT-induced conformational changes.

BACKGROUND: Whether early detection and treatment of prostate cancer (PCa) will reduce disease-related mortality remains uncertain. As a result, tools are needed to facilitate informed decision making. While there have been several decision aids (DAs) developed and tested, very few have included an exercise to help men clarify their values and preferences about PCa screening. Further, only one DA has utilized an interactive web-based format, which allows for an expansion and customization of the material. We describe the development of two DAs, a booklet and an interactive website, each with a values clarification component and designed for use in diverse settings. METHODS: We conducted two feasibility studies to assess men's (45-70 years) Internet access and their willingness to use a web- vs. a print-based tool. The booklet was adapted from two previous versions evaluated in randomized controlled trials (RCTs) and the website was created to closely match the content of the revised booklet. Usability testing was conducted to obtain feedback regarding draft versions of the materials. The tools were also reviewed by a plain language expert and the interdisciplinary research team. Feedback on the content and presentation led to iterative modifications of the tools. RESULTS: The feasibility studies confirmed that the Internet was a viable medium, as the majority of men used a computer, had access to the Internet, and Internet use increased over time. Feedback from the usability testing on the length, presentation, and content of the materials was incorporated into the final versions of the booklet and website. Both the feasibility studies and the usability testing highlighted the need to address men's informed decision making regarding screening. CONCLUSIONS: Informed decision making for PCa screening is crucial at present and may be important for some time, particularly if a definitive recommendation either for or against screening does not emerge from ongoing prostate cancer screening trials. We have detailed our efforts at developing print- and web-based DAs to assist men in determining how to best meet their PCa screening preferences. Following completion of our ongoing RCT designed to test these materials, our goal will be to develop a dissemination project for the more effective tool. TRIAL REGISTRATION: NCT00623090.

President Barack Obama 'is in excellent health' and likely to remain able to carry out his duties for the rest of his term, his doctor said after completing Mr. Obama's first routine medical checkup since he took office last year. Mr. Obama, 48, continues to struggle to stop his 30-year smoking habit and needs to modify his diet, said Dr. [Jeffrey Kuhlman], a navy captain who led the medical team that performed Mr. Obama's physical Sunday. As for Mr. Obama's smoking, Mr. [Robert Gibbs] said the president had tried to quit but had 'admitted lapses.' It is not known how frequently Mr. Obama smokes, or what the figure is for his total 'pack years,' a standard measure of a smoker's risk for diseases like lung cancer

[...] the president has chronic tendinitis in his left knee area, occasionally takes a nonsteroidal anti-inflammatory drug for that condition and needs a modified exercise regimen, including a lower leg muscle strengthening program, Dr. Kuhlman's report said. Mr. Obama showed no evidence of heart disease from an electrocardiogram and a test known as an electron beam CT scan that looks for calcified areas in coronary arteries that may be evidence of coronary artery disease

BACKGROUND:The presence of coronary artery calcium (CAC) is an independent marker of increased risk of cardiovascular disease (CVD) events and mortality. However, the predictive value of thoracic aorta calcification (TAC), which can be additionally identified without further scanning during assessment of CAC, is unknown. METHODS:We followed a cohort of 8401 asymptomatic individuals (mean age: 53+/-10 years, 69% men) undergoing cardiac risk factor evaluation and TAC and CAC testing with electron beam computed tomography. Multivariable Cox proportional hazards models were developed to predict all-cause mortality based on the presence of TAC. RESULTS:During a median follow-up period of 5 years, 124 (1.5%) deaths were observed. Overall survival was 96.9% and 98.9% for those with and without detectable TAC, respectively (p<0.0001). Compared to those with no TAC, the hazard ratio for mortality in the presence of TAC was 3.25 (95% CI: 2.28-4.65, p<0.0001) in unadjusted analysis. After adjusting for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking and family history of premature coronary artery disease, and presence of CAC the relationship remained robust (HR 1.61, 95% CI: 1.10-2.27, p=0.015). Likelihood ratio chi(2) statistics demonstrated that the addition of TAC contributed significantly in predicting mortality to traditional risk factors alone (chi(2)=13.62, p=0.002) as well as risk factors+CAC (chi(2)=5.84, p=0.02) models. CONCLUSION/CONCLUSIONS:In conclusion, the presence of TAC was associated with all-cause mortality in our study; this relationship was independent of conventional CVD risk factors as well as the presence of CAC.

BACKGROUND: Pay-for-performance initiatives have been suggested as a way to improve the quality of patient care and provide incentives to improve providers' performance. The Centers for Medicare & Medicaid Services has endorsed such programs to improve quality of care. OBJECTIVE: To examine the state of quality initiatives endorsed by the Centers for Medicare & Medicaid Services in which institutions, provider groups, and physicians are awarded incentives based on adherence to composite metrics. METHOD: A literature search was conducted using the keywords "pay-for-performance," "quality improvement," "medical errors," and "physician incentive plans." RESULTS: Although quality of care has improved in healthcare settings that engage in pay-for-performance initiatives, what can be attributed to payer-incentive programs is uncertain. Studies demonstrate that, of the 25 hospitals classified by the Centers for Medicare & Medicaid Services to be in the lowest decile of quality improvements, all still made significant progress in adhering to quality metrics after participation in the study. Financial rewards, however, were distributed based on a predetermined threshold established by the Centers for Medicare & Medicaid Services to be given only to participants who fell in the top 2 deciles. Penalties were incurred by the 51 hospitals that were within the bottom 2 deciles despite making substantial improvements. At such institutions, large minority communities and Medicaid populations comprise the patient populations. Other pay-for-performance schemes, such as employer-based purchasing, consumer health-spending accounts, and collaborative groups, were studied, with little data to support definite benefits. CONCLUSIONS: Examining rates of improvement in adherence to pay-for-performance initiatives when determining how to distribute financial rewards should be studied alongside the current classification by absolute deciles. By rewarding rates of improvement, potential elimination of quality disparities for hospitals that serve large Medicaid and minority populations can be achieved, because such organizations are encouraged to invest in quality improvement as a result of substantial progress made. Although alternative strategies like employer-driven value-based purchasing and collaboratives seem promising, the long-term effects of such initiatives still need to be studied. Creating greater financial incentives for individual providers to participate in pay-for-performance programs for many years to come will remain a challenge.

The Health Maintenance Organization Research Network (HMORN), a consortium of 16 health care delivery systems with integrated research divisions, held its annual meeting in Danville, Pennsylvania in April of 2009 and was attended by more than 260 researchers and operational leaders from HMORN organizations, pharmaceutical companies, the National Cancer Institute, and the Agency for Healthcare Research and Quality. The 2009 meeting was held from April 26(th) to April 29(th) at the Henry Hood Center for Health Research, and was hosted by Geisinger Health System. The conference theme was 'Clinical Effectiveness: Leadership in Comparative Effectiveness and Translational Research.' This article provides some background on the network, its research activities, and the annual conference. This issue of Clinical Medicine & Research also includes selected scientific abstracts presented at the meeting

A Morel-Lavallee lesion is a relatively rare condition involving a closed, degloving injury to the pelvis, resulting in a blood-filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia. This injury typically occurs following high-speed trauma. We describe a case that occurred in a professional American football player who was treated with percutaneous decompression and evacuation of the hematoma. The player returned to playing football at the professional level 22 days after the injury without residual deformity or disability