Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens

Cardiovascular Drugs and Therapy - Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent...     

Improving quality of care for acute myocardial infarction: The Guidelines Applied in Practice (GAP) Initiative

Context  Quality of care of patients with acute myocardial infarction (AMI) has received intense attention. However, it is unknown if a structured initiative for improving care of patients with AMI can be effectively implemented at a wide variety of hospitals. Objective  To measure the effects of a quality improvement project on adherence to evidence-based therapies for patients with AMI. Design and Setting  The Guidelines Applied in Practice (GAP) quality improvement project, which consisted of baseline measurement, implementation of improvement strategies, and remeasurement, in 10 acute-care hospitals in southeast Michigan. Patients  A random sample of Medicare and non-Medicare patients at baseline (July 1998–June 1999; n = 735) and following intervention (September 1–December 15, 2000; n = 914) admitted at the 10 study centers for treatment of confirmed AMI. A random sample of Medicare patients at baseline (January–December 1998; n = 513) and at remeasurement (March–August 2001; n = 388) admitted to 11 hospitals that volunteered, but were not selected, served as a control group. Intervention  The GAP project consisted of a kickoff presentation; creation of customized, guideline-oriented tools designed to facilitate adherence to key quality indicators; identification and assignment of local physician and nurse opinion leaders; grand rounds site visits; and premeasurement and postmeasurement of quality indicators. Main Outcome Measures  Differences in adherence to quality indicators (use of aspirin, -blockers, and angiotensin-converting enzyme [ACE] inhibitors at discharge; time to reperfusion; smoking cessation and diet counseling; and cholesterol assessment and treatment) in ideal patients, compared between baseline and postintervention samples and among Medicare patients in GAP hospitals and the control group. Results  Increases in adherence to key treatments were seen in the administration of aspirin (81% vs 87%; P = .02) and -blockers (65% vs 74%; P = .04) on admission and use of aspirin (84% vs 92%; P = .002) and smoking cessation counseling (53% vs 65%; P = .02) at discharge. For most of the other indicators, nonsignificant but favorable trends toward improvement in adherence to treatment goals were observed. Compared with the control group, Medicare patients in GAP hospitals showed a significant increase in the use of aspirin at discharge (5% vs 10%; P<.001). Use of aspirin on admission, ACE inhibitors at discharge, and documentation of smoking cessation also showed a trend for greater improvement among GAP hospitals compared with control hospitals, although none of these were statistically significant. Evidence of tool use noted during chart review was associated with a very high level of adherence to most quality indicators. Conclusions  Implementation of guideline-based tools for AMI may facilitate quality improvement among a variety of institutions, patients, and caregivers. This initial project provides a foundation for future initiatives aimed at quality improvement.      

The effect of myopia on the position of the ora serrata.

This article evaluated the effect of myopia on the position of the ora serrata relative to the extraocular muscle insertions. In this prospective case series, 11 patients were evaluated during scleral buckling procedures. Intraoperative measurements of the distance from the ora serrata to the muscle insertion in each quadrant were compared to baseline refractive error. The distance between the ora serrata and the muscle insertion increased with increasing myopia superonasally and inferonasally. The surgeon must be aware of the need to position a scleral buckle more posteriorly with increasing myopia to avoid improper scleral buckling position and consequent surgical failure.     

Use of consumer survey data to target cessation messages to smokers through mass media

Objectives. We identified the mass media channels that reach the most cigarette smokers in an attempt to more effectively target smoking cessation messages.Methods. Reach estimates and index scores for smokers were taken from 2002–2003 ConsumerStyles and HealthStyles national surveys of adults (N=11660) to estimate overall and demographic-specific exposure measures for television, radio, newspapers, and magazines.Results. Smokers viewed more television, listened to more radio, and read fewer magazines and newspapers than did nonsmokers. Nearly one third of smokers were regular daytime or late-night television viewers. Selected cable television networks (USA, Lifetime, and Discovery Channel) and selected radio genres, such as classic rock and country, had high reach and were cost-efficient channels for targeting smokers.Conclusions. Certain mass media channels offer efficient opportunities to target smoking cessation messages so they reach relatively large audiences of smokers at relatively low cost. The approach used in this study can be applied to other types of health risk factors to improve health communication planning and increase efficiency of program media expenditures.One of the basic principles of communication planning is to understand audiences better; doing so makes it possible to develop messages most likely to resonate with target audiences and reach them more frequently.1^,2 Audience segmentation is one of the core tools that enables communication and marketing planners to better understand their audiences.3^,4 One objective of audience segmentation is to identify the communication channels through which an audience receives information.5^,6 Knowledge of communication channels is especially important given the resource constraints typical in public health communication and social marketing efforts and the increasing fragmentation of media channels.3^,7 Investing time and resources in delivering messages through channels inappropriate or inefficient for reaching intended audiences is economically wasteful and unlikely to have the intended effect.1^,2^,8Surprisingly, to our knowledge no published studies have addressed the communication channels through which cigarette smokers regularly receive information, and whether channels used by smokers differ from those used by nonsmokers. Furthermore, it is not known if communication channels differ among subgroups of smokers (e.g., by demographic characteristics). If smokers pay attention to distinctive communication channels, mass media efforts designed to increase the use of cessation services, such as telephone quit lines can be better planned to target those distinctive channels.From a communication or marketing planning perspective, it is more important to know the size of the intended audience that could be exposed to messages (reach) than the extent of smoking among specific channel users (prevalence). For example, if a television show had a smoking prevalence among viewers of 15% but attracted 40% of all smokers (reach), the potential effect of a cessation message would be fairly large compared with a show for which 50% of viewers were smokers (prevalence) but who constituted only 1% of all smokers (reach). The cost for placing mass media advertisements, as well as the likelihood that a media company would permit the placement of an unpaid message such as a public service announcement, is directly related to reach: mass communication companies charge higher advertising rates to reach audiences with larger numbers of people.9 The cost for running a 30-second advertisement during the Super Bowl can exceed $2 million because of the overall large audience size10; however, this is not likely to be the most cost-efficient approach to expose smokers to cessation ads, especially given the limited budgets for many tobacco control programs.We used a nationally representative survey to examine measures of mass media channel use among respondents who smoke and respondents who don’t smoke cigarettes. The mass media channels included preferred television genres, networks, and programs; preferred radio genres; newspaper use; and magazines read regularly. Additionally, we compared mass media exposure measures by smoking status and stratified by age, gender, and race/ethnicity.     

Edge co-occurrence in natural images predicts contour grouping performance

The human brain manages to correctly interpret almost every visual image it receives from the environment. Underlying this ability are contour grouping mechanisms that appropriately link local edge elements into global contours. Although a general view of how the brain achieves effective contour grouping has emerged, there have been a number of different specific proposals and few successes at quantitatively predicting performance. These previous proposals have been developed largely by intuition and computational trial and error. A more principled approach is to begin with an examination of the statistical properties of contours that exist in natural images, because it is these statistics that drove the evolution of the grouping mechanisms. Here we report measurements of both absolute and Bayesian edge co-occurrence statistics in natural images, as well as human performance for detecting natural-shaped contours in complex backgrounds. We find that contour detection performance is quantitatively predicted by a local grouping rule derived directly from the co-occurrence statistics, in combination with a very simple integration rule (a transitivity rule) that links the locally grouped contour elements into longer contours.     

Stereotactic radiotherapy in three weekly fractions for the management of vestibular schwannomas

Purpose

This study evaluates the rates of tumor control, hearing preservation and cranial nerve toxicity with the use of CyberKnife stereotactic radiotherapy consisting of 2100?cGy to the 80% isodose line delivered in three weekly fractions to treat vestibular schwannomas.

Aggressive lymphoma subtype is a risk factor for venous thrombosis. Development of lymphoma - specific venous thrombosis prediction models

Venous thromboembolic events (VTE) are a frequent complication of lymphoma. We conducted a retrospective analysis to compare VTE risk in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Subjects were randomly assigned to training and validation sets to identify risk factors of VTE and evaluate risk model performance, including the Khorana score. A group of 790 patients were diagnosed from 2002 to 2014 (DLBCL = 542, FL = 248). Median follow- up was 49 months. We observed 106 VTE, with higher incidence in DLBCL (5-year cumulative incidence = 16.3% vs 3.8% in FL patients). Five-year OS for patients with VTE was 51.4% vs 73.1% in patients without VTE (P < .001). Baseline VTE risk factors identified in the training cohort included lymphoma subtype, previous VTE, ECOG performance status ≥2, decreased albumin, increased calcium, elevated WBC, absolute lymphocyte count or monocyte count, and presence of bulky disease. Addition of new variables to the Khorana score improved its performance measured by Akaike information criterion and Concordance index. A new risk model including lymphoma subtype, albumin, WBC count, and bulky disease was validated in time-based ROC analyses. These findings were confirmed in the validation cohort. Lymphoma subtypes have different VTE risk. The effect of lymphoma subtype was independent from disease burden and the use of systemic therapy. The Khorana risk-score was validated in time to event analyses, and a more robust lymphoma-specific VTE risk score is proposed. These findings suggest lymphoma patients with highest VTE risk can be identified with baseline parameters.     

Evaluation of Five Buffers for Inactivation of Monkeypox Virus and Feasibility of Virus Detection Using the Panther Fusion® Open Access System

Rapid diagnosis is key to containing viral outbreaks. However, for the current monkeypox outbreak the major deterrent to rapid testing is the requirement for higher biocontainment of potentially infectious monkeypox virus specimens. The current CDC guidelines require the DNA extraction process before PCR amplification to be performed under biosafety level 3 unless vaccinated personnel are performing assays. This increases the turn-around time and makes certain laboratories insufficiently equipped to handle specimens from patients with suspected monkeypox infection. We investigated the ability of five commercially available lysis buffers and heat for inactivation of monkeypox virus. We also optimized the use of monkeypox virus in Hologic^® Panther Specimen Lysis Buffer for detection of virus in the Panther Fusion^® Open Access System using published generic and clade specific monkeypox virus primers and probes.     

Mechanisms of reversible protein glutathionylation in redox signaling and oxidative stress

Reversible protein S-glutathionylation (protein-SSG) is an important post-translational modification, providing protection of protein cysteines from irreversible oxidation and serving to transduce redox signals. Analogous to phosphatases, glutaredoxin (GRx) enzymes catalyze deglutathionylation of proteins, regulating diverse intracellular signaling pathways. Recently, other enzymes have been reported to exhibit deglutathionylating activity, but their contribution to intracellular protein deglutathionylation is uncertain. Currently, no enzyme has been shown to serve as a catalyst of S-glutathionylation in situ, although potential prototypes are reported, including human GRx1 and the pi isoform of glutathione-S-transferase (GSTpi). Further insight into cellular mechanisms of protein glutathionylation and deglutathionylation will enrich our understanding of redox signal transduction and potentially identify new therapeutic targets for diseases in which oxidative stress perturbs normal redox signaling. Accordingly, this review focuses primarily on mechanisms of catalysis in mammalian systems.     

Grafting of massive tibial subchondral bone defects in a caprine model using beta-tricalcium phosphate versus autograft

OBJECTIVE: This study evaluated the ability of beta-tricalcium phosphate particles (beta-TCP) and autograft (AUTO) to maintain joint surface morphology when used to supplement massive subchondral bone defects in a caprine model. DESIGN: This was a prospective, parallel arm study with 2 experimental arms and a control group. METHODS: Unilateral, 11 mm diameter, 25 mm deep cylindrical defects were created in tibial subchondral bone of anesthetized goats (n = 16) and filled with autograft or beta-tricalcium phosphate particles. The contralateral limbs served as internal controls. Goats were killed at 3 months and both tibiae harvested. Molds made of the tibial plateau surface were used to create positive casts from which medial and lateral tibial plateau surfaces of both experimental (beta-tricalcium phosphate particles, autograft) and control limbs were digitized in 3 dimensions. Mirror images of the medial condyle surface contours from the controls were superimposed onto the experimental surfaces and deviations were compared using a Student t test (alpha = 0.05). Tibiae were then cut sagittally into medial (biomechanics) and lateral (histology) halves. Compressive modulus within the defect area was assessed by indentation to 2.0 mm at 0.2 mm per second using a 6-mm diameter pin. Specimens from the lateral tibial plateau were processed for undecalcified histology and the area of bone within the defect region measured. The articular surface of 86% of the autograft and 0% of the beta-tricalcium phosphate particles group had degenerative changes, with 29% of autograft goats exhibiting large-scale plateau collapse. Mean surface deviation for autograft was significantly greater than for beta-tricalcium phosphate particles (2.19 +/- 1.49 mm versus 0.78 +/- 0.19 mm), as was maximum surface deviation (11.19 +/- 8.02 mm versus 4.39 +/- 1.33 mm) (P < 0.05). The compressive modulus within the defect area for control animals was significantly higher than the experimental groups (P < 0.05). Significantly more bone was regenerated within beta-tricalcium phosphate particle-grafted defects compared to autograft (P < 0.05). These results indicated that beta-tricalcium phosphate particles might be a useful graft material for local repair of load bearing skeletal sites such as depressed tibial plateau fractures.