bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Cardiovascular Morbidity and Mortality in Type 2 Diabetes Is Associated With the Glutathione S Transferase Theta–Null Genotype
Authors: Doney Alex S.F. , Lee Simon , Leese Graham P. , Morris Andrew D. , Palmer Colin N.A.
Published: June 2005

Background—

Glutathione S-transferases (GSTs) modulate oxidative stress, and variation in GST genes has been associated with cardiovascular disease risk. We prospectively determined smoking-related cardiovascular morbidity by GST genotype in a large cohort of individuals with type 2 diabetes using a population-based diabetes research database (DARTS).

Methods and Results—

We performed a cohort study of 2015 individuals with type 2 diabetes. Individuals were genotyped for the Ile105Val variant of GSTP1 and the deleted variants of GSTT1 and GSTM1. Clinical characteristics, smoking status, and incidence of subsequent cardiovascular events were obtained by examining the DARTS databases. Variation in the GSTP1 and GSTM1 genes was not associated with smoking-related risk of death or cardiovascular events. There was an increase in the rate of cardiovascular events in smokers lacking the GSTT1 gene compared with smokers with the GSTT1 gene intact (hazard ratio [HR], 1.96;
P
=0.001). This excess of cardiovascular events was due to both strokes (HR, 2.7;
P
=0.008) and myocardial infarctions (HR, 1.9;
P
=0.006). The rate of death as a result of a cardiovascular event was even more markedly increased in the GSTT1-null smokers (HR, 2.7;
P
=0.001), with a 2-fold increase in myocardial infarction fatality ratio. These effects translated into an increase in overall death and a decrease in age at death. We also found that the GSTT1− genotype was associated with progression of both diabetic retinopathy and nephropathy (
P
=0.005 and
P
=0.01, respectively), although we found little evidence for an interaction with smoking.

Conclusions—

Genetic absence of the GSTT1 enzyme is an independent and powerful predictor of premature vascular morbidity and death in individuals with type 2 diabetes.
Critical Role of Endogenous Thrombospondin-1 in Preventing Expansion of Healing Myocardial Infarcts
Authors: Frangogiannis Nikolaos G. , Ren Guofeng , Dewald Oliver , Zymek Pawel , Haudek Sandra , Koerting Anna , Winkelmann Kim , Michael Lloyd H. , Lawler Jack , Entman Mark L.
Published: June 2005

Background—

Matricellular proteins are extracellular matrix proteins that do not contribute directly to tissue integrity but are capable of modulating cell function. We hypothesized that the matricellular protein thrombospondin (TSP)-1, a potent inhibitor of angiogenesis and activator of transforming growth factor (TGF-β), is induced in healing myocardial infarcts and plays a role in suppressing the postinfarction inflammatory response, inhibiting local angiogenesis, and limiting expansion of granulation tissue into the noninfarcted area.

Methods and Results—

We used a canine and a murine model of reperfused infarction. TSP-1 mRNA was induced in canine infarcts after 1 hour of ischemia and 3 to 7 days of reperfusion. TSP-1 protein showed a strikingly selective localization in the extracellular matrix, microvascular endothelium, and a subset of mononuclear cells of the infarct border zone after 5 to 28 days of reperfusion. Isolated canine venous endothelial cells showed low-level constitutive expression of TSP-1 mRNA, which was markedly induced by TGF-β, and basic fibroblast growth factor. Murine infarcts also had marked TSP-1 deposition in the border zone. Infarcted TSP-1
−/−
mice exhibited sustained upregulation of the chemokines monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and interferon-γ–inducible protein-10/CXCL10 and the cytokines interleukin-1β, interleukin-6, and TGF-β, suggesting an enhanced and prolonged postinfarction inflammatory response. In addition, TSP-1
−/−
mice had markedly increased macrophage and myofibroblast density in infarcts and in remodeling noninfarcted myocardial areas neighboring the myocardial scar, suggesting expansion of granulation tissue formation into the noninfarcted territory. TSP-1
−/−
animals had more extensive postinfarction remodeling than wild-type mice, although infarct size was similar in both groups.

Conclusions—

The infarct border zone may be capable of modulating the healing process through its unique extracellular matrix content. The selective endogenous expression of TSP-1 in the infarct border zone may serve as a “barrier,” limiting expansion of granulation tissue and protecting the noninfarcted myocardium from fibrotic remodeling.
Strut Position, Blood Flow, and Drug Deposition
Authors: Balakrishnan Brinda , Tzafriri Abraham R. , Seifert Philip , Groothuis Adam , Rogers Campbell , Edelman Elazer R.
Published: June 2005

Background—

The intricacies of stent design, local pharmacology, tissue biology, and rheology preclude an intuitive understanding of drug distribution and deposition from drug-eluting stents (DES).

Methods and Results—

A coupled computational fluid dynamics and mass transfer model was applied to predict drug deposition for single and overlapping DES. Drug deposition appeared not only beneath regions of arterial contact with the strut but surprisingly also beneath standing drug pools created by strut disruption of flow. These regions correlated with areas of drug-induced fibrin deposition surrounding DES struts in porcine coronary arteries. Fibrin deposition immediately distal to individual isolated drug-eluting struts was twice as great as in the proximal area and for the stent as a whole was greater in distal segments than proximal segments. Adjacent and overlapping stent struts increased computed arterial drug deposition by far less than the sum of their combined drug load. In addition, drug eluted from the abluminal stent strut surface accounted for only 11% of total deposition, whereas, remarkably, drug eluted from the adluminal surface accounted for 43% of total deposition. Thus, local blood flow alterations and location of drug elution on the strut were far more important in determining arterial wall drug deposition and distribution than were drug load or arterial wall contact with coated strut surfaces.

Conclusions—

Simulations that coupled strut configurations with flow dynamics correlated with in vivo effects and revealed that drug deposition occurs less via contact between drug coating and the arterial wall than via flow-mediated deposition of blood-solubilized drug.
Intracellular Proatherogenic Events and Cell Adhesion Modulated by Extracellular Thiol/Disulfide Redox State
Authors: Go Young-Mi , Jones Dean P.
Published: June 2005

Background—

Oxidative stress, a contributing factor to atherosclerosis, causes oxidation of biological thiols, which can be quantified in terms of the thiol/disulfide redox. The major thiol/disulfide redox couple in human plasma is cysteine (Cys) and its disulfide, cystine (CySS). Although atherosclerosis has previously been associated with Cys/CySS oxidation, whether oxidation of Cys/CySS contributes in a causal way to atherosclerosis development is not known. We examined the function of extracellular Cys/CySS redox potential (E
h
) in the regulation of early events of atherosclerosis using cultured aortic endothelial cells and monocytes as a vascular model system.

Methods and Results—

To determine the range of thiol/disulfide redox state in human plasma, we analyzed levels of Cys, CySS, glutathione (GSH), and glutathione disulfide (GSSG) and calculated E
h
according to the Nernst equation. E
h
of Cys/CySS and GSH/GSSG was −120 to −20 and −200 to −50 mV, respectively. To approximate this range, endothelial cells were exposed to initial E
h
from −150 mV (most reduced) to 0 mV (most oxidized). Compared with more reduced E
h
, oxidized E
h
of Cys/CySS stimulated H
2
O
2
but not nitric oxide production, activated nuclear factor-κB, increased expression of adhesion molecules (intercellular adhesion molecule-1, platelet endothelial cell adhesion molecule-1, P-selectin), and stimulated monocytes binding to endothelial cells. Extracellular E
h
regulated thiol/disulfide redox states of extracellular membrane proteins and H
2
O
2
production, indicating that variation in extracellular E
h
is detected and signaled at the cell surface.

Conclusions—

The extracellular thiol/disulfide E
h
of the Cys/CySS couple plays a key role in regulating early events of atherosclerosis and could be useful as a potential marker for vascular disease risk.
Diabetes Enhances Vulnerability to Particulate Air Pollution–Associated Impairment in Vascular Reactivity and Endothelial Function
Authors: O’Neill Marie S. , Veves Aristidis , Zanobetti Antonella , Sarnat Jeremy A. , Gold Diane R. , Economides Panayiotis A. , Horton Edward S. , Schwartz Joel
Published: June 2005

Background—

Epidemiological studies suggest that people with diabetes are vulnerable to cardiovascular health effects associated with exposure to particle air pollution. Endothelial and vascular function is impaired in diabetes and may be related to increased cardiovascular risk. We examined whether endothelium-dependent and -independent vascular reactivity was associated with particle exposure in individuals with and without diabetes.

Methods and Results—

Study subjects were 270 greater-Boston residents. We measured 24-hour average ambient levels of air pollution (fine particles [PM
2.5
], particle number, black carbon, and sulfates [SO
4
2−
]) ≈500 m from the patient examination site. Pollutant concentrations were evaluated for associations with vascular reactivity. Linear regressions were fit to the percent change in brachial artery diameter (flow mediated and nitroglycerin mediated), with the particulate pollutant index, apparent temperature, season, age, race, sex, smoking history, and body mass index as predictors. Models were fit to all subjects and then stratified by diagnosed diabetes versus at risk for diabetes. Six-day moving averages of all 4 particle metrics were associated with decreased vascular reactivity among patients with diabetes but not those at risk. Interquartile range increases in SO
4
2−
were associated with decreased flow-mediated (−10.7%; 95% CI, −17.3 to −3.5) and nitroglycerin-mediated (−5.4%; 95% CI, −10.5 to −0.1) vascular reactivity among those with diabetes. Black carbon increases were associated with decreased flow-mediated vascular reactivity (−12.6%; 95% CI, −21.7 to −2.4), and PM
2.5
was associated with nitroglycerin-mediated reactivity (−7.6%; 95% CI, −12.8 to −2.1). Effects were stronger in type II than type I diabetes.

Conclusions—

Diabetes confers vulnerability to particles associated with coal-burning power plants and traffic.
Percutaneous Coronary Intervention Versus Conservative Therapy in Nonacute Coronary Artery Disease
Authors: Katritsis Demosthenes G. , Ioannidis John P.A.
Published: June 2005

Background—

Percutaneous coronary intervention (PCI) has been shown to improve symptoms compared with conservative medical treatment in patients with stable coronary artery disease (CAD); however, there is limited evidence on the effect of PCI on the risk of death, myocardial infarction, and subsequent revascularization. Therefore, we performed a meta-analysis of 11 randomized trials comparing PCI to conservative treatment in patients with stable CAD.

Methods and Results—

A total of 2950 patients were included in the meta-analysis (1476 received PCI, and 1474 received conservative treatment). There was no significant difference between the 2 treatment strategies with regard to mortality, cardiac death or myocardial infarction, nonfatal myocardial infarction, CABG, or PCI during follow-up. By random effects, the risk ratios (95% CIs) for the PCI versus conservative treatment arms were 0.94 (0.72 to 1.24), 1.17 (0.88 to 1.57), 1.28 (0.94 to 1.75), 1.03 (0.80 to 1.33), and 1.23 (0.80 to 1.90) for these 5 outcomes, respectively. A possible survival benefit was seen for PCI only in trials of patients who had a relatively recent myocardial infarction (risk ratio 0.40, 95% CI 0.17 to 0.95). Except for PCI during follow-up, there was no significant between-study heterogeneity for any outcome.

Conclusions—

In patients with chronic stable CAD, in the absence of a recent myocardial infarction, PCI does not offer any benefit in terms of death, myocardial infarction, or the need for subsequent revascularization compared with conservative medical treatment.
Appropriate and Inappropriate Ventricular Therapies, Quality of Life, and Mortality Among Primary and Secondary Prevention Implantable Cardioverter Defibrillator Patients
Authors: Sweeney Michael O. , Wathen Mark S. , Volosin Kent , Abdalla Ismaile , DeGroot Paul J. , Otterness Mary F. , Stark Alice J.
Published: June 2005

Background—

Implantable cardioverter defibrillators (ICDs) reduce mortality in primary and secondary prevention. Quality of life, mortality, appropriate therapies for specific ventricular rhythms, and inappropriate therapies for supraventricular tachycardia (SVT) were compared among 582 patients (primary prevention=248; secondary prevention=334) in PainFREE Rx II, a 634-patient prospective, randomized study of antitachycardia pacing or shocks for fast ventricular tachycardia (FVT).

Methods and Results—

ICDs were programmed identically with 3 zones (ventricular tachycardia [VT] <188 bpm; FVT=188 to 250 bpm; ventricular fibrillation [VF] >250 bpm) but randomized to antitachycardia pacing or shock as initial therapy for FVT. All treated episodes with electrograms were adjudicated. Primary prevention patients had lower ejection fractions and more coronary artery disease. β-Blocker use, antiarrhythmic drug use, and follow-up duration were similar. Over 11±3 months, 1563 treated episodes were classified as VT (n=740), FVT (n=350), VF (n=77), and SVT (n=396). The distribution of VT, FVT, and VF was not different between primary and secondary prevention patients (respectively, VT 52% versus 54%, FVT 35% versus 35%, and VF 14% versus 10%). More secondary prevention patients had appropriate therapies (26% versus 18%,
P
=0.02), but among these patients, the median number of episodes per patient was similar. Inappropriate therapies occurred in 15% of both groups and accounted for similar proportions of all detected and treated episodes (46% in primary prevention patients versus 34% in secondary prevention patients,
P
=0.09). Quality of life improved modestly in both groups, and mortality was similar.

Conclusions—

Primary prevention patients are slightly less likely to have appropriate therapies than secondary prevention patients, but episode density is similar among patients with appropriate therapies. SVT resulted in more than one third of therapies in both groups, but quality of life and mortality were similar.
Perceived Danger in Urban Public Space
Authors: Blöbaum Anke , Hunecke Marcel
Published: June 2005

What are the most relevant factors influencing perceived danger in urban public space? To answer this question, a field experiment of students( N = 122) was carried out on a German university campus within which perceived danger was analyzed under systematic variation of lighting, prospect, and opportunities of escape. Two standardized questionnaires were used to record the following: perceived danger, avoidance behavior, trait anxiety, psychological gender, and experience as victims. The findings provide empirical support for the importance of the three physical factors and of the biological sex. The effect of opportunities to escape seems to be the strongest factor. It appears to be even more important than biological sex and psychological gender (masculinity and femininity). The results clearly show the necessity of reducing behavior constraints by redesigning fear-related physical features.
Housing Tenure and Psychological Well-Being During Adolescence
Authors: Cairney John
Published: June 2005

Although a substantial body of work has demonstrated that housing tenure (home ownership vs. renting) is a determinant of health, much less work has focused on this relationship between children and adolescents. This is a significant omission as there is good reason to hypothesize that the effect of housing status on health may change with age. In particular, growing independence and reduced exposure to the residential environment may attenuate the association between housing tenure and health as children age. Using a large representative sample of adolescents, ages 12 to 19 years old, the hypothesis that age moderates the relationship between housing tenure and psychological well-being is tested. The findings, in general, support the hypothesis. Future directions for research are discussed.
Growth, Development, and Farming in an Ohio Exurban Region
Authors: Smith Molly Bean , Sharp Jeff S.
Published: June 2005

The mixing of newcomers, longtime nonfarm residents, and farm household residents in exurban areas has the potential to lead to conflicts over community change and farming. Data from a survey of residents of an Ohio exurban region are analyzed to identify attitudinal differences among three sets of exurban residents. Several attitudinal differences among farm households, newcomers, and long-time residents are identified with farm household residents reporting greater concern about the effects of growth on local rural character than both newcomers and longtime nonfarm residents did. Farm household respondents were also more tolerant and accepting of agricultural annoyances than were either newcomers or longtime residents. All sets of residents are supportive of efforts to preserve local farmland. A conclusion of this exurban case study is that conflicts about land use and community change may have more to do with farm versus nonfarm interest than with length of residence in the community.
Outcomes of Border Health Spanish/English Chronic Disease Self-management Programs
Authors: Lorig Kate R. , Ritter Philip L. , Jacquez Anna
Published: May 2005

Purpose

The purpose of this study was to evaluate the community-based Chronic Disease Self-management Program (CDSMP) and the Spanish-language version (Tomando Control de Su Salud) programs as delivered in settings along the Texas/New Mexico/Mexico border. The programs had proven effective in randomized trials, and the authors wished to determine if they would be as effective when administered by others to different populations.

Methods

The El Paso Diabetes Association administered the CDSMP and Tomando to 445 persons with chronic illness (two thirds with diabetes) in Texas, New Mexico, and Mexico. Four-month and 1-year outcomes were compared to baseline using t tests of change scores. Regression models were used to test whether baseline demographics and self-efficacy were associated with positive outcomes of the programs.

Results

Participants showed improvements in health behaviors, health status, and self-efficacy at both 4 month and 1 year. Baseline self-efficacy and 4-month change in self-efficacy were significantly associated with improved 1- year outcomes.

Conclusions

The CDSMP and Tomando are effective when used in settings other than that of the original study for populations other than those for which they were initially developed.
Diabetes Management in San Diego’s Chamorro Community
Authors: Wu Phillis L. , Sadler Georgia Robins , Nguyen Victoria , Shi Manli , Gilpin Elizabeth A. , Cruz Lee Ann C. , Blas Lillian A. , Cruz Jesus A.
Published: May 2005

Purpose

The purpose of this study was to assess the diabetes risk status, incidence, and morbidity within San Diego’s Chamorro community as a foundation to help community leaders and health care providers create culturally customized health promotion interventions.

Methods

The Behavioral Risk Factor Surveillance Survey was used to query a randomly selected, convenience sample of San Diego Chamorros (N = 228) drawn from the Chamorro Directory International. Based on individual survey responses, participants were mailed personalized health-promoting information. Subsequently, they received information that addressed the most commonly observed overall threats to the Chamorro community’s health.

Results

A higher than average prevalence of diabetes and gestational diabetes was reported by study participants along with a high prevalence of the risk factors associated with the premature onset of diabetes and its consequences.

Conclusion

Collaborative partnerships between health professionals and community leaders can help identify opportunities and strategies for improving the health of the nation’s population subgroups. San Diego’s Chamorro community leaders now have a clearer understanding of the prevalence of diabetes risk factors within their community and can begin working with public health educators to create culturally aligned diabetes prevention and management programs. Given the willingness of Chamorro leaders to get involved in the development of a diabetes awareness campaign and the community’s closely knit social network, it should be possible to promote (1) community participation in the intervention program, (2) an increase in the community’s adherence to recommended behavioral changes, and (3) identification of additional program modifications that will further enhance the program’s cultural relevance.
Population-Based Assessment of Diabetes Care and Self-management Among Puerto Rican Adults in New York City
Authors: Hosler Akiko S. , Melnik Thomas A.
Published: May 2005

Purpose

The purpose of this study was to assess the status of diabetes medical care and self-management among adult Puerto Ricans in New York City.

Methods

A random-digit-dialing telephone survey with a dual-frame sampling design was employed to obtain a probability sample of adult Puerto Ricans with diagnosed diabetes (n = 606). Demographic characteristics, health status, and indicators of diabetes medical care and self- management were collected using the standard Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. A statewide sample of adults with diagnosed diabetes (n = 232) was obtained from the BRFSS for comparison.

Results

Compared to New York State adults, Puerto Ricans were significantly less likely to receive annual A1C testing (72.7% vs 84.9%), cholesterol testing (67.5% vs 87.2%), blood-pressure-lowering medication (82.4% vs 91.9%), and pneumococcal vaccination (19.3% vs 28.5%, among those aged 18 to 64 years). Puerto Ricans were also less likely to take aspirin every day or every other day to prevent cardiovascular complications (30.6% vs 40.7%). Puerto Ricans were younger and more likely to have lower educational attainment and lower income than New York State adults, but they were not significantly disadvantaged in access to health care indicated by rates of health insurance coverage, having a particular place for medical care, and frequencies of seeing a provider for diabetes.

Conclusions

These findings support the need to introduce culturally sensitive and linguistically appropriate diabetes education programs for Puerto Ricans and continue system-based diabetes care quality improvement efforts in the areas of prevention and control of cardiovascular complications, adult immunization, and A1C testing.
Barriers to Diabetes Education in Urban Patients Perceptions, Patterns, and Associated Factors
Authors: Rhee Mary K. , Cook Curtiss B. , El-Kebbi Imad , Lyles Robert H. , Dunbar Virginia G. , Panayioto Rita M. , Berkowitz Kathy J. , Boyd Barbara , Broussard Sandra , George Christopher D.
Published: May 2005

Purpose

This study explored patients’ perceptions of barriers to diabetes education among a mostly African American population of adults with diabetes.

Methods

A survey was conducted among 605 new patients attending an urban outpatient diabetes clinic. The questionnaire gathered information on issues patients believed would adversely affect their ability to learn about diabetes. The type and frequency of education barriers were evaluated, and variables associated with reporting an obstacle were analyzed.

Results

Average patient age was 50 years, diabetes duration was 5.6 years, body mass index was 32 kg/m2, and hemoglobin A1C was 9.1%. The majority (56%) were women, 89% were African American, and 95% had type 2 diabetes. Most respondents (96%) had received some prior instruction in diabetes care; however, 53% anticipated future difficulties learning about diabetes. The most commonly cited concerns were poor vision (74%) and reading problems (29%). Patients with a perceived barrier to diabetes education were older (P < .001) than were persons without a barrier, and they differed in both employment and educational status (both P < .001). In adjusted analyses, older age, male gender, being disabled, and having an elementary education or less were associated with a significantly increased likelihood of having a barrier to diabetes education, whereas having a college education decreased the odds. Higher hemoglobin A1C levels also tended to be associated with a greater chance of reporting an education barrier (P = .05).

Conclusions

A substantial number of persons anticipated a barrier to diabetes education. Interventions at multiple levels that address the demographic and socioeconomic obstacles to diabetes education are needed to ensure successful self-management training.
Competencies and Imitability in the Pharmaceutical Industry: An Analysis of Their Relationship with Firm Performance
Authors: De Carolis Donna Marie
Published: June 2005

Two research questions are addressed in this article. First, does technological competence enhance firm performance. Second, does competitor imitation of firm knowledge hurt performance. The relationships between technological competence, imitability and performance are basic premises in the resource-based view, yet there has been little empirical testing of them. Measures of technological competence and imitability are developed. These variables, together with measures of marketing and regulatory competence, are tested for their impact on firm performance in the pharmaceutical industry. Imitability has a negative and significant impact on accounting and market-based performance measures. Contrary to expectations, technological competence is inversely related to market-based performance measures and positively related to accounting measures. Research and managerial implications for the findings are discussed.
The Response Strategies of Dominant US Firms to Japanese Challengers
Authors: Hopkins H. Donald
Published: June 2005

Six case studies are used to examine the response strategies of dominant US firms to the entry of Japanese challengers into their domestic industries. This study examines the question of whether it is better to respond quickly with individual competitive responses or wait until a broad strategic reorientation is possible. The results suggest that the US firms that had a slower but more concentrated and aggressive response lost less market share than firms that responded quickly.
Integrating the business curriculum with a comprehensive case study: A prototype
Authors: Markulis Peter M. , Howe Harry , Strang Daniel R.
Published: June 2005

Business schools continue to grapple with the issue of curriculum integration. Although faculty are encouraged to work conjointly and students are told that theories, concepts, and techniques learned in one course will be used in future courses, the challenge of integrationfrom course to course remains elusive. This article presents a model for curriculum integration developed by the business school at the State University of New York at Geneseo. The model uses a comprehensive case based on a real-world insurance company. Incoming business students will be presented with a synopsis of the case in their first year of business school. The same case with the relevant topical additions will continue to be used in all subsequent primary business courses. The article presents the rationale, methodology, and curriculum development of the case. The article also outlines how the school plans to integrate the case into the upper-level business courses.
An algorithm for incorporating company reputation into business simulations: Variations on the Gold standard
Authors: Cannon Hugh M. , Schwaiger Manfred
Published: June 2005

Gold recently presented a system-dynamic-based approach to the design of business simulations. In it, he argued that the focus of simulation design efforts have mostly been carried out at the subsystem level, developing independent algorithms that follow inconsistent logic. As a result, they do not lend themselves to integration into a single, dynamically interactive model. To address this, he drew on the economic theory of the firm to develop and test a system of interacting algorithms that gives equal emphasis to both demand and supply factors. Most important, Gold’s approach provides a common, theoretically anchored platform for integrating potentially conflicting functional algorithms. This article tests the robustness of this approach by using Gold’s model as a vehicle for capturing the effects of company reputation, a phenomenon that has emerged from a totally different (management and marketing) research tradition.
Allostatic Load: A Mechanism of Socioeconomic Health Disparities?
Authors: Szanton Sarah L. , Gill Jessica M. , Allen Jerilyn K.
Published: May 2005

Although research on health disparities has been prioritized by the National Institutes of Health, the Institute of Medicine, and Healthy People 2010, little has been published that examines the biology underlying health disparities. Allostatic load is a multisystem construct theorized to quantify stress-induced biological risk. Differences in allostatic load may reflect differences in stress exposure and thus provide a mechanistic link to understanding health disparities. The purpose of this systematic review is to examine the construct of allostatic load and the published studies that employ it in an effort to understand whether the construct can be useful in quantifying health disparities. The published literature demonstrates that allostatic load is elevated in those of low socioeconomic status (SES) as compared to those of high SES. The reviewed articles vary in the justification for inclusion of variables. Recommendations for future research are made in the contexts of measurement, methodology, and racial composition of participants.
Maternal Race/Ethnicity and Predictors of Pregnancy and Infant Outcomes
Authors: Shiao Shyang-Yun Pamela K. , Andrews Claire M. , Helmreich Rebecca Jo
Published: May 2005

Objective. To examine predictors of pregnancy and infant outcomes, including maternal race/ethnicity. Design. Prospective and observational follow-up of high-risk pregnancies and births. Participants. Three hundred fifty-four mothers and their preterm and/or high-risk live-born neonates were closely followed in three tertiary care centers from the prenatal to postnatal periods for potential high-risk and/or preterm births that required neonatal resuscitations. Major Outcome Measures. Pregnancy complications, birth complications, and infant outcomes were examined in conjunction with maternal factors, including preexisting health problems, health behaviors (smoking, alcohol consumption, prenatal visits), and the birth setting (tertiary care centers or community hospitals). Results. About 22% of these infants were transferred into the tertiary care centers from the community hospitals right after birth; the rest were born in the centers. According to regression analyses, predictors of the birth setting were race (White vs. non-White), maternal health behaviors, pregnancy complications, fetal distress, and the presence of congenital defects for infants (p < .001). Predictors for fetal distress included race (Whites) and pregnancy-induced hypertension (p < .003). Predictors for lower birth weight included race (non-Whites), maternal cigarette smoking, pregnancy complications, fetal distress, and congenital defects (p < .001). Infant mortality rate was 3.9% for these high-risk infants, with the highest rate in infants born to Black mothers (8%). Conclusions. There are obvious health disparities among White and non-White women experiencing high-risk pregnancies and births. Future studies are needed to develop interventions targeted to different racial/ethnic groups during pregnancy to reduce preterm and high-risk births.
The Perverse Consequences of Electoral Reform in the United States
Authors: Berinsky Adam J.
Published: June 2005

A number of electoral reforms have been enacted in the United States in the past three decades that are designed to increase turnout by easing restrictions on the casting of ballots. Both proponents and opponents of electoral reforms agree that these reforms should increase the demographic representativeness of the electorate by reducing the direct costs of voting, thereby increasing turnout among less-privileged groups who, presumably, are most sensitive to the costs of coming to the polls. In fact, these reforms have been greatly contested because both major political parties believe that increasing turnout among less-privileged groups will benefit Democratic politicians. I review evidence from numerous studies of electoral reform to demonstrate that reforms designed to make it easier for registered voters to cast their ballots actually increase, rather than reduce, socioeconomicbiases in the composition of the voting public. I conclude with a recommendation that we shift the focus of electoral reform from an emphasis on institutional changes to a concentration on political engagement.
What Do They Know and How Do They Know It?
Authors: Baybeck Brady , McClurg Scott D.
Published: June 2005

The connection between the individual and his or her aggregate geographic environment, usually defined as the neighborhood, is a key component of the contextual model of social influence. However, there is substantial anecdotal evidence that people have very little knowledge or connection to their neighborhood. In this article, the authors explore the connection by using data from the South Bend Study to answer two questions: What do people know about objective conditions of their neighborhoods? Second, do these conditions influence perceptions people have of their neighborhoods?The authors find that (a) people have a good deal of knowledge about the objective conditions, and (b) even after controlling for individual factors, these conditions positively influence how people perceive their status within the neighborhood. In short, there is a connection between the individual and the geographic context.
The Political Participation and Engagement of Muslim Americans
Authors: Jamal Amaney
Published: June 2005

Although studies on civic and political engagement highlight the importance of religious institutions in the political mobilization of Americans, few studies have examined the role of religious institutions in ethnic or minority communities. Furthermore, little is known about the causal mechanisms that link minorities in religious institutions to broader forms of political participation. Through an examination of patterns of Muslim American political behavior and their levels of mosque participation, the author argues that the mosque, similar to other religious institutions in the United States, takes on the multifaceted role of mobilization vehicle and school of civic participation. The author also discovers that mosques promote and foster a sense of group consciousness among Arab and Black Muslims.
Evaluability Assessment in Juvenile Justice
Authors: Finckenauer James O. , Margaryan Satenik , Sullivan Mercer L.
Published: June 2005

An evaluability assessment of three programs of the Juvenile Justice Commission of the State of New Jersey was undertaken. Operation Hook-Up, the Hudson County YAP Challenge Program, and the Monmouth County Bullying Prevention Project were assessed. This included interviewing program personnel, site visits, reviewing the record-keeping systems, and meeting with the staff of the Juvenile Justice Commission and of the programs. This assessment enabled the researchers to acquire firsthand knowledge of the programs that led to the development of tailored evaluation designs for two programs. This article describes the programs, the assessment, and the bases for our recommendations.
The Construct of Psychopathy and its Potential Contribution to the Study of Serious, Violent, and Chronic Youth Offending
Authors: Vaughn Michael G. , Howard Matthew O.
Published: June 2005

This article examines the construct of psychopathy and its potential to enhance current understanding of serious, violent, and chronic (SVC) juvenile offending. Historical, definitional, diagnostic, etiological, and assessment issues pertaining to psychopathy are discussed and a conceptual framework of antisocial subtypes incorporating biological and social factors is presented. Implications of psychopathy-related findings for future theory, research, policy, and practice in the juvenile justice system are elucidated.
Involvement of Runx1 in the down-regulation of fetal liver kinase-1 expression during transition of endothelial cells to hematopoietic cells
Authors: Hirai Hideyo , Samokhvalov Igor M , Fujimoto Tetsuhiro , Nishikawa Satomi , Imanishi Jiro , Nishikawa Shin-Ichi
Published: June 2005

During early mouse embryogenesis, fetal liver kinase-1 (Flk-1), a receptor for vascular endothelial growth factor, and Runx1, a runt domain transcription factor, have prerequisite roles in the generation of hematopoietic lineages. Flk-1 expression is maintained in successive stages from mesodermal to endothelial cells and is down-regulated in nascent hematopoietic cells, whereas Runx1 (Runt-related transcription factor 1) is expressed in embryonic sites of hematopoietic cell de novo generation and in practically all hematopoietic organs. Here we show that Runx1 represses Flk-1 during the development of hemogenic endothelial cells into hematopoietic cells. We established embryonic stem cell clones carrying the Venus gene, a modified version of yellow fluorescence protein, in the Runx1 locus and cultured them on OP9 cells. Flk-1+ cells appeared on day 3.5, and Runx1+ cells first appeared from the Flk-1+ fraction on day 4.5. The Flk-1+Runx1+ cells rapidly stopped expressing Flk-1 with further incubation and eventually gave rise to CD45+ or TER119+ cells. Runx1 repressed Flk-1 promoter transcriptional activity in an endothelial cell line, and this repression required intact DNA-binding and transactivating domains of Runx1 protein. The repressor activity of Runx1 endogenous Flk-1 was also confirmed overexpressing Runx1 in embryonic stem cell differentiation cultures. These results provide novel insight into the role Runx1 during the development of hematopoietic cell lineages.
HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation
Authors: Muthumani Karuppiah , Choo Andrew Y. , Hwang Daniel S. , Premkumar Arumugam , Dayes Nathanael S. , Harris Crafford , Green Douglas R. , Wadsworth Scott A. , Siekierka John J. , Weiner David B.
Published: June 2005

The human immunodeficiency virus (HIV) has been reported to target noninfected CD4 and CD8 cells for destruction. This effect is manifested in part through up-regulation of the death receptor Fas ligand (FasL) by HIV-1 negative factor (Nef), leading to bystander damage. However, the signal transduction and transcriptional regulation of this process remains elusive. Here, we provide evidence that p38 mitogen-activated protein kinase (MAPK) is required for this process. Loss-of-function experiments through dominant-negative p38 isoform, p38 siRNA, and chemical inhibitors of p38 activation suggest that p38 is necessary for Nef-induced activator protein-1 (AP-1) activation, as inhibition leads to an attenuation of AP-1-dependent transcription. Furthermore, mutagenesis of the FasL promoter reveals that its AP-1 enhancer element is required for Nef-mediated transcriptional activation. Therefore, a linear pathway for Nef-induced FasL expression that encompasses p38 and AP-1 has been elucidated. Furthermore, chemical inhibition of the p38 pathway attenuates HIV-1-mediated bystander killing of CD8 cells in vitro. (Blood. 2005;106:2059-2068)
Defective killing of dendritic cells by autologous natural killer cells from acute myeloid leukemia patients
Authors: Fauriat Cyril , Moretta Alessandro , Olive Daniel , Costello Régis T.
Published: June 2005

At the frontier between innate and adaptive immunity, dendritic cells (DCs) secrete numerous cytokines and express costimulatory molecules that initiate or enhance natural killer (NK) and T-lymphocyte responses. NK cells also regulate DC physiology by killing immature DCs (iDCs), thus limiting inflammation and inappropriate T-lymphocyte tolerization. In a previous study, we have reported that NK cells from acute myeloid leukemia patients (AML-NK cells) have deficient natural cytotoxicity receptor (NCR) expression. Herein, we analyzed the consequences of such a defect regarding the regulatory role of AML-NK cells in DC physiology. We show that NK cells display poor cytolytic capacities against DCs derived from healthy donor monocytes or derived from autologous leukemic blasts. These data point to a novel defect in the regulation of adaptive immune responses initiated by DCs in AML patients. This may lead to specific T-lymphocyte tolerization by spontaneous or ex vivo expanded iDCs expressing leukemia-derived antigens. (Blood. 2005;106: 2186-2188)
Long-term mixed chimerism after immunologic conditioning and MHC-mismatched stem-cell transplantation is dependent on NK-cell tolerance
Authors: Westerhuis Geert , Maas Wendy G. E. , Willemze Roel , Toes René E. M. , Fibbe Willem E.
Published: June 2005

T-cell tolerance is mandatory for major histocompatibility complex (MHC)-mismatched stem-cell transplantation without cytoreduction. Here, we used a cytotoxicity assay based on the infusion of differentially carboxyfluorescein succinimidyl ester (CFSE)-labeled syngeneic and donor splenocytes to determine the survival of donor cells in vivo. In vivo cytotoxicity data showed that treatment with anti-CD40 ligand monoclonal antibody in combination with a low dose of MHC-mismatched bone marrow cells was sufficient to induce T-cell tolerance. However, CFSE-labeled donor cells were still eliminated. A similar elimination pattern was observed in T-cell and natural killer T-cell (NKT-cell)-deficient mice, suggesting the involvement of natural killer (NK) cells. Indeed, in vivo NK-cell depletion resulted in a prolonged survival of CFSE-labeled donor cells, confirming the role of NK cells in this process. Transplantation of a megadose of MHC-mismatched bone marrow cells was required for a complete survival of CFSE-labeled donor cells. This NK-cell tolerance was donor specific and was associated with mixed chimerism. Additional NK-cell depletion significantly enhanced engraftment and allowed long-term chimerism after transplantation of a relatively low dose of donor bone marrow cells. These data demonstrate the importance of NK cells in the rejection of MHC-mismatched hematopoietic cells and may explain the high numbers of bone marrow cells required for transplantation over MHC barriers. (Blood. 2005;106:2215-2220)
Symptoms, lactate and exercise limitation at peak cycle ergometry in adults with cystic fibrosis
Authors: Moorcroft A. J. , Dodd M. E. , Morris J. , Webb A. K.
Published: June 2005

The purpose of this study was to investigate symptoms, lactate accumulation and limiting factors at peak exercise in cystic fibrosis (CF) patients.

In total, 104 CF adults attending an adult CF centre and 27 controls performed progressive cycle ergometry to a symptom-limited maximum. Measurements taken at peak exercise included: heart rate, ventilation, oxygen uptake, carbon dioxide output, oxygen saturation and blood lactate. Symptom scores of perceived breathlessness and muscle effort were recorded using Borg scales.

The CF subjects had a lower mean body mass index, forced expiratory volume in one second (FEV1) and peak oxygen uptake than controls. Peak lactate concentrations were very similar to controls (mean±sd6.8±2.0 mmol·L−1versus7.4±1.0 mmol·L−1). Symptom scores were no different to controls for either breathlessness (4.5±2.0versus4.3±1.0) or perceived muscle effort (6.1±2.0versus6.5±1.0), with higher scores for muscle effort than breathlessness in both groups. In addition, peak ventilation was lower than the predicted maximum, and high peak heart rates were recorded supporting nonpulmonary factors as important in limiting peak exercise. Peak oxygen uptake was correlated with FEV1.

Comparison of CF subjects with mild or moderate pulmonary disease and controls revealed similar exercise responses. In contrast, those CF patients with severe lung disease (FEV1<40% predicted) had significantly higher breathlessness, lower muscle effort scores, lower peak lactate, lower peak heart rate and a mean ventilation exceeding predicted, thus confirming that ventilation was the major factor limiting exercise.

In conclusion, cystic fibrosis subjects have a reduced peak exercise capacity, but their exercise response is similar to controls in generating high blood-lactate concentrations and symptoms of muscle effort in excess of dyspnoea. Nonpulmonary factors influence peak performance more in those without severe disease.
A comparison of video and autofluorescence bronchoscopy in patients at high risk of lung cancer
Authors: Chhajed P. N. , Shibuya K. , Hoshino H. , Chiyo M. , Yasufuku K. , Hiroshima K. , Fujisawa T.
Published: June 2005

The aim of this study was to compare the diagnostic yield of flexible video bronchoscopy (FVB) and autofluorescence bronchoscopy (i.e.lung imaging fluorescence endoscopy (LIFE)) in 151 patients at a high risk of lung cancer and with moderate dysplasia or worse on sputum cytology mass screening.

Findings from FVB and LIFE were classified as either normal, abnormal or suspicious for cancer. Endobronchial biopsies (EBX) were obtained from abnormal or suspicious areas on FVB and/or LIFE, or randomly when FVB and LIFE were normal. Moderate dysplasia and worse were defined as pathologically positive.

Overall, 83 out of 343 (24%) EBX were pathologically positive. The sensitivity of FVB was 72% and LIFE 96%. Relative sensitivity of LIFE over FVB was 1.33. Specificities of FVB and LIFE were 53 and 23%, respectively. The numbers of pathologically positive EBX from sites designated normal, abnormal or suspicious were: from FVB, 23 out of 162 (14%), 37 out of 151 (25%) and 23 out of 30 (77%); from LIFE, three out of 69 (4%), 44 out of 212 (21%) and 36 out of 62 (58%). In normal or abnormal areas at FVB, there was a significant increase in the yield of EBX guided by abnormal and suspicious sites noted at LIFE.

In conclusion, endobronchial biopsies of suspicious findings from lung imaging fluorescence endoscopy and flexible video bronchoscopy have a good diagnostic yield. Lung imaging fluorescence endoscopy is more useful when flexible video bronchoscopy is either normal or abnormal.