Showing papers by "Tufts University published in 2002"
Journal Article•
TL;DR: In the early 1990s, the National Kidney Foundation (K/DOQI) developed a set of clinical practice guidelines to define chronic kidney disease and to classify stages in the progression of kidney disease.
10,265 citations
TL;DR: A number of theoretical frameworks have been developed to explain the gap between the possession of environmental knowledge and environmental awareness, and displaying pro-environmental behavior as discussed by the authors, but no definitive explanation has yet been found.
Abstract: Numerous theoretical frameworks have been developed to explain the gap between the possession of environmental knowledge and environmental awareness, and displaying pro-environmental behavior. Although many hundreds of studies have been undertaken, no definitive explanation has yet been found. Our article describes a few of the most influential and commonly used analytical frameworks: early US linear progression models; altruism, empathy and prosocial behavior models; and finally, sociological models. All of the models we discuss (and many of the ones we do not such as economic models, psychological models that look at behavior in general, social marketing models and that have become known as deliberative and inclusionary processes or procedures (DIPS)) have some validity in certain circumstances. This indicates that the question of what shapes pro-environmental behavior is such a complex one that it cannot be visualized through one single framework or diagram. We then analyze the factors that have been f...
6,108 citations
TL;DR: The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years for identification and characterization of CVD events.
Abstract: The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality.
3,367 citations
Book•
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TL;DR: A user interface is that portion of an interactive computer system that communicates with the user as mentioned in this paper. User interfaces include any aspect of the system that is visible to the user, such as a keyboard, mouse, or display.
Abstract: A user interface is that portion of an interactive computer system that communicates with the user. Design of the user interface includes any aspect of the system that is visible to the user. Once, all computer users were specialists in computing, and interfaces consisted of jumper wires in patch boards, punched cards (q.v.) prepared offline, and batch printouts. Today a wide range of nonspecialists use computers, and keyboards, mice, and graphical displays are the most common interface hardware. The user interface is becoming a larger and larger portion of the software in a computer system--and a more important portion, as broader groups of people use computers. As computers become more powerful, the critical bottleneck in applying computer-based systems to solve problems is more often in the user interface rather than in the computer hardware or software.
2,234 citations
Kaiser Permanente1, University of Colorado Denver2, American Cancer Society3, Rutgers University4, San Diego State University5, National Institutes of Health6, University of California, San Francisco7, Centers for Disease Control and Prevention8, Duke University9, University at Buffalo10, University of Illinois at Chicago11, Harvard University12, Pennsylvania State University13, Tufts University14, University of Arizona15, Fred Hutchinson Cancer Research Center16, University of Utah17, Yeshiva University18, Vanderbilt University19
TL;DR: This committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk, recognizing that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors.
Abstract: The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.
1,957 citations
TL;DR: Self-management education improves GHb levels at immediate follow-up, and increased contact time increases the effect, suggesting that learned behaviors change over time.
Abstract: Objective To evaluate the efficacy of self-management education on GHb in adults with type 2 diabetes. Research design and methods We searched for English language trials in Medline (1980-1999), Cinahl (1982-1999), and the Educational Resources Information Center database (ERIC) (1980-1999), and we manually searched review articles, journals with highest topic relevance, and reference lists of included articles. Studies were included if they were randomized controlled trials that were published in the English language, tested the effect of self-management education on adults with type 2 diabetes, and reported extractable data on the effect of treatment on GHb. A total of 31 studies of 463 initially identified articles met selection criteria. We computed net change in GHb, stratified by follow-up interval, tested for trial heterogeneity, and calculated pooled effects sizes using random effects models. We examined the effect of baseline GHb, follow-up interval, and intervention characteristics on GHb. Results On average, the intervention decreased GHb by 0.76% (95% CI 0.34-1.18) more than the control group at immediate follow-up; by 0.26% (0.21% increase - 0.73% decrease) at 1-3 months of follow-up; and by 0.26% (0.05-0.48) at > or = 4 months of follow-up. GHb decreased more with additional contact time between participant and educator; a decrease of 1% was noted for every additional 23.6 h (13.3-105.4) of contact. Conclusions Self-management education improves GHb levels at immediate follow-up, and increased contact time increases the effect. The benefit declines 1-3 months after the intervention ceases, however, suggesting that learned behaviors change over time. Further research is needed to develop interventions effective in maintaining long-term glycemic control.
1,757 citations
TL;DR: Reviews of the data suggest that the direct actions of estrogen on blood are less important than previously thought, and that estrogen-induced alterations in serum lipids account for only approximately one third of the observed clinical benefits of estrogen.
Abstract: The incidence of cardiovascular disease differs significantly between men and women, in part because of differences in risk factors and hormones.1 The incidence of atherosclerotic diseases is low in premenopausal women, rises in postmenopausal women, and is reduced to premenopausal levels in postmenopausal women who receive estrogen therapy.1–3 Until recently, the atheroprotective effects of estrogen were attributed principally to the hormone's effects on serum lipid concentrations. However, estrogen-induced alterations in serum lipids account for only approximately one third of the observed clinical benefits of estrogen.3–5 Reviews of the data suggest that the direct actions of estrogen on blood . . .
1,742 citations
Baylor College of Medicine1, Cleveland Clinic2, University of Utah3, University of Illinois at Chicago4, National Institutes of Health5, University of Alabama6, Emory University7, Washington University in St. Louis8, University of California, Davis9, Tufts University10, Yeshiva University11, Harvard University12, University of Rochester13, Wake Forest University14, Vanderbilt University15, Duke University16
TL;DR: Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.
Abstract: Background The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain. Methods We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer. Results In the standard-dose group, the mean (±SD) urea-reduction ratio was 66.3±2.5 percent, the single-pool Kt/V was 1.32±0.09, and the equilibrated Kt/V was 1.16±0.08; in the high-dose group, the values were 75.2±2.5 percent, 1.71±0.11, and 1.53±0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3±7 ml per minute in the low-flux group and 34±11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as com...
1,670 citations
TL;DR: Survival among mechanically ventilated patients depends not only on the factors present at the start of mechanical ventilation, but also on the development of complications and patient management in the intensive care unit.
Abstract: ContextThe outcome of patients receiving mechanical ventilation for particular
indications has been studied, but the outcome in a large number of unselected,
heterogeneous patients has not been reported.ObjectiveTo determine the survival of patients receiving mechanical ventilation
and the relative importance of factors influencing survival.Design, Setting, and SubjectsProspective cohort of consecutive adult patients admitted to 361 intensive
care units who received mechanical ventilation for more than 12 hours between
March 1, 1998, and March 31, 1998. Data were collected on each patient at
initiation of mechanical ventilation and daily throughout the course of mechanical
ventilation for up to 28 days.Main Outcome MeasureAll-cause mortality during intensive care unit stay.ResultsOf the 15 757 patients admitted, a total of 5183 (33%) received
mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean
(SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall
mortality rate in the intensive care unit was 30.7% (1590 patients) for the
entire population, 52% (120) in patients who received ventilation because
of acute respiratory distress syndrome, and 22% (115) in patients who received
ventilation for an exacerbation of chronic obstructive pulmonary disease.
Survival of unselected patients receiving mechanical ventilation for more
than 12 hours was 69%. The main conditions independently associated with increased
mortality were (1) factors present at the start of mechanical ventilation
(odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR,
3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway
pressure >35 cm H2O), and (3) developments occurring over the course
of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO2 to fraction of inspired oxygen
<100).ConclusionSurvival among mechanically ventilated patients depends not only on
the factors present at the start of mechanical ventilation, but also on the
development of complications and patient management in the intensive care
unit.
1,621 citations
TL;DR: A strong association between myocardial viability on noninvasive testing and improved survival after revascularization in patients with chronic CAD and LV dysfunction is demonstrated.
1,257 citations
TL;DR: The pH of intracellular compartments in eukaryotic cells is a carefully controlled parameter that affects many cellular processes, including intrACEllular membrane transport, prohormone processing and transport of neurotransmitters, as well as the entry of many viruses into cells.
Abstract: The pH of intracellular compartments in eukaryotic cells is a carefully controlled parameter that affects many cellular processes, including intracellular membrane transport, prohormone processing and transport of neurotransmitters, as well as the entry of many viruses into cells. The transporters responsible for controlling this crucial parameter in many intracellular compartments are the vacuolar (H+)-ATPases (V-ATPases). Recent advances in our understanding of the structure and regulation of the V-ATPases, together with the mapping of human genetic defects to genes that encode V-ATPase subunits, have led to tremendous excitement in this field.
TL;DR: This review examines the growing evidence that GC concentrations in free-living reptiles, amphibians, and birds, but not mammals, are commonly elevated during the breeding season and test three hypotheses with different focuses on GC's energetic or behavioral effects, as well as onGC's role in preparing the animal for subsequent stressors.
TL;DR: Intravitreal triamcinolone is a promising therapeutic method for diabetic macular edema that fails to respond to conventional laser photocoagulation and complications do not appear to be prohibitive.
TL;DR: These findings establish additional mechanisms by which statins may specifically preempt disordered vascular wall pathology and constitute physiological evidence that EPC mobilization represents a functionally relevant consequence of statin therapy.
Abstract: Background— Primary and secondary prevention trials suggest that statins possess favorable effects independent of cholesterol reduction. We investigated whether statin therapy may also accelerate reendothelialization after carotid balloon injury. Methods and Results— Simvastatin treatment in 34 male Sprague-Dawley rats accelerated reendothelialization of the balloon-injured arterial segments (reendothelialized area at 2 weeks, 12.3±1.8 versus 5.4±1.1 mm2, P< 0.01) and resulted in a dose-dependent (0.2 or 1 mg/kg IP) significant reduction in neointimal thickening at 2, 3, and 4 weeks compared with saline-injected controls (n=18). To elucidate the mechanism, we investigated the contribution of bone marrow–derived endothelial progenitor cells (EPCs) by bone marrow transplantation from Tie2/lacZ mice to background mice or nude rats. X-gal staining of mouse carotid artery specimens revealed a 2.9-fold increase in the number of β-gal–positive cells per square millimeter appearing on the carotid artery luminal s...
Duke University1, Harvard University2, Emory University3, University of Western Ontario4, University of Missouri5, National Institutes of Health6, Baptist Health7, Oregon Health & Science University8, Virginia Commonwealth University9, Mount Sinai St. Luke's and Mount Sinai Roosevelt10, Tufts University11, Thomas Jefferson University12, University of California, San Francisco13
TL;DR: Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing, and reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life.
Abstract: Background Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. Methods We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. Results The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 9...
TL;DR: The results support the conclusion that properly prepared silkworm fiber matrices, aside from providing unique benefits in terms of mechanical properties as well as biocompatibility and slow degradability, can provide suitable biomaterial matrices for the support of adult stem cell differentiation toward ligament lineages.
TL;DR: It is suggested that vitamin D deficiency is unlikely in the two seasonal subpopulations of noninstitutionalized adolescents and adults that can be validly assessed in NHANES III and that insufficiency occurred fairly frequently in younger individuals, especially in the winter/lower latitude subsample.
TL;DR: The mechanisms by which cancer cells stimulate pathological neovascularization mimic those utilized by normal cells to foster physiological angiogenesis, an essential process in which the vascular tree is remodeled by the growth of new capillaries from preexisting vessels.
Abstract: Often those diseases most evasive to therapeutic intervention usurp the human body's own cellular machinery or deregulate normal physiological processes for propagation. Tumor-induced angiogenesis is a pathological condition that results from aberrant deployment of normal angiogenesis, an essential process in which the vascular tree is remodeled by the growth of new capillaries from preexisting vessels. Normal angiogenesis ensures that developing or healing tissues receive an adequate supply of nutrients. Within the confines of a tumor, the availability of nutrients is limited by competition among actively proliferating cells, and diffusion of metabolites is impeded by high interstitial pressure (Jain RK. Cancer Res 47: 3039-3051, 1987). As a result, tumor cells induce the formation of a new blood supply from the preexisting vasculature, and this affords tumor cells the ability to survive and propagate in a hostile environment. Because both normal and tumor-induced neovascularization fulfill the essential role of satisfying the metabolic demands of a tissue, the mechanisms by which cancer cells stimulate pathological neovascularization mimic those utilized by normal cells to foster physiological angiogenesis. This review investigates mechanisms of tumor-induced angiogenesis. The strategies used by cancer cells to develop their own blood supply are discussed in relation to those employed by normal cells during physiological angiogenesis. With an understanding of blood vessel growth in both normal and abnormal settings, we are better suited to design effective therapeutics for cancer.
TL;DR: Aqueous-based electrospining of silk and silk/PEO blends provides potentially useful options for the fabrication of biomaterial scaffolds based on this unique fibrous protein.
TL;DR: Evidence indicates that B-1a cells can derive from adult precursors expressing an appropriate specificity when the (self-) antigen is present, and the CD5 molecule can function as a negative regulator of BCR signaling that may help prevent inappropriate activation of autoreactive B- 1a cells.
Abstract: Whether B-1a (CD5+) cells are a distinct lineage derived from committed fetal/neonatal precursors or arise from follicular B-2 cells in response to BCR ligation and other, unknown signals remains controversial. Recent evidence indicates that B-1a cells can derive from adult precursors expressing an appropriate specificity when the (self-) antigen is present. Antibody specificity determines whether a B cell expressing immunoglobulin transgenes has a B-2, B-1a or marginal zone (MZ) phenotype. MZ cells share many phenotypic characteristics of B-1 cells and, like them, appear to develop in response to T independent type 2 antigens. Because fetal-derived B cell progenitors fail to express terminal deoxynucleotidyl transferase (TdT) and for other reasons, they are likely to express a repertoire that allows selection into the B-1a population. As it is selected by self-antigen, the B-1 repertoire tends to be autoreactive. This potentially dangerous repertoire is also useful, as B-1 cells are essential for resistance to several pathogens and they play an important role in mucosal immunity. The CD5 molecule can function as a negative regulator of BCR signaling that may help prevent inappropriate activation of autoreactive B-1a cells.
TL;DR: In vitro and animal studies provide strong evidence that tea polyphenols may possess the bioactivity to affect the pathogenesis of several chronic diseases, especially cardiovascular disease and cancer, but international correlations do not support this relationship.
Abstract: Tea is an important dietary source of flavanols and flavonols. In vitro and animal studies provide strong evidence that tea polyphenols may possess the bioactivity to affect the pathogenesis of several chronic diseases, especially cardiovascular disease and cancer. However, the results from epidemiological and clinical studies of the relationship between tea and health are mixed. International correlations do not support this relationship although several, better controlled case-referent and cohort studies suggest an association with a moderate reduction in the risk of chronic disease. Conflicting results between human studies may arise, in part, from confounding by socioeconomic and lifestyle factors as well as by inadequate methodology to define tea preparation and intake. Clinical trials employing putative intermediary indicators of disease, particularly biomarkers of oxidative stress status, suggest tea polyphenols could play a role in the pathogenesis of cancer and heart disease.
TL;DR: It is demonstrated that mechanical stimulation in vitro, without ligament‐selective exogenous growth and differentiation factors, induces the differentiation of mesenchymal progenitor cells from the bone marrow into a ligament cell lineage in preference to alternative paths.
Abstract: Growth factors, hormones, and other regulatory molecules are traditionally required in tissue engineering studies to direct the differentiation of progenitor cells along specific lineages. We demonstrate that mechanical stimulation in vitro, without ligament-selective exogenous growth and differentiation factors, induces the differentiation of mesenchymal progenitor cells from the bone marrow into a ligament cell lineage in preference to alternative paths (i.e., bone or cartilage cell lineages). A bioreactor was designed to permit the controlled application of ligament-like multidimensional mechanical strains (translational and rotational strain) to the undifferentiated cells embedded in a collagen gel. The application of mechanical stress over a period of 21 days up-regulated ligament fibroblast markers, including collagen types I and III and tenascin-C, fostered statistically significant cell alignment and density and resulted in the formation of oriented collagen fibers, all features characteristic of ligament cells. At the same time, no up-regulation of bone or cartilage-specific cell markers was observed.
TL;DR: A single intracoronary infusion of rFGF2 does not improve exercise tolerance or myocardial perfusion but does show trends toward symptomatic improvement at 90 (but not 180) days.
Abstract: Background— Single-bolus intracoronary administration of fibroblast growth factor-2 (FGF2) improved symptoms and myocardial function in a phase I, open-label trial in patients with coronary artery disease. We conducted the FGF Initiating RevaScularization Trial (FIRST) to evaluate further the efficacy and safety of recombinant FGF2 (rFGF2). Methods and Results— FIRST is a multicenter, randomized, double-blind, placebo-controlled trial of a single intracoronary infusion of rFGF2 at 0, 0.3, 3, or 30 μg/kg (n=337 patients). Efficacy was evaluated at 90 and 180 days by exercise tolerance test, myocardial nuclear perfusion imaging, Seattle Angina Questionnaire, and Short-Form 36 questionnaire. Exercise tolerance was increased at 90 days in all groups and was not significantly different between placebo and FGF-treated groups. rFGF2 reduced angina symptoms as measured by the angina frequency score of the Seattle Angina Questionnaire (overall P=0.035) and the physical component summary scale of the Short-Form 36 ...
TL;DR: The development and initial implementation of a continuous disease severity scale that uses objective, readily available variables to predict mortality risk in patients with end‐stage liver disease and reduce the emphasis on waiting time is described.
TL;DR: Four classes of mutants defective in infection models of the lung, lung and blood, and nasopharynx were identified, thus demonstrating the ex‐istence of tissue‐specific pneumococcal virulence factors.
Abstract: Streptococcus pneumoniae (the pneumococcus) is carried in the nasopharynx of healthy individuals, but can spread to other host sites and lead to pneumonia, bacteraemia, otitis media and meningitis. Although it is logical to think a priori that differential gene expression would contribute to the ability of this pathogen to colonize different sites, in fact very few genes have been demonstrated to play tissue-specific roles in virulence or carriage. Using signature-tagged mutagenesis to screen 6149 mariner-transposon insertion strains, we identified 387 mutants attenuated for infection in a murine model of pneumonia. Among these mutants are ones with disruptions in a number of putative tissue-specific transcriptional regulators, surface proteins, metabolic proteins and proteins of unknown function, most of which had not previously been associated with virulence. A subset of these, including most of those with insertions in putative transcriptional regulators,was examined for phenotypes in murine models of bacteraemia and nasopharyngeal carriage. Four classes of mutants defective in infection models of the: (I) lung, (II) lung and blood, (III) lung and nasopharynx,and (IV) all three tissues were identified, thus demonstrating the existence of tissue-specific pneumococcal virulence factors. Included in these strains were two with disruptions in a genetic locus that putatively codes for a transcriptional regulator, three surface proteins and three sortase homologues. Mutation analysis revealed that three of the seven genes in this locus are virulence factors that are specific to mucosal surfaces.
TL;DR: Clinical trials are examining the anticancer properties of exogenous highly sulphated HSGAGs, including heparin and low-molecular-weight heparins, in addition to small oligosaccharideheparin mimetics.
Abstract: Cell-surface/extracellular-matrix heparan-sulphate glycosaminoglycans (HSGAGs) are complex polysaccharides that are ubiquitous in nature, and that regulate several aspects of cancer biology, including tumorigenesis, tumour progression and metastasis. Recently gained insights into the structure of HSGAGs have extended our understanding of their role in the oncogenic process. At present, clinical trials are examining the anticancer properties of exogenous highly sulphated HSGAGs, including heparin and low-molecular-weight heparins, in addition to small oligosaccharide heparin mimetics. Combined with our more intricate understanding of HSGAG structure, this emerging structure–activity approach opens exciting avenues for the generation of polysaccharide-based anticancer therapeutics.
TL;DR: In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.
Abstract: Background Diabetes mellitus, impaired fasting glucose level, or insulin resistance are associated with increased risk of cardiovascular disease. Objectives To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes. Methods Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized controlled trial that enrolled 2531 men with coronary heart disease (CHD), a high-density lipoprotein cholesterol level of 40 mg/dL or less (≤1.04 mmol/L), and a low-density lipoprotein cholesterol level of 140 mg/dL or less (≤3.63 mmol/L). Subjects received either gemfibrozil (1200 mg/d) or matching placebo and were followed up for an average of 5.1 years. In this article, we report the composite end point (CHD death, stroke, or myocardial infarction). Results Compared with those with a normal fasting glucose level, risk was increased in subjects with known diabetes (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.44-2.43; P = .001) and those with newly diagnosed diabetes (HR, 1.72; 95% CI, 1.10-2.68; P = .02). In persons without diabetes, a fasting plasma insulin level of 39 µU/mL or greater (≥271 pmol/L) was associated with a 31% increased risk of events ( P = .03). Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P = .004). The reduction in CHD death was 41% (HR, 0.59; 95% CI, 0.39-0.91; P = .02). Among individuals without diabetes, gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile (risk reduction, 35%; P = .04). Conclusion In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.
TL;DR: In vivo, gene-modified EPCs facilitate the strategy of cell transplantation to augment naturally impaired neovascularization in an animal model of experimentally induced limb ischemia.
Abstract: Background— Previous studies have established that bone marrow–derived endothelial progenitor cells (EPCs) are present in the systemic circulation In the current study, we investigated the hypothesis that gene transfer can be used to achieve phenotypic modulation of EPCs Methods and Results— In vitro, ex vivo murine vascular endothelial growth factor (VEGF) 164 gene transfer augmented EPC proliferative activity and enhanced adhesion and incorporation of EPCs into quiescent as well as activated endothelial cell monolayers To determine if such phenotypic modulation may facilitate therapeutic neovascularization, heterologous EPCs transduced with adenovirus encoding VEGF were administered to athymic nude mice with hindlimb ischemia; neovascularization and blood flow recovery were both improved, and limb necrosis/autoamputation were reduced by 637% in comparison with control animals The dose of EPCs used for the in vivo experiments was 30 times less than that required in previous trials of EPC transplanta
TL;DR: The Hq mutation is identified as a proviral insertion in the apoptosis-inducing factor (Aif) gene, causing about an 80% reduction in AIF expression, and neurons damaged by oxidative stress in both the cerebellum and retina of Hq mutant mice re-enter the cell cycle before undergoing apoptosis.
Abstract: Harlequin (Hq) mutant mice have progressive degeneration of terminally differentiated cerebellar and retinal neurons. We have identified the Hq mutation as a proviral insertion in the apoptosis-inducing factor (Aif) gene, causing about an 80% reduction in AIF expression. Mutant cerebellar granule cells are susceptible to exogenous and endogenous peroxide-mediated apoptosis, but can be rescued by AIF expression. Overexpression of AIF in wild-type granule cells further decreases peroxide-mediated cell death, suggesting that AIF serves as a free radical scavenger. In agreement, dying neurons in aged Hq mutant mice show oxidative stress. In addition, neurons damaged by oxidative stress in both the cerebellum and retina of Hq mutant mice re-enter the cell cycle before undergoing apoptosis. Our results provide a genetic model of oxidative stress-mediated neurodegeneration and demonstrate a direct connection between cell cycle re-entry and oxidative stress in the ageing central nervous system.
TL;DR: The authors currently face multiresistant infectious disease organisms that are difficult and, sometimes, impossible to treat successfully and must encourage the return of the susceptible commensal flora to curb the resistance problem.
Abstract: Antibiotic resistance has become a major clinical and public health problem within the lifetime of most people living today. Confronted by increasing amounts of antibiotics over the past 60 years, bacteria have responded to the deluge with the propagation of progeny no longer susceptible to them. While it is clear that antibiotics are pivotal in the selection of bacterial resistance, the spread of resistance genes and of resistant bacteria also contributes to the problem. Selection of resistant forms can occur during or after antimicrobial treatment; antibiotic residues can be found in the environment for long periods of time after treatment. Besides antibiotics, there is the mounting use of other agents aimed at destroying bacteria, namely the surface antibacterials now available in many household products. These too enter the environment. The stage is thus set for an altered microbial ecology, not only in terms of resistant versus susceptible bacteria, but also in terms of the kinds of microorganisms surviving in the treated environment. We currently face multiresistant infectious disease organisms that are difficult and, sometimes, impossible to treat successfully. In order to curb the resistance problem, we must encourage the return of the susceptible commensal flora. They are our best allies in reversing antibiotic resistance.