Publications

The majority of percutaneous coronary interventions (PCIs) are carried out in nonurgent situations, primarily in patients with stable coronary artery disease. Recent trials have concluded that for patients with stable coronary artery disease, treatment with optimal medical therapy versus optimal medical therapy plus PCI yields equivalent outcomes in terms of morbidity and future risk of myocardial infarction. Since PCI is a procedure with risk, it is important to identify patients for whom the benefit of the procedure outweighs the harms. PCI may be beneficial in certain subgroups, such as patients with moderate-to-severe ischemia on noninvasive testing. Although current guidelines require documentation of ischemia prior to elective PCI and this strategy is cost effective, pre-PCI stress testing appears to be underutilized, potentially leading to PCI being performed in patients who may not derive benefit from the procedure.

BACKGROUND

Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner.

METHODS

MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography.

RESULTS

We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness.

CONCLUSIONS

Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy.

BACKGROUND

Mutations in the human filaggrin gene (FLG) are associated with atopic dermatitis (AD) and are presumed to provoke a barrier abnormality. Yet additional acquired stressors might be necessary because the same mutations can result in a noninflammatory disorder, ichthyosis vulgaris.

OBJECTIVE

We examined here whether FLG deficiency alone suffices to produce a barrier abnormality, the basis for the putative abnormality, and its proinflammatory consequences.

METHODS

By using the flaky-tail mouse, which lacks processed murine filaggrin because of a frameshift mutation in the gene encoding profilaggrin that mimics some mutations in human AD, we assessed whether FLG deficiency provokes a barrier abnormality, further localized the defect, identified its subcellular basis, and assessed thresholds to irritant- and hapten-induced dermatitis.

RESULTS

Flaky-tail mice exhibit low-grade inflammation with increased bidirectional, paracellular permeability of water-soluble xenobiotes caused by impaired lamellar body secretion and altered stratum corneum extracellular membranes. This barrier abnormality correlates with reduced inflammatory thresholds to both topical irritants and haptens. Moreover, when exposed repeatedly to topical haptens at doses that produce no inflammation in wild-type mice, flaky-tail mice experience a severe AD-like dermatosis with a further deterioration in barrier function and features of a T(H)2 immunophenotype (increased CRTH levels plus inflammation, increased serum IgE levels, and reduced antimicrobial peptide [mBD3] expression).

CONCLUSIONS

FLG deficiency alone provokes a paracellular barrier abnormality in mice that reduces inflammatory thresholds to topical irritants/haptens, likely accounting for enhanced antigen penetration in FLG-associated AD.

BACKGROUND

Noninfectious nonallergic rhinitis (NINAR) is characterized by self-reported hyperreactivity to nonspecific physical or chemical stimuli. The relationship between these two classes of triggers is not well established, however. We compared NINAR subjects with predominantly physical or chemical triggers versus normal controls with respect to subjective (symptomatic) and objective (obstructive) responses to cold, dry air challenge.

METHODS

We studied 14 NINAR subjects and 10 normal controls. Exposures consisted of 15 minutes of cold dry air (0 degrees C/5% RH) or warm moist air (25 degrees C/50% RH) on two separate days a week apart. Subjects rated symptoms using visual analog scales and had their nasal airway resistance measured at baseline, immediately after, and at 15-minute intervals for 1 hour postexposure.

RESULTS

The majority of NINAR subjects reported physical triggers as more troublesome than chemical. Immediately postprovocation, the mean net proportional change in nasal airway resistance from baseline was +0.18 in NINAR (physical), +0.05 in NINAR (chemical), and -0.01 in control subjects (NS). However, a pooled linear regression by number of physical triggers (0-5) revealed a 7.5% increase in cold air-induced nasal airway resistance per trigger reported (p<0.05). Similarly, raising the criterion number of physical triggers from >or=1 to >or=2 also distinguished NINAR subjects from controls in a bivariate analysis.

CONCLUSION

Either considering self-reported physical triggers as a continuous scale (0-5) or requiring more physical triggers (>or=2 rather than >or=1) to define NINAR successfully predicts objective nasal reactivity to cold air provocation.

In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable.

OBJECTIVE

This project analyzed the psychometric properties of the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture (HSOPSC) including factor structure, interitem reliability and intraclass correlations, usefulness for assessment, predictive validity, and sensitivity.

METHODS

The survey was administered to 454 health care staff in 3 hospitals before and after a series of multidisciplinary interventions designed to improve safety culture. Respondents (before, 434; after, 368) included nurses, physicians, pharmacists, and other hospital staff members.

RESULTS

Factor analysis partially confirmed the validity of the HSOPSC subscales. Interitem consistency reliability was above 0.7 for 5 subscales; the staffing subscale had the lowest reliability coefficients. The intraclass correlation coefficients, agreement among the members of each unit, were within recommended ranges. The pattern of high and low scores across the subscales of the HSOPSC in the study hospitals were similar to the sample of Pacific region hospitals reported by the Agency for Healthcare Research and Quality and corresponded to the proportion of items in each subscale that are worded negatively (reverse scored). Most of the unit and hospital dimensions were correlated with the Safety Grade outcome measure in the tool.

CONCLUSION

Overall, the tool was shown to have moderate-to-strong validity and reliability, with the exception of the staffing subscale. The usefulness in assessing areas of strength and weakness for hospitals or units among the culture subscales is questionable. The culture subscales were shown to correlate with the perceived outcomes, but further study is needed to determine true predictive validity.

BACKGROUND

A low level of formal education is becoming accepted as a risk factor for Alzheimer's disease (AD). Although increasing attention has been paid to differences in educational quality, no previous studies addressed participants' own characterizations of their overall performance in school. We examined whether self-assessed school performance is associated with AD beyond the effects of educational level alone.

METHODS

Participants were drawn from the population-representative Aging, Demographics, and Memory Study (ADAMS, 2000-2002). The ADAMS participants were asked about their performance in school. Possible response options included "above average," "average," or "below average." The ADAMS participants also underwent a full neuropsychological battery, and received a research diagnosis of possible or probable AD.

RESULTS

The 725 participants (mean age, 81.8 years; 59% female; 16% African-American) varied in self-assessed educational performance: 29% reported "above average," 64% reported "average," and 7% reported "below average" school performance. Participants with a lower self-assessed school performance had higher proportions of AD: 11% of participants with "above average" self-assessed performance had AD, as opposed to 12% of participants with "average" performance and 26% of participants with "below average" performance (P < 0.001). After controlling for subjects' years in school, a literacy test score (Wide-Range Achievement Test), age, sex, race/ethnicity, apolipoprotein E-epsilon4 status, socioeconomic status, and self-reported comorbidities, respondents with "below average" self-assessed school performance were four times more likely to have AD compared with those of "average" performance (odds ratio, 4.0; 95% confidence interval, 1.2-14). "Above average" and "average" self-assessed school performance did not increase or decrease the odds of having AD (odds ratio, 0.9; 95% confidence interval, 0.5-1.7).

CONCLUSIONS

We suggest an association between "below average" self-assessed school performance and AD beyond the known association with formal education. Efforts to increase cognitive reserve through better school performance, in addition to increasing the number of years of formal education in early life, may be important in reducing vulnerability throughout the life course.

Inadequate nutrient intake is common in cancer patients and is associated with poor outcomes. Social factors may contribute to inadequate nutrient intake, although they have not been studied. The purpose of this study was to investigate social factors that may contribute to undereating in older adults with cancer. Participants included 30 patients, 17 women and 13 men, aged 70-99 years, who were diagnosed with pancreatic, colon, breast, lymphoma, skin, and head and neck cancers. Both participants and caregivers interpreted weight loss as a positive health outcome of cancer. Furthermore, some patients who had lost weight worked to keep the weight off by going on special diets. Patients and caregivers imbued certain foods with health-promoting qualities without corroborating scientific evidence. Cancer- and treatment-related alterations in self-identity due to changes in their bodies, in taste, and in the manner in which they must eat caused cancer patients to experience frustration and embarrassment, which led to reduced nutritional intake. Despite their compromised nutritional status, patients did not discuss food and eating habits with their physicians. Behaviors and attitudes of patients and caregivers may lead to negative changes in eating behaviors beyond the cancer itself or its treatment or sequelae. Many of these behaviors are potentially modifiable with appropriate education, communication, and intervention.

This review assesses the strength of evidence relating periodontal disease and atherosclerotic disease (ischemic heart disease, peripheral arterial disease, and ischemic stroke). Periodontal disease and atherosclerotic disease may be linked causally, or their relationship could be explained, wholly or partially, by common risk factors. Many potential pathways for the relationship have been postulated. This article focuses on evaluating the overall body of evidence, according to the following standard causal inference criteria: strength of association, dose-response relationship, time sequence, consistency, specificity, biologic plausibility, and independence from confounding. Each criterion is reviewed and evaluated against the existing literature. In summary, the overall strength of evidence for causal criteria for the relation between periodontal disease and atherosclerotic disease is as follows: The magnitude and consistency of the association is stronger for ischemic stroke (and is low for ischemic heart disease), some evidence for dose response exists, time sequence has been established with more evidence for stroke, and there is definitely biologic plausibility for all these associations. Independence from confounding is also stronger for ischemic stroke and peripheral arterial disease. Specificity is not established for any of these associations, as there are multiple risk factors for atherosclerotic disease; however, specificity is not considered an important criterion for causality. Because the underlying pathogenesis of atherosclerosis is common across the diseases, it is likely that if additional studies show consistent associations, periodontal disease may be an important independent causal risk factor for atherosclerotic disease, especially for ischemic stroke.