Publications

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.

BACKGROUND

Transforming growth factor ss (TGFss) signaling has been shown to promote myocardial fibrosis and remodeling with coronary artery disease (CAD), and previous studies show a major role for fibrosis in the initiation of malignant ventricular arrhythmias (VA) and sudden cardiac arrest (SCA). Common single nucleotide polymorphisms (SNPs) in TGFss pathway genes may be associated with SCA.

OBJECTIVE

We examined the association of common SNPs among 12 candidate genes in the TGFss pathway with the risk of SCA.

METHODS

SNPs (n = 617) were genotyped in a case-control study comparing 89 patients with CAD and SCA caused by VA to 520 healthy control subjects.

RESULTS

Nineteen SNPs among 5 genes (TGFB2, TGFBR2, SMAD1, SMAD3, SMAD6) were associated with SCA after adjustment for age and sex. After permutation analysis to account for multiple testing, a single SNP in TGFBR2 (rs9838682) was associated with SCA (odds ratio: 1.66, 95% confidence interval: 1.08 to 2.54, P = .02).

CONCLUSION

We show an association between a common TGFBR2 polymorphism and risk of SCA caused by VA in the setting of CAD. If validated, these findings support the role of genetic variation in TGFss signaling in SCA susceptibility.

Pulmonary inflammation is associated with the development of bronchopulmonary dysplasia in premature infants. We have previously shown that perinatal pulmonary expression of human IL-1beta is sufficient to cause a lung disease similar to bronchopulmonary dysplasia, characterized by inflammation, impaired alveolarization, poor postnatal growth, and increased mortality in infant mice. The alphavbeta6 integrin plays a critical role in regulating inflammation in the adult lung. To study the role of the beta6 integrin subunit in neonatal inflammatory lung disease, we compared the pulmonary development in IL-1beta-expressing infant mice with wild-type or null beta6 integrin loci. Absence of the beta6 integrin subunit decreased the mortality and improved the postnatal growth of IL-1beta-expressing pups. The disrupted alveolar development of IL-1beta-expressing mice was improved by beta6 integrin deficiency. IL-1beta-expressing beta6(-/-) pups had shorter alveolar chord length and thinner alveolar walls than IL-1beta-expressing beta6(+/+) pups. In addition, the absence of the beta6 integrin subunit reduced IL-1beta-induced neutrophil and macrophage infiltration into the alveolar spaces. beta6 integrin subunit deficiency suppressed inflammation and goblet cell hyperplasia in the airways and alleviated airway remodeling in IL-1beta-expressing mice. The expression of the chemoattractant proteins, keratinocyte-derived chemokine, macrophage-inflammatory protein-2, calgranulin A, and calgranulin B, of osteopontin, and of the chitinase-like lectins, Ym1 and Ym2, was lower in IL-1beta-expressing beta6(-/-) than in IL-1beta-expressing beta6(+/+) mice. We conclude that absence of the beta6 integrin subunit protects the infant murine lung against IL-1beta-induced inflammation and injury.

Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.