Hardiness, depression, and emotional well-being and their association with appetite in older adults.

OBJECTIVES: To examine the associations between hardiness (defined as the ability to manage stress), depression, and emotional well-being and appetite in older adults. DESIGN: Cross-sectional. SETTING: Assisted-living facilities and senior centers in the Washington/Baltimore area. PARTICIPANTS: Two hundred ninety-two adults aged 60 and older. MEASUREMENTS: Depressive symptoms assessed using the 5-item Geriatric Depression Scale and categorized as 0 to 1 (normal, referent group) versus 2 to 5 (depressive symptoms present). Hardiness was measured using the 18-item Dispositional Resilience Scale II modified based on interviews with older adults and categorized as 67 or less (low hardiness) versus greater than 67 (normal, referent group). Appetite was measured using the Simplified Nutritional Appetite Questionnaire and categorized as 4 to 14 (poor appetite) versus 15 to 20 (normal, referent group). Emotional well-being was measured using a single question. RESULTS: Depression, hardiness, and emotional well-being were all significantly associated with appetite. In models controlling for confounders (data collection site, age, educational attainment, self-reported health, race, presence of chronic disease), fair to poor emotional well-being was most significantly associated with poor appetite (odds ratio (OR)=5.60, 95% confidence interval (CI)=2.60-12.07) and low commitment (a component of hardiness that indicates an individual's involvement in life) was also significantly associated with poor appetite (OR=1.35, 95% CI=1.13-1.61). CONCLUSION: These associations further elucidate the components of mental health that contribute to poor appetite in this population. Simple measures of self-reported mental health administered to older adults may predict poor appetite and lend themselves to potential interventions to prevent malnutrition and negative health outcomes.

Identification of radiation-induced expression changes in nonimmortalized human T cells.

In the event of a radiation accident or attack, it will be imperative to quickly assess the amount of radiation exposure to accurately triage victims for appropriate care. RNA-based radiation dosimetry assays offer the potential to rapidly screen thousands of individuals in an efficient and cost-effective manner. However, prior to the development of these assays, it will be critical to identify those genes that will be most useful to delineate different radiation doses. Using global expression profiling, we examined expression changes in nonimmortalized T cells across a wide range of doses (0.15-12 Gy). Because many radiation responses are highly dependent on time, expression changes were examined at three different times (3, 8, and 24 h). Analyses identified 61, 512 and 1310 genes with significant linear dose-dependent expression changes at 3, 8 and 24 h, respectively. Using a stepwise regression procedure, a model was developed to estimate in vitro radiation exposures using the expression of three genes (CDKN1A, PSRC1 and TNFSF4) and validated in an independent test set with 86% accuracy. These findings suggest that RNA-based expression assays for a small subset of genes can be employed to develop clinical biodosimetry assays to be used in assessments of radiation exposure and toxicity.

Identification of genes with abnormal expression changes in acute myeloid leukemia.

Acute myeloid leukemia (AML) is one of the most common and deadly forms of hematopoietic malignancies. We hypothesized that microarray studies could identify previously unrecognized expression changes that occur only in AML blasts. We were particularly interested in those genes with increased expression in AML, believing that these genes may be potential therapeutic targets. To test this hypothesis, we compared gene expression profiles between normal hematopoietic cells from 38 healthy donors and leukemic blasts from 26 AML patients. Normal hematopoietic samples included CD34+ selected cells (N = 18), unselected bone marrows (N = 10), and unselected peripheral bloods (N = 10). Twenty genes displayed AML-specific expression changes that were not found in the normal hematopoietic cells. Subsequent analyses using microarray data from 285 additional AML patients confirmed expression changes for 13 of the 20 genes. Seven genes (BIK, CCNA1, FUT4, IL3RA, HOMER3, JAG1, WT1) displayed increased expression in AML, while 6 genes (ALDHA1A, PELO, PLXNC1, PRUNE, SERPINB9, TRIB2) displayed decreased expression. Quantitative RT/PCR studies for the 7 over-expressed genes were performed in an independent set of 9 normal and 21 pediatric AML samples. All 7 over-expressed genes displayed an increased expression in the AML samples compared to normals. Three of the 7 over-expressed genes (WT1, CCNA1, and IL3RA) have already been linked to leukemogenesis and/or AML prognosis, while little is known about the role of the other 4 over-expressed genes in AML. Future studies will determine their potential role in leukemogenesis and their clinical significance.

Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia.

FLT3 internal tandem duplications (FLT3/ITDs) in the juxtamembrane domain are found in approximately 25% of acute myeloid leukemia (AML) patients, ranging in size from 3 to hundreds of nucleotides. We examined whether the sizes of FLT3/ITDs were associated with clinical outcomes in 151 AML patients enrolled in Southwest Oncology Group studies: S9333 and S9500. FLT3/ITDs were identified in 32% of patients (median ITD size = 39 nucleotides; range, 15-153 nucleotides). The CR rates were 35%, 67%, and 52% for patients with large (>or= 40), small (< 40), and no ITDs, respectively (P = .19). Increasing ITD size was associated with decreasing OS (estimated 5-year OS: large = 13%, small = 26%, and no ITD = 21%, P = .072) and RFS (estimated 5-year RFS: large = 13%, small = 27%, and no ITD = 34%, P = .017). These studies suggest that ITD size may have prognostic significance.