Sustained adrenergic signaling leads to increased metastasis in ovarian cancer via increased PGE2 synthesis.

Adrenergic stimulation adversely affects tumor growth and metastasis, but the underlying mechanisms are not well understood. Here, we uncovered a novel mechanism by which catecholamines induce inflammation by increasing prostaglandin E2 (PGE2) levels in ovarian cancer cells. Metabolic changes in tumors isolated from patients with depression and mice subjected to restraint stress showed elevated PGE2 levels. Increased metabolites, PTGS2 and PTGES protein levels were found in Skov3-ip1 and HeyA8 cells treated with norepinephrine (NE), and these changes were shown to be mediated by ADRB2 receptor signaling. Silencing PTGS2 resulted in significantly decreased migration and invasion in ovarian cancer cells in the presence of NE and decreased tumor burden and metastasis in restraint stress orthotopic models. In human ovarian cancer samples, concurrent increased ADRB2, PTGS2 and PTGES expression was associated with reduced overall and progression-free patient survival. In conclusion, increased adrenergic stimulation results in increased PGE2 synthesis via ADRB2-Nf-kB-PTGS2 axis, which drives tumor growth and metastasis.

Identifying Feasible Design Concepts for Products with Competing Performance Requirements by Metamodeling of Loss-Scaled Principal Components.

Engineering design often involves the determination of design variable settings to optimize competing performance requirements. In the early design stages we propose narrowing down the domain of design solutions using metamodels of principal components of the multiple performance levels that have been scaled by a multivariate quadratic loss function. The multivariate quadratic loss function is often used as the objective function in reaching optimal solutions because it utilizes the correlation structure of the design's performance metrics and penalizes off-target performance in a symmetrical manner. We also compare the computational performance of these loss-scaled principal components when used to solve for the design with minimal expected multivariate quadratic loss under three modeling approaches: response surface methodology, multivariate adaptive regression splines, and spatial point modeling. We demonstrate the technique on the design of the mechanical frame of an electric vehicle with six desired performance levels determined simultaneously by the dimensions of eight mechanical design elements. The method is the focus in this work.

Chronic low dose Adderall XR down-regulates cfos expression in infantile and prepubertal rat striatum and cortex.

We previously reported that treatment of prepubertal male rats with low, injected or oral, doses of methylphenidate stimulated cfos, fosB and arc expression in many areas of the developing brain. In the present study our objective was to determine whether the widely prescribed psychostimulant Adderall XR (ADD) exerted similar effects in infantile and prepubertal rat brain. We report here, for the first time, that low threshold doses of oral ADD, an extended-release mixture of amphetamine salts, now routinely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), also increased cfos expression in infantile (postnatal day 10; PD10) and prepubertal (PD24) rat brain. These threshold doses were correlated with blood levels of amphetamine determined by liquid chromatography-mass spectrometry. Moreover, we observed that chronic treatment with oral ADD (1.6 mg/kg; x 14 days) not only significantly down-regulated cfos expression following a final challenge dose of ADD in prepubertal (PD24) rat striatum and cortex, quantified in terms of FOS immunoreactivity (FOS-ir), but did so at a daily dose that was without effect with methylphenidate (MPH); that is a much higher oral dose of MPH (7.5 mg/kg; x 14 days) failed to induce down-regulation of cfos expression. Similar experiments in infantile rats (PD10), but using a threshold injected dose of ADD (1.25 mg/kg sc) also significantly reduced striatal and cingulate cortical FOS-ir. An additional finding in the prepubertal rats was that oral ADD-induced FOS-ir was observed in the cerebral cortex following doses lower than the threshold dose necessary to increase FOS-ir in the striatum. This was not the case in the PD10 rats. In conclusion, our efforts to calibrate biological responses, such as immediate early gene expression, to clinically relevant blood levels of stimulants confirmed that expression of cfos is very sensitive to repeated low doses of Adderall XR. It is now feasible to examine whether other genes are also affected in these young rats and if the changes we report are reversible. The implications of such studies should be relevant to the putative effects of psychostimulant treatment of very young children.

Socioeconomic status is associated with frailty: the Women's Health and Aging Studies.

BACKGROUND: Frailty is a common risk factor for morbidity and mortality in older adults. Although both low socioeconomic status (SES) and frailty are important sources of vulnerability, there is limited research examining their relationship. A study was undertaken to determine (1) the extent to which low SES was associated with increased odds of frailty and (2) whether race was associated with frailty, independent of SES. METHODS: A cross-sectional analysis of the Women's Health and Aging Studies using multivariable ordinal logistic regression modelling was conducted to estimate the relationship between SES measures and frailty status in 727 older women. Control variables included race, age, smoking status, insurance status and co-morbidities. RESULTS: Of the sample, 10% were frail, 46% were intermediately frail and 44% were robust. In adjusted models, older women with less than a high school degree had a threefold greater odds of frailty compared with more educated individuals. Those with an annual income of less than $10 000 had two times greater odds of frailty than wealthier individuals. These findings were independent of age, race, health insurance status, co-morbidity and smoking status. African-Americans were more likely to be frail than Caucasians (p<0.01). However, after adjusting for education, race was not associated with frailty. The effect of race was confounded by socioeconomic position. CONCLUSIONS: In this population-based sample, the odds of frailty were increased for those of low education or income regardless of race. The growing population of older adults with low levels of education and income renders these findings important.

Allostatic load and frailty in the women's health and aging studies.

BACKGROUND: Frailty involves decrements in many physiologic systems, is prevalent in older ages, and is characterized by increased vulnerability to disability and mortality. It is yet unclear how this geriatric syndrome relates to a preclinical cumulative marker of multisystem dysregulation. The purpose of this study was to evaluate whether allostatic load (AL) was associated with the geriatric syndrome of frailty in older community-dwelling women. METHODS: We examined the cross-sectional relationship between AL and a validated measure of frailty in the baseline examination of two complementary population-based cohort studies, the Women's Health and Aging studies (WHAS) I and II. This sample of 728 women had an age range of 70-79. We used ordinal logistic regression to estimate the relationship between AL and frailty controlling for covariates. RESULTS: About 10% of women were frail and 46% were prefrail. AL ranged from 0 to 8 with 91% of participants scoring between 0 and 4. Regression models showed that a unit increase in the AL score was associated with increasing levels of frailty (OR = 1.16, 95% CI = 1.04-1.28) controlling for race, age, education, smoking status, and comorbidities. CONCLUSION: This study suggests that frailty is associated with AL. The observed relationship provides some support for the hypothesis that accumulation of physiological dysregulation may be related to the loss of reserve characterized by frailty.

First Report of Iris yellow spot virus on Onion in Canada.

Iris yellow spot virus (IYSV; family Bunyaviridae, genus Tospovirus) is an economically important viral pathogen of onion vectored by onion thrips (Thrips tabaci Lindeman). Rapid spread of IYSV has occurred in the western United States and Georgia, with recent reports of IYSV from New York in the northeastern United States (1). In June and mid-July of 2007, symptomatic plants were found in Ontario, Canada in onions grown from sets in a home garden in Grey County (44°27'N, 80°53'W) and on a small commercial farm in Ottawa-Carleton County (45°14'N, 75°28'W), respectively. In the home garden, bleached, elongated lesions with tapered ends occurred on middle-aged leaves of 30% of 100 plants. By August 2007, 91% of these plants were symptomatic. In Ottawa-Carleton, two lesions with green centers and yellow borders occurred on a single leaf of a single plant in a field of 1,120 plants. Symptomatic leaf tissue tested positive for IYSV by IYSV-specific antiserum from Agdia Inc. (Elkhart, IN) in a double-antibody sandwich (DAS)-ELISA. These two isolated and remote finds of IYSV in Ontario prompted a survey in early August of 2007 of the Holland Marsh (44°5'N, 79°35'W), the largest onion-producing region in Ontario. Nine onion fields separated geographically across the Holland Marsh Region were scouted and one to three samples of symptomatic tissue per field were analyzed by DAS-ELISA. IYSV was confirmed in seven of nine (78%) fields surveyed and in 13 of 16 (81%) of the individual samples. A reverse transcription (RT)-PCR assay was used to verify the presence of IYSV in one new symptomatic tissue sample per field collected from three of the fields where IYSV was confirmed by ELISA. Primers specific to the small (S) RNA of IYSV (5'-TAA AAC AAA CAT TCA AAC AA-3' and 5'-CTC TTA AAC ACA TTT AAC AAG CAC-3') were used (2). The resulting 1.2-kb amplicon, which included the 772-bp nucleocapsid (N) gene was cloned and sequenced. Sequence analysis showed that the N gene of the Ontario isolate (GenBank Accession No. EU287943) shared 92 to 98% nucleotide sequence identity with known IYSV N gene sequences. The highest nucleotide sequence identity (98%) was with Genbank Accession Nos. DQ233475 and DQ233472. To our knowledge, this is the first report of IYSV infection of onion in Ontario and Canada. This finding confirms further spread of the virus within North America and the need for research to develop more effective management options to reduce the impact of IYSV on onion production. The finding of IYSV in remote and isolated locations where onions were grown from sets implies that the spread of IYSV via infected bulbs warrants further investigation as a potentially important route of distribution of the virus. References: (1) D. H. Gent et al. Plant Dis. 88:446, 2004. (2) H. R. Pappu et al. Arch. Virol. 151:1015, 2006.

Evaluation of sampling methodology for determining the population dynamics of onion thrips (Thysanoptera: Thripidae) in Ontario onion fields.

Onion thrips, Thrips tabaci Lindeman, are an economic pest of alliums worldwide. In Ontario onion-growing regions, seasonal abundance and population trends of onion thrips are not well known. The objectives of this research were to investigate onion thrips population dynamics by using both white sticky traps and plant counts, to gain insight into flight height, and to determine the genus and sex of thrips fauna present in monitored fields. Adult thrips were captured on white sticky traps placed in two commercial onion fields in the Thedford-Grand Bend Marsh region as early as mid-May in 2001, 2002, and 2003. Thrips were not recorded on onion plants in these fields until late June and early July. A comparison of sticky trap captures to plant counts revealed a strong, positive correlation, indicating that sticky traps, which consistently detected thrips earlier than plant counts, could be used instead of plant counts early in the season to monitor onion thrips populations. Pole traps placed in onion and an adjacent soybean, Glycine max (L.) Merr., field revealed that regardless of crop type, most thrips were captured 0.7-0.95 m above the soil surface. During this study, 70% of 137,000 thrips captured on sticky traps and 89% of 1,482 thrips captured in pan traps were female onion thrips. No male onion thrips were identified in this study: most of the remaining thrips were Frankliniella spp.

Secondary prevention of coronary artery disease in patients undergoing elective surgery for peripheral arterial disease.

The purpose of the study was to assess the implementation of secondary prevention guidelines of coronary artery disease (CAD) in patients undergoing peripheral revascularization surgery. The design was a descriptive study of the prevalence of cardiac risk factors and preventive pharmacological therapy in vascular surgical patients set in an academic medical center between July 1996 and February 1999. A total of 237 patients were recruited, 82 (35%) having carotid surgery and 155 (65%) having lower extremity bypass. Data were collected from an existing database of a study examining perioperative cardiac events in vascular surgery patients. The majority of patients were hypertensive and 58% of patients had a blood pressure >140/90 mmHg. Most patients (81%) reported a history of tobacco use and 23% were active smokers. Of the 41% of patients who were diabetic, 46% had a random glucose >140 mg/dl. Half of the patients took aspirin, 35% a lipid-lowering medication, 30% a beta-blocker. Patients with lower extremity disease were less likely than patients with carotid disease to be on aspirin (45% vs. 62%), a lipid-lowering agent (30% vs. 45%), or a beta-blocker (26% vs. 39%) (all p<0.05). Of patients with heart disease, more men than women were on aspirin (62% vs. 45%) (p<0.05). In conclusion, our findings suggest that patients presenting for vascular surgery have a high prevalence of modifiable CAD risk factors that are not being adequately managed. Preoperative examination of vascular patients is an important opportunity to assess and implement neglected secondary prevention measures.

Improving compliance in your dyslipidemic patient: an evidence-based approach.

PURPOSE: To synthesize the evidence from landmark clinical studies of lipid-lowering pharmacotherapy and nurse management of hyperlipidemia, discuss issues related to nonadherence, and proposes strategies for achieving long-term cholesterol control. DATA SOURCES: All publications of lipid-lowering clinical trials related to pharmacotherapy for dyslipidemias were accessed from a thorough Medline Search and reviewed by two nurse experts. CONCLUSIONS: Randomized controlled studies provide compelling evidence that reduction of blood cholesterol with pharmacotherapy reduces both first and subsequent coronary events. Nonetheless, inadequate provider and patient adherence to guidelines for lipid lowering remains prevalent. Studies show that nurses provide safe and effective care for patients with abnormal lipids. IMPLICATIONS: This article assists nurse practitioners in playing an active role in the implementation of the National Cholesterol Education Program Adult Treatment Panel III Report to be released in Spring 2001, where a strong emphasis will be placed on multidisciplinary approaches and adherence.

Global risk assessment for lipid therapy to prevent coronary heart disease.

Randomized clinical trials have established that lipid- lowering pharmacologic therapy can substantially reduce morbidity and mortality in patients with known coronary artery disease (CAD). Researchers are now working to define the role of lipid-lowering agents in the primary prevention of CAD to extend their benefit to patients at increased risk for future coronary events. The risk assessment models presently used for secondary prevention are not sufficient to identify high-risk, asymptomatic patients. Building on the accumulated data about the physiologic mechanisms and metabolic factors that contribute to CAD, novel serum markers and diagnostic tests are being critically studied to gauge their utility for the assessment of high-risk patients and occult vascular disease. New risk prediction models that combine traditional risk factors for CAD with the prudent use of new screening methods will allow clinicians to target proven risk reduction therapies at high-risk patients before they experience a cardiac event.

Genetics and cardiovascular disease.

The traditional risk factors associated with the development of cardiovascular disease (CVD) account for approximately 50% of the variability in the risk for developing heart disease. Research in the genetic basis of CVD has helped scientists begin to quantify the nature of the additional unexplained variance. CVD may result from a variety of genetic causes, including single-gene mutations, the combined effect of more than one mutation, and the interaction of multiple genes and environmental factors. This article describes genetic influences on risk factors for CVD, discusses three genetic CVD disorders, and highlights recent developments in genetic therapy for the treatment of CVD.

Knowledge of menopause and hormone replacement therapy use in low-income urban women.

Hormone replacement therapy (HRT) can have significant long-term health benefits in postmenopausal women, yet rates of HRT use are low, especially in low-income urban women. Previous research has revealed that knowledge of menopause is a key predictor of HRT use in this population. A descriptive cross-sectional survey of 215 perimenopausal and postmenopausal low-income urban women was carried out to characterize knowledge of menopause and HRT and factors associated with knowledge level. Sociodemographic characteristics, patterns of HRT use, and knowledge about menopause and HRT were collected through a structured interview. Results revealed a general lack of knowledge about menopause and HRT, particularly relative to heart disease and the role of HRT in prevention. Major independent predictors of increased knowledge (R2 = 0.31) were having talked with a healthcare provider about HRT, having at least a high school education, and being less than 60 years of age. These findings emphasize the key role of providers in educating this vulnerable population about menopause and HRT and the potential subsequent impact on HRT use.

Cholesterol management: an opportunity for nurse case managers.

There is compelling scientific evidence that the modification of cardiovascular risk factors, including hypercholesterolemia, can reduce the incidence of myocardial infarction, effectively extend survival, decrease the need for interventional procedures, and improve quality of life in persons with and without known cardiovascular disease. Unfortunately, neither the publication of results from clinical trials of cholesterol lowering alone nor the 1993 National Cholesterol Education Program Adult Treatment Panel (NCEP-ATPII) updated guidelines for the treatment of hypercholesterolemia have resulted in widespread changes in cholesterol management and control. Systematic nurse case management of dyslipidemias in patients with or at high risk for the development of coronary heart disease has the potential to improve compliance with NCEP-ATPII guidelines. In cooperation with physicians, nurses have the opportunity to address a major public health problem with the potential to eventually affect the more than 11 million people with coronary heart disease.

Changes in cholesterol levels in women after coronary artery bypass surgery.

OBJECTIVE: To examine the predictors of change in cholesterol levels in a cohort of women between the time of surgery and 1 year after coronary artery bypass graft surgery (CABG). DESIGN AND SETTING: This study was a prospective, descriptive study held at a Mid-Atlantic tertiary care medical center. METHODS: Lipid profiles, lifestyle behaviors, and other major coronary risk factors were measured at the time of surgery and again 12 months later from a consecutive convenience sample of 130 women who underwent first-time, isolated CABG. RESULTS: The sample population was 24% black and 76% white and had a mean age of 65 years and an average of 11 years of education. Although no statistically significant changes in cholesterol levels were observed, a majority (55%) of women had increases in total cholesterol level, whereas 45% had decreased total cholesterol level between baseline and 1 year of follow-up. After controlling for preoperative cholesterol values, a change in cholesterol level was independently predicted by ejection fraction, smoking status, and body mass index. At 1 year, plasma lipoprotein levels were not optimally managed, with high proportions of values exceeding national guidelines for secondary prevention. CONCLUSIONS: Women continue to have high cholesterol levels after CABG, putting them at high risk for future coronary heart disease events. Effective secondary prevention programs targeting multiple lifestyle behaviors and adequate pharmacotherapy are needed.

The Montefiore community children's project: a controlled study of cognitive and emotional problems of homeless mothers and children.

OBJECTIVES: This study compares the prevalence of emotional, academic, and cognitive impairment in children and mothers living in the community with those living in shelters for the homeless. METHOD: In New York City, 82 homeless mothers and their 102 children, aged 6 to 11, recruited from family shelters were compared to 115 nonhomeless mothers with 176 children recruited from classmates of the homeless children. Assessments included standardized tests and interviews. RESULTS: Mothers in shelters for the homeless showed higher rates of depression and anxiety than did nonhomeless mothers. Boys in homeless shelters showed higher rates of serious emotional and behavioral problems. Both boys and girls in homeless shelters showed more academic problems than did nonhomeless children. CONCLUSION: Study findings suggest a need among homeless children for special attention to academic problems that are not attributable to intellectual deficits in either children or their mothers. Although high rates of emotional and behavioral problems characterized poor children living in both settings, boys in shelters for the homeless may be particularly in need of professional attention.

Coronary risk factors in women one year after coronary artery bypass grafting.

Given the importance of risk factor management to long-term outcome following coronary artery bypass grafting (CABG) and the paucity of information on risk factor changes in women, a study was undertaken to examine the coronary risk factor status of women before and 1 year after CABG. This study was a prospective investigation of 130 women who underwent first-time, isolated CABG between February 1992 and October 1993. Lipid profiles, blood pressure, weight, smoking status, and other lifestyle behaviors were measured at the time of surgery and again 12 months later. The sample was 24% African American and had a mean age of 65 years and an average of 11 years of education. Substantial favorable changes in risk factor status occurred in the prevalence of smoking and the number of cigarettes smoked per day among smokers. Although the women experienced weight loss, 58% continued to be obese, and the self-reported dietary intake of fat, saturated fat, and cholesterol remained above the recommended levels of the National Cholesterol Education Program's Step II diet. Mean systolic and diastolic blood pressures significantly increased, and a substantial number of patients (54%) continued to exhibit hypertension at 1 year. No significant changes in plasma lipid concentrations were observed. At 1 year, one third of the women exceeded recommended levels for triglycerides, 78% for total cholesterol, and 92% for low-density lipoproteins. These findings indicate that women continue to have multiple coronary risk factors after CABG, putting them at high risk for future coronary heart disease events. Healthcare professionals need to target these women for effective secondary prevention.

Predictors of long-term change in functional status after coronary artery bypass graft surgery in women.

A cohort of 164 women who had undergone coronary artery bypass graft surgery (CABG) was followed for one year to examine changes in functional status and determine the relative influence of clinical, psychosocial and sociodemographic factors on change in functional status outcomes between 6 and 12 months after surgery. Clinical, psychosocial, sociodemographic and preoperative functional status data were collected by written questionnaire and personal interview at the time of surgery and again at 6 and 12 months after CABG. Functional status scores improved significantly from before to 6 months after CABG. Between 6 and 12 months post-CABG 65% sustained or continued to experience improvement in physical functioning, 83% in social and leisure activities, and 54% in psychological functioning. Predictors of sustained improvement in physical functioning were being married, younger age, low 6-month functioning, having an ejection fraction of 50% or greater, and being white. The significant predictors of sustained improvement in social and leisure activities and psychological functioning were being married and low 6-month psychological functioning, respectively. These data suggest that interventions to improve long-term outcomes in women undergoing CABG should take into account not only their age, functional capacity and level of functioning at 6 months post-CABG, but also their race and marital status as potential risk factors for long-term functional status disability.

Assessment of functional status in patients with cardiac disease.

The evaluation of functional status as an outcome for patients with cardiac disease has become common practice in both clinical settings and research studies. However, the measurement of functional status lacks conceptual clarity, frequently focuses on only one dimension of functioning, and overlooks the individuality of the patient. Some measures of functional status have questionable sensitivity to capture change over time, or the ability to discriminate between groups, and lack reports of reliability and validity testing. The purpose of this article is to discuss critical issues related to the evaluation of functional status, with a focus on objective and subjective measures of functional status frequently used in cardiac populations.

Risk factors in the offspring of women with premature coronary heart disease.

Some studies suggest that first-degree relatives of female patients with premature coronary heart disease (CHD) are at greater risk for early disease than if the proband is a male patient. To examine coronary risk factors, related knowledge, attitudes, and beliefs concerning CHD risk, we screened a sample of 87 apparently healthy offspring (56 female subjects and 31 male subjects) of women with documented premature CHD. More than half of the offspring had total and low-density lipoprotein cholesterol levels above the recommended levels for primary prevention, 31% were current smokers, and 56% exercised fewer than three times a week. A high proportion were overweight with a high prevalence of central obesity. A total of 13% had only one major risk factor, a family history of premature CHD, 10% had two risk factors, 23% had three, and 54% had four or more CHD risk factors. When compared with the Framingham cohort, 29% of sons and 30% of daughters exceeded their age- and sex-specific average risk for having CHD in 10 years. Only 28% identified heredity as a major cause of CHD, and 47% perceived their risk for future myocardial infarction as less than or equal to that of others their age. These findings suggest that adult children of women with premature CHD have a high prevalence of modifiable risk factors and do not perceive themselves to be at risk for CHD.