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1.  Association of Serial Measures of Cardiac Troponin T Using a Sensitive Assay With Incident Heart Failure and Cardiovascular Mortality in Older Adults 
Context
Older adults comprise the majority of new-onset heart failure (HF) diagnoses, but traditional risk-factor prediction models have limited accuracy in this population to identify those at highest risk for hospitalization or death.
Objectives
To determine if cardiac troponin T (cTnT) measured by a highly sensitive assay would be detectable in the majority of community-dwelling older adults, and if serial measures were associated with risk of HF hospitalization and cardiovascular death.
Design, Setting, and Participants
A longitudinal nationwide cohort study (Cardiovascular Health Study) of 4221 community-dwelling adults aged 65 years or older without prior HF who had cTnT measured using a highly sensitive assay at baseline (1989–1990) and repeated after 2 to 3 years (n = 2918).
Main Outcome Measures
New-onset HF and cardiovascular death were examined through June 2008 with respect to cTnT concentrations, accounting for clinical risk predictors.
Results
Cardiac troponin T was detectable (≥3.00 pg/mL) in 2794 participants (66.2%). During a median follow-up of 11.8 years, 1279 participants experienced new-onset HF and 1103 cardiovascular deaths occurred, with a greater risk of both end points associated with higher cTnT concentrations. Among those participants with the highest cTnT concentrations (>12.94 pg/mL), there was an incidence rate per 100 person-years of 6.4 (95% confidence interval [CI], 5.8–7.2; adjusted hazard ratio [aHR], 2.48; 95% CI, 2.04–3.00) for HF and an incidence rate of 4.8 (95% CI, 4.3–5.4; aHR, 2.91; 95% CI, 2.37–3.58) for cardiovascular death compared with participants with undetectable cTnT levels (incidence rate, 1.6; 95% CI, 1.4–1.8 and 1.1; 95% CI, 0.9–1.2 for HF and cardiovascular death, respectively). Among individuals with initially detectable cTnT, a subsequent increase of more than 50% (n = 393, 22%) was associated with a greater risk for HF (aHR, 1.61; 95% CI, 1.32–1.97) and cardiovascular death (aHR, 1.65; 95% CI, 1.35–2.03) and a decrease of more than 50% (n = 247, 14%) was associated with a lower risk for HF (aHR, 0.73; 95% CI, 0.54–0.97) and cardiovascular death (aHR, 0.71; 95% CI, 0.52–0.97) compared with participants with 50% or less change. Addition of baseline cTnT measurements to clinical risk factors was associated with only modest improvement in discrimination, with change in C statistic of 0.015 for HF and 0.013 for cardiovascular death.
Conclusion
In this cohort of older adults without known HF, baseline cTnT levels and changes in cTnT levels measured with a highly sensitive assay were significantly associated with incident HF and cardiovascular death.
doi:10.1001/jama.2010.1708
PMCID: PMC3559101  PMID: 21078811
2.  The frequency of hyperkalemia and its significance in chronic kidney disease 
Archives of internal medicine  2009;169(12):1156-1162.
Background
Hyperkalemia is a potential threat to patient safety in chronic kidney disease (CKD). This study determined the incidence of hyperkalemia in CKD and whether it is associated with excess mortality.
Methods
This retrospective analysis of a national cohort comprised of 2,103,422 records from 245,808 veterans with at least one hospitalization and at least one inpatient or outpatient serum potassium record during fiscal year 2005. CKD and treatment with ACE-I and/or ARBs (RAAS blockers) were the key predictors of hyperkalemia. Death within one day of a hyperkalemic event was the principal outcome.
Results
Of the 66,529 hyperkalemic events (3.2% of records), more occurred inpatient (34937 (52.7%)) versus outpatient (31322 (47.3%)). The adjusted rate of hyperkalemia was higher in patients with CKD than without CKD among individuals treated with RAAS blockers (7.67 vs. 2.30 per 100 patient months, p<0.0001) and those without RAAS blocker treatment (8.22 vs. 1.77 per 100 patient months, p<0.0001). The adjusted odds (OR) of death with a moderate (K+≥ 5.5 and < 6.0mg/dl) and severe (K+≥ 6.0 mg/dl) hyperkalemic event was highest with no CKD (OR: 10.32, 31.64, respectively), versus Stage 3 (5.35, 19.52), Stage 4 (OR: 5.73, 11.56), or Stage 5 CKD (OR: 2.31, 8.02) with all p<0.0001 versus normokalemia and no CKD.
Conclusion
The risk of hyperkalemia is increased with CKD, and its occurrence increases the odds of mortality within one day of the event. These findings underscore the importance of this metabolic disturbance as a threat to patient safety in CKD.
doi:10.1001/archinternmed.2009.132
PMCID: PMC3544306  PMID: 19546417
chronic kidney disease; hyperkalemia; patient safety
3.  Left ventricular ejection fraction assessment in older adults: An adjunct to natriuretic peptide testing to identify risk of new onset heart failure and cardiovascular death? 
Objectives
Determine whether assessment of left ventricular ejection fraction (LVEF) enhances prediction of new onset heart failure (HF) and cardiovascular mortality over and above N-terminal pro–B-type natriuretic peptide (NT-proBNP) level in older adults.
Background
Elevated NT-proBNP levels are common in older adults and associated with increased risk of HF.
Methods
NT-proBNP and LVEF were measured in 4,137 older adults free of HF. Repeat measures of NT-proBNP were performed 2–3 years later and echocardiography was repeated 5 years later (n=2,375) with a median follow-up of 10.7 years. The addition of an abnormal (<55%) LVEF (n=317 [7.7%]) to initially elevated or rising NT-proBNP levels was evaluated to determine risk of HF or cardiovascular mortality. Change in NT-proBNP levels were also assessed for estimating the risk of conversion from a normal to abnormal LVEF.
Results
For participants with a low baseline NT-proBNP level (<190 pg/mL) (n=2,918), addition of an abnormal LVEF didn’t improve the estimation of risk of HF and identified a moderate increase in adjusted risk for cardiovascular mortality (HR 1.69; 95%CI: 1.22 to 2.31). Among those whose NT-proBNP subsequently increased ≥ 25% to ≥190 pg/mL, an abnormal LVEF was likewise associated with an increased risk of cardiovascular mortality but not HF. Participants with an initially high NT-proBNP (≥190 pg/mL) were at greater risk overall for both outcomes, and those with an abnormal LVEF were at the highest risk. However, an abnormal LVEF did not improve model classification or risk stratification for either endpoint when added to demographic factors and change in NT-proBNP. An initially elevated NT-proBNP or rising level was associated with an increased risk of developing an abnormal LVEF.
Conclusion
Assessment of LVEF in HF free older adults based on NT-proBNP levels should be considered on an individual basis, as such assessments do not routinely improve prognostication.
doi:10.1016/j.jacc.2011.06.042
PMCID: PMC3540778  PMID: 21939835
Elderly; heart failure; echocardiography; natriuretic peptides; outcomes
4.  A study of mifepristone/IFN-γ-induced apoptosis of human cholangiocarcinoma cell line FRH-0201 in vitro 
OncoTargets and therapy  2012;5:335-342.
Objective
To investigate the effects of mifepristone, a progesterone receptor (PR) antagonist, through the proliferation of human cholangiocarcinoma cell line FRH-0201 in vitro and the possible mechanisms involved.
Methods
A two-step addition of poly-HRP anti-mouse immunoglobulin G detection system was used to detect the expression of PR in FRH-0201 cells. After treatments with various concentrations of mifepristone (10, 20, 40, 80, 160, and 320 μmol/L) at various time intervals (24, 48, and 72 hours), the rate of cell inhibition, the rate of cell apoptosis, and the expression of bax/bcl-2/Fas were analyzed with tetrazolium blue (MTT) assay, flow cytometry, reverse transcription polymerase chain reaction and Western blotting. The effect of mifepristone and mifepristone combined with interferon (IFN)-γ-inducing apoptosis on the cells was observed.
Results
Mifepristone remarkably inhibited the proliferation of FRH-0201 cells, which was revealed by MTT assay in a dose- and time-dependent manner. The inhibitory rate gradually increased following the increase of the dosage of mifepristone from a low dosage (10 μmol/L) to a high dosage (320 μmol/L) at different time intervals. Flow cytometry analysis showed mifepristone increased the rate of the FRH-0201 cell-line apoptosis. Notably, the rate of apoptosis increased markedly when the cells were pretreated with IFN-γ and then treated with mifepristone. In addition, mifepristone obviously upregulated bax and Fas expression and downregulated bcl-2 expression.
Conclusion
Mifepristone effectively inhibited the growth of PR-positive human cholangiocarcinoma cell line FRH-0201 in vitro through multiple mechanisms. Mifepristone combined with IFN-γ might therefore induce the apoptosis of the cell line, which is possibly a beneficial clinical scheme for patients suffering from cholangiocarcinoma.
doi:10.2147/OTT.S36098
PMCID: PMC3497892  PMID: 23180967
cholangiocarcinoma; apoptosis; mifepristone; progesterone; IFN-γ
5.  Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt✰ 
Urologic oncology  2011;null.
Objectives
To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men.
Materials and methods
We used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively.
Results
The study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n=169), and 527 controls. The odds of having either type of bladder cancer was lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0. 34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women.
Conclusions
These findings suggest that, even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared to women in South Egypt.
doi:10.1016/j.urolonc.2010.09.007
PMCID: PMC3146583  PMID: 21397529
Catechol-O-methyltransferase gene polymorphism; Urinary bladder cancer; Smoking; Schistosomiasis; Sex differences; Egypt
6.  Estrogen exposure and bladder cancer risk in Egyptian women 
Maturitas  2010;67(4):353-357.
Objective
To examine associations between reproductive history and urinary bladder cancer in Egyptian women.
Methods
We used questionnaire data from an ongoing, multicenter case-control study in Egypt. Controls were matched on age and residence area. This analysis focused on female cases with confirmed urothelial (UC) and squamous cell (SCC) carcinoma of the bladder.
Results
We recruited 779 women (540 controls, 239 cases; >98.0% nonsmokers). Younger age at menopause (<45 y) and older age at first pregnancy (>18 y) were factors significantly associated with increased risk of bladder cancer, even after adjusting for schistosomiasis history and other covariates in the multivariable logistic model; adjusted odds ratio and 95% confidence intervals were 1.98 (1.41, 2.77) and 6.26 (3.46, 11.34), respectively. On the other hand, multiple pregnancies or use of oral contraceptives were associated with decreased odds of having bladder cancer. Similar associations were observed with UC and SCC when analyzed separately; however, the magnitude of association with SCC was lower than with UC.
Conclusion
Our data suggest that early estrogen exposure, or the relative lack of it, plays a role in urinary bladder carcinoma development among Egyptian women.
doi:10.1016/j.maturitas.2010.07.014
PMCID: PMC3433170  PMID: 20813471
estrogen; bladder cancer; Egypt; epidemiology; risk factors
7.  Systematic Review of Measurement and Adjustment for Colonization Pressure in Studies of Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococci, and Clostridium difficile Acquisition 
OBJECTIVE
Colonization pressure is an important infection control metric. The aim of this study was to describe the definition and measurement of and adjustment for colonization pressure in nosocomial-acquisition risk factor studies of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Clostridium difficile.
METHODS
We performed a computerized search of studies of nosocomial MRSA, VRE, and C. difficile acquisition published before July 1, 2009, through MEDLINE. Studies were included if a study outcome was MRSA, VRE, or C. difficile acquisition; the authors identified risk factors associated with MRSA, VRE, or C. difficile acquisition; and the study measured colonization pressure.
RESULTS
The initial MEDLINE search yielded 505 articles. Sixty-six of these were identified as studies of nosocomial MRSA, VRE, or C. difficile acquisition; of these, 18 (27%) measured colonization pressure and were included in the final review. The definition of colonization pressure varied considerably between studies: the proportion of MRSA- or VRE-positive patients (5 studies), the proportion of MRSA- or VRE-positive patient-days (6 studies), or the total or mean number of MRSA-, VRE-, or C. difficile–positive patients or patient-days (7 studies) in the unit over periods of varying length. In 10 of 13 studies, colonization pressure was independently associated with MRSA, VRE, or C. difficile acquisition.
CONCLUSION
There is a need for a simple and consistent method to quantify colonization pressure in both research and routine clinical care to accurately assess the effect of colonization pressure on cross-transmission of antibiotic-resistant bacteria.
doi:10.1086/659403
PMCID: PMC3383663  PMID: 21515979
8.  A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study 
BMC Urology  2012;12:17.
Background
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. There is no reliably effective therapy for IC/PBS, and no generally accepted animal model for the disorder in which potential therapies can be tested. Bladder epithelial cells from IC/PBS patients make a small glycopeptide antiproliferative factor or "APF" that inhibits proliferation, decreases tight junction protein expression, increases paracellular permeability, and induces changes in gene expression of bladder epithelial cells in vitro that mimic abnormalities in IC/PBS patient biopsy specimens in vivo. We therefore determined the ability of a synthetic APF derivative to inhibit bladder epithelial repair in mice.
Methods
The bladder epithelium of female CBA/J mice was stripped by transurethral infusion of 3% acetic acid, and mice were subsequently treated daily with one of three intravesical treatments [synthetic as-APF, inactive unglycosylated control peptide, or phosphate buffered saline carrier (PBS)] for 1–21 days. Fixed bladder sections were either stained with haematoxylin and eosin for determination of epithelial area by image analysis, or incubated with anti-uroplakin III (UPIII) or anti-zonula occludens type 1 (ZO-1) antibodies for immunofluorescence microscopy. Epithelial measurement data were analyzed by a two-way analysis of variance (ANOVA); post hoc comparisons of multiple groups were carried out using the Tukey-Kramer method.
Results
Bladder epithelial repair was significantly attenuated in as-APF-treated mice as compared to control mice on days 3–21 (p < 0.05); the mean epithelial/total area over all measured days was also significantly lower in as-APF-treated mice vs. mice in either control group by post hoc analysis (p < 0.0001 for both comparisons). UPIII and ZO-1 expression was also decreased in as-APF-treated mice as compared to mice in either control group by day 7 (UPIII) or day 14 (ZO-1).
Conclusions
This model demonstrates in vivo effects of as-APF which abrogates bladder epithelial repair and expression of UPIII and ZO-1 in CBA/J mice following transurethral acetic acid infusion. As bladder epithelial thinning, decreased UPIII expression, and decreased ZO-1 expression are histopathologic features of IC/PBS patient biopsies, this model may be useful for studying the pathophysiology of IC/PBS and the effect of potential therapies.
doi:10.1186/1471-2490-12-17
PMCID: PMC3459789  PMID: 22682521
Interstitial cystitis; Painful bladder syndrome; Mouse model
9.  Patient Understanding of Diabetes Self-Management: Participatory Decision-Making in Diabetes Care 
Objective:
Our aim was to determine whether patient participation in decision-making about diabetes care is associated with understanding of diabetes self-management and subsequent self-care practices. We also identified issues that would impact messaging for use in mobile diabetes communication.
Research Design and Methods:
A cross-sectional observational study was conducted with type 2 diabetes patients (n = 81) receiving their care at the University of Maryland Joslin Diabetes Center. A convenience sample of patients were eligible to participate if they were aged 25–85 years, had type 2 diabetes, spoke English, and visited their physician diabetes manager within the past 6 months. In-person patient interviews were conducted at the time of clinic visits to assess patient understanding of diabetes management, self-care practices, and perceptions of participation in decision-making about diabetes care.
Results:
African Americans reported fewer opportunities to participate in decision-making than Caucasians, after controlling for education [mean difference (MD) = -2.4, p = .02]. This association became insignificant after controlling for patient–physician race concordance (MD = -1.5, p = .21). Patient understanding of self-care was predicted by having greater than high school education (MD = 3.6, p = .001) and having physicians who involved them in decision-making about their care. For each unit increase in understanding of diabetes self-care, the mean patient self-care practice score increased by 0.16 (p = .003), after adjustment for patient race and education.
Conclusions:
Patient participation in decision-making is associated with better understanding of care. Participation in decision-making plays a key role in patient understanding of diabetes self-management and subsequent self-care practices. Patients with limited education need specific instruction in foot care, food choices, and monitoring hemoglobin A1c.
PMCID: PMC3192639  PMID: 21722588
literacy; mobile; participatory; self-care
10.  Bacillus anthracis-derived edema toxin (ET) counter-regulates movement of neutrophils and macromolecules through the endothelial paracellular pathway 
BMC Microbiology  2012;12:2.
Background
A common finding amongst patients with inhalational anthrax is a paucity of polymorphonuclear leukocytes (PMNs) in infected tissues in the face of abundant circulating PMNs. A major virulence determinant of anthrax is edema toxin (ET), which is formed by the combination of two proteins produced by the organism, edema factor (EF), which is an adenyl cyclase, and protective antigen (PA). Since cAMP, a product of adenyl cyclase, is known to enhance endothelial barrier integrity, we asked whether ET might decrease extravasation of PMNs into tissues through closure of the paracellular pathway through which PMNs traverse.
Results
Pretreatment of human microvascular endothelial cell(EC)s of the lung (HMVEC-L) with ET decreased interleukin (IL)-8-driven transendothelial migration (TEM) of PMNs with a maximal reduction of nearly 60%. This effect required the presence of both EF and PA. Conversely, ET did not diminish PMN chemotaxis in an EC-free system. Pretreatment of subconfluent HMVEC-Ls decreased transendothelial 14 C-albumin flux by ~ 50% compared to medium controls. Coadministration of ET with either tumor necrosis factor-α or bacterial lipopolysaccharide, each at 100 ng/mL, attenuated the increase of transendothelial 14 C-albumin flux caused by either agent alone. The inhibitory effect of ET on TEM paralleled increases in protein kinase A (PKA) activity, but could not be blocked by inhibition of PKA with either H-89 or KT-5720. Finally, we were unable to replicate the ET effect with either forskolin or 3-isobutyl-1-methylxanthine, two agents known to increase cAMP.
Conclusions
We conclude that ET decreases IL-8-driven TEM of PMNs across HMVEC-L monolayers independent of cAMP/PKA activity.
doi:10.1186/1471-2180-12-2
PMCID: PMC3277462  PMID: 22230035
11.  Differential Macrophage Polarization Promotes Tissue Remodeling and Repair in a Model of Ischemic Retinopathy 
Scientific Reports  2011;1:76.
Diabetic retinopathy is the leading cause of visual loss in individuals under the age of 55. Umbilical cord blood (UCB)–derived myeloid progenitor cells have been shown to decrease neuronal damage associated with ischemia in the central nervous system. In this study we show that UCB-derived CD14+ progenitor cells provide rescue effects in a mouse model of ischemic retinopathy by promoting physiological angiogenesis and reducing associated inflammation. We use confocal microscopy to trace the fate of injected human UCB-derived CD14+ cells and PCR with species-specific probes to investigate their gene expression profile before and after injection. Metabolomic analysis measures changes induced by CD14+ cells. Our results demonstrate that human cells differentiate in vivo into M2 macrophages and induce the polarization of resident M2 macrophages. This leads to stabilization of the ischemia-injured retinal vasculature by modulating the inflammatory response, reducing oxidative stress and apoptosis and promoting tissue repair.
doi:10.1038/srep00076
PMCID: PMC3216563  PMID: 22355595
12.  Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers 
BMC Cancer  2011;11:374.
Background
Making a definitive preoperative diagnosis of solitary pulmonary nodules (SPNs) found by CT has been a clinical challenge. We previously demonstrated that microRNAs (miRNAs) could be used as biomarkers for lung cancer diagnosis. Here we investigate whether plasma microRNAs are useful in identifying lung cancer among individuals with CT-detected SPNs.
Methods
By using quantitative reverse transcriptase PCR analysis, we first determine plasma expressions of five miRNAs in a training set of 32 patients with malignant SPNs, 33 subjects with benign SPNs, and 29 healthy smokers to define a panel of miRNAs that has high diagnostic efficiency for lung cancer. We then validate the miRNA panel in a testing set of 76 patients with malignant SPNs and 80 patients with benign SPNs.
Results
In the training set, miR-21 and miR-210 display higher plasma expression levels, whereas miR-486-5p has lower expression level in patients with malignant SPNs, as compared to subjects with benign SPNs and healthy controls (all P ≤ 0.001). A logistic regression model with the best prediction was built on the basis of miR-21, miR-210, and miR-486-5p. The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.86 in distinguishing lung tumors from benign SPNs with 75.00% sensitivity and 84.95% specificity. Validation of the miRNA panel in the testing set confirms their diagnostic value that yields significant improvement over any single one.
Conclusions
The plasma miRNAs provide potential circulating biomarkers for noninvasively diagnosing lung cancer among individuals with SPNs, and could be further evaluated in clinical trials.
doi:10.1186/1471-2407-11-374
PMCID: PMC3175224  PMID: 21864403
13.  Increased Circulating Level of the Survival Factor GP88 (Progranulin) in the Serum of Breast Cancer Patients When Compared to Healthy Subjects 
Introduction:
GP88 (PC-Cell Derived Growth Factor, progranulin) is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC) and healthy volunteers (HV).
Methods:
An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay.
Results:
Serum GP88 level was 28.7 + 5.8 ng/ml in HV and increased to 40.7 + 16.0 ng/ml (P = 0.007) for stage 1–3 and 45.3 + 23.3 ng/ml (P = 0.0007) for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression.
Conclusion:
These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC.
doi:10.4137/BCBCR.S7224
PMCID: PMC3140268  PMID: 21792312
progranulin; GP88; breast cancer; biomarker
14.  Gender, Alcohol Consumption Patterns, and Engagement in Sexually Intimate Behaviors Among Adolescents and Young Adults in Nha Trang, Viet Nam 
Youth & society  2011;43(1):118-141.
A randomly selected cross-sectional survey was conducted with 880 youth (16 to 24 years) in Nha Trang City to assess relationships between alcohol consumption and sexual behaviors. A timeline followback method was employed. Chi-square, generalized logit modeling and logistic regression analyses were performed. Of the sample, 78.2% male and 56.1% female respondents ever consumed alcohol. Males reporting sexual behaviors (vaginal, anal, oral sex) had a significantly higher calculated peak BAC of 0.151 compared to 0.082 for males reporting no sexual intimacy (p < .0001). Females reporting sexual behaviors had a peak BAC of 0.072 compared to 0.027 for those reporting no sexual intimacy (p = .016). Fifty percent of (33/66) males and 30.4% (7/23) females report event specific drinking and engagement in sexual behaviors. Males reporting 11+ drinks in 30 days had more sexual partners than those reporting 1 to 10 drinks (p = .037). Data suggest different physical and psychosocial mediators between alcohol consumption and sexual behaviors by gender.
doi:10.1177/0044118X09351285
PMCID: PMC3045200  PMID: 21373363
adolescent; alcohol use; sexual behaviors
15.  Altered miRNA Expression in Sputum for Diagnosis of Non-small Cell Lung Cancer 
SUMMARY
Analysis of molecular genetic markers in biological fluids has been proposed as a useful tool for cancer diagnosis. MicroRNAs (miRNAs) are small regulatory RNAs that are frequently dysregulated in lung cancer and have shown promise as tissue-based markers for its prognostication. The aim of this study was to determine whether aberrant miRNA expression can be used as a marker in sputum specimen for the diagnosis of non-small cell lung cancer (NSCLC). Experimental Design: Expressions of mature miRNAs, mir-21 and mir-155, were examined by real-time reverse transcription polymerase chain reaction (RT-PCR) and normalized to that of control miRNA, U6B, in sputum of 23 patients with NSCLC and 17 cancer-free subjects. The data was compared with conventional sputum cytology for the diagnosis of lung cancer. All endogenous miRNAs were present in sputum in a remarkably stable form and sensitively and specifically detected by real-time RT-PCR. Mir-21 expression in the sputum specimens was significantly higher in cancer patients (76.32 ± 9.79) than cancer-free individuals (62.24±3.82) (p<0.0001). Furthermore, overexpression of mir-21 showed highly discriminative receiver-operator characteristic (ROC) curve profile, clearly distinguishing cancer patients from cancer-free subjects with areas under the ROC curve at 0.902 ± 0.054. Detection of mir-21 expression produced 69.66% sensitivity and 100.00% specificity in diagnosis of lung cancer, as compared with 47.82% sensitivity and 100.00% specificity by sputum cytology. The measurement of altered miRNA expression in sputum could be a useful noninvasive approach for the diagnosis of lung cancer.
doi:10.1016/j.lungcan.2009.04.004
PMCID: PMC2846426  PMID: 19446359
MicroRNA; sputum; lung cancer; real-time RT-PCR; diagnosis
16.  Measuring Health Behaviors and Landline Telephones: Potential Coverage Bias in a Low-Income, Rural Population 
Public Health Reports  2009;124(4):495-502.
SYNOPSIS
Objectives
Population-based landline telephone surveys are potentially biased due to inclusion of only people with landline telephones. This article examined the degree of telephone coverage bias in a low-income population.
Methods
The Charles County Cancer Survey (CCCS) was conducted to evaluate cancer screening practices and risk behaviors among low-income, rural residents of Charles County, Maryland. We conducted face-to-face interviews with 502 residents aged 18 years and older. We compared the prevalence of health behaviors and cancer screening tests for those with and without landline telephones. We calculated the difference between whole sample estimates and estimates for only those respondents with landline telephones to quantify the magnitude of telephone coverage bias.
Results
Of 499 respondents who gave information on telephone use, 80 (16%) did not have landline telephones. We found differences between those with and without landline telephones for race/ethnicity, health-care access, insurance coverage, and several types of cancer screening. The absolute coverage bias ranged up to 6.5 percentage points. Simulation scenarios showed the magnitude of telephone coverage bias decreases as the percent of the population with landline telephone coverage increases, and as landline telephone coverage increases, the estimates from a landline telephone survey would approximate the estimates from a face-to-face survey.
Conclusions
Our findings highlighted the need for targeted face-to-face surveys to supplement telephone surveys to more fully characterize hard-to-reach subpopulations. Our findings also indicated that landline telephone-based surveys continue to offer a cost-effective method for conducting large-scale population studies in support of policy and public health decision-making.
PMCID: PMC2693163  PMID: 19618786
17.  Colonization Sites of USA300 Methicillin-Resistant Staphylococcus aureus in Residents of Extended Care Facilities 
BACKGROUND
The anterior nares are the most sensitive single site for detecting methicillin-resistant Staphylococcus aureus (MRSA) colonization. Colonization patterns of USA300 MRSA colonization are unknown.
OBJECTIVES
To assess whether residents of extended care facilities who are colonized with USA300 MRSA have different nares or skin colonization findings, compared with residents who are colonized with non-USA300 MRSA strains.
METHODS
The study population included residents of 5 extended care units in 3 separate facilities who had a recent history of MRSA colonization. Specimens were obtained weekly for surveillance cultures from the anterior nares, perineum, axilla, and skin breakdown (if present) for 3 weeks. MRSA isolates were categorized as USA300 MRSA or non-USA300 MRSA.
RESULTS
Of the 193 residents who tested positive for MRSA, 165 were colonized in the anterior nares, and 119 were colonized on their skin. Eighty-four percent of USA300 MRSA–colonized residents had anterior nares colonization, compared with 86% of residents colonized with non-USA300 MRSA (P=.80). Sixty-six percent of USA300 MRSA–colonized residents were colonized on the skin, compared with 59% of residents colonized with non-USA300 MRSA (P=.30).
CONCLUSIONS
Colonization patterns of USA300 MRSA and non-USA300 MRSA are similar in residents of extended care facilities. Anterior nares cultures will detect most—but not all—people who are colonized with MRSA, regardless of whether it is USA300 or non-USA300 MRSA.
doi:10.1086/596114
PMCID: PMC2852096  PMID: 19239380
18.  Prevalence of pressure ulcers on hospital admission among nursing home residents transferred to the hospital 
The purpose of this study was to compare the prevalence of pressure ulcers among newly hospitalized nursing home residents and among newly hospitalized patients from nonnursing home settings. Study participants were at least 65 years old and admitted through the emergency department to one of two study hospitals. Research nurses ascertained the presence of pressure ulcers (stage 1–4) by visual skin assessment on the third day following admission to the hospital unit. Other data were collected by clinical examination, interview, and medical record review. The prevalence of preexisting pressure ulcers at the time of admission was 26.2% among those admitted from a nursing home and 4.8% among those admitted from another living situation (odds ratio 5.5, 95% confidence interval 4.3–7.1). After adjustment for confounders, the association between admission from a nursing home and pressure ulcer prevalence on admission was reduced (odds ratio 1.51, 95% confidence interval 1.03–2.23). These results indicate that admission from a nursing home is a potent marker for pressure ulcer risk and that the excess risk is largely mediated by the higher prevalence of pressure ulcer risk factors among patients admitted from a nursing home. The results highlight the importance of continuity of care across transitions between care settings.
doi:10.1111/j.1524-475X.2008.00373.x
PMCID: PMC2839543  PMID: 18471251
19.  Cytokine Changes During Interferon-beta Therapy in Multiple Sclerosis: Correlations with Interferon dose and MRI response 
Journal of neuroimmunology  2007;185(1-2):168-174.
We investigated serum (IL-10 and IL-12p70) and cellular cytokine levels (IL-10, IL-12p40, IL-12p70, IFN-γ) in stimulated PBMC over 24 weeks in 15 Relapsing Remitting Multiple Sclerosis (MS) patients randomized to receive once-weekly (qw) IFN-β-1a 30 ug intramuscularly (IM) (n=8) or three-times-weekly (tiw) IFN-β-1a 44 ug subcutaneously (SC) (n=7). Overall, IFN-β treatment increased cellular IL-10 (p<0.01) levels and the ratios of cellular IL-10/IL-12p40 (p<0.01) and IL-10/IL-12p70 (p<0.02) while cellular IFN-γ levels were reduced (P<0.01). Serum IL-10 levels were decreased in non-responders to therapy based on MRI-defined criteria (p<0.01) but did not change in responders over the course of treatment. In addition, non-responders demonstrated a decrease in serum IL-10/IL-12p70 ratio (p=0.031) and a decrease in cellular IL-12p70 (p<0.02). A decrease in cellular IFN-γ was observed in responders (p=0.013). This is the first study that compares cytokine changes between the two IFN-β regimes and demonstrates that serum IL-10 levels decrease in those patients who continue to have active MRI lesions while on interferon-beta therapy.
doi:10.1016/j.jneuroim.2007.01.011
PMCID: PMC1894687  PMID: 17328965
multiple sclerosis; interferon-beta; interleukin-10; interleukin-12; interferon-gamma; biomarker
20.  Body Mass Index and Up-to-Date Colorectal Cancer Screening Among Marylanders Aged 50 Years and Older 
Preventing Chronic Disease  2006;3(3):A88.
Introduction
Overweight and obese individuals are at increased risk for developing and dying from colorectal cancer. Studies suggest that overweight and obese women are more likely to avoid or delay cancer screening. Our objective was to determine whether overweight or obese adults aged 50 years and older living in Maryland in 2002 were less likely to be up-to-date with colorectal cancer screening than normal and underweight adults.
Methods
The relationship between body mass index and colorectal cancer screening was evaluated based on responses from 3436 participants aged 50 years and older to the Maryland Cancer Survey 2002, a population-based random-digit–dial telephone survey. The survey contains self-reported information on colorectal cancer screening, height, weight, and potential confounders. Logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, sex, race, employment, marital status, education, area of residence, and health-care–related variables.
Results
Overall, 64.9% of Marylanders aged 50 and older were up-to-date with colorectal cancer screening. Compared with normal and underweight individuals, overweight individuals had similar odds of being up-to-date with colorectal cancer screening (OR, 1.05; 95% CI, 0.83–1.33). Obese individuals had slightly lower odds, but this difference was not statistically significant (OR, 0.84; 95% CI, 0.65–1.09). Recommendation by a health care provider for colorectal cancer screening was strongly associated with up-to-date colorectal cancer screening (OR, 36.7; 95% CI, 28.7–47.0).
Conclusion
Our study shows no statistically significant association between body mass index levels and up-to-date colorectal cancer screening. We recommend that physicians and other health care providers increase up-to-date colorectal cancer screening rates in the population by referring their patients for appropriate screening.
PMCID: PMC1636718  PMID: 16776889
21.  Measuring Impact of Antimicrobial Resistance 
Emerging Infectious Diseases  2005;11(6):982-983.
doi:10.3201/eid1105.041220
PMCID: PMC3367576
Keywords: Antimicrobial resistance; bloodstream infection; central venous catheters; intensive care unit; cohort study; adults; mortality
22.  Inflammatory Cytokine Response to Vibrio vulnificus Elicited by Peripheral Blood Mononuclear Cells from Chronic Alcohol Users Is Associated with Biomarkers of Cellular Oxidative Stress  
Infection and Immunity  2003;71(7):4212-4216.
Vibrio vulnificus is the leading cause of death in the United States associated with the consumption of raw seafood, particularly oysters. In epidemiological studies, primary septicemia and inflammation-mediated septic shock caused by V. vulnificus is strongly associated with liver disease, often in the context of chronic alcohol abuse. The present study was undertaken to determine whether clinical biomarkers of liver function or cellular oxidative stress are associated with peripheral blood mononuclear cell inflammatory cytokine responses to V. vulnificus. Levels of interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha elicited in response to V. vulnificus and measured in cell supernatants were not associated with the liver biomarkers aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or the AST/ALT ratio. In contrast, reduced glutathione (GSH) levels were associated with the release of all four cytokines (IL-1β [R2 = 0.382; P = 0.006], IL-6 [R2 = 0.393; P = 0.005], IL-8 [R2 = 0.487; P = 0.001], and TNF-α [R2 = 0.292; P = 0.021]). Those individuals with below-normal GSH levels produced significantly less proinflammatory cytokines in response to V. vulnificus. We hypothesize that persons with markers for cellular oxidative stress have increased susceptibility to V. vulnificus septicemia.
doi:10.1128/IAI.71.7.4212-4216.2003
PMCID: PMC161976  PMID: 12819121
23.  A data review and re-assessment of ovarian cancer serum proteomic profiling 
BMC Bioinformatics  2003;4:24.
Background
The early detection of ovarian cancer has the potential to dramatically reduce mortality. Recently, the use of mass spectrometry to develop profiles of patient serum proteins, combined with advanced data mining algorithms has been reported as a promising method to achieve this goal. In this report, we analyze the Ovarian Dataset 8-7-02 downloaded from the Clinical Proteomics Program Databank website, using nonparametric statistics and stepwise discriminant analysis to develop rules to diagnose patients, as well as to understand general patterns in the data that may guide future research.
Results
The mass spectrometry serum profiles derived from cancer and controls exhibited numerous statistical differences. For example, use of the Wilcoxon test in comparing the intensity at each of the 15,154 mass to charge (M/Z) values between the cancer and controls, resulted in the detection of 3,591 M/Z values whose intensities differed by a p-value of 10-6 or less. The region containing the M/Z values of greatest statistical difference between cancer and controls occurred at M/Z values less than 500. For example the M/Z values of 2.7921478 and 245.53704 could be used to significantly separate the cancer from control groups. Three other sets of M/Z values were developed using a training set that could distinguish between cancer and control subjects in a test set with 100% sensitivity and specificity.
Conclusion
The ability to discriminate between cancer and control subjects based on the M/Z values of 2.7921478 and 245.53704 reveals the existence of a significant non-biologic experimental bias between these two groups. This bias may invalidate attempts to use this dataset to find patterns of reproducible diagnostic value. To minimize false discovery, results using mass spectrometry and data mining algorithms should be carefully reviewed and benchmarked with routine statistical methods.
doi:10.1186/1471-2105-4-24
PMCID: PMC165662  PMID: 12795817

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