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1.  Gene Expression Profiling Analysis of Castration-Resistant Prostate Cancer 
Background
Prostate cancer is a global health issue. Usually, men with metastatic disease will progress to castration-resistant prostate cancer (CRPC). We aimed to identify the differentially expressed genes (DEGs) in tumor samples from non-castrated and castrated men from LNCaP Orthotopic xenograft models of prostate cancer and to study the mechanisms of CRPC.
Material/Methods
In this work, GSE46218 containing 4 samples from non-castrated men and 4 samples from castrated men was downloaded from Gene Expression Omnibus. We identified DEGs using limma Geoquery in R, the Robust Multi-array Average (RMA) method in Bioconductor, and Bias methods, followed by constructing an integrated regulatory network involving DEGs, miRNAs, and TFs using Cytoscape. Then, we analyzed network motifs of the integrated gene regulatory network using FANMOD. We selected regulatory modules corresponding to network motifs from the integrated regulatory network by Perl script. We preformed gene ontology (GO) and pathway enrichment analysis of DEGs in the regulatory modules using DAVID.
Results
We identified total 443 DEGs. We built an integrated regulatory network, found three motifs (motif 1, motif 2 and motif 3), and got two function modules (module 1 corresponded to motif 1, and module 2 corresponded to motif 2). Several GO terms (such as regulation of cell proliferation, positive regulation of macromolecule metabolic process, phosphorylation, and phosphorus metabolic process) and two pathways (pathway in cancer and Melanoma) were enriched. Furthermore, some significant DEGs (such as CAV1, LYN, FGFR3 and FGFR3) were related to CPRC development.
Conclusions
These genes might play important roles in the development and progression of CRPC.
doi:10.12659/MSM.891193
PMCID: PMC4306671  PMID: 25592164
Genes, abl; Neurology; Prostatic Neoplasms
2.  Dysregulation of cell cycle related genes and microRNAs distinguish the low- from high-risk of prostate cancer 
Diagnostic Pathology  2014;9(1):156.
Background
Prostate cancer (PCa) is a biologically heterogeneous disease with considerable variation in clinical aggressiveness. In this study, bioinformatics was used to detect the patterns of gene expression alterations of PCa patients.
Methods
The gene expression profile GSE21034 and GSE21036 were downloaded from Gene Expression Omnibus (GEO) database. Significantly changed mRNA transcripts and microRNAs were identified between subtypes with favorable (cluster 2) and unfavorable (cluster 5) prognosis by two-side unequal variances t test. MicroRNAs and their potential target genes were identified by TargetScan and miRTarBase, respectively. Besides, the overlapped genes between the target genes of microRNAs and mRNA transcripts were assessed by Fisher’ exact test (one side). The functional annotation was performed by DAVID, followed by construction of protein-protein interaction (PPI) network.
Results
Compared to cluster 2, 1556 up-regulated and 1288 down-regulated transcripts were identified in cluster 5. Total 28 microRNAs were up-regulated and 30 microRNAs were down-regulated in cluster 5. Besides, 12 microRNAs target transcripts were significantly overlapped with down-regulated transcripts in cluster 5 with none of them was found overlapped with up-regulated transcripts. Functional annotation showed that cell cycle was the most significant function. In the PPI network, BRCA1, CDK1, TK1 and TRAF2 were hub protein of signature genes in cluster 5, and TGFBR1, SMAD2 and SMAD4 were hub proteins of signature gnens in cluster 2.
Conclusions
Our findings raise the possibility that genes related with cell cycle and dysregulated miRNA at diagnosis might have clinical utility in distinguishing low- from high-risk PCa patients.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_156
doi:10.1186/s13000-014-0156-1
PMCID: PMC4215008  PMID: 25257132
Prostate cancer; Differentially expressed genes; MicroRNAs
3.  Differentially expressed genes and interacting pathways in bladder cancer revealed by bioinformatic analysis 
Molecular Medicine Reports  2014;10(4):1746-1752.
The goal of this study was to identify cancer-associated differentially expressed genes (DEGs), analyze their biological functions and investigate the mechanism(s) of cancer occurrence and development, which may provide a theoretical foundation for bladder cancer (BCa) therapy. We downloaded the mRNA expression profiling dataset GSE13507 from the Gene Expression Omnibus database; the dataset includes 165 BCa and 68 control samples. T-tests were used to identify DEGs. To further study the biological functions of the identified DEGs, we performed a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Next, we built a network of potentially interacting pathways to study the synergistic relationships among DEGs. A total of 12,105 genes were identified as DEGs, of which 5,239 were upregulated and 6,866 were downregulated in BCa. The DEGs encoding activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT) proteins, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and interleukin (IL)-10 were revealed to participate in the significantly enriched immune pathways that were downregulated in BCa. KEGG enrichment analysis revealed 7 significantly upregulated and 47 significantly downregulated pathways enriched among the DEGs. We found a crosstalk interaction among a total of 44 pathways in the network of BCa-affected pathways. In conclusion, our results show that BCa involves dysfunctions in multiple systems. Our study is expected to pave ways for immune and inflammatory research and provide molecular insights for cancer therapy.
doi:10.3892/mmr.2014.2396
PMCID: PMC4148370  PMID: 25050631
bladder cancer; differentially expressed genes; interacting pathways; enrichment analysis; immune and inflammation-related pathways
4.  Long-term Effects of Renin-Angiotensin System–Blocking Therapy and a Low Blood Pressure Goal on Progression of Hypertensive Chronic Kidney Disease in African Americans 
Archives of internal medicine  2008;168(8):10.1001/archinte.168.8.832.
Background
Antihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD.
Methods
Multicenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20–65 mL/min/1.73 m2). Following a 3×2-factorial trial (1995–2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and β-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002–2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death.
Results
During each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2).
Conclusion
Despite the benefits of renin-angiotensin system–blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term.
doi:10.1001/archinte.168.8.832
PMCID: PMC3870204  PMID: 18443258
5.  Baseline Predictors of Renal Disease Progression in the African American Study of Hypertension and Kidney Disease 
Journal of the American Society of Nephrology : JASN  2006;17(10):10.1681/ASN.2005101101.
Patients with chronic kidney disease have an increased risk for progression to ESRD. The purpose of this study was to examine factors that predict increased risk for adverse renal outcomes. Cox regression was performed to assess the potential of 38 baseline risk factors to predict the clinical renal composite outcome of 50% or 25-ml/min per 1.73 m2 GFR decline or ESRD among 1094 black patients with hypertensive nephrosclerosis (GFR 20 to 65 ml/min per 1.73 m2). Patients were trial participants who had been randomly assigned to one of two BP goals and to one of three antihypertensive regimens and followed for a range of 3 to 6.4 yr. In unadjusted and adjusted analyses, baseline proteinuria was consistently associated with an increased risk for adverse renal outcomes, even at low levels of proteinuria. The relationship of proteinuria with adverse renal outcomes also was evident in analyses that were stratified by level of GFR, which itself was associated with adverse renal outcomes but only at levels <40 ml/min. Other factors that were significantly associated with increased renal events after adjustment for baseline GFR, age, and gender, both with and without adjustment for baseline proteinuria, included serum creatinine, urea nitrogen, and phosphorus. In black patients with hypertensive nephrosclerosis, increased proteinuria, reduced GFR, and elevated levels of serum creatinine, urea nitrogen and phosphorus were directly associated with adverse clinical renal events. These findings identify a subset of this high-risk population that might benefit from even more aggressive treatment.
doi:10.1681/ASN.2005101101
PMCID: PMC3833081  PMID: 16959828
6.  Risk of Hyperkalemia in Nondiabetic Patients With Chronic Kidney Disease Receiving Antihypertensive Therapy 
Transplantation  2011;92(7):10.1097/TP.0b013e31822dc36b.
Background
The incidence and factors associated with hyperkalemia in patients with chronic kidney disease (CKD) treated with angiotensin converting enzyme inhibitors (ACEIs) and other antihypertensive drugs was investigated using the African American Study of Kidney Disease and Hypertension (AASK) database.
Methods
A total of 1094 nondiabetic adults with hypertensive CKD (glomerular filtration rate [GFR], 20–65 mL/min/1.73 m2) were followed for 3.0 to 6.4 years in the AASK trial. Participants were randomly assigned to ACEI, β-blocker (BB), or dihydropyridine calcium channel blocker (CCB). The outcome variables for this analysis were a serum potassium level higher than 5.5 mEq/L (to convert to millimoles per liter, multiply by 1.0), or a clinical center initiated hyperkalemia stop point.
Results
A total of 6497 potassium measurements were obtained, and 80 events in 51 subjects were identified (76 events driven by a central laboratory result and 4 driven by a clinical center–initiated hyperkalemia stop point). Compared with a GFR higher than 50 mL/min/1.73 m2, after multivariable adjustment, the hazard ratio (HR) for hyperkalemia in patients with a GFR between 31 and 40 mL/min/1.73 m2 and a GFR lower than 30 mL/min/1.73 m2 was 3.61 (95% confidence interval [CI], 1.42–9.18 [P=.007]) and 6.81 (95% CI, 2.67–17.35 [P<.001]), respectively; there was no increased risk of hyperkalemia if GFR was 41 to 50 mL/min/1.73 m2. Use of ACEIs was associated with more episodes of hyperkalemia compared with CCB use (HR, 7.00; 95% CI, 2.29–21.39 [P<.001]) and BB group (HR, 2.85; 95% CI, 1.50–5.42 [P=.001]). Diuretic use was associated with a 59% decreased risk of hyperkalemia.
Conclusions
In nondiabetic patients with hypertensive CKD treated with ACEIs, the risk of hyperkalemia is small, particularly if baseline and follow-up GFR is higher than 40 mL/min/1.73 m2. Including a diuretic in the regimen may markedly reduce risk of hyperkalemia.
doi:10.1097/TP.0b013e31822dc36b
PMCID: PMC3831506  PMID: 21832957
7.  Effect of Nadir CD4+ T Cell Count on Clinical Measures of Periodontal Disease in HIV+ Adults before and during Immune Reconstitution on HAART  
PLoS ONE  2013;8(10):e76986.
Background
The contribution of HIV-infection to periodontal disease (PD) is poorly understood.  We proposed that immunological markers would be associated with improved clinical measures of PD.
Methods
We performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART) <2 years. PD was characterized clinically as the percent of teeth with ≥1 site with periodontal probing depth (PPD) ≥5.0mm, recession (REC) >0mm, clinical attachment level (CAL) ≥4.0mm, and bleeding on probing (BOP) at ≥4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD.
Results
Forty (40) subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/µl (p<0.001) and HIV RNA decreased by 0.5 log10 copies/ml (p<0.001); concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001). Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04) and CAL (9.06%; p<0.001). Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027), and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively). Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD.
Conclusion
Degree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults.
doi:10.1371/journal.pone.0076986
PMCID: PMC3795634  PMID: 24146949
8.  Effect of Intensive Blood Pressure Control on Cardiovascular Remodeling in Hypertensive Patients with Nephrosclerosis 
Pulse pressure (PP), a marker of arterial system properties, has been linked to cardiovascular (CV) complications. We examined (a) association between unit changes of PP and (i) composite CV outcomes and (ii) development of left-ventricular hypertrophy (LVH) and (b) effect of mean arterial pressure (MAP) control on rate of change in PP. We studied 1094 nondiabetics with nephrosclerosis in the African American Study of Kidney Disease and Hypertension. Subjects were randomly assigned to usual MAP goal (102–107 mmHg) or a lower MAP goal (≤92 mmHg) and randomized to beta-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker. After covariate adjustment, a higher PP was associated with increased risk of CV outcome (RR = 1.28, CI = 1.11–1.47, P < 0.01) and new LVH (RR = 1.26, CI = 1.04–1.54, P = 0.02). PP increased at a greater rate in the usual than in lower MAP groups (slope ± SE: 1.08 ± 0.15 versus 0.42 ± 0.15 mmHg/year, P = 0.002), but not by the antihypertensive treatment assignment. Observations indicate that control to a lower MAP slows the progression of PP, a correlate of cardiovascular remodeling and complications, and may be beneficial to CV health.
doi:10.1155/2013/120167
PMCID: PMC3786477  PMID: 24102027
9.  Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease 
The New England journal of medicine  2010;363(10):918-929.
BACKGROUND
In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients.
METHODS
We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years.
RESULTS
During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01).
CONCLUSIONS
In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)
doi:10.1056/NEJMoa0910975
PMCID: PMC3662974  PMID: 20818902
10.  Longitudinal Progression Trajectory of GFR Among Patients With CKD 
Background
The traditional paradigm of glomerular filtration rate (GFR) progression among chronic kidney disease (CKD) patients is a steady, nearly linear decline over time. We describe individual GFR progression trajectories over twelve years of follow-up among participants in the African American Study of Kidney Disease and Hypertension (AASK).
Study Design
Longitudinal, observational study
Setting & Participants
846 AASK patients with at least 3 years of follow-up and 8 GFR estimates.
Measurements
Longitudinal GFR estimates (eGFR) from creatinine-based equations.
Predictors
Patient demographic and clinical features.
Outcomes
Probability of a nonlinear trajectory and probability of a period of nonprogression, calculated for each patient from a Bayesian model of individual eGFR trajectories.
Results
Three hundred and fifty-two (41.6%) patients exhibited a greater than 0.9 probability of having either a nonlinear trajectory or a prolonged nonprogression period; in 559 (66.1%), the probability was larger than 0.5. Baseline eGFR > 40 mL/min/1.73m2 and urine protein-creatinine < 0.22 g/g were associated with a higher likelihood of a nonprogression period. Seventy-four patients (8.7%) had both a substantial period of stable or increasing eGFR and a substantial period of rapid eGFR decline.
Limitations
Clinical trial population; absence of direct GFR measurements.
Conclusions
In contrast to the traditional paradigm of steady GFR progression over time, many CKD patients have a non-linear GFR trajectory or a prolonged period of nonprogression. These findings highlight the possibility that stable kidney disease progression can accelerate, and, conversely provide hope that CKD need not be relentlessly progressive. These results should encourage researchers to identify time-dependent factors associated with periods of nonprogression and other desirable trajectories.
doi:10.1053/j.ajkd.2011.12.009
PMCID: PMC3312980  PMID: 22284441
Chronic kidney disease; estimated glomerular filtration rate; nonlinear progression; longitudinal cohort study; African American; slope
11.  Quality of Life and Psychosocial Factors in African Americans with Hypertensive Chronic Kidney Disease 
Health-related quality of life (HRQOL) is poorly understood in patients with chronic kidney disease (CKD) prior to end-stage renal disease. The association between psychosocial measures and HRQOL has not been fully explored in CKD, especially in African Americans. We performed a cross-sectional analysis of HRQOL and its association with sociodemographic and psychosocial factors in African Americans with hypertensive CKD.
There were 639 participants in the African American Study of Kidney Disease and Hypertension Cohort Study. The Short Form-36 was used to measure HRQOL. The Diener Satisfaction with Life Scale measured life satisfaction, the Beck Depression Inventory-II assessed depression, the Coping Skills Inventory-Short Form measured coping, and the Interpersonal Support Evaluation List-16 was used to measure social support.
Mean participant age was 60 years at enrollment, and 61% were male. Forty-two percent reported a household income below $15,000/year. Higher levels of social support, coping skills, and life satisfaction were associated with higher HRQOL, while unemployment and depression were associated with lower HRQOL (p<0.05). There was a significant positive association between higher estimated glomerular filtration rate (eGFR) with the Physical Health Composite (PHC) score (p=0.004) but not the Mental Health Composite (MHC) score (p=0.24).
Unemployment was associated with lower HRQOL, and lower eGFR was associated with lower PHC. African Americans with hypertensive CKD with better social support and coping skills had higher HRQOL. This study demonstrates an association between CKD and low HRQOL and highlights the need for longitudinal studies to further examine this association.
doi:10.1016/j.trsl.2011.09.004
PMCID: PMC3240805  PMID: 22153804
12.  A Prospective Cohort Study of Periodontal Disease Measures and Cardiovascular Disease Markers in HIV-Infected Adults 
AIDS Research and Human Retroviruses  2011;27(11):1157-1166.
Abstract
The determinants of HIV-associated cardiovascular disease (CVD) are not well understood. Periodontal disease (PD) has been linked to CVD but this connection has not been examined in HIV infection. We followed a cohort of HIV-infected adults to ascertain whether PD was associated with carotid artery intima media thickness (IMT) and brachial artery flow-mediated dilation (FMD). We performed a longitudinal observational study of HIV-infected adults on HAART for <2 years with no known heart disease. PD was characterized clinically and microbiologically. Cardiovascular disease was assessed by IMT/FMD. Linear mixed models assessed cross-sectional and longitudinal associations between PD and FMD/IMT. Forty three HIV+ adults completed a median of 24 (6–44) months on the study. Defining delta to be the change in a variable between baseline and a follow-up time, longitudinally, on average and after adjusting for change in time, CVD-specific and HIV-specific potential confounding covariates, a 1-log10 increase in delta Porphyromonas gingivalis was associated with a 0.013 mm increase in delta IMT (95% CI: 0.0006–0.0262; p=0.04). After adjusting for the same potential confounding covariates, a 10% increase in delta gingival recession was associated with a 2.3% increase in delta FMD (95% CI: 0.4–4.2; p=0.03). In a cohort of HIV-infected adults, an increase in subgingival Porphyromonas gingivalis, a known periodontal pathogen, was significantly associated with longitudinal increases in IMT, while increased gingival recession, which herein may represent PD resolution, was significantly associated with longitudinal improvement in FMD. In the context of HIV infection, PD may contribute to CVD risk. Intervention studies treating PD may help clarify this association.
doi:10.1089/aid.2010.0320
PMCID: PMC3206743  PMID: 21443451
13.  Limitations of analyses based on achieved blood pressure: Lessons from the AASK trial 
Hypertension  2011;57(6):1061-1068.
Blood pressure (BP) guidelines that set target BP levels often rely on analyses of achieved BP from hypertension treatment trials. The objective of this paper was to compare the results of analyses of achieved BP to intention-to-treat analyses on renal disease progression. Participants (n=1,094) in the African-American Study of Kidney Disease and Hypertension Trial were randomized to either: (1) usual BP goal defined by a mean arterial pressure (MAP) goal of 102–107 mmHg or (2) lower BP goal defined by a MAP goal of ≤ 92 mmHg. Median follow-up was 3.7 years. Primary outcomes were rate of decline in measured glomerular filtration rate (GFR) and a composite of a decrease in GFR by > 50% or >25 ml/min/1.73m2, requirement for dialysis, transplantation, or death. Intention-to-treat analyses showed no evidence of a BP effect on either the rate of decline in GFR or the clinical composite outcome. In contrast, the achieved BP analyses showed that each 10 mm Hg increment in mean follow-up achieved MAP was associated with a 0.35 (95% CI 0.08 – 0.62, p = 0.01) ml/min/1.73m2 faster mean GFR decline and a 17% (95% CI 5% – 32%, p = 0.006) increased risk of the clinical composite outcome. Analyses based on achieved BP lead to markedly different inferences than traditional intention-to-treat analyses, due in part to confounding of achieved BP with co- morbidities, disease severity and adherence. Clinicians and policy makers should exercise caution when making treatment recommendations based on analyses relating outcomes to achieved BP.
doi:10.1161/HYPERTENSIONAHA.111.169367
PMCID: PMC3150108  PMID: 21555676
blood pressure control; African Americans; hypertension treatment; renal disease
14.  Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease 
Kidney international  2011;80(6):670-678.
This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease.
doi:10.1038/ki.2011.153
PMCID: PMC3237701  PMID: 21633409
AASK (African American Study of Kidney Disease and Hypertension); cardiovascular events; chronic kidney disease; depression
15.  Sociodemographic factors contribute to the depressive affect among African Americans with chronic kidney disease 
Kidney international  2010;77(11):1010-1019.
Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50–60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups.
doi:10.1038/ki.2010.38
PMCID: PMC3114445  PMID: 20200503
AASK (African American Study of Kidney Disease and Hypertension); chronic kidney disease; clinical epidemiology; depression; quality of life
16.  Uric Acid and Long-term Outcomes in CKD 
Background
Hyperuricemia is prevalent in chronic kidney disease (CKD); however data are limited on the relationship of uric acid levels with long term outcomes in this patient population.
Study Design
Cohort Study
Setting & Participants
The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial (N=840), conducted 1989–1993, to examine the effects of strict blood pressure control and dietary protein restriction on progression of stage 3–4 CKD. This analysis included 838 patients.
Predictor
Uric acid
Outcomes & Measurements
The study evaluated the association of baseline uric acid levels with all-cause mortality, cardiovascular (CVD) mortality, and kidney failure.
Results
Mean (SD) age was 52 (12) years, glomerular filtration rate was 33 (12) ml/min/1.73m2, and uric acid was 7.63 (1.66) mg/dl. During a median follow-up of 10 years, 208 (25%) participants died of any cause, 127 (15%) from CVD, and 553 (66%) reached kidney failure. In multivariate models, the highest tertile of uric acid was associated with increased risk of all-cause (HR, 1.57 [95% CI, 1.07–2.32]) mortality, a trend towards CVD mortality (HR, 1.47 [95% CI, 0.90–2.39]) and no association with kidney failure (HR, 1.20 [95% CI, 0.95–1.51), compared to the lowest tertile. In continuous analyses, a 1-mg/dl higher uric acid was associated with 17% increased risk of all-cause (HR, 1.17 [95% CI, 1.05–1.30]), and 16% increased risk of CVD mortality (HR, 1.16 [95% CI, 1.01–1.33]), but was not associated with kidney failure (HR, 1.02 [95% CI, 0.97–1.07]).
Limitations
Primary analyses were based on single measurement of uric acid. The results are primarily generalizable to relatively young white patients with predominantly non-diabetic CKD.
Conclusions
In stage 3–4 CKD, hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality but not kidney failure.
doi:10.1053/j.ajkd.2008.12.021
PMCID: PMC2691553  PMID: 19303683
17.  Role of the Adipose Tissue in Determining Muscle Mass in Patients with Chronic Kidney Disease 
Objective
Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD); however, its etiology is unclear. We hypothesized that adipocyte-derived proteins leptin and adiponectin, inflammation (C-reactive protein –CRP), and insulin resistance (Homeostasis Model Assessment –HOMA); implicated in the malnutrition-inflammation complex syndrome commonly seen in maintenance dialysis patients, would be associated with the loss of muscle mass in earlier stages of CKD. Arm muscle area was used as an indicator of muscle mass.
Setting
The Modification of Diet in Renal Disease (MDRD) Study cohort of people with CKD stages 3 and 4 was used for analysis.
Main Outcome Measures
Regression models were carried out to examine the relationships of leptin, adiponectin, CRP, and HOMA with arm muscle area (the main study outcome).
Results
Arm muscle area was 39 ± 15 cm2 (mean ± standard deviation, SD) and adiponectin levels were 13 ± 7 μg/mL. Median and (inerquartile range, IQR) concentrations were: 9.0 (13.6) ng/mL for leptin, 2.3 (4.9) mg/L for CRP, and 2.4 (2.0) form HOMA. Higher leptin [beta coefficient and (95% confidence interval): −6.9 (−8.7, −5.1), P<0.001] and higher CRP [−2.7 (−3.9, −1.4), P<0.001] were associated with lower arm muscle area. There was a trend toward lower arm muscle area with higher adiponectin (P=0.07) but no association with HOMA (P=0.80).
Conclusion
Leptin and CRP were associated with lower muscle mass in subjects with CKD stages 3–4. Further studies are needed to understand the mechanisms underlying these associations and to develop targeted interventions for this patient population.
doi:10.1053/j.jrn.2007.05.006
PMCID: PMC2699417  PMID: 17720100
Chronic kidney disease; arm muscle area; adipokines; inflammation; insulin resistance
18.  High capacity mercury adsorption on freshly ozone-treated carbon surfaces 
Carbon  2008;46(3):518-524.
A set of carbon materials was treated by a choice of common oxidizers to investigate the mercury capture capacities at varying temperature conditions. It was found that ozone treatment dramatically increases the mercury capture capacity of carbon surfaces by factors up to 134, but the activity is easily destroyed by exposure to the atmosphere, to water vapor, or by mild heating. Freshly ozone-treated carbon surfaces are shown to oxidize iodide to iodine in solution and this ability fades with aging. FTIR analysis shows broad C–O stretch features from 950 to 1300 cm−1, which decay upon atmospheric exposure and are similar to the C-O-C asymmetric stretch features of ethylene secondary ozonide. The combined results suggest that the ultra-high mercury capture efficiency is due to a subset of labile C-O functional groups with residual oxidizing power that are likely epoxides or (epoxide-containing) secondary ozonides. The results open the possibility for in situ ozonolysis to create high-performance carbon-based Hg sorbents.
doi:10.1016/j.carbon.2007.12.019
PMCID: PMC2614278  PMID: 19255621

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