Longitudinal, population-based study of racial/ethnic differences in colorectal cancer survival: impact of neighborhood socioeconomic status, treatment and comorbidity

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods.</p> <p>Methods</p> <p>This study evaluated the joint effects of sociodemographic factors, tumor characteristics, census-based socioeconomic status (SES), treatment, and comorbidities on survival after colorectal cancer among and within racial/ethnic groups, using the SEER-Medicare database for patients diagnosed in 1992–1996, and followed through 1999.</p> <p>Results</p> <p>Unadjusted colorectal cancer-specific mortality rates were higher among Blacks and Hispanic males than whites (relative rates (95% confidence intervals) = 1.34 (1.26–1.42) and 1.16 (1.04–1.29), respectively), and lower among Japanese (0.78 (0.70–0.88)). These patterns were evident for all-cause mortality, although the magnitude of the disparity was larger for colorectal cancer mortality. Adjustment for stage accounted for the higher rate among Hispanic males and most of the lower rate among Japanese. Among Blacks, stage and SES accounted for about half of the higher rate relative to Whites, and within stage III colon and stages II/III rectal cancer, SES completely accounted for the small differentials in survival between Blacks and Whites. Comorbidity did not appear to explain the Black-White differentials in colorectal-specific nor all-cause mortality, beyond stage, and treatment (surgery, radiation, chemotherapy) explained a very small proportion of the Black-White difference. The fully-adjusted relative mortality rates comparing Blacks to Whites was 1.14 (1.09–1.20) for all-cause mortality and 1.21 (1.14–1.29) for colorectal cancer specific mortality. The sociodemographic, tumor, and treatment characteristics also had different impacts on mortality within racial/ethnic groups.</p> <p>Conclusion</p> <p>In this comprehensive analysis, race/ethnic-specific models revealed differential effects of covariates on survival after colorectal cancer within each group, suggesting that different strategies may be necessary to improve survival in each group. Among Blacks, half of the differential in survival after colorectal cancer was primarily attributable to stage and SES, but differences in survival between Blacks and Whites remain unexplained with the data available in this comprehensive, population-based, analysis.</p

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

The Drosophila melanogaster host model

The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed

Novel benzidine and diaminofluorene prolinamide derivatives as potent hepatitis C virus NS5A inhibitors

Our study describes the discovery of a series of highly potent hepatitis C virus (HCV) NS5A inhibitors based on symmetrical prolinamide derivatives of benzidine and diaminofluorene. Through modification of benzidine, L-proline, and diaminofluorene derivatives, we developed novel inhibitor structures, which allowed us to establish a library of potent HCV NS5A inhibitors. After optimizing the benzidine prolinamide backbone, we identified inhibitors embedding meta-substituted benzidine core structures that exhibited the most potent anti-HCV activities. Furthermore, through a battery of studies including hERG ligand binding assay, CYP450 binding assay, rat plasma stability test, human liver microsomal stability test, and pharmacokinetic studies, the identified compounds 24, 26, 27, 42, and 43 are found to be nontoxic, and are expected to be effective therapeutic anti-HCV agents. (C) 2015 Elsevier Masson SAS. All rights reserved.1143sciescopu