Meta-analysis: Racial Disparities in Prostate Cancer Survival and Case-Control Study: Association between Family History of Cancers, Obesity and Prostate Cancer

This is a compilation of 3 abstracts for the three manuscripts included in this dissertation. I. Meta-Analysis: Racial Disparities in Prostate Cancer Survival: Prostate cancer is the second leading cause of cancer-related mortality in men. Previous studies have drawn inconsistent conclusions on racial differences in prostate cancer survival. This meta-analysis was conducted to investigate the relationship between race and survival from prostate cancer. A systematic review of published articles from 1968 to 2007 assessing survival from prostate cancer among African American and White men was conducted. The search yielded 20 eligible published manuscripts. Analysis of unadjusted studies showed African American men have an increased risk of all-cause mortality (Hazard ratio (HR) = 1.47, 95% confidence interval (CI): 1.31, 1.65, P \u3c 0.001). However, examination of adjusted studies showed no difference (HR = 1.07, 95% CI: 0.94, 1.22, P = 0.308). No statistically significant difference was observed in prostate cancer-specific survival in both analyses using unadjusted (HR = 1.11, 95% CI: 0.94, 1.31, P = 0.209) and adjusted studies (HR = 1.15, 95% CI: 0.95, 1.41, P = 0.157). There was evidence of heterogeneity that was unexplained by factors analyzed in overall survival but explained by stage in prostate cancer-specific survival. This meta-analysis concludes that there are no racial differences in the overall and prostate cancer-specific survival between African American and White men. II. Case-Control study: Association between Family History of Cancers and Prostate Cancer: Family history of prostate cancer is an established risk factor for prostate cancer. However, the relationship between family history of cancers other than prostate cancer and prostate cancer risk is inconclusive. This study sought to examine the association between family history of cancers and prostate cancer. A case-control study was conducted in which cases and controls were randomly selected from a large urology clinic in Central Virginia. Cases were 600 histologically confirmed prostate cancer patients who were diagnosed between January 2000 and December 2005, and controls were 686 patients who visited the clinic during the same period and diagnosed with urological illnesses other than cancers and prostate-related problems. Data on family history of cancers, lifestyle and demographic factors were collected. Unconditional logistic regression analysis was used to estimate the odds ratios and the corresponding 95% confidence intervals after adjustment for potential confounding factors. Multiple comparisons adjustments were made using Bonferroni adjustment. Men with family history of any cancer in first-degree relatives including parents (OR=2.42, 95% CI: 1.53, 3.84) and parents only (OR=1.90, 95% CI: 1.23, 2.94) were at increased risk of developing prostate cancer compared to men with no such family history of cancer. Significant increased risk was also observed with family history of prostate cancer in first-degree relatives (OR=2.68, 95% CI: 1.53, 4.69) and parents only (OR=3.26, 95% CI: 1.71, 6.24) compared to men with no family history of prostate cancer. Even after adjustments for multiple comparisons, the significance persisted both in first-degree relatives (OR=2.68, 95% CI: 1.16, 6.21) and parents alone (OR=3.26, 95% CI: 1.24, 8.63). No association was found with family history of other cancers including breast, colon, lung, skin, digestive tract, stomach, liver, pancreas, female cancers, urogenital, urinary bladder, brain, blood and lymph node and other cancers and risk of prostate cancer. This study demonstrated an increased prostate cancer risk for men with a family history of any cancer or prostate cancer in first-degree relatives including parents and parents alone. Health care providers need to be aware of the potential risk of family history of cancers on prostate cancer. III. Case-Control study: Association between Obesity and Prostate Cancer: Obesity is a major public health problem in the United States. Several studies have investigated the association between obesity and prostate cancer risk. However the impact of early-adult obesity on prostate cancer is not well studied. This study proposes to investigate the relationship between prostate cancer and early-onset obesity and current obesity. A case-control study was conducted to investigate the relationship between obesity and prostate cancer in a large urology clinic population in Central Virginia. Cases included histologically confirmed prostate cancer patients of all stages and grades diagnosed from January 2000 to December 2005. Controls were patients who were diagnosed with urological illness other than cancers and prostate-related problems. Self-reported data was collected on anthropometric, lifestyle and demographic factors through a mail survey. Unconditional logistic regression analysis was conducted to investigate the association between prostate cancer and early-onset obesity (BMI at age 18) and current obesity. Odds ratios and corresponding 95% confidence intervals were calculated after accounting for significant interaction terms and adjusting for potential confounding variables. This study showed statistically significant association between BMI at age 18 and prostate cancer risk in the multivariate analysis when BMI was evaluated as a continuous variable. There was a 7% decrease in the odds of prostate cancer risk for every 1 kg/m(2) increment in BMI at age 18 (OR=0.93, 95% CI: 0.87, 0.98). Analysis of BMI at age 18 as a categorical variable also showed reduced risk though statistically non-significant. Obese men (OR=0.62, 95% CI: 0.12, 3.08) and overweight men (OR=0.60, 95% CI: 0.35, 1.05) had a non-significant decreased risk of developing prostate cancer compared to normal weight men at age 18. Examination of current BMI showed a non-statistically significant decreased risk of prostate cancer when examined as a continuous variable. However, there was significant interaction between current BMI treated categorically and age. This study concludes that there is decreased prostate cancer risk associated with increasing BMI at age 18. Future large prospective studies are needed to better understand the association between early-onset obesity and risk of prostate cancer and explore the biological factors associated especially in the early ages. This document was created in Microsoft Word 2003

Nested reverse transcriptase–polymerase chain reactions targeting the messenger RNA of icl2, hspx, and rRNAP1 genes to detect viable Mycobacterium tuberculosis directly from clinical specimens

AbstractThere is an urgent need for a rapid and reliable test to detect actively multiplying Mycobacterium tuberculosis directly from clinical specimens for an early initiation of the appropriate antituberculous treatment. This study was aimed at the optimization and application of nested reverse transcriptase–PCR (nRT–PCR) targeting the messenger RNA of the icl2, hspx, and rRNAP1 genes directly from sputum specimens, and their evaluation against the culture by the BACTEC MicroMGIT mycobacterial culture system. 203 Sputum samples from clinically suspected tuberculosis patients and 30 control specimens (clinically proven viral or bacterial infections other than tuberculosis) were included in this study. The mycobacterial culture was performed by the BACTEC MicroMGIT system following the manufacturer’s instructions. The primers for nRT–PCRs targeting icl2, hspx, and rRNAP1 genes were indigenously designed using the Primer-BLAST software, and optimized for sensitivity and specificity. The icl2, hspx, and rRNAP1 genes were able to pick up 63.9%, 67.2%, and 58.75%, respectively, of culture-negative sputum specimens collected from clinically suspected tuberculosis patients. However, three (1.4%) were negative for nRT–PCR, but M. tuberculosis culture positive. All the 30 controls were negative for culture by the BACTEC MicroMGIT method and all three nRT–PCR. The novel nRT–PCRs targeting icl2, hspx, and rRNAP1 genes developed in this study are rapid and reliable diagnostic tools to detect viable M. tuberculosis directly from sputum specimens. However, further study by including a larger number of sputum specimens needs to be carried out to ascertain the diagnostic utility of the novel nRT–PCRs optimized in the study

Chronic exposure to incretin metabolites GLP-1(9-36) and GIP(3-42) affect islet morphology and beta cell health in high fat fed mice

The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to their major circulating metabolites GLP-1(9-36) and GIP(3-42). This study investigates the possible effects of these metabolites, and the equivalent exendin molecule Ex(9-39), on pancreatic islet morphology and constituent alpha and beta cells in high-fat diet (HFD) fed mice. Male Swiss TO-mice (6-8 weeks-old) were maintained on a HFD or normal diet (ND) for 4 months and then received twice-daily subcutaneous injections of GLP-1(9-36), GIP(3-42), Ex(9-39) (25 nmol/kg bw) or saline vehicle (0.9% (w/v) NaCl) over a 60-day period. Metabolic parameters were monitored and excised pancreatic tissues were used for immunohistochemical analysis. Body weight and assessed metabolic indices were not changed by peptide administration. GLP-1(9-36) significantly (

Active safety monitoring of newly marketed medications in a distributed data network: application of a semi-automated monitoring system

We developed a semi-automated active monitoring system that uses sequential matched-cohort analyses to assess drug safety across a distributed network of longitudinal electronic healthcare data. In a retrospective analysis, we showed that the system would have identified cerivastatin-induced rhabdomyolysis. In this study, we evaluated whether the system would generate alerts for three drug-outcome pairs: rosuvastatin and rhabdomyolysis (known null association), rosuvastatin and diabetes mellitus, and telithromycin and hepatotoxicity (two examples for which alerting would be questionable). During >5 years of monitoring, rate differences (RDs) comparing rosuvastatin to atorvastatin were -0.1 cases of rhabdomyolysis per 1,000 person-years (95% CI, -0.4, 0.1) and -2.2 diabetes cases per 1,000 person-years (95% CI, -6.0, 1.6). The RD for hepatotoxicity comparing telithromycin to azithromycin was 0.3 cases per 1,000 person-years (95% CI, -0.5, 1.0). In a setting in which false positivity is a major concern, the system did not generate alerts for three drug-outcome pairs

6-Phenyl-5,6-dihydrobenzoimidazo1,2-cquinazoline

In the title compound, C20H15N3, the molecules are linked by N - H⋯N hydrogen bonds. © 2005 International Union of Crystallography Printed in Great Britain - all rights reserved

Microbial Degradation of Lobster Shells to Extract Chitin Derivatives for Plant Disease Management

International audienceBiodegradation of lobster shells by chitinolytic microorganisms are an environment safe approach to utilize lobster processing wastes for chitin derivation. In this study, we report degradation activities of two microbes, " S223 " and " S224 " isolated from soil samples that had the highest rate of deproteinization, demineralization and chitinolysis among ten microorganisms screened. Isolates S223 and S224 had 27.3 and 103.8 protease units mg −1 protein and 12.3 and 11.2 µg ml −1 of calcium in their samples, respectively, after 1 week of incubation with raw lobster shells. Further, S223 contained 23.8 µg ml −1 of N-Acetylglucosamine on day 3, while S224 had 27.3 µg ml −1 on day 7 of incubation with chitin. Morphological observations and 16S rDNA sequencing suggested both the isolates were Streptomyces. The culture conditions were optimized for efficient degradation of lobster shells and chitinase (∼30 kDa) was purified from crude extract by affinity chromatography. The digested lobster shell extracts induced disease resistance in Arabidopsis by induction of defense related genes (PR1 > 500-fold, PDF1.2 > 40-fold) upon Pseudomonas syringae and Botrytis cinerea infection. The study suggests that soil microbes aid in sustainable bioconversion of lobster shells and extraction of chitin derivatives that could be applied in plant protection

Evaluation of optic neuritis following human papillomavirus vaccination

To assess the relationship between human papillomavirus (HPV) vaccination and occurrence of optic neuritis (ON) and to evaluate a claims-based algorithm for identification of ON. Females of 9–26 year olds in the HealthCore's Integrated Research Database (HIRDSM) with and without claims evidence of HPV vaccination between 2007 and 2012 were included in this study. Potential ON cases were identified using the claims-based algorithm, positive predictive value (PPV) was determined using medical chart review. For the claims analysis, two study designs, a self-controlled temporal scan statistic and a retrospective matched cohort analysis, were used. ON was defined based on an algorithm developed using diagnosis and procedure codes from the medical claims. The PPV for ON cases using charts that had enough information for reviewers to make a determination was 62.5% (95% CI: 49.5%–74.3%). With the self-controlled temporal scan statistic, the primary analysis restricting on recommended vaccination schedule timing showed an increased risk of potential ON after second dose (RR = 3.39; p = 0.03), this finding was not confirmed for any of the additional analyses performed for individual or combined doses. With the cohort design, there was no increased risk of potential ON following vaccination in either individual or combined dose analyses. The risk of potential ON was higher among participants with a history of prior autoimmune diseases. In conclusion, identifying confirmed ON cases through administrative claims data proved challenging. The claims-based analysis in this study did not provide evidence for an association of ON with HPV vaccination

Macrocyclic Glycohybrid Toolbox Identifies Novel Antiangiogenesis Agents from Zebrafish Assay

A practical and modular approach to obtain a diverse set of 14-membered macrocyclic compounds from carbohydrates is developed that utilizes functional groups at C-1 and C-5. The evaluation of this toolbox in various zebrafish assays led to the identification of <b>2.7f</b> as an antiangiogenesis agent

14-Membered Macrocyclic Ring-Derived Toolbox: The Identification of Small Molecule Inhibitors of Angiogenesis and Early Embryo Development in Zebrafish Assay

A highly practical and modular synthesis to obtain a diverse 14-membered ring-based macrocyclic toolbox is achieved. These compounds were further tested in zebrafish assays related to early embryonic development, angiogenesis, and neurogenesis, respectively. <b>1.4c</b> was identified as an antiangiogenesis agent