An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer

Background: Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease. Methods: We investigated urinary samples (n ¼ 121) from patients with bladder cancer (n ¼ 68) and age-matched controls (n ¼ 53). Fifteen miRs were quantified using real-time PCR. Results: We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs 15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA Po0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance). Conclusion: The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed

Initial impact and cost of a nationwide population screening campaign for diabetes in Brazil: A follow up study

<p>Abstract</p> <p>Background</p> <p>In 2001 Brazilian citizens aged 40 or older were invited to participate in a nationwide population screening program for diabetes. Capillary glucose screening tests and procedures for diagnostic confirmation were offered through the national healthcare system, diagnostic priority being given according to the severity of screening results. The objective of this study is to evaluate the initial impact of the program.</p> <p>Methods</p> <p>Positive testing was defined by a fasting capillary glucose ≥ 100 mg/dL or casual glucose ≥ 140 mg/dL. All test results were tabulated locally and aggregate data by gender and clinical categories were sent to the Ministry of Health. To analyze individual characteristics of screening tests performed, a stratified random sample of 90,106 tests was drawn. To describe the actions taken for positive screenees, a random sub-sample of 4,906 positive screenees was actively followed up through home interviews.</p> <p>Main outcome measures considered were the number of diabetes cases diagnosed and cost per case detected and incorporated into healthcare.</p> <p>Results</p> <p>Of 22,069,905 screening tests performed, we estimate that 3,417,106 (95% CI 3.1 – 3.7 million) were positive and that 346,168 (290,454 – 401,852) new cases were diagnosed (10.1% of positives), 319,157 (92.2%) of these being incorporated into healthcare. The number of screening tests needed to detect one case of diabetes was 64. As many cases of untreated but previously known diabetes were also linked to healthcare providers during the Campaign, the estimated number needed screen to incorporate one case into the healthcare system was 58. Total screening and diagnostic costs were US$26.19 million, the cost per diabetes case diagnosed being US$ 76. Results were especially sensitive to proportion of individuals returning for diagnostic confirmation.</p> <p>Conclusion</p> <p>This nationwide population-based screening program, conducted through primary healthcare services, demonstrates the feasibility, within the context of an organized national healthcare system, of screening campaigns for chronic diseases. Although overall costs were significant, cost per new case diagnosed was lower than previously reported. However, cost-effectiveness analysis based on more clinically significant outcomes needs to be conducted before this screening approach can be recommended in other settings.</p

Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection.</p> <p>Methods/design</p> <p>Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals.</p> <p>Discussion</p> <p>Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required.</p> <p>Trial registration</p> <p>Registration number NCT00721305.</p

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells