Diagnosis of childhood tuberculosis and host RNA expression in Africa

Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV

Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer.

Abstract Detection, treatment, and prediction of outcome for men with prostate cancer increasingly depend on a molecular understanding of tumor development and behavior. We characterized primary prostate cancer by monitoring expression levels of more than 8900 genes in normal and malignant tissues. Patterns of gene expression across tissues revealed a precise distinction between normal and tumor samples, and revealed a striking group of about 400 genes that were overexpressed in tumor tissues. We ranked these genes according to their differential expression in normal and cancer tissues by selecting for highly and specifically overexpressed genes in the majority of cancers with correspondingly low or absent expression in normal tissues. Several such genes were identified that act within a variety of biochemical pathways and encode secreted molecules with diagnostic potential, such as the secreted macrophage inhibitory cytokine, MIC-1. Other genes, such as fatty acid synthase, encode enzymes known as drug targets in other contexts, which suggests new therapeutic approaches

'Correction:'Peer chart audits: A tool to meet Accreditation Council on Graduate Medical Education (ACGME) competency in practice-based learning and improvement

<p>Abstract</p> <p>Background</p> <p>The Accreditation Council on Graduate Medical Education (ACGME) supports chart audit as a method to track competency in Practice-Based Learning and Improvement. We examined whether peer chart audits performed by internal medicine residents were associated with improved documentation of foot care in patients with diabetes mellitus.</p> <p>Methods</p> <p>A retrospective electronic chart review was performed on 347 patients with diabetes mellitus cared for by internal medicine residents in a university-based continuity clinic from May 2003 to September 2004. Residents abstracted information pertaining to documentation of foot examinations (neurological, vascular, and skin) from the charts of patients followed by their physician peers. No formal feedback or education was provided.</p> <p>Results</p> <p>Significant improvement in the documentation of foot exams was observed over the course of the study. The percentage of patients receiving neurological, vascular, and skin exams increased by 20% (from 13% to 33%) (p = 0.001), 26% (from 45% to 71%) (p < 0.001), and 18% (51%–72%) (p = 0.005), respectively. Similarly, the proportion of patients receiving a well-documented exam which includes all three components – neurological, vascular and skin foot exam – increased over time (6% to 24%, p < 0.001).</p> <p>Conclusion</p> <p>Peer chart audits performed by residents in the absence of formal feedback were associated with improved documentation of the foot exam in patients with diabetes mellitus. Although this study suggests that peer chart audits may be an effective tool to improve practice-based learning and documentation of foot care in diabetic patients, evaluating the actual performance of clinical care was beyond the scope of this study and would be better addressed by a randomized controlled trial.</p

Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study

BACKGROUND: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. METHODS AND FINDINGS: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87-100]; specificity 90%, 95% CI [80-97]) and TB from OD (sensitivity 93%, 95% CI [83-100]; specificity 88%, 95% CI [74-97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85-100]; specificity 94%, 95% CI [84-100]) and OD patients (sensitivity 100%, 95% CI [100-100]; specificity 96%, 95% CI [93-100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group. CONCLUSIONS: In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions. Please see later in the article for the Editors' Summary

A simple and efficient method for concentration of ocean viruses by chemical flocculation

Ocean viruses alter ecosystems through host mortality, horizontal gene transfer and by facilitating remineralization of limiting nutrients. However, the study of wild viral populations is limited by inefficient and unreliable concentration techniques. Here, we develop a new technique to recover viruses from natural waters using iron-based flocculation and large-pore-size filtration, followed by resuspension of virus-containing precipitates in a pH 6 buffer. Recovered viruses are amenable to gene sequencing, and a variable proportion of phages, depending upon the phage, retain their infectivity when recovered. This Fe-based virus flocculation, filtration and resuspension method (FFR) is efficient (> 90% recovery), reliable, inexpensive and adaptable to many aspects of marine viral ecology and genomics research