Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum.

CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer-specific gene panel to detect DNA methylation in sputum and plasma. This is a case-control study of subjects with suspicious nodules on CT imaging.

Comprehensive Translational Assessment of Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the comprehensive in vitro proarrhythmia assay (CiPA). We studied the effects of 26 drugs and 3 drug combinations on 2 commercially available iPSC-CM types using high-throughput voltage-sensitive dye and microelectrode-array assays being studied for the CiPA initiative and compared the results with clinical QT prolongation and torsade de pointes (TdP) risk. Concentration-dependent analysis comparing iPSC-CMs to clinical trial results demonstrated good correlation between drug-induced rate-corrected action potential duration and field potential duration (APDc and FPDc) prolongation and clinical trial QTc prolongation.

WFUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography: Part 5. Prostate.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced guidelines for the use of elastography techniques, including basic science, breast, liver and thyroid elastography. Here we present elastography in prostate diseases. For each available technique, procedure, reproducibility, results and limitations are analyzed and recommendations are given.

Resolution of Postural Orthostatic Tachycardia Syndrome After CT-Guided, Percutaneous T2 Ethanol Ablation for Hyperhidrosis.

Postural orthostatic tachycardia syndrome is characterized by orthostatic intolerance. Orthostasis (or other mild physical stress) triggers a cascade of inappropriate tachycardia, lightheadedness, palpitations, and often fainting. The underlying defect is sympathetic dysregulation of the heart, which receives its sympathetic tone from the cervical and upper thoracic sympathetic ganglia.

Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens.

Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A.

Complex Esophageal Reconstruction Procedures Have Acceptable Outcomes Compared With Routine Esophagectomy.

Background: Complex esophageal reconstruction (CER) is defined as restoring esophageal continuity in a previously operated field, using a nongastric conduit, or after esophageal diversion. This study compares the outcomes of CER with non-CER (NCER), which uses an undisturbed stomach for reconstruction.

Methods: This single-institution retrospective cohort study compares 75 CERs with 75 NCERs from 1995 to 2014 that were matched for cancer versus benign disease.

Reducing hypoxia and inflammation during invasive pulmonary aspergillosis by targeting the Interleukin-1 receptor.

Hypoxia as a result of pulmonary tissue damage due to unresolved inflammation during invasive pulmonary aspergillosis (IPA) is associated with a poor outcome. Aspergillus fumigatus can exploit the hypoxic microenvironment in the lung, but the inflammatory response required for fungal clearance can become severely disregulated as a result of hypoxia. Since severe inflammation can be detrimental to the host, we investigated whether targeting the interleukin IL-1 pathway could reduce inflammation and tissue hypoxia, improving the outcome of IPA.

A Non-canonical Melanin Biosynthesis Pathway Protects Aspergillus terreus Conidia from Environmental Stress.

Melanins are ubiquitous pigments found in all kingdoms of life. Most organisms use them for protection from environmental stress, although some fungi employ melanins as virulence determinants. The human pathogenic fungus Aspergillus fumigatus and related Ascomycetes produce dihydroxynaphthalene- (DHN) melanin in their spores, the conidia, and use it to inhibit phagolysosome acidification.

Comparing Children with ASD and Their Peers' Growth in Print Knowledge.

Many children with autism spectrum disorder (ASD) struggle with reading. An increased focus on emergent literacy skills-particularly print knowledge-might improve later reading outcomes. We analyzed longitudinal measures of print knowledge (i.

Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge.

Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge.

Robotic Versus Thoracoscopic Resection for Lung Cancer: Early Results of a New Robotic Program.

Background: Robot-assisted surgical techniques have been introduced in recent years as an alternative minimally invasive approach for lung surgery. While the advantage of video-assisted thoracoscopic surgery (VATS) over thoracotomy for anatomical lung resection has been extensively reported, the results of robotic video-assisted thoracoscopic surgery (RVATS) compared to VATS are still under investigation.

Methods: We performed a retrospective review of lung cancer patients, undergoing minimally invasive segmentectomy or lobectomy between December 2007 and May 2014.

Methylation of DACT2 accelerates esophageal cancer development by activating Wnt signaling.

Esophageal cancer is one of the most common malignancies worldwide. DACT2 is frequently methylated in human lung, hepatic, gastric and thyroid cancers. The methylation status and function of DACT2 remain to be elucidated in human esophageal cancer.

MicroRNA-223 controls the expression of histone deacetylase 2: a novel axis in COPD.

Unlabelled: Reduced activity of histone deacetylase 2 (HDAC2) has been described in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms resulting in decreased expression of this important epigenetic modifier remain unknown. Here, we employed several in vitro experiments to address the role of microRNAs (miRNAs) on the regulation of HDAC2 in endothelial cells. Manipulation of miRNA levels in human pulmonary artery endothelial cells (HPAEC) was achieved by using electroporation with anti-miRNAs and miRNA mimics.

Genetic architecture, biochemical underpinnings and ecological impact of floral UV patterning.

Floral attraction traits can significantly affect pollinator visitation patterns, but adaptive evolution of these traits may be constrained by correlations with other traits. In some cases, molecular pathways contributing to floral attraction are well characterized, offering the opportunity to explore loci potentially underlying variation among individuals. Here, we quantify the range of variation in floral UV patterning (i.

The glycolytic enzyme enolase represents a plasminogen-binding protein on the surface of a wide variety of medically important fungal species.

Allergies are an increasing issue in human health and can, eventually, cause severe anaphylactic shock. Aspergillus fumigatus and Candida albicans are leading causes of life-threatening invasive fungal infections in immunocompromised patients, but can also cause severe allergic responses in otherwise healthy individuals. The glycolytic enzyme enolase is known as a major allergen despite its function in intracellular metabolism.

Plasmodium vivax Malaria in Pregnant Women in the Brazilian Amazon and the Risk Factors Associated with Prematurity and Low Birth Weight: A Descriptive Study.

Introduction: Plasmodium vivax is the most prevalent malaria species in the American region. Brazil accounts for the higher number of the malaria cases reported in pregnant women in the Americas. This study aims to describe the characteristics of pregnant women with malaria in an endemic area of the Brazilian Amazon and the risk factors associated with prematurity and low birth weight (LBW).

Safety Lead Optimization and Candidate Identification: Integrating New Technologies into Decision-Making.

Discovery toxicology focuses on the identification of the most promising drug candidates through the development and implementation of lead optimization strategies and hypothesis-driven investigation of issues that enable rational and informed decision-making. The major goals are to [a] identify and progress the drug candidate with the best overall drug safety profile for a therapeutic area, [b] remove the most toxic drugs from the portfolio prior to entry into humans to reduce clinical attrition due to toxicity, and [c] establish a well-characterized hazard and translational risk profile to enable clinical trial designs. This is accomplished through a framework that balances the multiple considerations to identify a drug candidate with the overall best drug characteristics and provides a cogent understanding of mechanisms of toxicity.

Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors.

Background: The immune system plays an important role in cancer surveillance and therapy. Chemoradiation can cause severe treatment-related lymphopenia (TRL) (<500 cells/mm3) that is associated with reduced survival.

Materials And Methods: Data from 4 independent solid tumor studies on serial lymphocyte counts, prognostic factors, treatment, and survival were collected and analyzed.

The pathogenesis of pulmonary hypertension--an update.

Elevation of the mean pulmonary arterial pressure to ≥25 mm Hg within the low-pressure system of the pulmonary circulation is defined as pulmonary hypertension. Pulmonary hypertension may be the consequence of various clinical and pathophysiological entities. Many of these conditions, however, result in a final common pathway of pathogenesis.

Detecting Prostate Cancer.

Background: When prostate cancer is suspected, the prostate gland is biopsied with the aid of transrectal ultrasound (TRUS). The sensitivity of prostatic biopsy is about 50%. The fusion of magnetic resonance imaging (MRI) data with TRUS enables the targeted biopsy of suspicious areas.

Survival Following Lung Metastasectomy in Soft Tissue Sarcomas.

Background: The most common site of metastasis for soft tissue sarcomas (STSs) is the lung. In patients who are candidates for resection, metastasectomy improves survival. Debate remains, however, on approach and patient selection for surgery.

DREAMing: a simple and ultrasensitive method for assessing intratumor epigenetic heterogeneity directly from liquid biopsies.

Many cancers comprise heterogeneous populations of cells at primary and metastatic sites throughout the body. The presence or emergence of distinct subclones with drug-resistant genetic and epigenetic phenotypes within these populations can greatly complicate therapeutic intervention. Liquid biopsies of peripheral blood from cancer patients have been suggested as an ideal means of sampling intratumor genetic and epigenetic heterogeneity for diagnostics, monitoring and therapeutic guidance.