A proteogenomic signature of age-related macular degeneration in blood.

Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown.

Weighting and aggregating expert ecological judgments.

Performance weighted aggregation of expert judgments, using calibration questions, has been advocated to improve pooled quantitative judgments for ecological questions. However, there is little discussion or practical advice in the ecological literature regarding the application, advantages or challenges of performance weighting. In this paper we (1) illustrate how the IDEA protocol with four-step question format can be extended to include performance weighted aggregation from the Classical Model, and (2) explore the extent to which this extension improves pooled judgments for a range of performance measures.

Scurvy: an unusual complication of paediatric cancer treatment.

Scurvy is a disease that is rarely encountered in modern medicine. A condition that was classically associated with sailors, its incidence has decreased dramatically since the discovery of its association with vitamin C deficiency. We present the case of a 2-year-old boy, whose treatment for neuroblastoma was complicated by gastrointestinal disease, which necessitated enteral feeding.

Mycoplasma infection and hypoxia initiate succinate accumulation and release in the VM-M3 cancer cells.

Succinate is known to act as an inflammatory signal in classically activated macrophages through stabilization of HIF-1α leading to IL-1β production. Relevant to this, hypoxia is known to drive succinate accumulation and release into the extracellular milieu. The metabolic alterations associated with succinate release during inflammation and under hypoxia are poorly understood.

A Pictorial Review of Hepatobiliary Magnetic Resonance Imaging With Hepatocyte-Specific Contrast Agents: Uses, Findings, and Pitfalls of Gadoxetate Disodium and Gadobenate Dimeglumine.

Magnetic resonance imaging (MRI) has a well-established role as a highly specific and accurate modality for characterizing benign and malignant focal liver lesions. In particular, contrast-enhanced MRI using hepatocyte-specific contrast agents (HSCAs) improves lesion detection and characterization compared to other imaging modalities and MRI techniques. In this pictorial review, the mechanism of action of gadolinium-based MRI contrast agents, with a focus on HSCAs, is described.

Virtual monoenergetic reconstruction of contrast-enhanced dual energy CT at 70keV maximizes mural enhancement in acute small bowel obstruction.

Purpose: In patients with small bowel obstruction (SBO), it is challenging to detect early ischemia. The purpose of this study is to evaluate the quantitative and qualitative benefits of virtual monoenergetic image (VMI) reconstruction in the assessment of small bowel mural enhancement on dual source dual energy computed tomography (CT) scans of the abdomen.

Materials And Methods: Institutional review board approval was obtained, for this retrospective analysis.

Multiparametric magnetic resonance imaging-targeted biopsy for the detection of prostate cancer in patients with prior negative biopsy results.

Purpose: We aimed to determine the performance of multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer (PCa) in patients with prior negative transrectal ultrasound-guided prostate biopsy (TRUS-B) results.

Materials And Methods: Between 2010 and 2013, 2,416 men underwent TRUS-B or an mpMRI or both at Vancouver General Hospital. Among these, 283 men had persistent suspicion of PCa despite prior negative TRUS-B finding.

Multiparametric magnetic resonance imaging enhances detection of significant tumor in patients on active surveillance for prostate cancer.

Objective: To determine whether multiparametric magnetic resonance imaging (MRI) of the prostate (mpMRI) combined with MRI fusion technology during transrectal ultrasound-guided biopsy can enhance the detection of significant disease in patients with apparent low-risk prostate cancer on active surveillance (AS).

Materials And Methods: We reviewed the charts of 603 patients on AS for localized prostate cancer between January 2006 and September 2013. mpMRI before repeat transrectal ultrasound-guided biopsy was obtained in 111 patients, of whom 69 underwent subsequent fusion biopsy (39 true and 30 cognitive) in addition to standard template biopsy.

Glucose attenuates hypoxia-induced changes in endothelial cell growth by inhibiting HIF-1α expression.

Hyperglycaemia and hypoxia play essential pathophysiological roles in diabetes. We determined whether hyperglycaemia influences endothelial cell growth under hypoxic conditions in vitro. Using a Ruskinn Invivo 400 Hypoxia Workstation, bovine aortic endothelial cells (BAEC) were exposed to high glucose concentrations (25 mM glucose) under normoxic or hypoxic conditions before cell growth (balance of proliferation and apoptosis) was assessed by fluorescence-activated cell sorting (FACS) analysis, proliferating cell nuclear antigen (pCNA), Bcl-x and caspase-3 protein expression and activity.

Minimizing the cost of keeping options open for conservation in a changing climate.

Policy documents advocate that managers should keep their options open while planning to protect coastal ecosystems from climate-change impacts. However, the actual costs and benefits of maintaining flexibility remain largely unexplored, and alternative approaches for decision making under uncertainty may lead to better joint outcomes for conservation and other societal goals. For example, keeping options open for coastal ecosystems incurs opportunity costs for developers.

The role of shear-induced transforming growth factor-β signaling in the endothelium.

Objective: Vascular endothelial cells (ECs) are continuously exposed to blood flow that contributes to the maintenance of vessel structure and function; however, the effect of hemodynamic forces on transforming growth factor-β (TGF-β) signaling in the endothelium is poorly described. We examined the potential role of TGF-β signaling in mediating the protective effects of shear stress on ECs.

Approach And Results: Human umbilical vein ECs (HUVECs) exposed to shear stress were compared with cells grown under static conditions.

Vascular endothelial growth factor is important for brown adipose tissue development and maintenance.

Vascular endothelial growth factor (VEGF) is critical for angiogenesis, but also has pleiotropic effects on several nonvascular cells. Our aim was to investigate the role of VEGF in brown adipose tissue (BAT). We show that VEGF expression increases 2.

Expression and role of VEGF--a in the ciliary body.

Purpose: The role of VEGF-A in the normal ciliary body is largely unexplored. The ciliary body is similar in many respects to the choroid plexus of the brain, and we demonstrated previously the importance of VEGF-A in maintenance of choroid plexus vasculature and ependymal cells. Therefore, the role of VEGF-A in ciliary body homeostasis was explored.

Evaluation of potential responses to invasive non-native species with structured decision making.

In managing invasions and colonizations of non-native species, eradication or control efforts must proceed quickly. There are 2 challenges in taking such quick action. First, managers frequently have to choose among complex and often competing environmental, social, and economic objectives.

Role of shear-stress-induced VEGF expression in endothelial cell survival.

Vascular endothelial growth factor (VEGF) plays a crucial role in developmental and pathological angiogenesis. Expression of VEGF in quiescent adult tissue suggests a potential role in the maintenance of mature blood vessels. We demonstrate, using a Vegf-lacZ reporter mouse model, that VEGF is expressed by arterial but not by venous or capillary endothelial cells (ECs) in vivo.

Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity.

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. In advanced AMD, new vessels from choriocapillaris (CC) invade through the Bruch's membrane (BrM) into the retina, forming choroidal neovascularization (CNV). BrM, an elastic lamina that is located between the retinal pigment epithelium (RPE) and CC, is thought to act as a physical and functional barrier against CNV.

Expression and role of VEGF in the adult retinal pigment epithelium.

Purpose: Despite a lack of active angiogenesis, VEGF is expressed in nearly every adult tissue, and recent evidence suggests that VEGF may serve as a survival factor for both vascular and nonvascular tissues. VEGF blockade is a widely used treatment for neovascular diseases such as wet age-related macular degeneration (AMD). Therefore, it was sought in this study to evaluate the expression and role of endogenous VEGF in RPE.

TGF-β signaling is required for maintenance of retinal ganglion cell differentiation and survival.

Purpose: To determine the role of TGF-β1 in the maintenance of retinal ganglion cell line (RGC-5) differentiation and integrity.

Methods: RGC-5 cells were differentiated in media conditioned by human non-pigmented ciliary epithelial cells (HNPE) for 4 days before treatment with TGF-β1 for 24 h. Cells were examined for morphological changes and harvested for western blot and real-time PCR analysis.

Microvascular retinal endothelial and pericyte cell apoptosis in vitro: role of hedgehog and Notch signaling.

Purpose: Aberrant retinal blood flow is a hallmark of retinopathies and may be a causative factor in their pathophysiology. In this study, the effects of pulsatile flow on hedgehog and Notch control of retinal endothelial cell and pericyte apoptosis were examined.

Methods: The levels of hedgehog and Notch signaling components in bovine retinal endothelial cells (BRECs) and pericytes (BRPs) were examined in vitro under static conditions and after exposure to pulsatile flow, with a perfused transcapillary co-culture system.

The role of pulsatile flow in controlling microvascular retinal endothelial and pericyte cell apoptosis and proliferation.

Aims: Aberrant retinal blood flow is a hallmark of various retinopathies and may be a causative factor in the pathology associated with these conditions. We examined the effects of pulsatile flow on bovine retinal endothelial cell (BREC) and bovine retinal pericyte (BRP) apoptosis and proliferation.

Methods And Results: Co-cultured BRECs and BRPs were exposed to low (0.

Effects of active hexose correlated compound on frequency of CD4+ and CD8+ T cells producing interferon-γ and/or tumor necrosis factor-α in healthy adults.

Active hexose correlated compound (AHCC) is a natural compound with the potential to be used as an immunoenhancer in cases in which the immune system is compromised. The purpose of this study was to evaluate the effects of this compound on the immune function of healthy adults aged 50 years or more. The production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α by CD4(+) and CD8(+) T cells was measured by flow cytometry in peripheral blood obtained from subjects at different time points after AHCC intake.