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Objective: To develop a tool for estimating the 10-year risk of death from other causes in men with localized prostate cancer., Subjects and Methods: We identified 2,425 patients from the Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, age <80, newly diagnosed with clinical stage T1-T3a prostate cancer from 1/1/1998-12/31/2009, with follow-up through 2/28/2013. We developed a Fine and Gray competing-risks model for 10-year other cause mortality considering age, patient-reported comorbid medical conditions, component scores and items of the SF-36 Health Survey, activities of daily living, and sociodemographic characteristics. Model discrimination and calibration were compared to predictions from Social Security life table mortality risk estimates., Results: Over a median follow-up of 7.7 years, 76 men died of prostate-specific causes and 465 died of other causes. The strongest predictors of 10-year other cause mortality risk included increasing age at diagnosis, higher approximated Charlson Comorbidity Index score, worse patient-reported general health (fair or poor vs. excellent-good), smoking at diagnosis, and marital status (all other vs. married) (all p<0.05). Model discrimination improved over Social Security life tables (c-index of 0.70 vs. 0.59, respectively). Predictions were more accurate than predictions from the Social Security life tables, which overestimated risk in our population., Conclusions: We provide a tool for estimating the 10-year risk of dying from other causes when making decisions about treating prostate cancer using pre-treatment patient-reported characteristics., Competing Interests: JW received unrestricted research grants from British American Tobacco (Investments) Limited for smoking-related quality of life research which did not fund this work. JW also discloses employment by John Ware Research Group, a commercial company. The other authors have no other competing interests. These disclosures do not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Genetically modified (GM) foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt)-maize (MON810) on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA)-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma.

Background: Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils., Methodology/principal Findings: An ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h-72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs., Conclusion/significance: We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time.

Background: Non-invasive in vivo imaging strategies are of high demand for longitudinal monitoring of inflammation during disease progression. In this study we present an imaging approach using near infrared fluorescence (NIRF) imaging in combination with a polyanionic macromolecular conjugate as a dedicated probe, known to target L- and P-selectin and C3/C5 complement factors., Methodology/principal Findings: We investigated the suitability of dendritic polyglycerol sulfates (dPGS), conjugated with a hydrophilic version of the indocyanine green label with 6 sulfonate groups (6S-ICG) to monitor sites of inflammation using an experimental mouse model of allergic asthma. Accumulation of the NIRF-conjugated dPGS (dPGS-NIRF) in the inflamed lungs was analyzed in and ex vivo in comparison with the free NIRF dye using optical imaging. Commercially available smart probes activated by matrix metalloproteinase's (MMP) and cathepsins were used as a comparative control. The fluorescence intensity ratio between lung areas of asthmatic and healthy mice was four times higher for the dPGS in comparison to the free dye in vivo at four hrs post intravenous administration. No significant difference in fluorescence intensity between healthy and asthmatic mice was observed 24 hrs post injection for dPGS-NIRF. At this time point ex-vivo scans of asthmatic mice confirmed that the fluorescence within the lungs was reduced to approximately 30% of the intensity observed at 4 hrs post injection., Conclusions/significance: Compared with smart-probes resulting in a high fluorescence level at 24 hrs post injection optical imaging with dPGS-NIRF conjugates is characterized by fast uptake of the probe at inflammatory sites and represents a novel approach to monitor lung inflammation as demonstrated in mice with allergic asthma.

Weevils can devastate food legumes in developing countries, but genetically modified peas (Pisum sativum), chickpeas and cowpeas expressing the gene for alpha-amylase inhibitor-1 (αAI) from the common bean (Phaseolus vulgaris) are completely protected from weevil destruction. αAI is seed-specific, accumulated at high levels and undergoes post-translational modification as it traverses the seed endomembrane system. This modification was thought to be responsible for the reported allergenicity in mice of the transgenic pea but not the bean. Here, we observed that transgenic αAI peas, chickpeas and cowpeas as well as non-transgenic beans were all allergenic in BALB/c mice. Even consuming non-transgenic peas lacking αAI led to an anti-αAI response due to a cross-reactive response to pea lectin. Our data demonstrate that αAI transgenic peas are not more allergenic than beans or non-transgenic peas in mice. This study illustrates the importance of repeat experiments in independent laboratories and the potential for unexpected cross-reactive allergic responses upon consumption of plant products in mice.

We assessed the effect of short-term feeding of genetically modified (GM: Bt MON810) maize on immune responses and growth in weanling pigs and determined the fate of the transgenic DNA and protein in-vivo. Pigs were fed a diet containing 38.9% GM or non-GM isogenic parent line maize for 31 days. We observed that IL-12 and IFNγ production from mitogenic stimulated peripheral blood mononuclear cells decreased (P<0.10) following 31 days of GM maize exposure. While Cry1Ab-specific IgG and IgA were not detected in the plasma of GM maize-fed pigs, the detection of the cry1Ab gene and protein was limited to the gastrointestinal digesta and was not found in the kidneys, liver, spleen, muscle, heart or blood. Feeding GM maize to weanling pigs had no effect on growth performance or body weight. IL-6 and IL-4 production from isolated splenocytes were increased (P<0.05) in response to feeding GM maize while the proportion of CD4(+) T cells in the spleen decreased. In the ileum, the proportion of B cells and macrophages decreased while the proportion of CD4(+) T cells increased in GM maize-fed pigs. IL-8 and IL-4 production from isolated intraepithelial and lamina propria lymphocytes were also increased (P<0.05) in response to feeding GM maize. In conclusion, there was no evidence of cry1Ab gene or protein translocation to the organs and blood of weaning pigs. The growth of pigs was not affected by feeding GM maize. Alterations in immune responses were detected; however, their biologic relevance is questionable.

Background: The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood., Results: We analyzed the immunological consequences of the interaction of MHC class II (I-Au) restricted 11-mer peptides of myelin basic protein with amino acid substitutions at position 4. These mutant peptides differ in MHC binding affinity, CD4+ T cell priming, and alter the severity of peptide-induced experimental allergic encephalomyelitis. Using molecular dynamics, a computational method of quantifying intrinsic movements of proteins at high resolution, we investigated conformational changes in MHC upon peptide binding. We found that irrespective of peptide binding affinity, MHC deformation appears to influence costimulation, which then leads to effective T cell priming and disease induction. Although this study compares in vivo and molecular dynamics results for three altered peptide ligands, further investigation with similar complexes is essential to determine whether spatial rearrangement of peptide-MHC and costimulatory complexes is an additional level of T cell regulation.