Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner

<p>Abstract</p> <p>Background</p> <p>Elevated levels of air pollution are associated with increased risk of lung cancer. Particulate matter (PM) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation, a lung cancer risk factor. Vanadium pentoxide (V₂O₅) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans. In the current investigation we examined the influence of genetic background on susceptibility to V₂O₅-induced inflammation and evaluated whether V₂O₅functions as a tumor promoter using a 2-stage (initiation-promotion) model of pulmonary neoplasia in mice.</p> <p>Results</p> <p>A/J, BALB/cJ (BALB), and C57BL/6J (B6) mice were treated either with the initiator 3-methylcholanthrene (MCA; 10 μg/g; i.p.) or corn oil followed by 5 weekly aspirations of V₂O₅or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment. Susceptibility to V₂O₅-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid (BALF), and chemokines, transcription factor activity, and MAPK signaling were quantified in lung homogenates. We found that treatment of animals with MCA followed by V₂O₅promoted lung tumors in both A/J (10.3 ± 0.9 tumors/mouse) and BALB (2.2 ± 0.36) mice significantly above that observed with MCA/PBS or V₂O₅alone (<it>P </it>< 0.05). No tumors were observed in the B6 mice in any of the experimental groups. Mice sensitive to tumor promotion by V₂O₅were also found to be more susceptible to V₂O₅-induced pulmonary inflammation and hyperpermeability (A/J>BALB>B6). Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1, higher NFκB and c-Fos binding activity, as well as sustained ERK1/2 activation in lung tissue.</p> <p>Conclusions</p> <p>In this study we demonstrate that V₂O₅, an occupational and environmentally relevant metal oxide, functions as an <it>in vivo </it>lung tumor promoter among different inbred strains of mice. Further, we identified a positive relationship between tumor promotion and susceptibility to V₂O₅-induced pulmonary inflammation. These findings suggest that repeated exposures to V₂O₅containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways.</p

Charter School Demand and Effectiveness: A Boston Update

This report begins with a focus on applications to charter schools. While much attention has been focused on charter school waitlists, waitlist data can be misleading. It includes duplicates, but also includes waitlists that have been rolled over from year to year and might be an unrealistic measure of demand. Instead, the authors investigate three factors related to demand: the yearly percentage of each middle school and high school class that applies to a charter in our lottery sample; the percentage of applicants that receive an offer from a charter school; and where students ultimately attend. This report also examines the demographic makeup of charter school enrollees and compare it to BPS. The next section follows the path of charter school students and report their performance in charters using the evidence from the lotteries. The lottery sample now covers many more charter schools. The 2009 report included findings from eight schools. This report includes MCAS results through 2012 from 12 schools and many more cohorts from the original schools, with additional newly opened schools contributing to the demand analysis. In addition to updating the test score results from the 2009 report, this report breaks down the test score effects by student subgroups. Trends are investigated over time in charter performance and by school groups. Finally, this report gives results using statistical controls, which allow the authros to estimate effects for attending charter schools that do not have sufficient lottery records for the more rigorous lottery based analysis. The lottery sample now contains almost all Boston charter schools with entry grades at middle or high school

Differences in visceral adipose tissue and biochemical cardiometabolic risk markers in elite rugby union athletes of Caucasian and Polynesian descent

Polynesian individuals are leaner with greater musculature than Caucasians of an equivalent size, and this genetically different morphology provides a physique that is often compatible with success in a number of sports, including rugby union. Evidence indicates that Polynesians have greater stores of absolute and relative abdominal fat mass and this is known to confer cardiometabolic risk. The aims of this study were to (1) explore the relationship between ethnicity, visceral adipose tissue (VAT), and cardiometabolic disease risk markers in elite Caucasian and Polynesian rugby union athletes, and (2) assess the impact of a pre-season training programme on these markers. Twenty-two professional rugby union athletes of Caucasian (n = 11) and Polynesian (n = 11) descent underwent physique assessment via surface anthropometry, dual-energy X-ray absorptiometry, and magnetic resonance imaging before and after an 11-week pre-season. A fasted blood test was undertaken at both time points. Compared to Caucasians, at baseline Polynesians displayed significantly higher VAT (771 ± 609 cm3 vs 424 ± 235 cm3; p = 0.043), triglycerides (1.0 ± 0.9 mmol/L vs 0.6 ± 0.2 mmol/L; p = 0.050), and low-density lipoprotein cholesterol (3.1 ± 0.9 mmol/L vs 2.3 ± 0.7 mmol/L; p = 0.019). Similar changes were observed in both groups over the pre-season period in VAT and blood biochemical markers. Polynesian rugby union athletes were more likely than Caucasians to exhibit risk factors associated with cardiometabolic disease, such as elevated VAT and unfavourable lipid profiles. Further longitudinal research is required to identify and explain the short- and long-term risk of cardiometabolic disease in athletes of Polynesian descent

N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study

Background Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. Objectives This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. Methods Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF. Results Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR− was 0.09 (95% CI: 0.05 to 0.13). Conclusions In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF

Infection by a foliar endophyte elicits novel arabidopside-based plant defence reactions in its host, Cirsium arvense

Endophytic fungi live asymptomatically within plants. They are usually regarded as non-pathogenic or even mutualistic, but whether plants respond antagonistically to their presence remains unclear, particularly in the little-studied associations between endophytes and nong-raminoid herbaceous plants. We investigated the effects of the endophyte Chaetomium cochlioides on leaf chemistry in Cirsium arvense. Plants were sprayed with spores; leaf material from both subsequent new growth and the sprayed leaves was analysed 2 wk later. Infection frequency was 91% and63% for sprayed and new growth, respectively, indicating that C. cochlioides rapidly infects new foliage. Metabolomic analyses revealed marked changes in leaf chemistry with infection, especially in new growth. Changes in several novel oxylipin metabolites were detected, including arabi-dopsides reported here for the first time in a plant species other than Arabidopsis thaliana,and a jasmonate-containing galactolipid. The production of these metabolites in response to endophyte presence, particularly in newly infected foliage, suggests that endophytes elicit similar chemical responses in plants to those usually produced following wounding, herbivory and pathogen invasion. Whether en-dophytes benefit their hosts may depend on a complex series of chemically mediated interactions between the plant, the endophyte, other microbial colonists and natural enemies