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Background—The prevalence of pre–diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results—We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: 6.5%) and known diabetes mellitus compared with those with HbA1c Conclusions—In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre–diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c

Whole genome sequences of Neisseria meningitidis strains Z2491 and MC58 and Neisseria gonorrhoeae FA1090 were analyzed for Correia repeats (CR) and CR-enclosed elements (CREE). A total of 533, 516, and 256 copies of CR and 270, 261, and 102 copies of CREE were found in these three genomes, respectively. The lengths of CREE range from 28 to 348 bp, and the lengths of multicopy CREE appear mainly in the ranges of 154 to 156 bp and 105 to 107 bp. The distribution of CREE lengths is similar between the two N. meningitidis genomes, with a greater number of 154- to 156-bp CREE (163 and 152 copies in N. meningitidis strain Z2491 and N. meningitidis strain MC58, respectively) than 105- to 107-bp CREE (72 and 77 copies). In the N. gonorrhoeae strain FA1090 genome there are relatively more 105- to 107-bp CREE (51 copies) than 154- to 156-bp CREE (36 copies). The genomic distribution of 107-bp CREE also shows similarity between the two N. meningitidis strains (15 copies share the same loci) and differences between N. meningitidis strains and N. gonorrhoeae FA1090 (only one copy is located in the same locus). Detailed sequence analysis showed that both the terminal inverted repeats and the core regions of CREE are composed of distinct basic sequence blocks. Direct TA dinucleotide repeats exist at the termini of all CREE. A survey of DNA sequence upstream of the sialyltransferase gene, lst , in several Neisseria isolates showed that 5 N. meningitidis strains contain a 107-bp CREE in this region but 25 N. gonorrhoeae strains show an exact absence of a 105-bp sequence block (i.e., the 107-bp CREE without a 5′ TA dinucleotide) in the same region. Whole-genome sequence analysis confirmed that this 105-bp indel exists in many homologous 107-bp CREE loci. Thus, we postulate that all CREE are made of target TA with indels of various lengths. Analysis of 107-bp CREE revealed that they exist predominantly in intergenic regions and are often near virulence, metabolic, and transporter genes. The abundance of CREE in Neisseria genomes suggests that they may have played a role in genome organization, function, and evolution. Their differential distribution in different pathogenic Neisseria strains may contribute to the distinct behaviors of each Neisseria species.

Organic farming (OF) has been believed to be capable of curtailing some hazardous effects associated with chemical farming (CF). However, debates also exist on whether OF can feed a world with increasing human population. We hypothesized that some improvements on OF may produce adequate crops and reduce environmental pollutions from CF. This paper makes comparative analysis of crop yield, soil organic matter and economic benefits within the practice on Biodiversity Management of Organic Farming (BMOF) at Hongyi Organic Farm (HOF) over eight years and between BMOF and CF. Linking crop production with livestock to maximal uses of by-products from each production and avoid xenobiotic chemicals, we have achieved beneficial improvement in soil properties, effective pest and weed control, and increased crop yields. After eight years experiment, we have obtained a gradual but stable increase in crop yields with a 9.6-fold increase of net income. The net income of HOF was 258,827 dollars and 24,423 dollars in 2014 and 2007 respectively. Thus, BMOF can not only feed more population, but also increase adaptive capacity of agriculture ecosystems and gain much higher economic benefits.

Background Dietary exposure from food to toxic inorganic arsenic (iAs) in the general U.S. population has not been well studied. Objectives The goal of this research was to quantify dietary As exposure and analyze the major contributors to total As (tAs) and iAs. Another objective was to compare model predictions with observed data. Methods Probabilistic exposure modeling for dietary As was conducted with the Stochastic Human Exposure and Dose Simulation–Dietary (SHEDS-Dietary) model, based on data from the National Health and Nutrition Examination Survey. The dose modeling was conducted by combining the SHEDS-Dietary model with the MENTOR-3P (Modeling ENvironment for TOtal Risk with Physiologically Based Pharmacokinetic Modeling for Populations) system. Model evaluation was conducted via comparing exposure and dose-modeling predictions against duplicate diet data and biomarker measurements, respectively, for the same individuals. Results The mean modeled tAs exposure from food is 0.38 μg/kg/day, which is approximately 14 times higher than the mean As exposures from the drinking water. The mean iAs exposure from food is 0.05 μg/kg/day (1.96 μg/day), which is approximately two times higher than the mean iAs exposures from the drinking water. The modeled exposure and dose estimates matched well with the duplicate diet data and measured As biomarkers. The major food contributors to iAs exposure were the following: vegetables (24%); fruit juices and fruits (18%); rice (17%); beer and wine (12%); and flour, corn, and wheat (11%). Approximately 10% of tAs exposure from foods is the toxic iAs form. Conclusions The general U.S. population may be exposed to tAs and iAs more from eating some foods than from drinking water. In addition, this model evaluation effort provides more confidence in the exposure assessment tools used.

Over the past 20 months, reports claiming the generation of induced pluripotent stem (iPS) cells with characteristics identical to those of embryonic stem (ES) cells from nonembryonic tissue have captured great attention in both the scientific community and the general public. In the light of the continuing controversy over the use of ES cells, these reports have profound ramifications. This review calls into question the validity of many claims made in these reports--claims that have led to the rapid and premature acceptance of using iPS cells as a viable alternative to using normal stem cells for regenerative therapy. How convincing is the evidence supporting the various claims made for the iPS cells? Are there other more plausible explanations for the same observations? What are these iPS cells? Are they really safe for therapeutic use? Should the iPS technique be considered, in the absence of any direct evidence for induction and reprogramming, as a realistic alternative for somatic cell nuclear transfer (SCNT) to generate ES-like cells? This review attempts to encourage reflections on and offer alternative views for key aspects of iPS cells and studies.

α-2,3-Sialyltransferase (Lst) is expressed on the outer membrane of Neisseria gonorrhoeae and Neisseria meningitidis and sialylates surface lipooligosaccharide (LOS), facilitating resistance to complement-mediated killing. The enzyme is constitutively expressed from a single gene ( lst ) and does not undergo antigenic or phase variation. We observed that Triton X-100 extracts of N. gonorrhoeae strain F62 contain about fivefold more sialyltransferase (Stase) activity than extracts of N. meningitidis strain MC58 ⊄3 a serogroup B acapsulate mutant. We confirmed and expanded upon this observation by showing that extracts of 16 random N. gonorrhoeae isolates contain various amounts of Stase activity, but, on average, 2.2-fold-more Stase activity than extracts of 16 N. meningitidis clinical isolates, representing several serogroups and nongroupable strains. Northern and real-time reverse transcription-PCR analysis of lst transcript levels in N. gonorrhoeae and N. meningitidis revealed that N. gonorrhoeae strains express more lst transcript than N. meningitidis strains. Although transcript levels correlate with average Stase activity observed in the two species, there was not a direct correlation between lst transcript levels and Stase activity among individual isolates of each species. Comparison of lst upstream (5′ lst ) regions of N. gonorrhoeae and N. meningitidis revealed striking sequence differences characteristic of the two pathogens. N. gonorrhoeae 5′ lst regions possess 30-bp and 13-bp elements present as single elements or as tandem repeats that exist only as single elements in the 5′ lst regions of N. meningitidis isolates. In addition, the 5′ lst regions of N. meningitidis strains have 105-bp transposon-like Correia elements which are absent in N. gonorrhoeae . Chromosomal N. gonorrhoeae 5′ lst :: lacZ translational fusions expressed 4.75 ± 0.09-fold ( n = 4) higher β-galactosidase (β-gal) activity than N. meningitidis 5′ lst :: lacZ fusions in a host-independent manner, indicating differential expression is governed at least in part by sequence variations in the 5′ lst regions. Reporter fusion assays and promoter-mapping analysis revealed that N. gonorrhoeae and N. meningitidis use different promoters with different strengths to transcribe lst . In N. gonorrhoeae , a strong sigma 70 promoter 80 bp upstream of the translational start site is used to transcribe lst , whereas this promoter is inactive in N. meningitidis . In N. meningitidis , a weak sigma 70 promoter at the 3′ terminus of a 105-bp Correia repeat-enclosed element 99 bp upstream of the translational start site is used to transcribe lst . We conclude that differential Stase expression between N. gonorrhoeae and N. meningitidis is due at least in part to differential lst gene transcription.

To examine factors influencing long-term ozone (O3) exposures by children living in urban communities, the authors analyzed longitudinal data on personal, indoor, and outdoor O3 concentrations, as well as related housing and other questionnaire information collected in the one-year-long Harvard Southern California Chronic Ozone Exposure Study. Of 224 children contained in the original data set, 160 children were found to have longitudinal measurements of O3 concentrations in at least six months of 12 months of the study period. Data for these children were randomly split into two equal sets: one for model development and the other for model validation. Mixed models with various variance-covariance structures were developed to evaluate statistically important predictors for chronic personal ozone exposures. Model predictions were then validated against the field measurements using an empirical best-linear unbiased prediction technique. The results of model fitting showed that the most important predictors for personal ozone exposure include indoor O3 concentration, central ambient O3 concentration, outdoor O3 concentration, season, gender, outdoor time, house fan usage, and the presence of a gas range in the house. Hierarchical models of personal O3 concentrations indicate the following levels of explanatory power for each of the predictive models: indoor and outdoor O3 concentrations plus questionnaire variables, central and indoor O3 concentrations plus questionnaire variables, indoor O3 concentrations plus questionnaire variables, central O3 concentrations plus questionnaire variables, and questionnaire data alone on time activity and housing characteristics. These results provide important information on key predictors of chronic human exposures to ambient O3 for children and offer insights into how to reliably and cost-effectively predict personal O3 exposures in the future. Furthermore, the techniques and findings derived from this study also have strong implications for selecting the most reliable and cost-effective exposure study design and modeling approaches for other ambient pollutants, such as fine particulate matter and selected urban air toxics.

Five bacterial strains were isolated from anaerobic enrichment cultures that had originated from inoculations with samples collected from the deep subsurface environments of the millions-of-years-old, geologically and hydrologically isolated Piceance Basin in Colorado. Small-subunit rRNA gene-based analyses indicated that all of these bacteria were closely related to Thermoanaerobacter ethanolicus , with similarities of 99.4 to 99.5%. Three isolates (X513, X514, and X561) from the five bacterial strains were used to examine physiological characteristics. These thermophilic bacteria were able to use acetate, glucose, hydrogen, lactate, pyruvate, succinate, and xylose as electron donors while reducing Fe(III), cobalt(III), chromium(VI), manganese(IV), and uranium(VI) at 60°C. One of the isolates (X514) was also able to utilize hydrogen as an electron donor for Fe(III) reduction. These bacteria exhibited diverse mineral precipitation capabilities, including the formation of magnetite (Fe 3 O 4 ), siderite (FeCO 3 ), rhodochrosite (MnCO 3 ), and uraninite (UO 2 ). The gas composition of the incubation headspace and the ionic composition of the incubation medium exerted profound influences on the types of minerals formed. The susceptibility of the thermophilic Fe(III)-reducing cultures to metabolic inhibitors specific for ferric reductase, hydrogenase, and electron transport indicated that iron reduction by these bacteria is an enzymatic process.

An important factor in evaluating health risk of near-road air pollution is to accurately estimate the traffic-related vehicle emission of air pollutants. Inclusion of traffic parameters such as road length/area, distance to roads, and traffic volume/intensity into models such as land use regression (LUR) models has improved exposure estimation. To better understand the relationship between vehicle emissions and near-road air pollution, we evaluated three traffic density-based indices: Major-Road Density (MRD), All-Traffic Density (ATD) and Heavy-Traffic Density (HTD) which represent the proportions of major roads, major road with annual average daily traffic (AADT), and major road with commercial annual average daily traffic (CAADT) in a buffered area, respectively. We evaluated the potential of these indices as vehicle emission-specific near-road air pollutant indicators by analyzing their correlation with black carbon (BC), a marker for mobile source air pollutants, using measurement data obtained from the Near-road Exposures and Effects of Urban Air Pollutants Study (NEXUS). The average BC concentrations during a day showed variations consistent with changes in traffic volume which were classified into high, medium, and low for the morning rush hours, the evening rush hours, and the rest of the day, respectively. The average correlation coefficients between BC concentrations and MRD, ATD, and HTD, were 0.26, 0.18, and 0.48, respectively, as compared with −0.31 and 0.25 for two commonly used traffic indicators: nearest distance to a major road and total length of the major road. HTD, which includes only heavy-duty diesel vehicles in its traffic count, gives statistically significant correlation coefficients for all near-road distances (50, 100, 150, 200, 250, and 300 m) that were analyzed. Generalized linear model (GLM) analyses show that season, traffic volume, HTD, and distance from major roads are highly related to BC measurements. Our analyses indicate that traffic density parameters may be more specific indicators of near-road BC concentrations for health risk studies. HTD is the best index for reflecting near-road BC concentrations which are influenced mainly by the emissions of heavy-duty diesel engines.

Magnetite is a common product of bacterial iron reduction and may serve as a potential physical indicator of biological activity in geological settings. Here the authors report the formation of single-domain magnetite under laboratory conditions by a thermophilic fermentative bacterial strain TOR-39 that was isolated from the deep subsurface. Time-course analyses were performed at 65 C to study the effect of bacterial activity on solution chemistry and magnetite formation during the growth of TOR-39. Run products were examined by transmission electron microscopy. Magnetite particles formed exclusively outside of bacterial cells and exhibited octahedral shapes having relatively equal length and width (

Thermophilic (45° to 75°C) bacteria that reduce amorphous Fe(III)-oxyhydroxide to magnetic iron oxides have been discovered in two geologically and hydrologically isolated Cretaceous- and Triassic-age sedimentary basins in the deep (>860 meters below land surface) terrestrial subsurface. Molecular analyses based on 16 S ribosomal RNA (rRNA) gene sequences revealed that some of these bacteria represent an unrecognized phylogenetic group of dissimilatory Fe(III)-reducing bacteria. This discovery adds another dimension to the study of microbial Fe(III) reduction and biogenic magnetism. It also provides examples for understanding the history of Fe(III)-reducing microorganisms and for assessing possible roles of such microorganisms on hot primitive planets.

A simple assay for quantifying O-demethylation activity is desired for investigating the microbial utilization of phenylmethylethers. Detailed experiments showed that the titanium (III) nitrilotriacetate–vicinal diol colorimetric assay produced better results when Ti(III) and vicinal diols were mixed at ratios closer to 1:1 within the appropriate pH range and when the absorbance was measured at the wavelength of maximum absorbance. Vanillate was found to be a better substrate than syringate and ferulate for the determination of O-demethylating activity by Ti(III). The Ti(III) colorimetric assay was sensitive, detecting as low as 10 μM of vicinal diol. A low concentration (

Studies have shown that the US population continues to be exposed to polychlorinated biphenyls (PCBs), despite their ban more than three decades ago, but the reasons are not fully understood. The objectives of this paper are to characterize patterns of PCBs in blood by age, gender, and ethnicity, and identify major exposure factors. EPA's Stochastic Human Exposure and Dose Simulation (SHEDS)-dietary exposure model was applied, combining fish tissue PCB levels from a NYC Asian Market survey with National Health and Nutrition Examination Survey (NHANES) dietary consumption data, and then linked with blood biomarkers for the same NHANES study subjects. Results reveal that the mean concentration of total PCBs in blood was higher with increasing age; however, for the same age, gender, and ethnicity, the blood PCB concentrations measured in the later NHANES survey were significantly lower than those in the earlier one. The decrease within an age group between the two survey periods lessened with increasing age. Blood PCBs among different ethnicities ranked differently between the older and the younger age groups within each survey. Non-Hispanic Blacks had significantly higher blood PCBs for the >30 year age group. For the 12 to ≤30 year age group, the "Asian, Pacific Islander, Native American or multiracial" group had the highest values, with patterns fairly consistent with fish consumption and modeled PCB exposure patterns. We conclude that for younger people, patterns correspond to reduced environmental contamination over time, and are strongly associated with fish consumption and dietary exposures. Higher PCB concentrations in blood of the older population may partially reflect past exposures to higher environmental PCB concentrations, particularly before the ban.

NHANES subjects self-identified as “Asian, Pacific Islander, Native American, or multiracial” (A/P/N/M) have higher levels of blood organic mercury than other racial/ethnic groups; however, the reasons for this have been unclear. This research uses exposure modeling to determine the reasons for elevated blood methylmercury (MeHg) levels, and also extends previous analyses of observed NHANES blood levels. The probabilistic SHEDS-Dietary model was applied, using MeHg fish residue data from FDA's Total Diet Study (1990–2002) combined with NHANES/WWEIA (1999–2006) fish consumption data, to generate exposure estimates by race/ethnicity, age group, and fish type. Statistical analyses of blood methylmercury levels in the (6 times larger) 1999–2006 NHANES data were compared against previous published results for 1999–2002 data.The A/P/N/M group has higher fish intake, modeled MeHg exposures, and blood levels than the general population and other racial/ethnic groups. Tuna, other saltwater fish, and other freshwater fish are key food types driving dietary MeHg exposure. The 1–

In our article (Xue et al. 2010), we cited Petito Boyce et al. (2008) based on their major conclusion stated at the end of their abstract that, “typical and high-end background exposures to inorganic arsenic in U.S. populations do not present elevated risks of carcinogenicity.” We agree with Petito Boyce et al. that we “missed an opportunity to provide additional support for” our overall conclusions, and very much appreciate that they have offered this detailed comparison showing the agreement between our modeling results. Our discussion of Petito Boyce et al. (2008)’s conclusions was intended to bolster the need to develop a more comprehensive analysis of the sources of inorganic arsenic exposure, not to suggest that their exposure analysis was incomplete or inaccurate.

A side-by-side comparison was made between a conventional vial system and a novel bottle system for cultivating flies and testing the effect of chemical exposure on the lifespan of the flies. While the two cultivation systems yielded very similar results for the effect of DEHP (di[2-ethylhexyl] phthalate) on reducing the lifespan of fruit fly Drosophila melanogaster, the new bottle system has many advantages over the conventional vial system. The bottle system allowed long-term cultivation of flies in the same bottle and thus eliminated the need for transferring of flies between vials. Foods/nutrients were provided as fresh moisture medium coated on a glass slide vertically hanged in the center of the bottle. Fly discharges and dead flies were collected onto a draw horizontally inserted into the bottom of the bottle. These features have resulted in great convenience for cultivating flies and reduced labor and media cost. The effective separation of food from discharge may allow accurate mass balance measurement and thus yield more definitive observations for understanding the actual role of calorie restriction (CR) or dietary-restriction (DR) in fly metabolism and longevity.

Censorship is the suppression of speech or, respectively, deletion of written communications each of which has likely truthful contents, but which may be considered objectionable, harmful, sensitive, or inconvenient to the government or media organizations as determined by a censor. Science is knowledge covering general truths or the operation of general laws. Thus, from a linguistic and logical point of view, these two words should never be tied together, unless some government or media organization are afraid of truths and thus have to suppress the communication of those truths.

BackgroundOccurrence of tumors at multiple sites is a hallmark of malignant cancers and contributes to the high mortality of cancers. The formation of multi-site cancers (MSCs) has conventionally been regarded as a result of hematogenous metastasis. However, some MSCs may appear as unusual in the sense of vascular dissemination pattern and therefore be explained by alternative metastasis models or even by non-metastatic independent formation mechanisms.ResultsThrough literature review and incorporation of recent advance in understanding aging and development, we identified two alternative mechanisms for the independent formation of MSCs: 1) formation of separate tumors from cancer-initiating cells (CICs) mutated at an early stage of development and then diverging as to their physical locations upon further development, 2) formation of separate tumors from different CICs that contain mutations in some convergent ways. Either of these processes does not require long-distance migration and/or vascular dissemination of cancer cells from a primary site to a secondary site. Thus, we classify the formation of these MSCs from indigenous CICs (iCICs) into a new mechanistic category of tumor formation – multigenesis.ConclusionA multigenesis view on multi-site cancer (MSCs) may offer explanations for some "unusual metastasis" and has important implications for designing expanded strategies for the diagnosis and treatment of cancers.ReviewersThis article was reviewed by Carlo C. Maley nominated by Laura F. Landweber and Razvan T. Radulescu nominated by David R. Kaplan. For the full reviews, please go to the Reviewers' comments section.

The correspondence by Cokol et al (2007) confirms a previous finding that some journals with a high impact factor (IF) publish more retractions than those with a low IF (Liu, 2006f). Their explanation is that high‐IF journals receive more scrutiny from the scientific community, and that therefore more publications are identified as flawed and subsequently retracted. Equally, they argue, low‐IF journals probably receive less attention and are therefore likely to contain more articles that ought to be retracted, but instead go unnoticed. However, this assumption is wrong and the conclusions they draw for low‐IF journals are not valid. The model by Cokol and co‐workers reflects a common view that a high IF means high quality. But the high IF for some journals is actually based—at least in part—on the high number of citations of their retracted papers (Liu, 2005a, 2007a). Rather than removing these ‘negative contributions’ from the IF calculation, these journals have continued to use their inflated IFs to promote their publications (Liu, 2006b). …