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Resistance to insecticides can hamper the control of mosquitoes such as Culex quinquefasciatus, known to vector arboviruses such as West Nile virus and others. The strong selective pressure exerted on a mosquito population by the use of insecticides can result in heritable genetic changes associated with resistance. We sought to characterize genetic differences between insecticide resistant and susceptible Culex quinquefasciatus mosquitoes using targeted DNA sequencing. To that end, we developed a panel of 122 genes known or hypothesized to be involved in insecticide resistance, and used an Ion Torrent PGM sequencer to sequence 125 unrelated individuals from seven populations in the southern U.S. whose resistance phenotypes to permethrin and malathion were known from previous CDC bottle bioassay testing. Data analysis consisted of discovering SNPs (Single Nucleotide Polymorphism) and genes with evidence of copy number variants (CNVs) statistically associated with resistance. Ten of the seventeen genes found to be present in higher copy numbers were experimentally validated with real-time PCR. Of those, six, including the gene with the knock-down resistance (kdr) mutation, showed evidence of a ≥ 1.5 fold increase compared to control DNA. The SNP analysis revealed 228 unique SNPs that had significant p-values for both a Fisher’s Exact Test and the Cochran-Armitage Test for Trend. We calculated the population frequency for each of the 64 nonsynonymous SNPs in this group. Several genes not previously well characterized represent potential candidates for diagnostic assays when further validation is conducted. [ABSTRACT FROM AUTHOR]

The Gram-negative pathogen, Acinetobacter baumannii has emerged as a global nosocomial health threat affecting the majority of hospitals in the U.S. and abroad. The redox protein thioredoxin has been shown to play several roles in modulation of cellular functions affecting various virulence factors in Gram-negative pathogens. This study aims to explore the role of thioredoxin-A protein (TrxA) in A. baumannii virulence. We determined that deletion of the TrxA gene did not significantly affect resistance to environmental stressors such as temperature, salt, and pH. However, TrxA was critical for survival in the presence of elevated levels of hydrogen peroxide. Lack of TrxA was associated with decreased expression of type IV pili related genes and an inability to undergo normal twitching motility. Interestingly, the TrxA-null mutant was able to form biofilms better than the wildtype (WT) and was observed to be significantly less virulent than the WT in a pulmonary infection model. These results are supportive of thioredoxin playing a key role in A. baumannii virulence. [ABSTRACT FROM AUTHOR]

Evidence of involvement of novel biomarkers in disease pathogenesis from research cohorts often precedes an understanding of their distributions in broader populations. This study aimed to estimate the distribution of fibroblast growth factor 23 (FGF-23), an endocrine hormone that helps to regulate serum phosphate levels, in the overall US population and in important subgroups. We used a predictive model generated using data from the Framingham Health Study to estimate FGF-23 values for adults in the US National Health and Nutrition Examination Survey and the size of patient subgroups with levels of FGF-23 above selected thresholds. To assess the face validity of our FGF-23 estimates, we examined the relationship between estimated FGF-23 and cardiovascular and all-cause mortality within NHANES using Kaplan-Meier estimates and Cox proportional-hazards regression models and compared it to that observed in Framingham. Estimated FGF-23 values from NHANES were lower (median [interquartile range] 47.4 [35.8, 64.0] vs. 67.0 [54.0, 85.0] RU/mL) than the observed FGF-23 values from the Framingham cohort. Age- and sex-adjusted 10-year all-cause mortality was significantly higher (hazard ratio 2.43 [95% confidence interval: 1.42, 4.16]) for subjects with estimated FGF-23 levels in the highest versus lowest quartile. Estimating the distribution of biomarker values in the general population by applying predictive equations from smaller research cohorts is feasible and can inform drug research decision making. [ABSTRACT FROM AUTHOR]

Latent tuberculosis infection (LTBI) treatment in persons at increased risk of disease progression is a key strategy with the strong potential to increase rate of tuberculosis (TB) decline in the United States. However, LTBI treatment in homeless persons, a population at high-risk of active TB disease, is usually associated with poor adherence. We describe the impact of using directly observed treatment (DOT) versus self-administered treatments (SAT) as an adherence-improving intervention to administer four months of daily rifampin regimen for LTBI treatment among homeless adults in Atlanta. Retrospective analysis of clinical care data on 274 homeless persons who initiated daily rifampin treatment for LTBI treatment at a county health department between January 2014 and December 2016 was performed. To reduce bias from non-random assignment of treatment, an inverse probability of treatment weighted (IPTW) logistic regression model was used to assess the effect of treatment type on treatment completion. Subgroup analyses were performed to assess heterogeneity of treatment effect on LTBI completion. Of 274 LTBI treatment initiators, 177 (65%) completed treatment [DOT 118/181 (65%), SAT 59/93 (63%)]. In the fully adjusted and weighted analysis, the odds of completing LTBI treatment on DOT was 40% higher than the odds of completing treatment by SAT [adjusted odds ratio (95% CI), aOR: 1.40 (1.07, 1.82), p = 0.014]. The unstable nature of homeless persons’ lifestyle makes LTBI treatment difficult for many reasons. Our study lends support to the use of DOT to improve LTBI treatment completion among subgroups of homeless persons on treatment with daily rifampin. [ABSTRACT FROM AUTHOR]

Sugarcane ripening in Louisiana is necessary to ensure adequate sucrose levels in early-season harvested sugarcane. The response of nine sugarcane cultivar’s yield components to glyphosate and trinexapac-ethyl ripeners was determined in field trials. Glyphosate (210 g ae ha-1) and trinexapac-ethyl (200 g ai ha-1) treatments failed to increase sucrose yields more than non-ripened sugarcane. Sugarcane ripened with glyphosate or trinexapac-ethyl increased theoretical recoverable sucrose (TRS) 4 to 12% more than non-ripened sugarcane in seven out of nine cultivars, but greater TRS values were counterpoised by lower sugarcane stalk weight. An unintentional consequence of reduced late-season vegetative growth may benefit growers by allowing them to harvest more sugarcane hectares to meet their daily load quota and exposes fewer hectares to a freeze event. The cultivars HoCP 00–950, Ho 09–804, and HoCP 09–840 were not responsive to glyphosate or trinexapac-ethyl ripeners and should not be treated. A delayed harvest from 28 to 49 days after treatment (DAT) coincided with greater TRS values and 17% more sucrose yield. [ABSTRACT FROM AUTHOR]

A small PCR-generated DNA fragment was introduced into a pharmaceutical grade ink as a molecular taggant, and the DNA tagged ink was delivered onto the surface of capsules by standard high-speed offset printing. The amount of DNA in the ink on each capsule is roughly 10−12 fold lower than that allowed as safe by the United States Food and Drug Administration (FDA) and the WHO with regards to acceptable limits of residual DNA. The printed ink on the capsule surface was sampled by swabbing, followed by direct analysis of the DNA-swab complex, without subsequent DNA purification. It was shown that DNA recovered from the ink by swabbing was suitable for PCR-CE analysis—a widely used method in forensic science and was also suitable for qPCR and isothermal DNA amplification, when coupled with portable devices similar to those used for environmental sampling and food safety testing. The data set a precedent: A small DNA fragment could be introduced as an excipient into a pharmaceutical application, and thereafter tracked through the pharmaceutical supply chain via forensic DNA authentication. [ABSTRACT FROM AUTHOR]

Author summary A subset of anti-infective drugs are increasingly unavailable for patients in the United States due to pricing or withdrawal from the market. Timely market solutions are needed. We assert that solutions to ensure access to some essential anti-infective agents lie outside capital markets and that public-private partnerships may be the most viable solution. [ABSTRACT FROM AUTHOR]

Greatly enhanced atmospheric carbon dioxide (CO2) levels relative to well-mixed marine air are observed during periods of offshore winds at coastal sensor platforms in Monterey Bay, California, USA. The highest concentrations originate from urban and agricultural areas, are driven by diurnal winds, and peak in the early morning. These enhanced atmospheric levels can be detected across a ~100km wide nearshore area and represent a significant addition to total oceanic CO2 uptake. A global estimate puts the added sea-air flux of CO2 from these greatly enhanced atmospheric CO2 levels at 25 million tonnes, roughly 1% of the ocean’s annual CO2 uptake. The increased uptake over the 100 km coastal swath is of order 20%, indicating a potentially large impact on ocean acidification in productive coastal waters. [ABSTRACT FROM AUTHOR]

'HoneySweet', a transgenic plum (Prunus domestica) resistant to plum pox virus through RNAi, was deregulated in the U.S. in 2011. The compositional study of 'HoneySweet' fruit was expanded to include locations outside of the US as well as utilizing a wide variety of comparators and different collection years to see the variability possible. The results revealed that plums have a wide variation in composition and that variation among locations was greater than variation among cultivars. This was also the case for different years at one location. The results supported the supposition that the transgene and insertion event had no significant effect on the composition of 'HoneySweet' fruit even under virus pressure, and that it fell in the normal range of composition of commercially grown plums. It also suggested that the effect of environment is as great as that of genetics on the fruit composition of plums. [ABSTRACT FROM AUTHOR]

Many countries have passed environmental laws aiming at preserving natural ecosystems, such as the Endangered Species Act of 1973 in the United States. Although those regulations seem to have improved preservation, they may have had unintended consequences in energy production. Here we show that while environmental constraints on hydropower may have preserved the wilderness and wildlife by restricting the development of hydroelectric projects, they led to more greenhouse gas emissions. Environmental regulations gave rise to a replacement of hydropower, which is a renewable, relatively low-emitting source of energy, with conventional fossil-fuel power, which is highly polluting. Our estimates indicate that, on average, each megawatt of fossil fuel power-generating capacity added to the grid because of environmental constraints on hydropower development led to an increase in annual carbon dioxide emissions of about 1,400 tons. Environmental regulations focusing only on the preservation of ecosystems appear to have encouraged electric utilities to substitute dirtier fuels for hydropower in electricity generation. [ABSTRACT FROM AUTHOR]

Climate change is affecting the growth, phenology, and distribution of species across northeastern United States. In response to these changes, some species have been adversely impacted while others have benefited. One species that has benefited from climate change, historically and in response to experimental treatments, is common ragweed (Ambrosia artemisiifolia), a widely distributed annual weed and a leading cause of hay fever in North America. To better understand how climate change may affect the distribution of common ragweed, we built a maximum entropy (Maxent) predictive model using climate and bioclimatic data and over 700 observations across the eastern U.S. Our model performed well with an AUC score of 0.765 using four uncorrelated variables, including precipitation seasonality, mean diurnal temperature range, August precipitation, and January maximum temperature. After building and testing our model, we then projected potential future common ragweed distribution using a suite of 13 global climate models (GCMs) under two future greenhouse gas scenarios for mid and late-century. In addition to providing georeferenced hot spots of potential future expansion, we also provide a metric of confidence by evaluating the number of GCMs that agree. We show a substantial contraction of common ragweed in central Florida, southern Appalachian Mountains, and northeastern Virginia and areas of potential expansion at the northern margins of its current distribution, notably in northeastern U.S. However, the vast majority of this increase is projected to occur by mid-century and may be moderated somewhat by the 2070s, implying that common ragweed may be sensitive to climatic variability. Although other factors and modeling approaches should be explored, we offer preliminary insight into where common ragweed might be a new concern in the future. Due to the health impacts of ragweed, local weed control boards may be well advised to monitor areas of expansion and potentially increase eradication efforts. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to clarify whether serum matrix metalloproteinase 3 (MMP-3) levels are associated with an effect of iguratimod as add-on therapy to biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA). Methods: Forty three patients with RA were treated with iguratimod as add-on therapy to bDMARDs. They were classified into remission and non-remission groups at 24 weeks of iguratimod therapy. Remission was defined as a state with a disease activity score (DAS) <2.6 in 28 joints (termed DAS remission) and total power Doppler ultrasound (US) score <3 (termed US remission). The serum MMP-3 levels at baseline and at 12 weeks were compared between these two groups. Results: There were no significant differences in the serum MMP-3 levels at baseline between the DAS and US remission groups and the non-remission group. The serum MMP-3 levels at 12 weeks in the US remission group were significantly lower than those in the non-remission group. The ratios of the serum MMP-3 levels at baseline to those at 12 weeks in both the DAS and US remission groups were significantly lower than those in the non-remission group. An MMP-3 ratio <0.86 was determined as the cut-off value to predict US remission at 24 weeks. Conclusion: Our findings suggest that the ratios of the serum MMP-3 levels at baseline to those at 12 weeks could be used to predict remission in RA patients who are administered iguratimod as an add-on to bDMARDs. [ABSTRACT FROM AUTHOR]

Background: In many regions globally, buildings designed for harnessing heat during the cold exacerbate thermal exposures during heat waves (HWs) by maintaining elevated indoor temperatures even when high ambient temperatures have subdued. While previous experimental studies have documented the effects of ambient temperatures on cognitive function, few have observed HW effects on indoor temperatures following subjects' habitual conditions. The objective was to evaluate the differential impact of having air conditioning (AC) on cognitive function during a HW among residents of AC and non-AC buildings using a prospective observational cohort study.Methods: We followed 44 students (mean age = 20.2 years; SD = 1.8 years) from a university in the Greater Boston area, Massachusetts in the United States living in AC (n = 24) and non-AC (n = 20) buildings before, during, and after a HW. Two cognition tests were self-administered daily for a period of 12 days (July 9-July 20, 2016), the Stroop color-word test (STROOP) to assess selective attention/processing speed and a 2-digit, visual addition/subtraction test (ADD) to evaluate cognitive speed and working memory. The effect of the HW on cognitive function was evaluated using difference-in-differences (DiD) modelling.Findings: Mean indoor temperatures in the non-AC group (mean = 26.3°C; SD = 2.5°C; range = 19.6-30.4°C) were significantly higher (p < 0.001) than in the AC group (mean = 21.4°C; SD = 1.9°C; range = 17.5-25.0°C). DiD estimates show an increase in reaction time (STROOP = 13.4%, p < 0001; ADD = 13.3%, p < 0.001) and reduction in throughput (STROOP = -9.9%, p < 0.001; ADD = -6.3%, p = 0.08) during HWs among non-AC residents relative to AC residents at baseline. While ADD showed a linear relationship with indoor temperatures, STROOP was described by a U-shaped curve with linear effects below and above an optimum range (indoor temperature = 22°C-23°C), with an increase in reaction time of 16 ms/°C and 24 ms/°C for STROOP and ADD, respectively. Cognitive tests occurred right after waking, so the study is limited in that it cannot assess whether the observed effects extended during the rest of the day. Although the range of students' ages also represents a limitation of the study, the consistent findings in this young, healthy population might indicate that greater portions of the population are susceptible to the effects of extreme heat.Conclusions: Cognitive function deficits resulting from indoor thermal conditions during HWs extend beyond vulnerable populations. Our findings highlight the importance of incorporating sustainable adaptation measures in buildings to preserve educational attainment, economic productivity, and safety in light of a changing climate. [ABSTRACT FROM AUTHOR]

Background: The social and economic consequences of the global financial crisis (GFC) of 2007–9 has had serious impacts on population health, economic prospects, and overall wellbeing in all generations, particularly Millennials, Generation X, and Baby Boomers. The ways in which intergenerational inequality and global economic crises have affected population health, particularly with respect to excessive drinking and substance use in disadvantaged population groups has been understudied. Consequently, in this article, we seek to characterise the effects of the GFC on national trends in binge alcohol and substance use among Millennials, Generation X, and Baby Boomers. By doing so, we aim to contribute to a fuller understanding of the ways in which socioeconomic disadvantage engendered by the GFC has disparately affected the wellbeing of these generational cohorts. Methods and findings: We present results from National Survey on Drug Use and Health from 2007–16 to characterise binge alcohol and substance use among different generational cohorts in the United States during and after the GFC. Bivariate descriptive analysis and maximum-likelihood logit regressions focused on: (a) individual substances and binge drinking, (b) poly-use and (c) any use to simultaneously model how socioeconomic, demographic, and health characteristics were related to past-month substance use and to report the social, economic, and demographic correlates of substance use. Socioeconomic vulnerability was captured on a five-point scale comprised of: (1) health insurance status, (2) government assistance, (3) income, (4) self rated health, and (5) employment status. Millennials showed generally higher risk of binge alcohol and substance use during 2007–16 than Generation X, while Baby Boomers generally exhibited lower risk. Comparison of individual and poly-use patterns for the birth cohorts before and after reveals: Millennials were at significantly increased risk of use of binge alcohol (AOR = 1.51; 95% CI = 1.46–1.56), cocaine (AOR = 1.19; 95% CI = 1.03–1.37), heroin (AOR = 1.39; 95% CI = 1.01–1.91), and oxycontin (AOR = 2.33; 95% CI = 1.74–3.12) than Gen X while Baby Boomers were at significantly reduced risk of all substances. Nevertheless, Millennials were at significantly reduced risk of crack use (AOR = 0.33; 95% CI = 0.25–0.43) and poly-use (AOR = 0.56; 95% CI = 0.45–0.70) compared to Gen X. These differences may be related to measures of austerity and socioeconomic vulnerability. Millennials exhibited the highest vulnerability related to austerity with an average vulnerability score of 0.97 (95% CI = 0.96–0.98) while Baby Boomers exhibited the lowest average vulnerability score of 0.65 (95% CI = 0.64–0.66) with Generation X in between with 0.72 (95% CI = 0.71–0.73). Increased social and economic vulnerability after the 2007 crisis is strongly associated with higher rates of substance use in all generations. Conclusion: Millennials have been especially affected by socioeconomic changes associated with the GFC as reflected by their heightened vulnerability and increased use of binge alcohol and other substances compared to preceding generations. These findings suggest that attention is needed to address disparities in socioeconomic vulnerability, relationships to substance use and overall mental health of Millennials to mitigate the potential long term negative impacts of the GFC. In the context of a continuing international opioid and heroin crisis, the ways in which Millennials have been differentially affected warrants much greater attention both from policymakers and from researchers. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) has been reported to have a negative effect on bone mineral density (BMD) in Asian populations. Whether such an association exists in Western populations is less clear. Methods: This cross-sectional analysis of data from NHANES III, a United States national health survey conducted from 1988 to 1994, included 6089 participants aged 40–75 years, selected after excluding people with hepatitis virus serology, elevated alcohol consumption, decreased renal function, or steroid use, and pregnant females. The main outcome, BMD at the femoral neck, was measured using dual-energy X-ray absorptiometry. The primary exposure, NAFLD, was defined as moderate or severe hepatic steatosis diagnosed using abdominal ultrasonography. Result: After controlling for gender and menopausal status, race/ethnicity, age and body mass index, NAFLD was not significantly associated with BMD (beta coefficient: −0.006, 95%CI: −0.016, 0.003). A secondary analysis categorized participants with NAFLD according to their serum alanine aminotransferase (ALT) levels into high and normal ALT NAFLD groups, and compared these with the non-NAFLD group. NAFLD with higher levels of ALT was associated with lower levels of BMD (beta coefficient: −0.023, 95% CI: −0.044, −0.002). Conclusion: This study showed a relationship between NAFLD with high ALT and lower BMD in the general U.S. population. [ABSTRACT FROM AUTHOR]

Background: Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine's pharmacology and the user's biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris became the first major tobacco company to admit nicotine's addictiveness. Evolving definitions of addiction have historically affected subsequent policymaking. This article examines how Philip Morris internally conceptualized addiction immediately before and after this announcement.Methods and Findings: We analyzed previously secret, internal Philip Morris documents made available as a result of litigation against the tobacco industry. We compared these documents to public company statements and found that Philip Morris's move from public denial to public affirmation of nicotine's addictiveness coincided with pressure on the industry from poor public approval ratings, the Master Settlement Agreement (MSA), the United States government's filing of the Racketeer Influenced and Corrupt Organizations (RICO) suit, and the Institute of Medicine's (IoM's) endorsement of potentially reduced risk products. Philip Morris continued to research the causes of addiction through the 2000s in order to create successful potentially reduced exposure products (PREPs). While Philip Morris's public statements reinforce the idea that nicotine's pharmacology principally drives smoking addiction, company scientists framed addiction as the result of interconnected biological, social, psychological, and environmental determinants, with nicotine as but one component. Due to the fragmentary nature of the industry document database, we may have missed relevant information that could have affected our analysis.Conclusions: Philip Morris's research suggests that tobacco industry activity influences addiction treatment outcomes. Beyond nicotine's pharmacology, the industry's continued aggressive advertising, lobbying, and litigation against effective tobacco control policies promotes various nonpharmacological determinants of addiction. To help tobacco users quit, policy makers should increase attention on the social and environmental dimensions of addiction alongside traditional cessation efforts. [ABSTRACT FROM AUTHOR]

Tenofovir (TFV), a nucleotide reverse transcriptase inhibitor, requires two phosphorylation steps to form a competitive inhibitor of HIV reverse transcriptase. Adenylate kinase 2 (AK2) has been previously demonstrated to phosphorylate tenofovir to tenofovir-monophosphate, while creatine kinase, muscle (CKM), pyruvate kinase, muscle (PKM) and pyruvate kinase, liver and red blood cell (PKLR) each have been found to phosphorylate tenofovir-monophosphate to the pharmacologically active tenofovir-diphosphate. In the present study, genomic DNA isolated from dried blood spots collected from 505 participants from Bangkok, Thailand; Cape Town, South Africa; and New York City, USA were examined for variants in AK2, CKM, PKM, and PKLR using next-generation sequencing. The bioinformatics tools SIFT and PolyPhen predicted that 19 of the 505 individuals (3.7% frequency) carried variants in at least one kinase that would result in a decrease or loss of enzymatic activity. To functionally test these predictions, AK2 and AK2 variants were expressed in and purified from E. coli, followed by investigation of their activities towards tenofovir. Interestingly, we found that purified AK2 had the ability to phosphorylate tenofovir-monophosphate to tenofovir-diphosphate in addition to phosphorylating tenofovir to tenofovir-monophosphate. Further, four of the six AK2 variants predicted to result in a loss or decrease of enzyme function exhibited a ≥30% decrease in activity towards tenofovir in our in vitro assays. Of note, an AK2 K28R variant resulted in a 72% and 81% decrease in the formation of tenofovir-monophosphate and tenofovir-diphosphate, respectively. These data suggest that there are naturally occurring genetic variants that could potentially impact TFV activation. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is the third leading cause of cancer related deaths in the United States. Several dietary factors have been identified that modify pancreatic cancer risk, including low folate levels. In addition to nutrition and lifestyle determinants, folate status may be influenced by genetic factors such as single nucleotide polymorphisms (SNPs). In the present study, we investigated the association between folate levels, genetic polymorphisms in genes of the folate pathway, and pancreatic cancer. Methods: Serum and red blood cell (RBC) folate levels were measured in pancreatic cancer and control subjects. Genotypes were determined utilizing Taqman probes and SNP frequencies between cases and controls were assessed using Fisher’s exact test. Logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence intervals (CIs) to measure the association between genotypes and pancreatic cancer risk. The association between folate levels and SNP expression was calculated using one-way ANOVA. Results: Mean RBC folate levels were significantly lower in pancreatic cancer cases compared to unrelated controls (508.4 ± 215.9 ng/mL vs 588.3 ± 229.2 ng/mL, respectively) whereas serum folate levels were similar. Irrespective of cancer status, several SNPs were found to be associated with altered serum folate concentrations, including the D919G SNP in methionine synthase (MTR), the L474F SNP in serine hydroxymethyl transferase 1 (SHMT1) and the V175M SNP in phosphatidyl ethanolamine methyltransferase (PEMT). Further, the V allele of the A222V SNP and the E allele of the E429A SNP in methylene tetrahydrofolate reductase (MTHFR) were associated with low RBC folate levels. Pancreatic cancer risk was found to be significantly lower for the LL allele of the L78R SNP in choline dehydrogenase (CHDH; OR = 0.29; 95% CI 0.12–0.76); however, it was not associated with altered serum or RBC folate levels. [ABSTRACT FROM AUTHOR]

The American diet has changed dramatically since 1958, when Congress gave the United States Food and Drug Administration (FDA) the authority to ensure the safety of chemicals in food. Since then, thousands of chemicals have entered the food system. Yet their long-term, chronic effects have been woefully understudied, their health risks inadequately assessed. The FDA has been sluggish in considering scientific knowledge about the impact of exposures—particularly at low levels and during susceptible developmental stages. The agency’s failure to adequately account for the risks of perchlorate—a well-characterized endocrine-disrupting chemical—to vulnerable populations is representative of systemic problems plaguing the regulation of chemicals in food. Today, we are faced with a regulatory system that, weakened by decades of limited resources, has fallen short of fully enforcing its mandates. The FDA’s inability to effectively manage the safety of hundreds of chemicals is putting our children’s health at risk. [ABSTRACT FROM AUTHOR]

Heterodera glycines, the soybean cyst nematode, is the most economically important plant-parasitic nematode on soybean production in the U.S. The objectives of this study were to evaluate the potential of plant growth-promoting rhizobacteria (PGPR) strains for mortality of H. glycines J2 in vitro and for reducing nematode population density on soybean in greenhouse, microplot, and field trials. The major group causing mortality to H. glycines in vitro was the genus Bacillus that consisted of 92.6% of the total 663 PGPR strains evaluated. The subsequent greenhouse, microplot, and field trials indicated that B. velezensis strain Bve2 consistently reduced H. glycines cyst population density at 60 DAP. Bacillus mojavensis strain Bmo3 suppressed H. glycines cyst and total H. glycines population density under greenhouse conditions. Bacillus safensis strain Bsa27 and Mixture 1 (Bve2 + Bal13) reduced H. glycines cyst population density at 60 DAP in the field trials. Bacillus subtilis subsp. subtilis strains Bsssu2 and Bsssu3, and B. velezensis strain Bve12 increased early soybean growth including plant height and plant biomass in the greenhouse trials. Bacillus altitudinis strain Bal13 increased early plant growth on soybean in the greenhouse and microplot trials. Mixture 2 (Abamectin + Bve2 + Bal13) increased early plant growth in the microplot trials at 60 DAP, and also enhanced soybean yield at harvest in the field trials. These results demonstrated that individual PGPR strains and mixtures can reduce H. glycines population density in the greenhouse, microplot, and field conditions, and increased yield of soybean. [ABSTRACT FROM AUTHOR]

Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris. LtEc is an extremely stable protein complex, resistant to autoxidation, and capable of transporting O2 to tissue when transfused into mammals. These characteristics render LtEc a promising candidate for the development of the next generation HBOCs. LtEc has a short half-life in circulation, limiting its application as a bridge over days, until blood became available. Conjugation with polyethylene glycol (PEG-LtEc) can extend LtEc circulation time. This study explores PEG-LtEc pharmacokinetics and pharmacodynamics. To study PEG-LtEc pharmacokinetics, hamsters instrumented with the dorsal window chamber were subjected to a 40% exchange transfusion with 10 g/dL PEG-LtEc or LtEc and followed for 48 hours. To study the vascular response of PEG-LtEc, hamsters instrumented with the dorsal window chamber received multiple infusions of 10 g/dL PEG-LtEc or LtEc solution to increase plasma LtEc concentration to 0.5, then 1.0, and 1.5 g/dL, while monitoring the animals’ systemic and microcirculatory parameters. Results confirm that PEGylation of LtEc increases its circulation time, extending the half-life to 70 hours, 4 times longer than that of unPEGylated LtEc. However, PEGylation increased the rate of LtEc oxidation in vivo. Vascular analysis verified that PEG-LtEc showed the absence of microvascular vasoconstriction or systemic hypertension. The molecular size of PEG-LtEc did not change the colloid osmotic pressure or blood volume expansion capacity compared to LtEc, due to LtEc’s already large molecular size. Taken together, these results further encourage the development of PEG-LtEc as an O2 carrying therapeutic. [ABSTRACT FROM AUTHOR]

Cryptosporidium is a common cause of sporadic diarrheal disease and outbreaks in the United States. Increasingly, immunochromatography-based rapid cartridge assays (RCAs) are providing community laboratories with a quick cryptosporidiosis diagnostic method. In the current study, the Centers for Disease Control and Prevention (CDC), the Association of Public Health Laboratories (APHL), and four state health departments evaluated RCA-positive samples obtained during routine Cryptosporidium testing. All samples underwent “head to head” re-testing using both RCA and direct fluorescence assay (DFA). Community level results from three sites indicated that 54.4% (166/305) of Meridian ImmunoCard STAT! positives and 87.0% (67/77) of Remel Xpect positives were confirmed by DFA. When samples were retested by RCA at state laboratories and compared with DFA, 83.3% (155/186) of Meridian ImmunoCard STAT! positives and 95.2% (60/63) of Remel Xpect positives were confirmed. The percentage of confirmed community results varied by site: Minnesota, 39.0%; New York, 63.9%; and Wisconsin, 72.1%. The percentage of confirmed community results decreased with patient age; 12.5% of community positive tests could be confirmed by DFA for patients 60 years of age or older. The percentage of confirmed results did not differ significantly by sex, storage temperature, time between sample collection and testing, or season. Findings from this study demonstrate a lower confirmation rate of community RCA positives when compared to RCA positives identified at state laboratories. Elucidating the causes of decreased test performance in order to improve overall community laboratory performance of these tests is critical for understanding the epidemiology of cryptosporidiosis in the United States (US). [ABSTRACT FROM AUTHOR]

Objectives: We report information about an unpublished 1970s study (“8-way” Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. Design: Double blinded, multi-centred, randomized placebo-controlled study. Setting: 14 clinics in the United States. Participants: 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. Interventions: Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. Outcomes: Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. Results: Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were “evaluated moderate or excellent” was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. Conclusion: The available information about this “8-way Bendectin” trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. Trial registration: Not registered. [ABSTRACT FROM AUTHOR]

Research suggests climate change beliefs among science teachers mirror those of the general public, raising questions of whether teachers may be perpetuating polarization of public opinion through their classrooms. We began answering these questions with a survey of middle school science teachers (n = 24) and their students (n = 369) in North Carolina, USA. Similar to previous studies, we found that though nearly all (92.1%) of students had teachers who believe that global warming is happening, few (12%) are in classrooms with teachers who recognize that global warming is anthropogenic. We found that teacher beliefs that global warming is happening and student climate change knowledge were the strongest predictors of student belief that global warming is happening and human caused. Conversely, teacher beliefs about human causes of global warming had no relationship with student beliefs, suggesting that science teachers’ low recognition of the causes of global warming is not necessarily problematic in terms of student outcomes. These findings may be explained by previous research suggesting adolescents interpret scientific information relatively independently of ideological constraints. Though teacher polarization may be problematic in its own right, it appears that as long as climate change information is presented in classrooms, students deduce anthropogenic causes. [ABSTRACT FROM AUTHOR]

Previous studies suggested a protective effect of vitamin D against skin cancer development. However, epidemiologic studies on orally taken vitamin D and risk of skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) are few. We prospectively evaluated whether total, dietary and supplemental vitamin D intake were associated with skin cancer risk based on 63,760 women in the Nurses' Health Study (1984–2010) and 41,530 men in the Health Professionals Follow-up Study (1986–2010). Dietary information on vitamin D intake was assessed every 2 to 4 years during the follow-up and cumulative averaged intake was used. We used Cox proportional hazard models to compute the hazard ratios (HR) and 95% confidence intervals (CI). Pooled HR of cohort-specific results were calculated using a random-effects model. During the follow-up, we documented 20,840 BCC, 2,329 SCC and 1,320 melanoma cases. Vitamin D consumption was not associated with the risk of SCC or melanoma but was modestly positively associated with BCC; the pooled HRs of BCC for extreme quintiles of vitamin D intake were 1.10 (95%CI = 1.05–1.15; Ptrend = 0.05) for total vitamin D and 1.13 (95% CI = 1.07 to 1.20; Ptrend <0.01) for dietary vitamin D. Stratified analysis according to sun exposure related factors showed similar results. In conclusion, vitamin D intake was positively associated with risk of BCC, while null associations were found with SCC and melanoma. Our data do not support a beneficial role of orally taken vitamin D on skin cancer carcinogenesis. [ABSTRACT FROM AUTHOR]

As part of a multi-institutional study of zoo elephant welfare, we evaluated female elephants managed by zoos accredited by the Association of Zoos and Aquariums and applied epidemiological methods to determine what factors in the zoo environment are associated with reproductive problems, including ovarian acyclicity and hyperprolactinemia. Bi-weekly blood samples were collected from 95 African (Loxodonta africana) and 75 Asian (Elephas maximus) (8–55 years of age) elephants over a 12-month period for analysis of serum progestogens and prolactin. Females were categorized as normal cycling (regular 13- to 17-week cycles), irregular cycling (cycles longer or shorter than normal) or acyclic (baseline progestogens, <0.1 ng/ml throughout), and having Low/Normal (<14 or 18 ng/ml) or High (≥14 or 18 ng/ml) prolactin for Asian and African elephants, respectively. Rates of normal cycling, acyclicity and irregular cycling were 73.2, 22.5 and 4.2% for Asian, and 48.4, 37.9 and 13.7% for African elephants, respectively, all of which differed between species (P < 0.05). For African elephants, univariate assessment found that social isolation decreased and higher enrichment diversity increased the chance a female would cycle normally. The strongest multi-variable models included Age (positive) and Enrichment Diversity (negative) as important factors of acyclicity among African elephants. The Asian elephant data set was not robust enough to support multi-variable analyses of cyclicity status. Additionally, only 3% of Asian elephants were found to be hyperprolactinemic as compared to 28% of Africans, so predictive analyses of prolactin status were conducted on African elephants only. The strongest multi-variable model included Age (positive), Enrichment Diversity (negative), Alternate Feeding Methods (negative) and Social Group Contact (positive) as predictors of hyperprolactinemia. In summary, the incidence of ovarian cycle problems and hyperprolactinemia predominantly affects African elephants, and increases in social stability and feeding and enrichment diversity may have positive influences on hormone status. [ABSTRACT FROM AUTHOR]

Compared to other population groups in the United States, caries (tooth decay) is a disproportionately prevalent disease among Latino populations, especially among low-income and rural sub-groups and children under five years of age. Fluoride is a primary preventive for caries. While water fluoridation is a major and effective public health means for delivering fluoride on a mass scale, it does not reach many rural areas or population groups such as Latinos who eschew drinking water from municipal sources. This study examines the acceptability to such groups of salt fluoridation, an alternate means of delivering fluoride long used on a global scale. An ethnographic study in California’s rural Central Valley was performed. Thirty individual interviews and 5 focus groups (N = 61) were conducted in Spanish to investigate low-income Latino migrant caregivers’ experiences, views and understandings of domestic salt, oral health, caries prevention and fluoride. Audio data were transcribed, translated, coded and thematically analyzed. Table salt was readily available and frequently consumed. Both adult and child daily sodium consumption was high. Despite a general feeling that it was good, and present in dentifrices or dietary supplements, most participants had little knowledge about fluoride. Concerns were raised about cardio-vascular and other possibly deleterious effects if an increase in salt consumption occurred because fluoridated salt was viewed as having ‘extra’ benefits. Once informed about fluoride’s safety and role in caries prevention, most participants expressed willingness to use fluoridated salt, especially if it benefitted children. Reassurance about its safety and benefits, and demonstration of its taste, were important aspects of acceptance. Taste was paramount. Participants would not consume more fluoridated salt than their current salt as that would result in unpleasant changes in food flavor and taste. While salt fluoridation is acceptable, the feasibility of producing and distributing fluoridated salt in the United States is, however, complex and challenging. [ABSTRACT FROM AUTHOR]

Reducing carbon dioxide (CO2) emissions from power plants can have important “co-benefits” for public health by reducing emissions of air pollutants. Here, we examine the costs and health co-benefits, in monetary terms, for a policy that resembles the U.S. Environmental Protection Agency’s Clean Power Plan. We then examine the spatial distribution of the co-benefits and costs, and the implications of a range of cost assumptions in the implementation year of 2020. Nationwide, the total health co-benefits were $29 billion 2010 USD (95% CI: $2.3 to $68 billion), and net co-benefits under our central cost case were $12 billion (95% CI: -$15 billion to $51 billion). Net co-benefits for this case in the implementation year were positive in 10 of the 14 regions studied. The results for our central case suggest that all but one region should experience positive net benefits within 5 years after implementation. [ABSTRACT FROM AUTHOR]

Urban grasslands, landscapes dominated by turfgrasses for aesthetic or recreational groundcovers, are rapidly expanding in the United States and globally. These managed ecosystems are often less diverse than the natural or agricultural lands they replace, leading to potential losses in ecosystem functioning. Research in non-urban systems has provided evidence for increases in multiple ecosystem functions associated with greater plant diversity. To test if biodiversity-ecosystem function findings are applicable to urban grasslands, we examined the effect of plant species and genotypic diversity on three ecosystem functions, using grassland assemblages of increasing diversity that were grown within a controlled environment facility. We found positive effects of plant diversity on reduced nitrate leaching and plant productivity. Soil microbial diversity (Mean Shannon Diversity, H’) of bacteria and fungi were also enhanced in multi-species plantings, suggesting that moderate increments in plant diversity influence the composition of soil biota. The results from this study indicate that plant diversity impacts multiple functions that are important in urban ecosystems; therefore, further tests of urban grassland biodiversity should be examined in situ to determine the feasibility of manipulating plant diversity as an explicit landscape design and function trait. [ABSTRACT FROM AUTHOR]

The parasitic mite Varroa destructor has a significant worldwide impact on bee colony health. In the absence of control measures, parasitized colonies invariably collapse within 3 years. The synthetic pyrethroids tau-fluvalinate and flumethrin have proven very effective at managing this mite within apiaries, but intensive control programs based mainly on one active ingredient have led to many reports of pyrethroid resistance. In Europe, a modification of leucine to valine at position 925 (L925V) of the V. destructor voltage-gated sodium channel was correlated with resistance, the mutation being found at high frequency exclusively in hives with a recent history of pyrethroid treatment. Here, we identify two novel mutations, L925M and L925I, in tau-fluvalinate resistant V. destructor collected at seven sites across Florida and Georgia in the Southeastern region of the USA. Using a multiplexed TaqMan® allelic discrimination assay, these mutations were found to be present in 98% of the mites surviving tau-fluvalinate treatment. The mutations were also found in 45% of the non-treated mites, suggesting a high potential for resistance evolution if selection pressure is applied. The results from a more extensive monitoring programme, using the Taqman® assay described here, would clearly help beekeepers with their decision making as to when to include or exclude pyrethroid control products and thereby facilitate more effective mite management programmes. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the US. Emerging employer-sponsored work health programs (WHP) and Digital Health Intervention (DHI) provide monitoring and guidance based on participants’ health risk assessments, but with uncertain success. DHI–mobile technology including online and smartphone interventions–has previously been found to be beneficial in reducing CVD outcomes and risk factors, however its use and efficacy in a large, multisite, primary prevention cohort has not been described to date. We analyzed usage of DHI and change in intermediate markers of CVD over the course of one year in 30,974 participants of a WHP across 81 organizations in 42 states between 2011 and 2014, stratified by participation log-ins categorized as no (n = 14,173), very low (<12/yr, n = 12,260), monthly (n = 3,360), weekly (n = 651), or semi-weekly (at least twice per week). We assessed changes in weight, waist circumference, body mass index (BMI), blood pressure, lipids, and glucose at one year, as a function of participation level. We utilized a Poisson regression model to analyze variables associated with increased participation. Those with the highest level of participation were slightly, but significantly (p<0.0001), older (48.3±11.2 yrs) than non-participants (47.7±12.2 yr) and more likely to be females (63.7% vs 37.3% p<0.0001). Significant improvements in weight loss were demonstrated with every increasing level of DHI usage with the largest being in the semi-weekly group (-3.39±1.06 lbs; p = 0.0013 for difference from weekly). Regression analyses demonstrated that greater participation in the DHI (measured by log-ins) was significantly associated with older age (p<0.001), female sex (p<0.001), and Hispanic ethnicity (p<0.001). The current study demonstrates the success of DHI in a large, community cohort to modestly reduce CVD risk factors in individuals with high participation rate. Furthermore, participants previously underrepresented in WHPs (females and Hispanics) and those with an increased number of CVD risk factors including age and elevated BMI show increased adherence to DHI, supporting the use of this low-cost intervention to improve CVD health. [ABSTRACT FROM AUTHOR]

Invasive feral swine (Sus scrofa) cause extensive damage to agricultural and wildlife resources throughout the United States. Development of sodium nitrite as a new, orally delivered toxicant is underway to provide an additional tool to curtail growth and expansion of feral swine populations. A micro-encapsulation coating around sodium nitrite is used to minimize detection by feral swine and maximize stability for the reactive molecule. To maximize uptake of this toxicant by feral swine, development a bait matrix is needed to 1) protect the micro-encapsulation coating so that sodium nitrite remains undetectable to feral swine, 2) achieve a high degree of acceptance by feral swine, and 3) be minimally appealing to non-target species. With these purposes, a field evaluation at 88 sites in south-central Texas was conducted using remote cameras to evaluate preferences by feral swine for several oil-based bait matrices including uncolored peanut paste, black-colored peanut paste, and peanut-based slurry mixed onto whole-kernel corn. These placebo baits were compared to a reference food, whole-kernel corn, known to be readily taken by feral swine (i.e., control). The amount of bait consumed by feral swine was also estimated using remote cameras and grid boards at 5 additional sites. On initial exposure, feral swine showed reduced visitations to the uncolored peanut paste and peanut slurry treatments. This reduced visitation subsided by the end of the treatment period, suggesting that feral swine needed time to accept these bait types. The black-colored peanut paste was visited equally to the control throughout the study, and enough of this matrix was consumed to deliver lethal doses of micro-encapsulated sodium nitrite to most feral swine during 1–2 feeding events. None of the treatment matrices reduced visitations by nontarget species, but feral swine dominated visitations for all matrices. It was concluded that black-colored peanut paste achieved satisfactory preference and consumption by feral swine, and no discernable preference by non-target species, compared to the other treatments. [ABSTRACT FROM AUTHOR]