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In the United States, breast cancer is one of the most common and the second leading cause of cancer-related death in women. Treatment modalities for mammary tumor are surgical removal of the tumor tissue followed by either chemotherapy or radiotherapy or both. Radiation therapy is a whole body irradiation regimen that suppresses the immune system leaving hosts susceptible to infection or secondary tumors. Boron neutron capture therapy (BNCT) in that regard is more selective, the cells that are mostly affected are those that are loaded with 109 or more 10B atoms. Previously, we have described that liposomal encapsulation of boron-rich compounds such as TAC and MAC deliver a high payload to the tumor tissue when injected intravenously. Here we report that liposome-mediated boron delivery to the tumor is inversely proportional to the size of the murine mammary (EMT-6) tumors. The plausible reason for the inverse ratio of boron and EMT-6 tumor size is the necrosis in these tumors, which is more prominent in the large tumors. The large tumors also have receding blood vessels contributing further to poor boron delivery to these tumors. We next report that the presence of boron in blood is essential for the effects of BNCT on EMT-6 tumor inhibition as direct injection of boron-rich liposomes did not provide any added advantage in inhibition of EMT-6 tumor in BALB/c mice following irradiation despite having a significantly higher amount of boron in the tumor tissue. BNCT reaction in PBMCs resulted in the modification of these cells to anti-tumor phenotype. In this study, we report the immunomodulatory effects of BNCT when boron-rich compounds are delivered systemically. [ABSTRACT FROM AUTHOR]

Prostate cancer was the most common form and had the second highest death rate of male cancer in the United States in 2015. Current diagnosis techniques, such as prostate-specific antigen tests, transrectal ultrasound scans, and biopsies, are often inconclusive, and in the latter case, invasive. Here, we explore the use of clofazimine hydrochloride nanoparticles (CFZ-HCl NPs), a repurposed formulation from an FDA-approved antimycobacterial agent, as a photoacoustic contrast agent for the evaluation of prostate cancer due to its macrophage-targeting capabilities and high optical absorbance at 495 nm. Using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, our results indicate a preferential accumulation of intravenously injected CFZ-HCl NPs in cancerous prostates over normal prostates. Differences in accumulation of CFZ-HCl NPs between cancerous and normal prostates were determined using a two-wavelength unmixing technique via ex vivo photoacoustic imaging. Thus, intravenous injection of CFZ-HCl NPs leads to differences in the interactions of the particles with cancerous vs normal prostates, while allowing for photoacoustic detection and analysis of prostate cancer. These findings could lead to the development of a new noninvasive technique for the detection and monitoring of prostate cancer progression in an animal model that can potentially be translated to human patients. [ABSTRACT FROM AUTHOR]

Virtual three-dimensional (3D) surface models of autopsied human brain hemispheres were constructed by integrating multiple two-dimensional (2D) photographs. To avoid gravity-dependent deformity, formalin-fixed hemispheres were placed on non-refractile, transparent acrylic plates, which allowed us to take 2D photographs from various different angles. Photogrammetric calculations using software (ReCap Pro cloud service, Autodesk, San Rafael, CA, USA) allowed us calculate the 3D surface of each brain hemisphere. Virtual brain models could be moved and rotated freely to allow smooth, seamless views from different angles and different magnifications. When viewing rotating 3D models on 2D screens, 3D aspects of the models were enhanced using motion parallax. Comparison of different brains using this method allowed us to identify disease-specific patterns of macroscopic atrophy, that were not apparent in conventional 2D photographs. For example, we observed frontal lobe atrophy in a progressive supranuclear palsy brain, and even more subtle atrophy in the superior temporal gyrus in amyotrophic lateral sclerosis-frontotemporal lobar degeneration. Thus, our method facilities recognition of gyral atrophy. In addition, it provides a much more powerful and suitable way of visualizing the overall appearance of the brain as a three-dimensional structure. Comparison of normal and diseased brains will allow us to associate different macroscopic changes in the brain to clinical manifestations of various diseases. [ABSTRACT FROM AUTHOR]

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]

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]

This goal of this study was to highlight the importance of minerals in the diet of fish for meeting micronutrient requirements in the human diet. First arsenic, calcium, cadmium, copper, iron, molybdenum, magnesium, manganese, sodium, phosphorus, potassium, selenium, and zinc concentrations of twelve commercially available tilapia samples were measured. The nutritional value of fillets in regard to their mineral content were assessed to establish potential health benefits or risks for consumers. The health benefit value of selenium was also calculated. Positive health benefit values indicate that tilapia fillets in the United States marketplace of this study do not pose health risks associated with mercury exposures. Selenium was the trace mineral of interest. After the market study, a seven-week fish feeding trial was conducted to study the influence of organic versus inorganic dietary selenium on Nile tilapia (Oreochromis niloticus). Fish were fed two different diets enriched with the same concentration (0.01g kg-1) of selenium in form of inorganic (sodium selenite) or organic (seleno-L-methionine) selenium in triplicate groups. There were no significant differences between growth and biometrics of fish fed different diets (p>0.05). At the end of trial twelve fish from each treatment were collected. Fillets of fish fed organic selenium had selenium concentrations of 0.55 ± 0.01 μg g-1 which were significantly (p<0.05) higher than fish fed inorganic selenium at levels of 0.22 ± 0.008 μg g-1 or fish samples from the marketplace with a selenium level of 0.2 ± 0.03 μg g-1. Fish fed organic selenium also had significantly higher (p<0.05) plasma and kidney selenium in comparison to fish fed inorganic selenium. No significant differences (p>0.05) were observed in glutathione peroxidase activities in either the plasma or liver of Nile tilapia in the different treatment groups. This study shows that organic selenium is a better option for production of Nile tilapia fillets rich in selenium. [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]

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]

After 40 years, the 1976 US Toxic Substances Control Act (TSCA) was revised under the Frank R. Lautenberg Chemical Safety for the 21st Century Act. Its original goals of protecting the public from hazardous chemicals were hindered by complex and cumbersome administrative burdens, data limitations, vulnerabilities in risk assessments, and recurring corporate lawsuits. As a result, countless chemicals were entered into commercial use without toxicological information. Few chemicals of the many identified as potential public health threats were regulated or banned. This paper explores the factors that have worked against a comprehensive and rational policy for regulating toxic chemicals and discusses whether the TSCA revisions offer greater public protection against existing and new chemicals. [ABSTRACT FROM AUTHOR]

Background: Military veterans may have higher rates of amyotrophic lateral sclerosis (ALS) mortality than non-veterans. Few studies, with sparse exposure information and mixed results, have studied relationships between military-related factors and ALS survival. We evaluated associations between military-related factors and ALS survival among U.S. military veteran cases. Methods: We followed 616 medical record-confirmed cases from enrollment (2005–2010) in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study until death or July 25, 2013, whichever came first. We ascertained vital status information from several sources within the Department of Veterans Affairs. We obtained information regarding military service, deployments, and 39 related exposures via standardized telephone interviews. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals. We adjusted for potential confounding and missing covariate data biases via inverse probability weights. We also used inverse probability weights to adjust for potential selection bias among a case group that included a disproportionate number of long-term survivors at enrollment. Results: We observed 446 deaths during 24,267 person-months of follow-up (median follow-up: 28 months). Survival was shorter for cases who served before 1950, were deployed to World War II, or mixed and applied burning agents, with HRs between 1.58 and 2.57. Longer survival was associated with exposure to: paint, solvents, or petrochemical substances; local food not provided by the Armed Forces; or burning agents or Agent Orange in the field with HRs between 0.56 and 0.73. Conclusions: Although most military-related factors were not associated with survival, associations we observed with shorter survival are potentially important because of the large number of military veterans. [ABSTRACT FROM AUTHOR]

Toxocariasis is one of the most common neglected infections of poverty in the U.S. with a reported National Health and Nutrition Examination Survey (NHANES) III (1988–1994) seroprevalence of 13.9% based on enzyme immunoassay testing. We reviewed NHANES data from 2011–2014 to assess current levels. Sera collected from NHANES 2011–2014 participants six years and older were tested for exposure using rTc-CTL-1 antigen, a more sensitive and specific recombinant antigen for IgG antibodies for Toxocara spp. These results were subdivided into children (age 6–17) and adults (age ≥ 18) and then compared between various sociodemographic characteristics. Given prior associations of Toxocara exposure with atopic disease and lead exposure, we also reviewed laboratory values including complete blood counts and blood and urine lead levels. Data from 13,509 individuals with Toxocara antibody results were examined including 3337 children (15.2%) and 10172 adults (84.8%). Overall seroprevalence was 5.1%. In adults increased antibody positivity occurred with non-White ethnicity, male gender, less than college-level education and lower income. Among children, increased antibody positivity was solely related to a lack of health insurance. Additionally, seropositivity was associated with increased blood lead and eosinophil levels in adults and both blood and urine lead levels in children. Relative to NHANES III (1988–1994), current data suggest an overall decrease in Toxocara spp. seroprevalence from 13.9% to 5.1%, however this may be artificially lowered due to difference in testing methods used. Persistent disparities appear to be associated with at-risk populations such as minority ethnicity and low socioeconomic status. [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]

Background: Paper currency by its very nature is frequently transferred from one person to another and represents an important medium for human contact with—and potential exchange of—microbes. In this pilot study, we swabbed circulating $1 bills obtained from a New York City bank in February (Winter) and June (Summer) 2013 and used shotgun metagenomic sequencing to profile the communities found on their surface. Using basic culture conditions, we also tested whether viable microbes could be recovered from bills. Results: Shotgun metagenomics identified eukaryotes as the most abundant sequences on money, followed by bacteria, viruses and archaea. Eukaryotic assemblages were dominated by human, other metazoan and fungal taxa. The currency investigated harbored a diverse microbial population that was dominated by human skin and oral commensals, including Propionibacterium acnes, Staphylococcus epidermidis and Micrococcus luteus. Other taxa detected not associated with humans included Lactococcus lactis and Streptococcus thermophilus, microbes typically associated with dairy production and fermentation. Culturing results indicated that viable microbes can be isolated from paper currency. Conclusions: We conducted the first metagenomic characterization of the surface of paper money in the United States, establishing a baseline for microbes found on $1 bills circulating in New York City. Our results suggest that money amalgamates DNA from sources inhabiting the human microbiome, food, and other environmental inputs, some of which can be recovered as viable organisms. These monetary communities may be maintained through contact with human skin, and DNA obtained from money may provide a record of human behavior and health. Understanding these microbial profiles is especially relevant to public health as money could potentially mediate interpersonal transfer of microbes. [ABSTRACT FROM AUTHOR]

Managed reef fish in the Atlantic Ocean of the southeastern United States (SEUS) support a multi-billion dollar industry. There is a broad interest in locating and protecting spawning fish from harvest, to enhance productivity and reduce the potential for overfishing. We assessed spatiotemporal cues for spawning for six species from four reef fish families, using data on individual spawning condition collected by over three decades of regional fishery-independent reef fish surveys, combined with a series of predictors derived from bathymetric features. We quantified the size of spawning areas used by reef fish across many years and identified several multispecies spawning locations. We quantitatively identified cues for peak spawning and generated predictive maps for Gray Triggerfish (Balistes capriscus), White Grunt (Haemulon plumierii), Red Snapper (Lutjanus campechanus), Vermilion Snapper (Rhomboplites aurorubens), Black Sea Bass (Centropristis striata), and Scamp (Mycteroperca phenax). For example, Red Snapper peak spawning was predicted in 24.7–29.0°C water prior to the new moon at locations with high curvature in the 24–30 m depth range off northeast Florida during June and July. External validation using scientific and fishery-dependent data collections strongly supported the predictive utility of our models. We identified locations where reconfiguration or expansion of existing marine protected areas would protect spawning reef fish. We recommend increased sampling off southern Florida (south of 27° N), during winter months, and in high-relief, high current habitats to improve our understanding of timing and location of reef fish spawning off the southeastern United States. [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]

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]

For more than three decades, foot and musculoskeletal conditions have been documented among both Asian [Elephas maximus] and African [Loxodonta africana] elephants in zoos. Although environmental factors have been hypothesized to play a contributing role in the development of foot and musculoskeletal pathology, there is a paucity of evidence-based research assessing risk. We investigated the associations between foot and musculoskeletal health conditions with demographic characteristics, space, flooring, exercise, enrichment, and body condition for elephants housed in North American zoos during 2012. Clinical examinations and medical records were used to assess health indicators and provide scores to quantitate conditions. Using multivariable regression models, associations were found between foot health and age [P value = 0.076; Odds Ratio = 1.018], time spent on hard substrates [P value = 0.022; Odds Ratio = 1.014], space experienced during the night [P value = 0.041; Odds Ratio = 1.008], and percent of time spent in indoor/outdoor exhibits during the day [P value < 0.001; Odds Ratio = 1.003]. Similarly, the main risk factors for musculoskeletal disorders included time on hard substrate [P value = 0.002; Odds Ratio = 1.050] and space experienced in indoor/outdoor exhibits [P value = 0.039; Odds Ratio = 1.037]. These results suggest that facility and management changes that decrease time spent on hard substrates will improve elephant welfare through better foot and musculoskeletal health. [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]

The U.S. health care sector is highly interconnected with industrial activities that emit much of the nation’s pollution to air, water, and soils. We estimate emissions directly and indirectly attributable to the health care sector, and potential harmful effects on public health. Negative environmental and public health outcomes were estimated through economic input-output life cycle assessment (EIOLCA) modeling using National Health Expenditures (NHE) for the decade 2003–2013 and compared to national totals. In 2013, the health care sector was also responsible for significant fractions of national air pollution emissions and impacts, including acid rain (12%), greenhouse gas emissions (10%), smog formation (10%) criteria air pollutants (9%), stratospheric ozone depletion (1%), and carcinogenic and non-carcinogenic air toxics (1–2%). The largest contributors to impacts are discussed from both the supply side (EIOLCA economic sectors) and demand side (NHE categories), as are trends over the study period. Health damages from these pollutants are estimated at 470,000 DALYs lost from pollution-related disease, or 405,000 DALYs when adjusted for recent shifts in power generation sector emissions. These indirect health burdens are commensurate with the 44,000–98,000 people who die in hospitals each year in the U.S. as a result of preventable medical errors, but are currently not attributed to our health system. Concerted efforts to improve environmental performance of health care could reduce expenditures directly through waste reduction and energy savings, and indirectly through reducing pollution burden on public health, and ought to be included in efforts to improve health care quality and safety. [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]

Ischemic heart disease (IHD) has been linked to exposures to airborne particles with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient environment and in occupational settings. Routine industrial exposure monitoring, however, has traditionally focused on total particulate matter (TPM). To assess potential benefits of PM2.5 monitoring, we compared the exposure-response relationships between both PM2.5 and TPM and incidence of IHD in a cohort of active aluminum industry workers. To account for the presence of time varying confounding by health status we applied marginal structural Cox models in a cohort followed with medical claims data for IHD incidence from 1998 to 2012. Analyses were stratified by work process into smelters (n = 6,579) and fabrication (n = 7,432). Binary exposure was defined by the 10th-percentile cut-off from the respective TPM and PM2.5 exposure distributions for each work process. Hazard Ratios (HR) comparing always exposed above the exposure cut-off to always exposed below the cut-off were higher for PM2.5, with HRs of 1.70 (95% confidence interval (CI): 1.11–2.60) and 1.48 (95% CI: 1.02–2.13) in smelters and fabrication, respectively. For TPM, the HRs were 1.25 (95% CI: 0.89–1.77) and 1.25 (95% CI: 0.88–1.77) for smelters and fabrication respectively. Although TPM and PM2.5 were highly correlated in this work environment, results indicate that, consistent with biologic plausibility, PM2.5 is a stronger predictor of IHD risk than TPM. Cardiovascular risk management in the aluminum industry, and other similar work environments, could be better guided by exposure surveillance programs monitoring PM2.5. [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]

There are currently over 2.5 million breast cancer survivors in the United States and, according to the American Cancer Society, 10 to 20 percent of these women will develop recurrent breast cancer. Early detection of recurrence can avoid unnecessary radical treatment. However, self-examination or mammography screening may not discover a recurring cancer if the number of surviving cancer cells is small, while biopsy is too invasive and cannot be frequently repeated. It is therefore important to identify non-invasive biomarkers that can detect early recurrence. The present paper develops a mathematical model of cancer recurrence. The model, based on a system of partial differential equations, focuses on tissue biomarkers that include the plasminogen system. Among them, only uPAR is known to have significant correlation to its concentration in serum and could therefore be a good candidate for serum biomarker. The model includes uPAR and other associated cytokines and cells. It is assumed that the residual cancer cells that survived primary cancer therapy are concentrated in the same location within a region with a very small diameter. Model simulations establish a quantitative relation between the diameter of the growing cancer and the total uPAR mass in the cancer. This relation is used to identify uPAR as a potential serum biomarker for breast cancer recurrence. [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]

Background: Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment) and acrolein's comparatively potent inhalation reference concentration of 0.02 µg/m3. Objectives: Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. Methods: NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old) in the NHIS (National Health Interview Survey) 2000 – 2009 (n = 271,348 subjects). A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. Results: In the highest quintile of outdoor acrolein exposure (0.05 – 0.46 µg/m3), there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI]  = 1.08 [0.98∶1.19]) relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29]) in a model limited to never smokers (n = 153,820). Conclusions: Chronic exposure to outdoor acrolein of 0.05 – 0.46 µg/m3 appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population. [ABSTRACT FROM AUTHOR]

We describe spatial patterns in environmental injustice and inequality for residential outdoor nitrogen dioxide (NO2) concentrations in the contiguous United States. Our approach employs Census demographic data and a recently published high-resolution dataset of outdoor NO2 concentrations. Nationally, population-weighted mean NO2 concentrations are 4.6 ppb (38%, p<0.01) higher for nonwhites than for whites. The environmental health implications of that concentration disparity are compelling. For example, we estimate that reducing nonwhites’ NO2 concentrations to levels experienced by whites would reduce Ischemic Heart Disease (IHD) mortality by ∼7,000 deaths per year, which is equivalent to 16 million people increasing their physical activity level from inactive (0 hours/week of physical activity) to sufficiently active (>2.5 hours/week of physical activity). Inequality for NO2 concentration is greater than inequality for income (Atkinson Index: 0.11 versus 0.08). Low-income nonwhite young children and elderly people are disproportionately exposed to residential outdoor NO2. Our findings establish a national context for previous work that has documented air pollution environmental injustice and inequality within individual US metropolitan areas and regions. Results given here can aid policy-makers in identifying locations with high environmental injustice and inequality. For example, states with both high injustice and high inequality (top quintile) for outdoor residential NO2 include New York, Michigan, and Wisconsin. [ABSTRACT FROM AUTHOR]