The World Health Organization recently proposed the inclusion of brominated congeners in addition to chlorinated congeners when computing the toxic equivalency (TEQ) of dioxin-like compounds (DLCs) in assessments of human health risks. In the present study, 12 polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) were analyzed by gas chromatography/high resolution mass spectrometry in the composited, archived biosolids that were collected in 32 U.S. states and the District of Columbia from 94 wastewater treatment plants by the United States Environmental Protection Agency in its 2001 national sewage sludge survey. Two PBDDs and five PBDFs were detected in the biosolids composites at varying frequencies (40–100%) with a total mean concentration of 10,000 ng/kg dry weight (range: 630–42,800), of which 1,2,3,4,6,7,8-hepta-BDF constituted about 95% by mass. Relative to commercial polybrominated diphenyl ether (PBDE) formulations, the ratio of PBDD/Fs to PBDEs in biosolids was 55-times higher (∼0.002% vs ∼0.11%), which indicates potential PBDE transformation or possibly additional sources of PBDD/Fs in the environment. The TEQ contribution of PBDD/Fs was estimated at 162 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (range: 15–672), which is equivalent to 75% (range: 12–96%) of the total TEQ in biosolids. The TEQ of DLCs released annually to U.S. soils as a result of the land application of biosolids was estimated at 720 g (range: 530–1600 g). Among all known DLCs determined in biosolids, brominated analogs contributed 370% more TEQ than did chlorinated congeners, which indicates the need to include brominated DLCs in the exposure and risk assessment of land-applied biosolids.

Widespread contamination of groundwater by chlorinated ethenes and their biological dechlorination products necessitates the reliable monitoring of liquid matrices; current methods approved by the U.S. Environmental Protection Agency (EPA) require a minimum of 5 mL of sample volume and cannot simultaneously detect all transformative products. This paper reports on the simultaneous detection of six chlorinated ethenes and ethene itself, using a liquid sample volume of 1 mL by concentrating the compounds onto an 85-µm carboxen-polydimenthylsiloxane solid-phase microextraction fiber in 5 min and subsequent chromatographic analysis in 9.15 min. Linear increases in signal response were obtained over three orders of magnitude (∼0.05 to ∼50 µM) for simultaneous analysis with coefficient of determination (R²) values of ≥ 0.99. The detection limits of the method (1.3–6 µg/L) were at or below the maximum contaminant levels specified by the EPA. Matrix spike studies with groundwater and mineral medium showed recovery rates between 79–108%. The utility of the method was demonstrated in lab-scale sediment flow-through columns assessing the bioremediation potential of chlorinated ethene-contaminated groundwater. Owing to its low sample volume requirements, good sensitivity and broad target analyte range, the method is suitable for routine compliance monitoring and is particularly attractive for interpreting the bench-scale feasibility studies that are commonly performed during the remedial design stage of groundwater cleanup projects.

Important antibiotics in human medicine have been used for many decades in animal agriculture for growth promotion and disease treatment. Several publications have linked antibiotic resistance development and spread with animal production. Aquaculture, the newest and fastest growing food production sector, may promote similar or new resistance mechanisms. This review of 650+ papers from diverse sources examines parallels and differences between land-based agriculture of swine, beef, and poultry and aquaculture. Among three key findings was, first, that of 51 antibiotics commonly used in aquaculture and agriculture, 39 (or 76%) are also of importance in human medicine; furthermore, six classes of antibiotics commonly used in both agriculture and aquaculture are also included on the World Health Organization’s (WHO) list of critically important/highly important/important antimicrobials. Second, various zoonotic pathogens isolated from meat and seafood were observed to feature resistance to multiple antibiotics on the WHO list, irrespective of their origin in either agriculture or aquaculture. Third, the data show that resistant bacteria isolated from both aquaculture and agriculture share the same resistance mechanisms, indicating that aquaculture is contributing to the same resistance issues established by terrestrial agriculture. More transparency in data collection and reporting is needed so the risks and benefits of antibiotic usage can be adequately assessed.

The threat of West Nile virus (WNV) epidemics with increasingly severe neuroinvasive infections demands the development and licensing of effective vaccines. To date, vaccine candidates based on inactivated, live-attenuated, or chimeric virus, and viral DNA and WNV protein subunits have been developed. Some have been approved for veterinary use or are under clinical investigation, yet no vaccine has been licensed for human use. Reaching the milestone of a commercialized human vaccine, however, may largely depend on the economics of vaccine production. Analysis suggests that currently only novel low-cost production technologies would allow vaccination to outcompete the cost of surveillance and clinical treatment. Here, we review progress using plants to address the economic challenges of WNV vaccine production. The advantages of plants as hosts for vaccine production in cost, speed and scalability, especially those of viral vector-based transient expression systems, are discussed. The progress in developing WNV subunit vaccines in plants is reviewed within the context of their expression, characterization, downstream processing, and immunogenicity in animal models. The development of vaccines based on enveloped and non-enveloped virus-like particles is also discussed. These advancements suggest that plants may provide a production platform that offers potent, safe and affordable human vaccines against WNV.

A meta-analysis was conducted to inform the epistemology, or theory of knowledge, of contaminants of emerging concern (CECs). The CEC terminology acknowledges the existence of harmful environmental agents whose identities, occurrences, hazards, and effects are not sufficiently understood. Here, data on publishing activity were analyzed for 12 CECs, revealing a common pattern of emergence, suitable for identifying past years of peak concern and forecasting future ones: dichlorodiphenyltrichloroethane (DDT; 1972, 2008), trichloroacetic acid (TCAA; 1972, 2009), nitrosodimethylamine (1984), methyl tert-butyl ether (2001), trichloroethylene (2005), perchlorate (2006), 1,4-dioxane (2009), prions (2009), triclocarban (2010), triclosan (2012), nanomaterials (by 2016), and microplastics (2022 ± 4). CECs were found to emerge from obscurity to the height of concern in 14.1 ± 3.6 years, and subside to a new baseline level of concern in 14.5 ± 4.5 years. CECs can emerge more than once (e.g., TCAA, DDT) and the multifactorial process of emergence may be driven by inception of novel scientific methods (e.g., ion chromatography, mass spectrometry and nanometrology), scientific paradigm shifts (discovery of infectious proteins), and the development, marketing and mass consumption of novel products (antimicrobial personal care products, microplastics and nanomaterials). Publishing activity and U.S. regulatory actions were correlated for several CECs investigated.

Osteosarcoma is the most common bone cancer in children and adolescents. Although 70% of patients with localized disease are cured with chemotherapy and surgical resection, patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T lymphocytes (CTLs) limit the development of metastatic osteosarcoma. We have investigated the role of PD-1, an inhibitory TNFR family protein expressed on CTLs, in limiting the efficacy of immune-mediated control of metastatic osteosarcoma. We show that human metastatic, but not primary, osteosarcoma tumors express a ligand for PD-1 (PD-L1) and that tumor-infiltrating CTLs express PD-1, suggesting this pathway may limit CTLs control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor-infiltrating CTLs during disease progression. Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcoma-reactive CTLs in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. Our results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy.

Processed municipal sewage sludges (MSS) are an abundant, unwanted by-product of wastewater treatment, increasingly applied to agriculture and forestry for inexpensive disposal and soil conditioning. Due to their high organic carbon and lipid contents, MSS not only is rich in carbon and nutrients but also represents a “sink” for recalcitrant, hydrophobic, and potentially bioaccumulative compounds. Indeed, many organics sequestered and concentrated in MSS meet the US Environmental Protection Agency’s definition of being persistent, bioaccumulative, and toxic (PBT). In a strategic effort, our research team at the Biodesign Institute has created the National Sewage Sludge Repository (NSSR), a large repository of digested MSSs from 164 wastewater treatment plants from across the USA, as part of the Human Health Observatory (H2O) at Arizona State University (ASU). The NSSR likely represents the largest archive of digested MSS specimens in the USA. The present study summarizes key findings gleaned thus far from analysis of NSSR samples. For example, we evaluated the content of toxicants in MSS and computed estimates of nationwide inventories of mass produced chemicals that become sequestrated in sludge and later are released into the environment during sludge disposal on land. Ongoing efforts document co-occurrence of a variety of PBT compounds in both MSS and human samples, while also identifying a large number of potentially harmful MSS constituents for which human exposure data are still lacking. Finally, we summarize future opportunities and invite collaborative use of the NSSR by the research community. The H2O at ASU represents a new resource and research tool for environmental scientists and the larger research community. As illustrated in this work, this repository can serve to (i) identify and prioritize emerging contaminants, (ii) provide spatial and temporal trends of contaminants, (iii) inform and evaluate the effectiveness of environmental policy-making and regulations, and (iv) approximate, ongoing exposures and body burdens of mass-produced chemicals in human society.

Perchloroethylene (PCE) is a highly utilized solvent in the dry cleaning industry because of its cleaning effectiveness and relatively low cost to consumers. According to the 2006 U.S. Census, approximately 28,000 dry cleaning operations used PCE as their principal cleaning agent. Widespread use of PCE is problematic because of its adverse impacts on human health and environmental quality. As PCE use is curtailed, effective alternatives must be analyzed for their toxicity and impacts to human health and the environment. Potential alternatives to PCE in dry cleaning include dipropylene glycol n-butyl ether (DPnB) and dipropylene glycol tert-butyl ether (DPtB), both promising to pose a relatively smaller risk. To evaluate these two alternatives to PCE, we established and scored performance criteria, including chemical toxicity, employee and customer exposure levels, impacts on the general population, costs of each system, and cleaning efficacy. The scores received for PCE were 5, 5, 3, 5, 3, and 3, respectively, and DPnB and DPtB scored 3, 1, 2, 2, 4, and 4, respectively. An aggregate sum of the performance criteria yielded a favorably low score of “16” for both DPnB and DPtB compared to “24” for PCE. We conclude that DPnB and DPtB are preferable dry cleaning agents, exhibiting reduced human toxicity and a lesser adverse impact on human health and the environment compared to PCE, with comparable capital investments, and moderately higher annual operating costs.

Cervical cancer is the most common malignancy among women particularly in developing countries, with human papillomavirus (HPV) 16 causing 50% of invasive cervical cancers. A plant-based HPV vaccine is an alternative to the currently available virus-like particle (VLP) vaccines, and would be much less expensive. We optimized methods to express HPV16 L1 protein and purify VLPs from tobacco (Nicotiana benthamiana) leaves transfected with the magnICON deconstructed viral vector expression system. L1 proteins were extracted from agro-infiltrated leaves using a series of pH and salt mediated buffers. Expression levels of L1 proteins and VLPs were verified by immunoblot and ELISA, which confirmed the presence of sequential and conformational epitopes, respectively. Among three constructs tested (16L1d22, TPL1d22, and TPL1F), TPL1F, containing a full-length L1 and chloroplast transit peptide, was best. Extraction of HPV16 L1 from leaf tissue was most efficient (> 2.5% of total soluble protein) with a low-salt phosphate buffer. VLPs were purified using both cesium chloride (CsCl) density gradient and size exclusion chromatography. Electron microscopy studies confirmed the presence of assembled forms of HPV16 L1 VLPs. Collectively; our results indicated that chloroplast-targeted transient expression in tobacco plants is promising for the production of a cheap, efficacious HPV16 L1 VLP vaccine. Studies are underway to develop plant VLPs for the production of a cervical cancer vaccine.

The botanical, Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overall in vivo effects of A. membranaceus on the human body. This study evaluates the physiological responses to A. membranaceus by measuring leukocyte, platelet, and cytokine responses as well as body temperature and blood pressure in healthy individuals after the in vivo administration of A. membranaceus. A dose-dependent increase in monocytes, neutrophils, and lymphocytes was measured 8–12 hours after administration and an increase in the number of circulating platelets was seen as early as 4 hours. A dynamic change in the levels of circulating cytokines was observed, especially in interferon-γ and tumor necrosis factor-α, IL-13, IL-6, and soluble IL-2R. Subjective symptoms reported by participants were similar to those typically experienced in viral type immune responses and included fatigue, malaise, and headache. Systolic and diastolic blood pressure were reduced within 4 hours after administration, while body temperature mildly increased within 8 hours after administration. In general, all responses returned to baseline values by 24 hours. Collectively, these results support the role of A. membranaceus in priming for a potential immune response as well as its effect on blood flow and wound healing.