Pharmaceutical and personal care products-induced stress symptoms and detoxification mechanisms in cucumber plants.

Contamination of agricultural soils by pharmaceutical and personal care products (PPCPs) resulting from the application of treated wastewater, biosolids and animal wastes constitutes a potential environmental risk in many countries. To date a handful of studies have considered the phytotoxicity of individual PPCPs in crop plants, however, little is known about the effect of PPCPs as mixtures at environmentally relevant levels. This study investigated the uptake and transport, physiological responses and detoxification of a mixture of 17 PPCPs in cucumber seedlings. All PPCPs were detected at higher concentrations in roots compared to leaves, with root activity inhibited in a dose-dependent manner. At 5-50 μg/L, the mature leaves exhibited burnt edges as well as a reduction in photosynthesis pigments. Reactive oxygen species (ROS) production and lipid peroxidation increased with increasing PPCP concentrations; and their contents were greater in roots than in leaves for all PPCP treatments. Enzymes involved in various functions, including oxidative stress (superoxide dismutase and ascorbate peroxidase) and xenobiotic metabolism (peroxidase and glutathione S-transferase), were elevated to different levels depending on the PPCP concentration. Glutathione content gradually increased in leaves, while a maxima occurred at 0.5 μg L-1 PPCPs in roots, followed by a decrease thereafter. This study illustrated the complexity of phytotoxicity after exposure to PPCP mixtures, and provided insights into the molecular mechanisms likely responsible for the detoxification of PPCPs in higher plants

Acetaminophen detoxification in cucumber plants via induction of glutathione S-transferases.

Many pharmaceutical and personal care products (PPCPs) enter agroecosystems during reuse of treated wastewater and biosolids, presenting potential impacts on plant development. Here, acetaminophen, one of the most-used pharmaceuticals, was used to explore roles of glutathione (GSH) conjugation in its biotransformation in crop plants. Acetaminophen was taken up by plants, and conjugated quickly with GSH. After exposure to 5 mg L-1 acetaminophen for 144 h, GSH-acetaminophen conjugates were 15.2 ± 1.3 nmol g-1 and 1.2 ± 0.1 nmol g-1 in cucumber roots and leaves, respectively. Glutathione-acetaminophen was also observed in common bean, alfalfa, tomato, and wheat. Inhibition of cytochrome P450 decreased GSH conjugation. Moreover, the GSH conjugate was found to further convert to cysteine and N-acetylcysteine conjugates. Glutathione S-transferase activity was significantly elevated after exposure to acetaminophen, while levels of GSH decreased by 55.4% in roots after 48 h, followed by a gradual recovery thereafter. Enzymes involved in GSH synthesis, regeneration and transport were consistently induced to maintain the GSH homeostasis. Therefore, GST-mediated conjugation likely played a crucial role in minimizing phytotoxicity of acetaminophen and other PPCPs in plants

Formation of biologically active benzodiazepine metabolites in Arabidopsis thaliana cell cultures and vegetable plants under hydroponic conditions.

The use of recycled water for agricultural irrigation comes with the concern of exposure to crops by contaminants of emerging concerns (CECs). The concentration of CECs in plant tissues will depend on uptake, translocation and metabolism in plants. However, relatively little is known about plant metabolism of CECs, particularly under chronic exposure conditions. In this study, metabolism of the pharmaceutical diazepam was investigated in Arabidopsis thaliana cells and cucumber (Cucumis sativus) and radish (Raphanus sativus) seedlings grown in hydroponic solution following acute (7 d)/high concentration (1 mg L-1), and chronic (28 d)/low concentration (1 μg L-1) exposures. Liquid chromatography paired with mass spectrometry, 14C tracing, and enzyme extractions, were used to characterize the metabolic phases. The three major metabolites of diazepam - nordiazepam, temazepam and oxazepam - were detected as Phase I metabolites, with the longevity corresponding to that of human metabolism. Nordiazepam was the most prevalent metabolite at the end of the 5 d incubation in A. thaliana cells and 7 d, 28 d seedling cultivations. At the end of 7 d cultivation, non-extractable residues (Phase III) in radish and cucumber seedlings accounted for 14% and 33% of the added 14C-diazepam, respectively. By the end of 28 d incubation, the non-extractable radioactivity fraction further increased to 47% and 61%, indicating Phase III metabolism as an important destination for diazepam. Significant changes to glycosyltransferase activity were detected in both cucumber and radish seedlings exposed to diazepam. Findings of this study highlight the need to consider the formation of bioactive transformation intermediates and different phases of metabolism to achieve a comprehensive understanding of risks of CECs in agroecosystems

Use of isotope dilution method to predict bioavailability of organic pollutants in historically contaminated sediments.

Many cases of severe environmental contamination arise from historical episodes, where recalcitrant contaminants have resided in the environment for a prolonged time, leading to potentially decreased bioavailability. Use of bioavailable concentrations over bulk chemical levels improves risk assessment and may play a critical role in determining the need for remediation or assessing the effectiveness of risk mitigation operations. In this study, we applied the principle of isotope dilution to quantify bioaccessibility of legacy contaminants DDT and PCBs in marine sediments from a Superfund site. After addition of 13C or deuterated analogues to a sediment sample, the isotope dilution reached a steady state within 24 h of mixing. At the steady state, the accessible fraction (E) derived by the isotope dilution method (IDM) ranged from 0.28 to 0.89 and was substantially smaller than 1 for most compounds, indicating reduced availability of the extensively aged residues. A strong linear relationship (R2=0.86) was found between E and the sum of rapid (Fr) and slow (Fs) desorption fractions determined by sequential Tenax desorption. The IDM-derived accessible concentration (Ce) was further shown to correlate closely with tissue residue in the marine benthic polychaete Neanthes arenaceodentata exposed in the same sediments. As shown in this study, the IDM approach involves only a few simple steps and may be readily adopted in laboratories equipped with mass spectrometers. This novel method is expected to be especially useful for historically contaminated sediments or soils, for which contaminant bioavailability may have changed significantly due to aging and other sequestration processes

Effects of contaminants of emerging concern on Megaselia scalaris (Lowe, Diptera: Phoridae) and its microbial community.

Drought, rising temperatures, and expanding human populations are increasing water demands. Many countries are extending potable water supplies by irrigating crops with wastewater. Unfortunately, wastewater contains biologically active, long-lived pharmaceuticals, even after treatment. Run-off from farms and wastewater treatment plant overflows contribute high concentrations of pharmaceuticals to the environment. This study assessed the effects of common pharmaceuticals on a cosmopolitan saprophagous insect, Megaselia scalaris (Diptera: Phoridae). Larvae were reared on artificial diets spiked with contaminants of emerging concern (CECs) at environmentally relevant concentrations. Female flies showed no oviposition preference for treated or untreated diets. Larvae exposed to caffeine in diets showed increased mortality, and larvae fed antibiotics and hormones showed signs of slowed development, especially in females. The normal sex ratio observed in M. scalaris from control diets was affected by exposure to caffeine and pharmaceutical mixture treatments. There was an overall effect of treatment on the flies' microbial communities; notably, caffeine fed insects displayed higher microbial variability. Eight bacterial families accounted for approximately 95% of the total microbes in diet and insects. Our results suggest that CECs at environmentally relevant concentrations can affect the biology and microbial communities of an insect of ecological and medical importance

Levels of Adoption of Electronic Health Records and Patient Safety: Effectiveness and Efficiency

Patient safety, including hospital acquired infections has become one of the major concerns in healthcare delivery in recent years Electronic health records are becoming an integral aspect of the health care delivery Health policies have been looking to improve quality / patient safety and efficiency of healthcare through the adoption of electronic health record (EHR) systems Can EHR adoption improve patient safety? Can EHR adoption reduce cost? H1: Patients treated at hospitals with a higher level of EHR adoption are less likely to incur poorer patient safety indicators H2: Patients treated at hospitals with a higher level of EHR adoption are more likely to incur lower costs for their respective patient safety indicator

Biodegradation of pyrene in sand, silt and clay fractions of sediment

Microbial degradation is the dominant pathway for natural attenuation of PAHs in environmental compartments such as sediments, which in turn depends on the bioavailability of PAHs. The bioavailability of PAHs has seldom been studied at the sediment particle size scale. We evaluated biodegradation of pyrene by Mycobacterium vanbaalenii PYR-1 as a function of sediment particle sizes, and investigated the relationship between the rate of degradation on sand, silt and clay particles with their individual desorption kinetics measured with the Tenax extraction method. Regression analysis showed that the total organic carbon (TOC), black carbon (BC), and specific surface area (SSA) of the specific particle size fractions, instead of the particle size scale itself, were closely related (P < 0.01) with the mineralization rate. While the fraction in the rapid desorption pool (Frapid) ranged from 0.11 to 0.38 for the whole sediments and different size groups, the fractions mineralized after 336-h incubation (0.52 to 0.72) greatly surpassed the Frapid values, suggesting utilization of pyrene in the slow desorption pool (Fslow). A biodegradation model was modified by imbedding a two-phase desorption relationship describing sequential Tenax extractions. Model analysis showed that pyrene sorbed on silt and clay aggregates was directly utilized by the degrading bacteria. The enhanced bioavailability may be attributed to the higher chemical concentration, higher TOC or larger SSA in the silt and clay fractions, which appeared to overcome the reduced bioavailability of pyrene due to sorption, making pyrene on the silt and clay particles readily available to degrading microbes. This conjecture merits further investigation

A Hypomorphic Myogenin Allele Reveals Distinct Myogenin Expression Levels Required for Viability, Skeletal Muscle Development, and Sternum Formation Volume 208, Number 1 (1999), pages 44–55

AbstractThe myogenic basic helix-loop-helix transcription factor myogenin plays an essential role in the differentiation of skeletal muscle and, secondarily, in rib and sternum formation during mouse development. However, virtually nothing is known about the quantitative requirements for myogenin in these processes. Here, we describe the generation of mice carrying a hypomorphic allele ofmyogenin,which expressesmyogenintranscripts at approximately one-fourth the level of the wild-typemyogeninallele. The hypomorphic allele in combination with wild-type andmyogenin-null alleles was used to create an allelic series. Embryos representing the complete range of genotypes from homozygous wild type to homozygous null were analyzed for their viability, ability to form normal ribs and sternum, and extent of skeletal muscle differentiation. Embryos carrying the hypomorphicmyogeninallele over a wild-type allele were normal. In embryos bearing homozygous hypomorphic alleles, the sternum developed normally and extensive skeletal muscle differentiation occurred. However, muscle hypoplasia and reduced muscle-specific gene expression were apparent in these embryos, and the mice were not viable as neonates. When the hypomorphic allele was placed over amyogenin-null allele, the resulting embryos had sternum defects resembling homozygousmyogenin-null embryos, and there was severe muscle hypoplasia. Our results demonstrate that skeletal muscle formation is highly sensitive to the absolute levels of myogenin and that correct sternum formation, skeletal muscle differentiation, and viability each require distinct threshold levels of myogenin

Nonlinear interactions between radiation belt electrons and chorus waves: dependence on wave amplitude modulation

We use test particle simulations to model the interaction between radiation belt electrons and whistler mode chorus waves by focusing on wave amplitude modulations. We quantify the pitch angle and energy changes due to phase trapping and phase bunching (including both advection and scattering) for electrons with various initial energies and pitch angles. Three nonlinear regimes are identified in a broad range of pitch angle-energy space systematically, each indicating different nonlinear effects. Our simulation results show that wave amplitude modulations can extend the nonlinear regimes, while significantly reducing electron acceleration by phase trapping. By including amplitude modulations, the “advective” changes in pitch angle and energy caused by phase bunching are reduced, while the “diffusive” scattering due to phase bunching is enhanced. Our study demonstrates the importance of wave amplitude modulations in nonlinear effects and suggests that they need to be properly incorporated into future theoretical and numerical studies.Accepted manuscrip