Sorption behaviour and toxicity of an herbicide safener "cyprosulfamide".

Cyprosulfamide is a herbicide safener that works against the injurious effects of herbicides such as isoxaflutole, dicamba, nicosulfuron, tembotrione, thiencarbazone-methyl. However, its sorption behaviour in soils and toxicity to aquatic organisms are yet to be thoroughly examined. This study determined the octanol-water partition coefficient, sorption properties, acute and chronic toxic effects, and potency of cyprosulfamide to the cladoceran water flea (Daphnia magna). The influence of soil properties such as organic carbon content, cation exchange capacity, pH, and field capacity on adsorption and desorption properties were also examined. The Log Kow (0.55) of cyprosulfamide was less than that of some other safeners, such as benoxacor or furilazole, found in aquatic environments. The sorption of cyprosulfamide to the soil was driven by pH, so sorption decreased with an increase in pH. Other characteristics, such as cation exchange capacity (CEC), organic carbon content, and field capacity, do not directly correlate with the distribution coefficient. Cyprosulfamide generally has a low affinity for soil and is thus mobile and prone to transport to surrounding surface waters. No lethality was observed at the highest concentration (120 mg/L) tested for acute toxicity to D. magna; hence the LC50 will be >120 mg/L. During chronic exposures, cyprosulfamide caused adverse effects at a concentration of 120 mg/L on the number of neonates and brood size. The death rate for the chronic study was a function of concentration and increased with days of exposure. Cyprosulfamide is unlikely to cause lethality to D. magna at relevant environmental concentrations.

Health status of fathead minnow (Pimephales promelas) populations in a municipal wastewater effluent-dominated stream in the Canadian prairies, Wascana Creek, Saskatchewan.

Their unique hydrological and climatic conditions render surface water systems in the southern Canadian Prairies at an elevated risk from exposure to contaminants released from municipal wastewater effluents (MWWEs). The aim of this study was to characterize the potential health effects and their underlying molecular mechanisms in populations of fathead minnow (Pimephales promelas; FHM) in Wascana Creek, an effluent dominated stream in Southern Saskatchewan, Canada. Studies were conducted during the spawning season in 2014 and 2015 to assess responses in terms of overall health, reproductive functions, plasma sex steroid hormone levels, and expression of selected genes along the hypothalamus-pituitary-gonadal axis. FHM downstream of the effluent fallout had lower gonadosomatic indices and significantly greater hepatosomatic indices compared to upstream populations. In both male and female FHMs, significantly greater occurrence and severity of gonadal degradation and delayed maturation were observed in downstream fish compared to upstream fish. Downstream males also displayed lower scores of secondary sexual characteristics and a decreasing trend in plasma 11-ketotestosterone levels. Interestingly, no indications of exposure to estrogenic compounds, such as occurrence of testicular oocytes were observed, which was in accordance with the lack of presence of key biomarkers of estrogenic exposure, such as induction of vitellogenin. In general, expression of the majority of transcripts measured in FHMs downstream of the effluent fallout was significantly downregulated, which supports observations of the general deterioration of the health and reproductive status of these fish. Chemical analysis indicated that 10 pharmaceuticals and personal care products (PPCPs) were present at the downstream site, some at sufficiently great concentrations that may present a risk to aquatic organisms. With continuous exposure to a diverse number of stressors including high nutrient and ammonia levels, the presence of a variety of PPCPs and other contaminants, Wascana Creek should be considered as an ecosystem at risk.

Prefertilization Exposure of Rainbow Trout Eggs to Per- and Polyfluoroalkyl Substances to Simulate Accumulation During Oogenesis.

Aqueous film-forming foams (AFFFs) are used in firefighting and are sources of per- and polyfluoroalkyl substances (PFAS) to the environment through surface runoff and groundwater contamination at defense and transportation sites. Little is known regarding the toxicity and bioaccumulation of newer AFFF formulations containing novel PFAS. To mimic maternal transfer of PFAS, prefertilization rainbow trout eggs were exposed to three PFAS using novel methodologies. Batches of unfertilized oocytes were exposed for 3 h to 0, 0.01, 0.1, 1, or 10 µg/ml separately to perfluorooctanoic acid, perfluorohexanoic acid, or perfluorooctanesulfonic acid in either coelomic fluid or Cortland's solution. After exposure, the gametes were fertilized and rinsed with dechlorinated water. Egg yolk was aspirated from a subset of fertilized eggs for PFAS quantification. Each PFAS was detected in yolks of eggs exposed to the respective PFAS, and yolk concentrations were directly proportional to concentrations in aqueous media to which they were exposed. Exposure in coelomic fluid or Cortland's solution resulted in similar concentrations of PFAS in egg yolks. Ratios of PFAS concentrations in oocytes to concentrations in exposure media (oocyte fluid ratios) were <0.99 when exposed from 0.01 to 10 µg/ml and <0.45 when exposed from 0.1 to 10 µg/ml for both media and all three PFAS, demonstrating that the water solubility of the chemicals was relatively great. Prefertilization exposure of eggs effectively introduced PFAS into unfertilized egg yolk. This method provided a means of mimicking maternal transfer to evaluate toxicity to developing embryos from an early stage. This method is more rapid and efficient than injection of individual fertilized eggs and avoids trauma from inserting needles into eggs. Environ Toxicol Chem 2021;40:3159-3165. © 2021 SETAC.

Ractopamine and Other Growth-Promoting Compounds in Beef Cattle Operations: Fate and Transport in Feedlot Pens and Adjacent Environments.

The current study represents a comprehensive investigation of the occurrence and fates of trenbolone acetate (TBA) and metabolites 17α-trenbolone (17α-TBOH), 17ß-TBOH, and trendione (TBO); melengesterol acetate (MGA); and the less commonly studied ß-andrenergic agonist ractopamine (RAC) in two 8 month cattle feeding trials and simulated rainfall runoff experiments. Cattle were administered TBA, MGA, or RAC, and their residues were measured in fresh feces, pen floor material, and simulated rainfall runoff from pen floor surfaces and manure-amended pasture. Concentrations of RAC ranged from 3600 ng g-1, dry weight (dw), in pen floor to 58 000 ng g-1 in fresh feces and were, on average, observed at 3-4 orders of magnitude greater than those of TBA and MGA. RAC persisted in pen floors (manure t1/2 = 18-49 days), and contamination of adjacent sites was observed, likely via transport of windblown particulates. Concentrations in runoff water from pen floors extrapolated to larger-scale commercial feedlots revealed that a single rainfall event could result in mobilization of gram quantities of RAC. This is the first report of RAC occurrence and fate in cattle feedlot environments, and will help understand the risks posed by this chemical and inform appropriate manure-management practices.

Reconstructing long-term trends in municipal sewage discharge into a small lake in northern Manitoba, Canada.

Ross Lake lies within the City of Flin Flon (Manitoba, Canada), a mining community originally formed by the Hudson Bay Mining and Smelting Company (now Hudbay Minerals Inc.) in 1927. At the time of this investigation, a continuous effluent stream from Hudbay Minerals (approximately 80 years) and a discontinuous and unknown amount of raw and minimally treated municipal sewage (>20 years, likely ending in 1951) was discharged into the north basin of the lake. Maximum concentrations of fecal sterols, such as coprostanol and terrestrial phytosterols, such as: ß-sitosterol, campesterol, stigmastanol were measured in vertical sections of sediment cores, collected from Ross Lake, in the 15-16-cm section, which likely corresponds to the 1930s. Concentrations of coprostanol increased from <1 µg g(-1) in older sediments, to 252.3 µg g(-1) organic carbon at the peak. Observed changes in concentrations of sterols, in combination with radiometric dating and changes to sediment physicochemical characteristics, support the conclusion that sediments of a depth of less than 17.5-cm depth were deposited during the post-industrial era from approximately 1930 onwards. Ratios of coprostanol to cholesterol>1, peaking at 3.6 are consistent with anecdotal information that municipal sewage was discharged into Ross Lake during the early years of urbanization, prior to changes in treatment of sewage and discharge practices that began in 1951. Finally, historical concentrations of terrestrial phytosterols followed trends similar to those of coprostanol and cholesterol and may possibly be the result of an increase in the flux of terrestrial organic matter into Ross Lake as the result of regional deforestation due to logging and fire.

Liver transplantation in 2013: challenges and controversies.

Liver transplantation has changed over the past 50 years from an experimental surgery to a life saving intervention that is the treatment of choice for selected patients with end stage liver disease. Since Starzl attempted the first liver transplant in 1963, the procedure has evolved into one that occurs over 12000 times a year worldwide and has one year survival rates approaching 90% and five year survival rates above 70%. With the success of liver transplantation, challenges and controversies have arisen as well. The aim of this review is to discuss the epidemiology of liver transplantation and highlight those challenges and controversies that exist. Current controversies include appropriate selection of recipients and equitable prioritization for allograft distribution. Future challenges include a decrement in donor quality and availability and an ageing medically complex patient and donor population. Addressing these challenges and controversies will dominate transplantation research for the foreseeable future.

Pharmacokinetics and in vivo potency of soluble epoxide hydrolase inhibitors in cynomolgus monkeys.

BACKGROUND AND PURPOSE: Soluble epoxide hydrolase inhibitors (sEHIs) possess anti-inflammatory, antiatherosclerotic, antihypertensive and analgesic properties. The pharmacokinetics (PK) and pharmacodynamics in terms of inhibitory potency of sEHIs were assessed in non-human primates (NHPs). Development of a sEHI for use in NHPs will facilitate investigations on the role of sEH in numerous chronic inflammatory conditions. EXPERIMENTAL APPROACH: PK parameters of 11 sEHIs in cynomolgus monkeys were determined after oral dosing with 0.3 mg·kg(-1). Their physical properties and inhibitory potency in hepatic cytosol of cynomolgus monkeys were examined. Dose-dependent effects of the two inhibitors 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the related acetyl piperidine derivative, 1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl) urea (TPAU), on natural blood eicosanoids, were determined. KEY RESULTS: Among the inhibitors tested, TPPU and two 4-(cyclohexyloxy) benzoic acid urea sEHIs displayed high plasma concentrations (>10 × IC(50)), when dosed orally at 0.3 mg·kg(-1). Although the 4-(cyclohexyloxy) benzoic acid ureas were more potent against monkey sEH than piperidyl ureas (TPAU and TPPU), the latter compounds showed higher plasma concentrations and more drug-like properties. The C(max) increased with dose from 0.3 to 3 mg·kg(-1) for TPPU and from 0.1 to 3 mg·kg(-1) for TPAU, although it was not linear over this range of doses. As an indication of target engagement, ratios of linoleate epoxides to diols increased with TPPU administration. CONCLUSION AND IMPLICATIONS: Our data indicate that TPPU is suitable for investigating sEH biology and the role of epoxide-containing lipids in modulating inflammatory diseases in NHPs.

Suitability of live and fire-killed small-diameter ponderosa and lodgepole pine trees for manufacturing a new structural wood composite.

Finding alternative uses for raw material from small-diameter trees is a critical problem throughout the United States. In western states, a lack of markets for small-diameter ponderosa pine (Pinus ponderosa) and lodgepole pine (Pinus contorta) can contribute to problems associated with overstocking. To test the feasibility of producing structural composite lumber (SCL) beams from these two western species, we used a new technology called steam-pressed scrim lumber (SPSL) based on scrimming technology developed in Australia. Both standing green and fire-killed ponderosa and lodgepole pine logs were used in an initial test. Fire-killed logs of both species were found to be unsuitable for producing SPSL but green logs were suitable for producing SPSL. For SPSL from green material, ponderosa pine had significantly higher modulus of rupture and work-to-maximum load values than did SPSL from lodgepole pine. Modulus of elasticity was higher for lodgepole pine. The presence of blows was greater with lodgepole pine than with ponderosa. Blows had a negative effect on the mechanical properties of ponderosa pine but no significant effect on the mechanical properties of SPSL from lodgepole pine. An evaluation of non-destructive testing methods showed that X-ray could be used to determine low density areas in parent beams. The use of a sonic compression wave tester for NDE evaluation of modulus of rupture showed some promise with SPSL but requires further research.

In situ hybridization to detect spatial gene expression in medaka.

A whole-animal tissue section in situ hybridization (ISH) system with radio-labeled probes was developed to detect differential gene expression among tissues of the small, oviparous teleost fish, Japanese medaka (Oryzias latipes). Because of its tissue- and gender-specific expression, gonadal aromatase (CYP19a) was selected as a model gene to demonstrate the potential of the system. The ISH system was validated with a 7d exposure to the model aromatase inhibitor, fadrozole. Fadrozole did not affect the magnitude of gene expression in testes, but significantly up-regulated CYP19a gene expression in ovaries. These results were confirmed with quantitative real-time-polymerase chain reaction (RT-PCR). Histological evaluation revealed that females exposed to 100microg/L fadrozole lacked mature oocytes. Male gonadal morphology was normal in all treatments. The ISH method developed in this study allowed tissue-specific resolution of gene expression in a whole animal model, as well as the ability to analyze cellular morphological detail in the same organism.

Outcome after complete percutaneous removal of infected pacemaker systems and implantable cardiac defibrillators.

The mortality of retained, infected pacemaker systems is high. We assessed the safety and rate of relapse of infection after complete percutaneous removal of leads of infected pacemaker systems. None of the 40 subjects experienced procedure-related mortality and there were no cases of relapse after a median duration of follow up of 8 years (range, 3 months to 12 years). Procedure-related complications and other adverse events during therapy are reported. Percutaneous removal of infected pacemakers in conjunction with appropriate antibiotic therapy is safe and effective.

Forced and unforced ocean temperature changes in Atlantic and Pacific tropical cyclogenesis regions.

Previous research has identified links between changes in sea surface temperature (SST) and hurricane intensity. We use climate models to study the possible causes of SST changes in Atlantic and Pacific tropical cyclogenesis regions. The observed SST increases in these regions range from 0.32 degrees C to 0.67 degrees C over the 20th century. The 22 climate models examined here suggest that century-timescale SST changes of this magnitude cannot be explained solely by unforced variability of the climate system. We employ model simulations of natural internal variability to make probabilistic estimates of the contribution of external forcing to observed SST changes. For the period 1906-2005, we find an 84% chance that external forcing explains at least 67% of observed SST increases in the two tropical cyclogenesis regions. Model "20th-century" simulations, with external forcing by combined anthropogenic and natural factors, are generally capable of replicating observed SST increases. In experiments in which forcing factors are varied individually rather than jointly, human-caused changes in greenhouse gases are the main driver of the 20th-century SST increases in both tropical cyclogenesis regions.

Sediment TCDD-EQs and EROD and MROD activities in Ranid frogs from agricultural and nonagricultural sites in Michigan (USA).

In vitro studies have demonstrated atrazine-mediated induction of 7-ethoxyresorufin O-deethylase (EROD) activity. EROD is an enzyme active in the metabolism of many compounds, including many xenobiotics. These studies have suggested that atrazine may affect reproductive function by altering steroid metabolism. The goal of this study was to determine whether relationships could be detected between measured atrazine concentrations in surface waters and the liver-somatic index (LSI) and EROD and 7-methoxyresorufin O-deethylase (MROD) activities in the livers of ranid frogs. In addition, sediment dioxin toxic equivalents (TCDD-EQs) were determined using the H4IIE-luc cell bioassay. Adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana), and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south central Michigan in the summer of 2003. Atrazine concentrations at nonagricultural sites ranged from less than the limit of quantification (0.17 microg atrazine/L) to 0.23 microg atrazine/L and did not exceed 1.2 microg atrazine/L at agricultural sites. Sediment TCDD-EQs were measurable only at one agricultural site. Of the measured parameters, only LSI values in adult male frogs differed significantly between agricultural and nonagricultural sites, with greater values observed at agricultural sites. In green frogs, EROD and MROD activities were measurable in both adult and juvenile frogs and were similar among sites. Median EROD activities ranged from 13 to 21 pmol/min/mg protein in adult male green frogs and from 5 to 13 pmol/min/mg protein in adult female green frogs. Juvenile frogs had greater EROD and MROD activities than adult frogs. Bullfrogs and leopard frogs had greater activities than did green frogs. Atrazine concentrations were significantly and negatively correlated with MROD activity in adult male green frogs (Spearman R = -0.800). LSI and EROD and MROD activities of adult female or juvenile green frogs were not significantly correlated with atrazine concentrations. These results suggest that atrazine does not appear to have a consistent association with EROD or MROD activities in wild-caught green frogs.

Use of an 'evidence-based implementation' strategy to implement evidence-based care of asthma into rural district hospital emergency departments.

INTRODUCTION: To determine if an evidence-based implementation (EBI) could lead to the successful implementation of evidence based care for adult asthma in small rural district hospitals. METHODS: A controlled trial involving eight small rural hospitals (four each in the study and control groups) was conducted. Retrospective pre-intervention audits were conducted at all eight hospitals for 7 months (1 January 2004 to 31 July 2004) and evidence-practice gaps identified. An EBI was then used to implement established guidelines for the management of asthma in the study hospitals. Post-intervention audits were then performed over a period of 7 months (1 October 2004 to 31 April 2005). RESULTS: There were 52 presentations of asthma in the study hospitals in the pre-implementation phase and 47 post-implementation. The corresponding numbers for the control hospitals were 46 and 42 respectively. There were no statistically significant differences in the severity between the groups. Following the EBI there were significant improvements at the study hospitals for the documentation of severity (8% to 62%, p <0.001), use of spirometry (12% to 62%, p <0.001) and the use of written short-term asthma plans (9% to 26%, p = 0.05). There was a decrease in use of ipratropium in mild asthma (44% to 30%, p = 0.228), an increase in the use of systemic steroids (61% to 72%, p = 0.255) and no change in prescribing antibiotics for afebrile patients with asthma (21% to 21% p = 0.956). There was no significant change in practice at the control hospitals except for a decrease in the use of systemic steroids (48% to 21%, p = 0.011). For the six clinical indicators aggregate there was a significant increase in compliance with guidelines at the study hospitals (36% to 62%, p < 0.001) but no change at the control hospitals (31% to 31%, p = 0.970). CONCLUSION: The pre-intervention audits demonstrated low levels of compliance with asthma guidelines across six clinical indicators. An EBI significantly improved compliance across these six indicators, and no improvement was noted in the control hospitals. This study demonstrates that an EBI can alter clinical practice in small rural district hospitals.

Water quality and fisheries in the Mersey estuary, England: A historical perspective.

The Mersey estuary, NW England, once had a prolific fishery but in the aftermath of the industrial revolution water quality and fisheries declined and the Mersey became infamous as one of the most polluted rivers in Europe. Until relatively recently, almost all industrial and domestic effluents were discharged without treatment resulting in abominable fouling of the shoreline, and long anoxic reaches in the upper estuary during the summer. In addition, there were unknown biological impacts resulting from a complex mixture of dangerous substances present in the river. Over 1000 million pound has been spent to remedy this situation and there is unequivocal evidence that this has had the desired effect. Dissolved oxygen is now generally >60% saturation, salmon are now found at the tidal-limit and the estuary is becoming ever more popular for sea angling. The river is no longer an embarrassing liability but is now perceived as an important asset in the economic regeneration of this region of the United Kingdom.

Plasma steroid hormone concentrations, aromatase activities and GSI in ranid frogs collected from agricultural and non-agricultural sites in Michigan (USA).

The triazine herbicide atrazine has been hypothesized to disrupt sexual development in frogs by up-regulating aromatase activity, resulting in greater estradiol (E2) concentrations and causing feminization in males. The goal of this study was to collect native ranid frogs from atrazine-exposed ponds and determine whether relationships exist between measured atrazine concentrations and the gonadosomatic index (GSI), plasma concentrations of testosterone (T), E2 or 11-ketotestosterone (KT), or with aromatase activity. In the summer of 2002 and 2003, adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana) and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south-central Michigan. Atrazine concentrations were below the limit of quantification at non-agricultural sites. Atrazine concentrations did not exceed 2 microg/L at most agricultural sites, but a concentration of 250 microg atrazine/L was measured in one sample from one site in 2002. Plasma steroid concentrations varied among locations. Aromatase activity was measurable in less than 11% of testes in adult males, and in less than 4% of testes in juvenile males. Median aromatase activities in ovaries of adult females ranged from 3 to 245 pmol/h/mg protein, and maximum activities were 2.5-fold greater in juveniles than in adults. Atrazine concentrations were not significantly correlated with any of the parameters measured in this study. These results indicate that atrazine does not up-regulate aromatase in green frogs in the wild, and does not appear to affect plasma steroid hormone concentrations.

Atrazine concentrations, gonadal gross morphology and histology in ranid frogs collected in Michigan agricultural areas.

The triazine herbicide atrazine has been suggested to be a potential disruptor of normal sexual development in male frogs. The goals of this study were to collect native ranid frogs from sites in agricultural and non-agricultural areas and determine whether hypothesised atrazine effects on the gonads could be observed at the gross morphological and histological levels. Juvenile and adult green frogs (Rana clamitans), bullfrogs (R. catesbeiana) and leopard frogs (R. pipiens) were collected in the summers of 2002 and 2003. Atrazine concentrations were below the limit of quantification at non-agricultural sites, and concentrations did not exceed 2 microg/L at most agricultural sites. One concentration greater than 200 microg atrazine/L was measured once at one site in 2002. Hermaphroditic individuals with both male and female gonad tissue in either one or both gonads, were found at a low incidence at both non-agricultural and agricultural sites, and in both adults and juveniles. Testicular oocytes (TO) were found in male frogs at most of the sites, with the greatest incidence occurring in juvenile leopard frogs. TO incidence was not significantly different between agricultural and non-agricultural sites with the exception of juveniles collected in 2003. Atrazine concentrations were not significantly correlated with the incidence of hermaphroditism, but maximum atrazine concentrations were correlated with TO incidence in juvenile frogs in 2003. However, given the lack of a consistent relationship between atrazine concentrations and TO incidence, it is more likely the TOs observed in this study result from natural processes in development rather than atrazine exposure.

The role of transthoracic echocardiography in excluding left sided infective endocarditis in Staphylococcus aureus bacteraemia.

In all patients with Staphylococcus aureus bacteraemia a transoesophageal echocardiogram is recommended to exclude infective endocarditis. We determined that a finding of normal to trivial valvular regurgitation on transthoracic echocardiogram in these patients significantly reduced the probability of infective endocarditis. Furthermore, in the absence of embolic phenomena the likelihood of infective endocarditis was less than 2%. This probability could be further reduced if the echocardiogram was performed greater than 5 days after the bacteraemia. Therefore, in the assessment of patients with S. aureus bacteraemia a transoesophageal echocardiogram is not always required to exclude infective endocarditis.

Assessing the elimination of estrogenic activity in advanced wastewater treatment with a reporter gene-based bioassay.

Estrogen-like chemicals, so-called xenoestrogens, have become a topic of concern because they are potentially capable of disturbing the hormonal balance of wildlife and humans. Effluents of wastewater treatment plants (WWTPs) are presumably the major source of xenoestrogens in the aquatic environment. In this study, we investigated eight WWTPs with respect to their input, elimination efficiency, and output of estrogenic activity by means of a reporter gene-based bioassay. All WWTPs employed activated sludge treatment with nitrification/denitrification and tertiary treatment (second nitrification and/or filtration). Estradiol equivalents (EEQs) in the influents of the WWTPs were between 5.7 and 65.8 ng/L. The greatest inputs were found in plants treating pure domestic sewage and in samples collected in winter. Process waters either had no estrogenic activity or EEQs in the range of raw sewage, depending on the source of the process water. EEQs of effluents ranged from mostly below quantification limit (0.8 ng/L) to a maximum of 5.4 ng/L in secondary and 1.4 ng/L in tertiary effluents. These findings demonstrate the elimination efficiency of the activated sludge treatment and the further improvement by additional tertiary treatment. However, several concentrated effluents elicited little, but detectable estrogenic responses in the bioassay.