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.

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.

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.

The evolution of climate over the last millennium.

Knowledge of past climate variability is crucial for understanding and modeling current and future climate trends. This article reviews present knowledge of changes in temperatures and two major circulation features-El Niño-Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO)-over much of the last 1000 years, mainly on the basis of high-resolution paleoclimate records. Average temperatures during the last three decades were likely the warmest of the last millennium, about 0.2 degrees C warmer than during warm periods in the 11th and 12th centuries. The 20th century experienced the strongest warming trend of the millennium (about 0.6 degrees C per century). Some recent changes in ENSO may have been unique since 1800, whereas the recent trend to more positive NAO values may have occurred several times since 1500. Uncertainties will only be reduced through more extensive spatial sampling of diverse proxy climatic records.

Precipitation Fluctuations over Northern Hemisphere Land Areas Since the Mid-19th Century.

An extensive array of measurements extending back to the mid-19th century was used to investigate large-scale changes in precipitation over Northern Hemisphere land areas. Significant increases in mid-latitude precipitation and concurrent decreases in low-latitude precipitation have occurred over the last 30 to 40 years. Although these large-scale trends are consistent with general circulation model projections of precipitation changes associated with doubled concentrations of atmospheric carbon dioxide, they should be viewed as defining large-scale natural climatic variability. Additional work to refine regional variations and address potential network inhomogeneitics is needed. This study attempts to show secular precipitation fluctuations over hemispheric and continental-scale areas of the Northern Hemisphere.

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.

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.

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.

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.

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.

Relationship between CD4 lymphocyte count and AIDS mortality, 1986-1991.

OBJECTIVE: To determine the relationship between CD4 lymphocyte count and short-term AIDS mortality, and to determine whether this relationship changed during 1986-1991. DESIGN: A retrospective analysis of CD4 lymphocyte counts in patients dying with AIDS and estimation of median survival in patients with a CD4 count < .50 x 10(6)/l. METHODS: Absolute CD4 lymphocyte count in the 6 months before death was available for 178 patients. The terminal CD4 count was compared in five cohorts of patients dying in 12-month periods from July 1986. Kaplan-Meier survival curves were constructed using survival from date of first absolute CD4 count < 50 x 10(6)/l in 271 patients and compared for each yearly cohort. RESULTS: The median terminal CD4 lymphocyte count for all patients was 10 x 10(6)/l. The median terminal CD4 counts for each yearly cohort were: 1986/1987, 100 (n = 13); 1987-1988, 10 (n = 27); 1988-1989, 10 (n = 30); 1989/1990, 20 (n = 59); 1990-1991, 10 (n = 58). There was a significant difference in the terminal CD4 count in the 1986-1987 period compared with all other years combined, but no further changes after 1987-1988. The median survival of all patients from date of first CD4 count < 50 x 10(6)/l was 11.9 months. There was no significant difference in median survival in each yearly cohort. CONCLUSIONS: There is a close correlation between CD4 lymphocyte count and short-term mortality in AIDS. Therapeutic advances over the past 5 years are not reflected by changes in CD4 count before death or improved survival in patients with very low CD4 counts.

Tumor necrosis factor-alpha in advanced HIV infection in the absence of AIDS-related secondary infections.

The effect of HIV infection on the production of tumor necrosis factor-alpha (TNF-alpha) was examined in patients with advanced human immunodeficiency virus (HIV) infection in the absence of AIDS-related secondary infections. Serum TNF-alpha and TNF-alpha production in vitro were measured by enzyme-linked immunosorbent assay in 26 male homosexuals with CDC stage IV HIV infection without active AIDS-related secondary infections. In vitro TNF-alpha production was assayed from cultured peripheral blood mononuclear cells (PBMs) or whole blood cultures under conditions for minimising endotoxin contamination. PBMs and whole blood were cultured with and without lipopolysaccharide (LPS). Results were compared with those for 13 HIV-seronegative age- and sex-matched controls. Serum TNF-alpha concentrations were 5 +/- 16 pg/ml in HIV-infected patients and 12 +/- 17 pg/ml in controls. TNF-alpha levels in unstimulated cultures of PBMs obtained from patients were 426 +/- 511 pg/ml and 456 +/- 428 pg/ml in control cultures. There was no difference between groups in the maximal responses of cultured PBMs to stimulation with LPS (2,229 +/- 1,593 pg/ml vs. 2,504 +/- 961 pg/ml). TNF-alpha levels from unstimulated and LPS-stimulated whole blood cultures were not significantly different after adjusting for the number of cultured monocytes (2,038 +/- 1,469 pg/ml vs. 1,511 +/- 488 pg/ml). In 10 patients (38%) the TNF-alpha levels from stimulated whole blood cultures were greater than the 95% confidence interval of the control group. TNF-alpha levels in patients were not significantly altered by antiretroviral therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

An improved radionuclide technique for the detection of altered pulmonary permeability.

Technegas, an ultra-fine dry aerosol with prolonged retention in the lungs, can be modified by altering the atmosphere in which the carbon particles are generated. The modified Technegas has much faster clearance from the lung. The half-time pulmonary clearances with modified Technegas were compared to those obtained with conventional 99mTc DTPA aerosol in 50 patients. Interstitial lung disease was suspected in 12 while 38 were infected with the human immunodeficiency virus and suspected of having opportunistic lung infection. In 22 nonsmokers in whom no evidence of active pulmonary pathology was demonstrable, the mean half-time with DTPA was 52.5 min whereas the mean half-time with modified aerosol was 10.1 min. The mean half-time in 14 smokers in whom there was also no evidence of active pulmonary disease was 28.3 min with DTPA and 7.0 min with the modified method. In the 14 patients in whom altered pulmonary permeability was demonstrated by a short DTPA half-time (mean 4.8 min) there was also an accelerated half-time with modified Technegas (mean 2.5 min). It is concluded that the modified Technegas procedure offers a simple but accurate method of identifying individuals having opportunistic infection or other diffuse lung pathology.

Conditional probability of multiple coronary graft failure.

To assess the potential capability of using artery-specific factors to predict the success of coronary bypass grafting, we classified each graft according to the type of graft (mammary, single vein, or multiple skip vein), the degree of obstruction in the native coronary artery, and the size of the grafted artery. The mean patency rates for each category of graft were determined by performing early postoperative (mean 6.6 months) arteriograms in 354 patients. We found that mammary arteries gave the best results for every graft category. Skip vein grafts had a higher mean patency rate than single vein grafts for arteries with obstructions between 70% and 90% and lumina less than 2.0 mm in diameter. The results for vein and skip grafts were equivalent for the category with arteries greater than 2.0 mm and obstruction greater than 90%. Vein grafts produced better results than skip grafts for the remaining categories. Patients were classified into subgroups according to the number of actually observed graft failures. The probabilities that specific numbers of grafts would fail were calculated for each patient. These probabilities were based upon the observed patency rates for the category appropriate for each graft and the hypothesis that individual grafts within a patient fail independently. We observed an excess number of patients with no failures or multiple failures than would be expected according to the hypothesis of independent failure and category-specific patency rates. Conversely, there were fewer patients than expected who had single failures. Therefore, we postulate that there may also be global factors which influence early graft patency.

Effect of pancreatic and leukocyte elastase on hydraulic conductivity in lung interstitial segments.

Elastase-induced changes in flow were used to quantify the degradation of lung interstitial elastin. Degassed rabbit lungs were inflated with silicon rubber via airways and vessels. The lungs were cut into 1-cm-thick sections. Two chambers were bonded to each section to enclose the interstitium surrounding an arterial segment. Flow of albumin solution (0-5 g/dl) between the chambers was followed by that of the albumin solution with 0.25 g/dl pancreatic elastase solution. Driving pressure was 5 cmH(2)0, and mean interstitial pressure was either 0 or 10 cmH(2)O. Elastase caused an increase in flow in approximately 70% of the interstitial segments and a reduction in flow in the remaining segments. The elastase-induced response in flow was independent of both albumin concentration and mean interstitial pressure. Leukocyte elastase (5 units/dl) produced flow responses similar to those of 0.25 g/dl pancreatic elastase. The increased flow of leukocyte elastase was reduced by a subsequent flow with 0.25 g/dl pancreatic elastase but enhanced by a subsequent flow with a 10-fold lower concentration. A change in the order of the elastase flows reversed the concentration-dependent responses. This behavior suggests a complex interaction among the interstitial fibers after degradation by pancreatic and leukocyte elastase. Endogenous elastase-induced increases in interstitial permeability might affect blood-lymph barrier permeability, whereas elastase-induced cessation of flow might be related to the alveolar septal wall destruction observed in emphysema.

Efficacy of fluconazole in cryptococcal meningitis.

In this clinical trial, oral fluconazole was used to treat cryptococcal meningitis in 32 patients with Acquired Immune Deficiency Syndrome (AIDS). In 11 patients who received 200 to 400 mg/day of fluconazole as primary therapy, a favorable clinical response was obtained in 67% of all evaluable patients. A negative cerebrospinal fluid (CSF) culture was also reported for 86% of these cases. Fluconazole was used as second-line therapy in an additional 15 patients who were not responsive to therapy with amphotericin B or amphotericin B combined with flucytosine. Positive clinical and mycologic responses were then obtained in more than 60% of these cases. Following successful treatment with fluconazole as either the primary or secondary antifungal agent, 26 patients were evaluated during maintenance therapy with 100 to 200 mg daily of fluconazole to prevent recurrence of disease. The relapse rate was 3.2 cases of cryptococcal meningitis per 1000 patient weeks, with a mean duration of 22 weeks for maintenance therapy. An additional six patients who were also treated with either amphotericin B alone or in combination with flucytosine but were asymptomatic or CSF culture negative when treatment with fluconazole was initiated were evaluated for the safety and efficacy of maintenance therapy. Thus, treatment of fluconazole appears to be efficacious as well as safe. The incidence of superimposed infections associated in these AIDS patients make it difficult to accurately assess any adverse effects.