Acute exposure and biomarkers assessment in rainbow trout exposed to selected pharmaceuticals.

Pharmaceuticals released from municipal effluents discharges pose a risk to aquatic organisms. The toxicity of 5 pharmaceuticals with distinct therapeutic actions were assessed in rainbow trout: olanzapine (antipsychotic), erythromycin (antibiotic), mycophenoate (immunosuppression), pinaverium (anti-inflammatory) and trazodone (sedative). Juveniles were exposed to these drugs for 96 h at concentrations between 64 µg/L up to 40 mg/L to reach lethality. Survival was determined and a suite of biomarkers was analyzed for drug biotransformation, oxidative stress/damage and metabolic activity at sublethal concentrations. The data revealed the following toxicity: olanzapine >trazodone>mycophenolate>pinaverium∼erythromycin based on mortality. The data also revealed that toxicity was associated to mass, pKa and hydrophobicity and the following sublethal effects: GST, LPO and DNA strand breaks. Pharmaceuticals with lower molecular weight, physiological pKa, moderate hydrophobicity, low biotransformation and DNA strand breaks were generally more toxic to fish. However, this should be considered as a general guide in identifying toxic pharmaceuticals in non-target organisms.

The influence of rainfall events on the toxicity of urban wastewaters to freshwater mussels Elliptio complanata.

The cumulative impacts of rainfall frequency and intensity towards the ecotoxicity of urban pollution is gaining more and more attention in these times of climate change. The purpose of this study was to examine the ecotoxicological impacts of combined sewers overflows and municipal effluent discharge sites during 3 periods (years) of varying intensity precipitations to freshwater mussels Elliptio complanata. Mussels were placed in benthic cages for 3 months during the summer at 2 overflow discharge and 8 km downstream sites including an upstream site for three consecutive years with low (164 mm), medium (182 mm) and high (248 mm) amounts of rain. The results revealed that the effects were mainly influenced by suspended matter loadings and to the dissolved components to a lesser extent. Impacts at the downstream and overflow sites were noticeable at the reproduction (vitellogenin), genotoxicity, neurotoxicity (dopamine and serotonin changes) levels in addition to xenobiotic biotransformation revealed by glutathione S-transferase activity and metallothioneins for organic and heavy metals respectively. The site downstream the effluent produced most of the effects compared to the overflow sites in the Saint-Lawrence River. However, the impacts of combined sewers overflows could become problematic in low dilution systems such as small river and lakes.

The geometry of the toxicity of silver nanoparticles to freshwater mussels.

The question about the influence of the geometry of silver nanoparticle (nAg) towards toxicity in aquatic organisms is largely unanswered. The purpose of this study was to examine if different geometries of nAg could initiate biophysical stress in the soft tissues of mussels. Freshwater Dreissenna bugensis mussels were exposed for 48 h at 15 °C to 10 and 50 µg/L of ionic Ag and to 3 forms of polyvinylpyrrolidone (PVP)-coated nAg of similar size: sphere, cube and prism. At the end of the exposure period, mussels were allowed to depurate overnight and the post-mitochondrial fraction of the soft tissues were analyzed for the levels of liquid crystals (LCs), changes in the activity and fractal dimensions of pyruvate kinase-lactate dehydrogenase (PK-LDH), F-actin and protein-ubiquitin (UB) levels. The data revealed that exposure to nAg forms lead to increased formation of LCs in increasing order of intensity: prismatic > cubic > spherical nAg. The activity in PK-LDH was decreased by all forms of nAg but not by ionic Ag+ (as with the following effects). Fractal kinetics of the PK-LDH system revealed that the nAg forms increased the spectral dimension (sD) in increasing order: spherical > cubic > prismatic nAg. A decrease in the fractal diffusion rate (fDR) with small changes in the fractal dimension (fD) was also obtained. The levels of F-actin and protein-UB were significantly affected for most forms of nAg and followed a pattern similar to LCs levels. In conclusion, the geometry of nAg could influence the formation of LCs, alter the fractal kinetics of the PK-LDH system, F-actin levels and protein damage in the soft tissues of freshwater mussels.

The influence of polystyrene nanoparticles on the fractal kinetics of lactate dehydrogenase.

Plastics are ubiquitous in the aquatic environment and their degradation of fragments down to the nanoscale level have raised concerns given their ability to pervade cells. The accumulation of nanoparticles could lead to molecular crowding which can alter the normal functioning of enzymes. The purpose of this study was to examine the influence of polystyrene nanoparticles (NPs) on the fractal kinetics of the lactate dehydrogenase reaction: pyruvate + NADH ↔ lactate + NAD+. The influence of NPs on LDH activity was examined first in vitro to highlight specific effects and secondly in mussels exposed to NPs in vivo for 24h at 15 °C. The reaction rates of LDH were determined with increasing concentrations of pyruvate to reach saturation at circa 1 mM pyruvate. The addition of F-actin, a known binding template for LDH, revealed a characteristic change in reaction rates associated with fractal organization. The addition of 50 and 100 nm transparent NPs also produced these changes. The fractal dimension was determined and revealed that both F-actin and NPs reduced the fractal dimension of the LDH reaction. The addition of viscosity sensor probe in the reaction media revealed viscosity waves during the reaction at low substrate concentrations thought to be associated to synchronized switching between the relaxed and tensed states of LDH. The amplitude and the frequency of viscosity waves were increased by both NPs and F-actin which were associated with increased reaction rates. In mussels exposed to NPs, the isolation of digestive gland subcellular fraction revealed that LDH activity was significantly influenced by the fractal dimension of the LDH reaction where a loss of affinity (high fractal KM) was detected in mussels exposed to the high concentrations of NPs. It is concluded that polystyrene NPs could change the biophysical properties of the cytoplasm such as the fractal organization of the intracellular environment during the LDH reaction.

The influence of surface coatings on the toxicity of silver nanoparticle in rainbow trout.

Silver nanoparticles (nAg) are often produced with different coatings that could influence bioavailability and toxicity in aquatic organisms. The purpose of this study was to examine the influence of 4 surface coatings of nAg of the same core size towards bioavailability and toxicity in juvenile rainbow trout (Oncorhynchus mykiss). Juveniles were exposed to 50 µg/L of 50 nm diameter nAg for 96 h at 15 °C with the following coatings: branched polyethylenimine (bPEI), citrate, polyvinylpyrrolidone (PVP) and silicate (Si). The data revealed that the coatings influenced hepatic Ag loadings in the following trend PVP > citrate > bPEI and Si with estimated bioavailability factors of 28, 18, 6 and 2 L/kg respectively. Hepatic Ag levels were significantly associated with DNA damage and inflammation as determined by arachidonate cyclooxygenase activity. The bPEI and citrate-coated nAg consistently produced the observed effects above in addition to increased mitochondrial electron transport activity and glutathione S-transferase activity. The absence of metallothionein and lipid peroxidation suggests that mechanisms other than the liberation of Ag+ were at play. In conclusion, surface coatings were shown to significantly influence bioavailability and toxic properties of nAg to rainbow trout juveniles.

Gene expression changes and toxicity of selected rare earth elements in rainbow trout juveniles.

Rare earth elements (REEs) are increasingly used in electronics industry and other areas of our economy and questions were raised about their impacts to the environment. The purpose of this study was to examine the lethal and sublethal toxicity of REEs in juvenile rainbow (Oncorhynchus mykiss) trout. The fish were exposed to increasing concentrations (0.064, 0.32, 1.6, 8 and 40 mg/L) of the following 7 REEs for 96 h at 15 °C: cerium (CeCl3), erbium (ErCl3), gadolinium (GdCl3), lanthanum (LaCl3), neodymium (NdCl3), samarium (SmCl3) and yttrium (YCl3). The mortality were determined and in the surviving fish, 10 target gene transcripts were measured in the liver to track changes in oxidative stress, DNA repair, tissue growth/proliferation, protein chaperoning, xenobiotic biotransformation and ammonia metabolism. The data revealed that Y, Sm, Er and Gd formed a distinct group based on toxicity (mortality) and gene expression changes. Electronegativity was significantly correlated (r = -0.8, p < 0.01) with the lethal concentration (LC50). Gene expression changes occurred at concentration circa 120 times lower than the LC50 and the following transcripts in protein chaperoning (heat shock proteins), DNA repair (growth arrest DNA Damage) and CYP1A1 gene expression involved in the metabolism of coplanar aromatic hydrocarbons were involved. In conclusion, the study revealed that the more electronegative REEs were the most toxic to trout juveniles and produced sublethal effects at concentrations 2 orders of magnitude lower than the lethal concentrations. The toxicity of REEs depends on the elements were toxicity involves specific pathways at the gene expression level.

The influence of surface waters on the bioavailability and toxicity of zinc oxide nanoparticles in freshwater mussels.

The release of engineered nanoparticles in the aquatic environment could pose a threat to the biota. The purpose of the study was to examine the influence of surface water characteristics on zinc oxide nanoparticles (nZnO) and ZnS04 toxicity to the freshwater mussel Dreissena polymorpha. Mussels were exposed to an equivalent concentration of 25 µg/L Zn as either nZnO or ZnSO4 for 96 h at 15 °C in 4 types of surface waters: green water (high conductivity and pH with low natural organic matter content), brown water (low conductivity and pH with high natural organic matter content), diluted municipal effluent (high conductivity and pH with high urban organic matter content) and aquarium water (treated green water with organic matter removed). After the exposure period, mussels were analyzed for air-time survival, total and labile Zn levels in tissues, lipid metabolism (phospholipase A2, triglycerides levels) and oxidative stress (glutathione S-transferase, arachidonate cyclooxygenase, lipid peroxidation). The data revealed that mussels exposed to ZnSO4 in controlled aquarium water accumulated more total and labile Zn tissues, decreased oxidative stress and triglycerides and increased air time survival. While nZnO had few effects in aquarium water, oxidative stress was enhanced and total Zn in tissues were decreased in brown water and diluted municipal effluent and triglycerides were higher in nZn-exposed mussels in brown water. Air-time survival was decreased in mussels kept in green water and nZnO. It was also decreased in mussels exposed to ZnSO4 in green water and diluted municipal effluent. In conclusion, the fate and toxic effects of Zn could be influenced by both the chemical form (nanoparticles or ionic Zn) and surface water properties in freshwater mussels.

Primary prevention of Clostridium difficile infections with a specific probiotic combining Lactobacillus acidophilus, L. casei, and L. rhamnosus strains: assessing the evidence.

Clostridium difficile infection (CDI) has become the leading healthcare-associated infection and cause of outbreaks around the world. Although various innovative treatments have been developed, preventive strategies using multi-faceted infection control programmes have not been successful in reducing CDI rates. The major risk factor for CDI is the disruption of the normally protective gastrointestinal microbiota, typically by antibiotic use. Supplementation with specific probiotics has been effective in preventing various negative outcomes, including antibiotic-associated diarrhoea and CDI. However, a consensus of which probiotic strains might prevent CDI has not been reached and meta-analyses report high degrees of heterogeneity when studies of different probiotic products are pooled together. We searched the literature for probiotics with sufficient evidence to assess clinical efficacy for the prevention of CDI and focused on one specific probiotic formulation comprised of three lactobacilli strains (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, Lactobacillus rhamnosus CLR2, Bio-K+) for its ability to prevent CDI in healthcare settings. A literature search on this probiotic formulation was conducted using electronic databases (PubMed, Google Scholar), abstracts from infectious disease and infection control meetings, and communications from the probiotic company. Supporting evidence was found for its mechanisms of action against CDI and that it has an excellent safety and tolerability profile. Evidence from randomized controlled trials and facility-level interventions that administer Bio-K+ show reduced incidence rates of CDI. This probiotic formulation may have a role in primary prevention of healthcare-associated CDI when administered to patients who receive antibiotics.

Elemental profiles of freshwater mussels treated with silver nanoparticles: A metallomic approach.

Nanoparticles released into the environment could pose a risk to resident organisms that feed on suspended particles in aquatic ecosystems. The purpose of this study was to examine the effects of silver nanoparticles (nanoAg) of different sizes in freshwater mussels using a multi-elemental (metallomic) approach in order to determine signature effects of nanoparticulate and ionic Ag. Mussels were exposed to three concentrations (0.8, 4 and 20µg/L) of 20-nm and 80-nm nanoAg and AgNO3 for 48h at 15°C. After the exposure period, mussels were placed in clean, aerated water for a depuration step and analyzed for the following total elements in gill, digestive gland and gonad tissues: Al, Ag, As, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Pb, Na, Ni, Se, Sr, Th, U, V and Zn. Metallothioneins (MT; digestive gland only) and lipid peroxidation (LPO) were also determined in gills, digestive glands and gonads. The 20-nm-diameter nanoAg was detected in all three tissues at 20µg/L, while the 80-nm nanoAg was detected more strongly in the digestive gland. Ionic Ag was found at higher levels in gills than in other tissues. Correlation analysis revealed that gonad Ag levels were significantly correlated with Al (r=0.28), V (r=0.28), Cr (r=0.31), Co (r=0.32), Se (r=0.34) and MT levels (r=0.28). Indeed, the MT levels in the digestive gland were significantly increased by 20-nm nanoAg (20µg/L) and 80-nm nanoAg (4µg/L) and AgNO3 (<0.8µg/L). LPO was observed in gills, digestive glands and even gonads for all Ag forms. Discriminant function analysis revealed that all forms of Ag differed from each other and from unexposed mussels, where ionic Ag was more closely related to the 80-nm-diameter nanoAg. Factorial analysis revealed that Ba, Ca, Co, Mn, Sr, U and Zn had consistently high factorial weights in all tissues; that explained 80% of the total variance. Moreover, the following elements showed strong correlations (r>0.7) with each other: Sr, Ba, Zn, Ca, Mg Cr, Mn and U. Comparisons of these elements with other elements showing low or no correlations (e.g., transition elements) revealed that these elements had significantly lower standard reduction potential and electronegativity, suggesting that stronger reducing elements were most influenced by the oxidizing effects of nanoAg and ionic Ag in tissues. Indeed, tissues with oxidative stress (LPO) had decreased levels for most of these reducing elements. We conclude that exposure to Ag nanoparticles produces a characteristic change in the elemental composition of gills, digestive gland and gonad tissues in freshwater mussels. Elements most responsive to oxidative stress were more influenced by both nanoAg and ionic Ag. Sr and Ba were readily decreased by Ag and appeared to respond more sensitively to nanoAg than to ionic Ag. The metallomic approach could contribute in the understanding of fundamental mode of action of nanoparticles in mussels.

Bioavailability and immunotoxicity of silver nanoparticles to the freshwater mussel Elliptio complanata.

The purpose of this study was to examine the effects of Ag nanoparticles (nAg) of two different sizes (20 and 80 nm) and Ag(+) on the immune system of the freshwater mussel Elliptio complanata. Mussels were exposed to increasing concentrations of nAg and dissolved Ag (AgNO3) for 48 h at 15°C and concentration of 0, 0.8, 4, or 20 µg/L. Immunocompetence was determined by hemocyte viability, phagocytosis, and cell cytotoxicity. Ag tissue loadings and levels of metallothioneins (MT), lipid peroxidation (LPO), and labile zinc (Zn) were also determined. Results revealed first that 20- and 80-nm nAg readily formed aggregates in freshwater. Ag was detected in soft tissues with each form of Ag with bioconcentration factors of 20, 9, and 7 for Ag(+), 20-nm nAg, and 80-nm nAg, respectively. Significant induction in phagocytosis and decreased cell cytotoxicity were observed. All forms of Ag were able to induce LPO in gills and digestive glands at concentrations below those from the initial fraction of dissolved Ag. The effects of nAg on MT levels in mussels were not discernible from those of dissolved Ag, but the 80-nm was 25-fold more potent than 20-nm nAg in inducing MT. Multivariate analysis revealed that the global responses of the 20- and 80-nm nAg were generally similar to those of dissolved Ag. Data also demonstrated that nAg are bioavailable for mussels where the immune system is a target during early exposure to nanoparticles.

Sublethal effects of silver nanoparticles and dissolved silver in freshwater mussels.

The increasing application of silver nanoparticles (nAg) in various consumer products has raised concerns regarding toxicological impacts in the environment. It is unclear at present whether the toxicity of nAg is mainly the result of the release of ionic Ag(+) in mussels. The freshwater mussel Elliptio complanata was exposed to increasing concentrations of 20-nm nAg, 80-nm nAg, and dissolved Ag(+) for 48 h at 15°C. The following biomarkers were used to determine the mode of action of nAg-induced adverse effects: metallothioneins (MT) (ionic Ag(+) release), lipid peroxidation (LPO) (ionic Ag(+) and nanosurface interactions), heat-shock proteins (HSP) (size-related effects), protein-ubiquitin levels (size-related effects), and DNA strand breaks (ionic Ag(+) and size effects). Results revealed that the response pattern of 80 nm nAg was more closely related to ionic Ag(+) than 20 nm nAg, suggesting a more important release of dissolved Ag from 80 nm nAg. Data showed that all forms of Ag were able to increase the levels of MT and LPO, which suggests the presence of ionic Ag(+) leads to oxidative stress. However, nanoparticles were also able to induce changes in protein-ubiquitin and to a lesser extent actinomyosin-ATPase, MT, and DNA strand breaks in the digestive gland in a manner different from Ag(+), which permitted discrimination of the forms of Ag. Moreover, LPO was closely associated with DNA strand breaks in the digestive gland and was not entirely explained by induction of MT, suggesting another type of toxic interaction. It was concluded that the presence of nAg not only increases the toxic loadings of released Ag ions but also generates other and perhaps cumulative effects of nanoparticle-induced toxicity related to size and surface properties.

The effects of zinc oxide nanoparticles on the metallome in freshwater mussels.

The use of zinc oxide nanoparticles (nanoZnO) as sunscreens has raised concerns about their safety and release in the aquatic environment through swimming activities and within municipally treated wastewaters. This study's purpose was to examine the effects of nanoZnO on the elemental composition (metallome) in exposed freshwater mussels, Elliptio complanata. Mussels were exposed for 21 days to an environmentally realistic (low) concentration (2 µg/L) of nanoZnO and zinc chloride. The mussels were also exposed to a physically and chemically treated municipal effluent (ME), both alone and in the presence of both forms of Zn. The metallome profile was characterized by the following 15 elements in gills, digestive gland and gonad tissues: Ag, Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, V and Zn. The levels of metallothioneins (MT) and lipid peroxidation (LPO) in the digestive gland were also measured as biomarkers of toxic effects. The data revealed that exposure to nanoZnO increased the total levels of Zn, MT and LPO in the digestive gland. Discriminate function analysis revealed that the digestive gland responded the most to exposure to either nanoZnO or Zn(2+). For nanoZnO, the observed changes in Al, As and Mo in the digestive gland offered the best discrimination from dissolved Zn(2+). Co-exposure of nanoZnO with the ME changed the metallome profile closer to dissolved Zn(2+), suggesting a common interaction site within the ME. This was observed in changes in Ni, Cu, Se and Zn in the digestive gland of exposed mussels. Canonical analysis of essential and non-essential elements revealed that exposure to nanoZnO increased the relationships between LPO and the sum of essential elements in the digestive gland. Conversely, exposure to dissolved Zn(2+) and the ME decreased the relationship between the sum of non-essential elements and LPO and MT. In conclusion, the use of a "metallomic" approach was used to discriminate changes following exposure to nanoZnO and dissolved Zn in freshwater mussels and provided insights into the interaction of forms of Zn in ME towards mussels.

Toxicity of silver nanoparticles to rainbow trout: a toxicogenomic approach.

Silver (Ag) nanoparticles are used as antimicrobial adjuvant in various products such as clothes and medical devices where the release of nano-Ag could contaminate the environment and harm wildlife. The purpose of this study was to examine the sublethal effects of nano-Ag and dissolved Ag on Oncorhynchus mykiss rainbow trout. Hepatic Ag contents and changes in gene expression were monitored to provide insights on bioavailability and mode of action of both forms of silver. Fish were exposed to increasing concentrations (0.06, 0.6 and 6 µg L(-1)) of nano-Ag (20 nm) and silver nitrate (AgNO(3)) for 96 h at 15°C. A gene expression analysis was performed in the liver using a DNA microarray of 207 stress-related genes followed by a quantitative polymerase chain reaction on a selection of genes for validation. The biochemical markers consisted of the determination of labile zinc, metallothioneins, DNA strand breaks, lipid peroxidation (LPO) and vitellogenin-like proteins. The analysis of total Ag in the aquarium water revealed that nano-Ag was mostly aggregated, with 1% of the total Ag being dissolved. Nevertheless, hepatic Ag content was significantly increased in exposed fish. Indeed, dissolved Ag was significantly more bioavailable than nano-Ag only at the highest concentration with 38 ± 10 and 11 ± 3 ng Ag mg(-1) proteins for dissolved and nano-Ag respectively. Exposure to both forms of Ag led to significant changes in gene expression for 13% of tested gene targets. About 12% of genes responded specifically to nano-Ag, while 10% of total gene targets responded specifically to dissolved Ag. The levels of vitellogenin-like proteins and DNA strand breaks were significantly reduced by both forms of Ag, but DNA break levels were lower with nano-Ag and could not be explained by the presence of ionic Ag. Labile zinc and the oxidized fraction of metallothioneins were increased by both forms of Ag, but LPO was significantly induced by nano-Ag only. A discriminant function analysis revealed that the responses obtained by biochemical markers and a selection of ten target genes were able to discriminate completely (100%) the effects of both forms of Ag. Exposure to nano-Ag involved genes in inflammation and dissolved Ag involved oxidative stress and protein stability. Hence, the toxicity of Ag will differ depending on the presence of Ag nanoparticles and aggregates.

Clinical and genetic knowledge and attitudes of patients with myotonic dystrophy type 1.

AIMS: The goal was to assess clinical and genetic knowledge and attitudes in patients affected by myotonic dystrophy type 1 (DM1). METHODS: Two hundred patients with molecular confirmation of the diagnosis of DM1 completed a multi-choice questionnaire. DM1 patients' knowledge and views were compared to clinically normal DM1 noncarriers (n = 264) and controls (n = 1,474). RESULTS: Knowledge of the DM1 mode of inheritance was better in noncarriers than in patients (p < 0.001). Noncarriers were more aware than DM1 patients of the common clinical characteristics of DM1 such as limitations in physical activities and problems related to employment, schooling, activities of daily living, parenthood, peer relationships, and personality (p < 0.001). Compared to controls, DM1 patients felt less informed about the availability of clinical genetic services (p < 0.05) and new genetic technologies (p < 0.001). Among patients, logistic regression revealed that each additional year of education (p < 0.05) and each additional 100 CTG repeats (p < 0.01), respectively, increased and decreased the odds of knowing the DM1 mode of inheritance by about 23% and 18% respectively, independently of age, age at onset of symptoms, gender, severity of muscular impairment, and intellectual quotient. CONCLUSIONS: DM1 patients' genetic knowledge is significantly dependent of the level of education and the number of CTG repeats. Healthcare providers should be aware of this situation in order to adjust counselling and education accordingly.

Polonium-210: lessons learned from the contamination of individual Canadians.

This paper describes the radioactive poisoning episode in London in 2006 and the Health Canada response to locate and test any Canadians who might have been contaminated by this event. The search strategies and testing methods are explained and the results given. The lessons learned are summarised and implications for vulnerable populations are discussed. The greatest public health impact was probably the generation of fear and concern, especially among those prone to health-related anxiety disorders. The groups of individuals at risk were effectively managed by a single point of contact system combined with rapid triage and counselling that was provided to everyone to address their individual concerns.

Ecotoxicity of CdTe quantum dots to freshwater mussels: impacts on immune system, oxidative stress and genotoxicity.

The purpose of this study was to examine the toxic effects of cadmium-telluride (CdTe) quantum dots on freshwater mussels. Elliption complanata mussels were exposed to increasing concentrations of CdTe (0, 1.6, 4 and 8 mg/L) and cadmium sulfate (CdSO(4), 0.5mg/L) for 24h at 15 degrees C. After the exposure period, they were removed for assessments of immunocompetence, oxidative stress (lipid peroxidation) and genotoxicity (DNA strand breaks). Preliminary experiments revealed that CdTe dissolved in aquarium water tended to aggregate in the particulate phase (85%) while 15% of CdTe was found in the dissolved phase. Immunotoxicity was characterized by a significant decrease in the number of hemocytes capable of ingesting fluorescent beads, and hemocyte viability. The cytotoxic capacity of hemocytes to lyse mammalian K-562 cells was significantly increased, but the number of circulating hemocytes remained unchanged. Lipid peroxidation was significantly increased at a threshold concentration of 5.6 mg/L in gills and significantly reduced in digestive glands at a threshold concentration <1.6 mg/L CdTe. The levels of DNA strand breaks were significantly reduced in gills at <1.6 mg/L CdTe. In digestive glands, a transient but marginal increase in DNA strand breaks occurred at the lowest concentration and dropped significantly at the higher concentrations. A multivariate analysis revealed that the various response patterns differed based on the concentration of CdTe, thus permitting the identification of biomarkers associated with the form (colloidal vs. molecular) of cadmium.

The correlation of CTG repeat length with material and social deprivation in myotonic dystrophy.

Socioeconomic deprivation has long been recognized as a prominent feature of myotonic dystrophy type 1 (DM1), but studies performed before the discovery of the mutation causing DM1 may have suffered an ascertainment bias towards the more severe forms of the disease. We have sought to clarify the relationship between CTG repeats, muscular impairment, and socioeconomic characteristics of 200 patients with DM1. Patients with DM1 reported lower educational attainment, lower employment rate, lower family income, and higher reliance on social assistance than the reference population. Logistic regression showed, on one hand, that CTG repeats and marital status were significant predictors of social assistance recipiency and, on the other hand, that CTG repeats and gender were significant predictors of low social support from family, after adjustment for age, gender, degree of muscular impairment, CTG repeats, educational level, and marital status. For example, each additional 100 CTG repeats was found to increase the odds of relying on social assistance by about 35% and having low social support by about 22%. The chances of experiencing socioeconomic deprivation are loaded heavily against patients with DM1. The relationship between increased CTG repeat length and higher risk of material and social deprivation must be acknowledged in the clinical management of DM1.

Laboratory and pilot-scale phosphate and ammonium removal by controlled struvite precipitation following coagulation and flocculation of swine wastewater.

To reduce the suspended solids load to a trickling filter installation, raw swine effluent was pre-treated with ferric chloride and a cationically charged polyacrylamide coagulant resulting in unexpected struvite accumulation downstream of this post-separation process. Using this pre-treated swine manure, struvite precipitation studies were carried out as a function of pH at laboratory and pilot batch and continuously operated scales. An optimal reaction time of 30 min was established for struvite precipitation in the pre-treated swine wastewater at pH 8.5, minimizing the co-precipitation of interfering minerals. Ferric chloride addition resulted in magnesium solubilization, such that no external additional source of magnesium was required for struvite formation. Aeration alone did not result in significant pH increases, so base addition was required for pH adjustment. X-ray diffraction revealed that the only crystalline phase produced was struvite. Removal of phosphate and ammonium attained 98% and 17% respectively in laboratory scale experiments. At the pilot-scale, removal attained 99% and 15% of phosphate and ammonium in both batch and continuously HRT = 1h) operated reactors.

Genetic Interactions Between Glycine max and Sclerotinia sclerotiorumUsing a Straw Inoculation Method.

Genetic interactions for disease response between cultivars of Glycine max and isolates of Scle-rotinia sclerotiorum were evaluated in controlled-environment inoculations of five soybean cultivars with four genetically unique isolates of S. sclerotiorum. The objective of this study was to identify host-pathogen interactions using isolates of the pathogen which had different geographical and crop-wise distribution as well as a different DNA-based fingerprint. To do so, 4-week-old soybean plants were inoculated with individual isolates of S. sclerotiorum using a straw inoculation method. Inoculated plants were incubated for 48 h in continuous leaf wetness and rated for disease severity 1 and 2 weeks after inoculation. Significant differences in disease severity were detected among the soybean cultivars, and NK S08-80 consistently had the lowest disease severity among the five cultivars tested. No significant differences in disease severity were observed among pathogen isolates and no significant interactions were detected between soybean cultivars and pathogen isolates. These results suggest the following interpretations: (i) either the clonal genotype of the four pathogen isolates as determined by mycelial compatibility and DNA fingerprint was not associated with level of virulence on the five soybean cultivars or (ii) the soybean cultivars themselves were not capable of revealing any differences in virulence among isolates that would be related to their genetic fingerprint or regional distribution. The results of this study are consistent with the practice of considering different isolates of S. scle-rotiorum sampled from soybean in the same geographical region as equivalent for the evaluation of soybean cultivars for resistance to Sclerotinia stem rot.

Addition of benfluorex to biguanide improves glycemic control in obese non-insulin-dependent diabetes: a double-blind study versus placebo.

The oral antidiabetic benfluorex lowers insulin resistance in liver and muscle without stimulating insulin secretion; it is more effective than a biguanide in lowering insulin and triglyceride levels and does not elevate lactate. This double-blind multicenter community study compared the addition of benfluorex versus placebo to diet plus metformin in 127 uncontrolled obese type II diabetics. After a 2-month run-in on diet plus metformin, overall mean glucose was 7.7 mmol/L or greater (fasting) and/or 11 mmol/L or greater (2 h after 75-g oral glucose), with 20% or greater excess body weight [body-mass index (women/men): > or = 26.9/> or = 27.2 kg/m2). Patients were then randomized to adjuvant benflouorex (n = 63; 150 mg t.i.d.) or placebo (n = 64) for 90 days, with centralized biochemical monitoring. On benfluorex, glucose decreased from day 0 to day 90 (fasting: 8.99+/-2.76 to 7.81+/-2.32 mmol/L, p = 0.002; 2 h post-load: 16.56+/-4.49 to 15.09+/-5.09 mmol/L, p = 0.029) versus increases on placebo (intergroup p = 0.003 and p = 0.001, respectively). HbA decreased on benfluorex (7.47+/-1.44 to 7.12+/-1.13%; p = 0.013) versus no change on placebo. Basal and stimulated insulin and C peptide did not change in either group. Body weight remained similar in both groups. Tolerability was good in both groups, with no increase in hypoglycemia on benfluorex. Adjuvant behfluorex improves glycemic control in obese type II diabetics uncontrolled by diet plus metformin. The combination is safe, well-tolerated and suitable for introduction into routine practice.