Sensitivity analysis of the Pesticide in Water Calculator model for applications in the Pampa region of Argentina.

Despite the widespread use of pesticides in the Pampa region of Argentina, mathematical models are rarely employed to predict pesticide fate due to the lack of regionally tested models and the absence of readily available databases to run such models. The objective of the current study was to perform a sensitivity analysis of the Pesticide in Water Calculator (PWC) model for the Pampa Region of Argentina. The sensitivity analysis was performed while simulating applications of 2,4-D (mobile, low Kd) and glyphosate (soil-binding, high Kd) in five localities of the Pampa region: Anguil, Paraná, Marcos Juárez, Pergamino and Tres Arroyos. The sensitivity of the various parameters involved in PWC modelling was evaluated though a two-steps sensitivity analysis which included a first screening of less sensitive parameters with Morris method, followed by a fully global sensitivity analysis of the remaining parameters using Sobol method. When ran under soil and climate conditions typical of the Pampa region of Argentina, PWC was most sensitive to 25% of the parameters evaluated. The sensitive parameters identified depended mainly on the nature of the pesticide molecule being modelled; the location and endpoint considered having much less influence on the sensitivity results. Sensitive parameters belonged to two main grand categories: (i) degradation rates of the pesticide in soil and water, and (ii) parameters descriptive of soil binding, runoff and erosion. The sensitivity analysis of the model PWC performed in the current study represents a crucial first step towards the development and expansion of probabilistic pesticide risk assessment in Argentina, and provides important parameterization criteria that will help obtaining more certain modelling results from PWC in Argentina and elsewhere.

Temporal (1970-2016) changes in human pressures and wetland response in the St. Lawrence River (Québec, Canada).

Temporal changes (1970-2016) in St. Lawrence River wetlands were assessed between Cornwall and Québec (≈400 km) to assess wetland response to cumulative anthropogenic pressures in the watershed. Emergent wetlands area and biomass of submerged aquatic vegetation (SAV) were contrasted among five regions subjected to sharply different water level/discharge regime (stabilized, semi-natural, tidal), nutrient concentrations and shoreline use (rural to urbanized). Between 1970 and 2016, over the growing season (April-Sept.), St. Lawrence River mean water level at Sorel dropped by ≈1 m and mean water temperature increased by ≈3 °C. Reductions in phosphorus concentrations (by ≈2-fold) were observed over time both in water and in SAV tissues, in phase with improvements of urban wastewater treatment and P-reduction in upstream Lake Ontario. Nitrate concentrations in water increased and SAV biomass decreased between the 1970s and 2008 in the downstream regions of Lake Saint-Pierre and fluvial corridor subjected to the cumulative impacts from urban centers and intensively farmed watersheds. Over the 1970-2010 period, dropping water levels yielded slightly increasing wetland areas, owing to the downslope colonization of emergent and submerged plants. In urbanized regions, emergent wetlands shifted towards drier assemblages dominated by invasive reed species. Encroachment of wetlands by agriculture accounted for most wetland losses in rural Lake Saint-Pierre, which holds the single largest area (197 km2) of continuous wetland habitat of the entire watershed. Our results highlight the strong response of riverine wetlands to a wide range of human pressures, including dropping water levels, changing nutrient concentrations, rising population and intensifying agriculture.

[Wernicke encephalopathy: Guiding thiamine prescription]. / Thiamine et encéphalopathie de Gayet-Wernicke : quelles règles de prescription ?

BACKGROUND AND AIM: Wernicke's encephalopathy (WE) is a medical emergency. The objective of this paper is to systematically review the literature published over the past 15 years pertaining to prophylactic and curative treatment of WE with thiamine. METHODS: A systematic literature search was performed using Medline to include all studies published between January 1, 2000 and December 31, 2015. RESULTS: Of the 316 abstracts identified, 20 met the final inclusion criteria. The evidence on the use of prophylactic thiamine was quite heterogeneous. The use of thiamine in this context largely depended on the evaluation of an individual's risk of developing WE. Use of prophylactic thiamine in low-risk patients is not universally indicated. When prescribed in this sub-population, the oral route is suggested but may be insufficient owing to its limited intestinal absorption and the high risk of non-compliance. High-risk patients need parenteral treatment with a recommended posology of 250 mg daily for 3 to 5 days. Intramuscular route is preferred in the outpatient setting, whereas intravenous route is suggested for inpatients. In cases where the diagnosis of WE is suspected or confirmed, a curative treatment with high-dose IV thiamine is justified. The evidence widely accepted in the literature is much clearer in this condition, with treatment regimens consisting of 500 mg IV 3 times daily for 3 to 5 days, followed by 250 mg IV daily for a minimum of 3 to 5 additional days. CONCLUSION: The literature does indicate that thiamine should be prescribed at high dosages, with the parenteral routes indicated in hospital settings and in high-risk patients. Based on the current literature review, we suggest treatment algorithms guiding thiamine prescription for WE.

Influence of gender and age on cognitive inhibition in late-onset depression: a case-control study.

OBJECTIVE: To compare cognitive inhibition performance between people with early-onset (EOD) or late-onset depression (LOD) and controls, and between women and men with LOD. METHODS: On the basis of a case-control design, global executive performance (Frontal Assessment Battery); verbal (Hayling), attention (Stroop), and motor (Go/No-Go) components of cognitive inhibition; mental shifting (Trail Making Test parts A and B); and updating in working memory (Wechsler Adult Intelligence Scale) were assessed in 40 participants (10 depressed women with LOD (i.e., ≥60 years old), 10 depressed women with EOD (i.e., <60 years old), 10 healthy women and 10 depressed men with LOD (i.e., ≥60 years old)). RESULTS: Older depressed women, irrespective of age of depression onset, had greater cognitive inhibition impairments (attention and verbal component) compared with healthy women. LOD was significantly associated with the attention component of cognitive inhibition impairment, unlike EOD (p = 0.026). No executive differences were found regarding age of first-onset depression in older depressed women, and between women and men with LOD. CONCLUSION: Cognitive inhibition impairment, and more specifically its attention component, was the main characteristic of depression in the studied sample of older adults, independently of gender and age of depression onset. It is essential to perform similar studies in both genders in view of future tailor-made therapeutic modalities.

Neuronal correlates of appetite regulation in patients with schizophrenia: is there a basis for future appetite dysfunction?

BACKGROUND: Given the undesired metabolic side effects of atypical antipsychotic medication it is important to understand the neuronal basis related to processing of appetite regulation in patients affected by schizophrenia. METHODS: Here we used functional magnetic resonance imaging (fMRI) to assess brain activity in response to food cues and neutral stimuli in twenty patients with schizophrenia and eleven healthy individuals. In addition to clinical and dietary habits assessments, we collected, in patients, measurements of fasting glucose, ghrelin, leptin, insulin, prolactin and lipids blood concentration and we correlated the cerebral activity with clinical and metabolic measures. RESULTS: Both groups engaged a common neuronal network while processing food cues, which included the left insula, primary sensorimotor areas, and inferior temporal and parietal cortices. Cerebral responses to appetitive stimuli in thalamus, parahippocampus and middle frontal gyri were specific only to schizophrenic patients, with parahippocampal activity related to hunger state and increasing linearly over time. Antipsychotic medication dosage correlated positively with a cognitive measure reflecting food cravings, whereas the severity of the disease correlated negatively with a cognitive measure indicating dietary restraint in eating habits. These cognitive variables correlated, in turn, with parahippocampal and thalamic neuronal activities, respectively. CONCLUSIONS: We identified a specific neural substrate underlying cognitive processing of appetitive stimuli in schizophrenia, which may contribute to appetite dysfunction via perturbations in processing of homeostatic signals in relation to external stimuli. Our results also suggest that both antipsychotic medication and the disease severity per se could amplify these effects, via different mechanisms and neuronal networks.

Neural changes associated with appetite information processing in schizophrenic patients after 16 weeks of olanzapine treatment.

There is evidence that some atypical antipsychotics, including olanzapine, can produce unwanted metabolic side effects, weight gain and diabetes. However, neuronal correlates of change related to food information processing have not been investigated with these medications. We studied the effect of a pharmacological manipulation with an antipsychotic known to cause weight gain on metabolites, cognitive tasks and neural correlates related to food regulation. We used functional magnetic resonance imaging in conjunction with a task requiring visual processing of appetitive stimuli in schizophrenic patients and healthy controls before and after 16 weeks of antipsychotic medication with olanzapine. In patients, the psychological and neuronal changes associated following the treatment correlated with appetite control measures and metabolite levels in fasting blood samples. After 16 weeks of olanzapine treatment, the patients gained weight, increased their waist circumference, had fewer positive schizophrenia symptoms, a reduced ghrelin plasma concentration and an increased concentration of triglycerides, insulin and leptin. In premotor area, somatosensory cortices as well as bilaterally in the fusiform gyri, the olanzapine treatment increased the neural activity related to appetitive information in schizophrenic patients to similar levels relative to healthy individuals. However, a higher increase in sensitivity to appetitive stimuli after the treatment was observed in insular cortices, amygdala and cerebellum in schizophrenic patients as compared with healthy controls. Furthermore, these changes in neuronal activity correlated with changes in some metabolites and cognitive measurements related to appetite regulation.

Determining soil contamination patterns in a residential district near a copper smelter.

In 1979, a preliminary survey conducted in a district located near a copper smelter revealed elevated lead levels in the blood of some children and in the soil. In 1989, a more comprehensive study was undertaken to determine the blood lead contamination of the children and to determine soil contamination patterns. A method was devised for evaluating soil contamination by equally weighting each area of a predetermined grid. Three zones of contamination provided indirect evidence that suggested a contribution of diffuse emissions, compared with stack emissions, and assisted in the determination of priorities for remedial action.

Blood lead level in children living close to a smelter area: 10 years later.

A survey conducted at the end of the summer of 1989 in Rouyn-Noranda showed that children living near the smelter had blood lead levels between 2.3 and 26.9 mg/dl. A comparison with a similar survey done in the same area in 1979 shows that there are fewer children today with a blood lead level higher than 20 mg/dl, that is 7 versus 18, ten years ago. The soil lead level of the area where these children live was elevated but comparable to that of 10 years ago, even if the smelter atmospheric lead emissions show an important decrease, as is the case for atmospheric lead contamination by leaded gas. Shall we reconsider our criteria for remedial action on the soil?

Blood lead and maximal urinary excretion of delta-aminolevulinic acid.

Reliability and ease of use are certainly the two major qualities of a screening test or medical surveillance in the workplace. The advantages of using a reliable urinary test thus are evident: the sampling is easy, rapid, noninvasive and, therefore, well accepted. Screening tests or medical surveillance can measure the toxic chemical itself, its metabolites or its consequences on metabolism. In this study the relation between blood lead levels--the most commonly used test for screening and surveillance of saturnism--and urinary excretion of delta-aminolevulinic acid (ALA-U) was measured. The original part of this study is that it takes into account the chronobiology of ALA-U excretion. The samples are collected in the afternoon when ALA urinary excretion is at its highest level. Using a 5 mg/g of creatinine level as a threshold to detect blood lead levels equal to or higher than 60 micrograms/dL the test has an 88% sensitivity, a 91% specificity and a 37% positive predictive value. No worker whose blood lead level is equal to or higher than 65 micrograms/dL has been missed. It is suggested that using 5 mg of ALA-U/g of creatinine as a threshold to prescreen workers who should have their blood lead level measured could be useful in workplaces where lead exposure is moderate or low.

[Drug abuse in youth.]. / L'abus de drogue chez les jeunes : Questions épistémologiques soulevées par une évaluation des modes de prévention et de traitement au Québec.

In an on-going review of the literature dealing with the assessment of drug abuse treatment and prevention programs, the authors indicate that changes are occurring in basic concepts : the concept of addiction has been expanded and a more systemic approach to drug use and abuse is more prevalent. An examination of the relationship between adolescent drug use and the related psychosocial images leads to an outline of two main evaluative approaches : the moralistic a priori approach and the empirical social approach. To efficiently prevent youthful drug abuse, they propose that primary preventive actions should focus on demand factors and be complemented with secondary preventive actions focused on supply factors.

Meiotic maturation of mouse oocytes in vitro: protein synthesis in nucleate and anucleate oocyte fragments.

Nucleate and anucleate fragments of mouse oocytes have been isolated following treatment of fully grown oocytes with cytochalasin B. The nucleate oocyte fragments resume meiosis in vitro, progressing from dictyate of the first meiotic prophase to metaphase II ('meiotic maturation'), and exhibit all of the changes in protein synthesis normally associated with meiotic maturation of mouse oocytes. The anucleate oocyte fragments also undergo certain of the changes in protein synthesis associated with meiotic maturation, despite the absence of nuclear progression. These results suggest that the acquisition of meiotic competence (i.e. the ability to undergo meiotic maturation) during growth of the mammalian oocyte is due to changes in the quality, rather than the quantity, of cytoplasm and that the reprogramming of protein synthesis during meiotic maturation is directed by RNA templates already present in the cytoplasm. The behaviour of anucleate oocyte fragments is discussed in terms of the proposed role for nucleoplasm in the initiation of changes in protein synthesis during meiotic maturation of mouse oocytes.

Cytochalasin B-induced pseudo-cleavage of mouse oocytes in vitro. II. Studies of the mechanism and morphological consequences of pseudocleavage.

Mouse oocytes are induced by cytochalasin B to undergo 'pseudocleavage' in vitro into 2 compartments, only one of which possesses microvilli. It has been found that this particular response to cytochalasin B is related to oocyte size and, possibly, to the acquisition of meiotic competence by the oocyte during its growth phase. Certain of the morphological events which characterize pseudocleavage have been determined using transmission and scanning electron microscopy. These events include: (i) an initial withdrawal of microvilli from the surface of the oocyte, together with the concomitant disappearance of microfilaments normally associated with the microvilli; (ii) the subsequent formation of a pseudocleavage furrow and contractile ring; and (iii) the reappearance of microvilli and associated microfilaments in one of the two resulting oocyte compartments. These changes in surface architecture are reflected in the distribution of fluorescein-conjugated lectins bound to the oocyte surface during pseudocleavage.

Meiotic maturation of mouse oocytes in vitro: inhibition of maturation at specific stages of nuclear progression.

In vitro studies of meiotic maturation of mouse oocytes have been carried out in the presence of several drugs. The individual steps of nuclear progression, including dissolution of the nuclear (germinal vesicle) membrane, condensation of dictyate chromatin into compact bivalents, formation of the first metaphase spindle, and extrusion of the first polar body, are each susceptible to one or more of these drugs. Germinal vesicle breakdown, the initial morphological feature characteristic of meiotic maturation, is inhibited by dibutyryl cyclic AMP. However, even in the presence of dibutyryl cyclic AMP, the nuclear membrane becomes extremely convoluted and condensation of chromatin is initiated but aborts at a stage short of compact bivalents. Germinal vesicle breakdown and chromatin condensation take place in an apparently normal manner in the presence of puromycin, Colcemid, or cytochalasin B. Nuclear progression is blocked at the circular bivalent stage when oocytes are cultured continuously in the presence of puromycin or Colcemid, whereas oocytes cultured in the presence of cytochalasin B proceed to the first meiotic metaphase, form an apparently normal spindle, and arrest. Emission of a polar body is inhibited by all of these drugs. The inhibitory effects of these drugs on meiotic maturation are reversible to varying degrees dependent upon the duration of exposure to the drug and upon the nature of the drug. These studies suggest that dissolution of the mouse oocyte's germinal vesicle and condensation of chromatin are not dependent upon concomitant protein synthesis or upon microtubules. On the other hand, the complete condensation of chromatin into compact bivalents apparently requires breakdown of the germinal vesicle. Failure of homologous chromosomes to separate after normal alignment on the meiotic spindle in the presence of cytochalasin B suggest that microfilaments may be involved in nuclear progression at this stage of maturation. Cytokinesis, in the form of polar body formation, is blocked when any one of the earlier events of maturation fails to take place.

Cytochalasin B-induced pseudo-cleavage of mouse oocytes in vitro: asymmetric localization of mitochondria and microvilli associated with a stage-specific response.

Mouse oocytes are induced by cytochalasin B to undergo 'pseudo-cleavage' in vitro into 2 equally sized and separable compartments. This response to the drug is dependent upon the meiotic state of the oocytes, as well as upon the presence of an intact zona pellucida. The resulting 2 cellular compartments can be completely separated from another and cultured in vitro. Each of the compartments possesses characteristic structural features. The most pronounced structural differences include: (i) the presence of a nucleus (germinal vesicle) and nucleolus in one compartment; (ii) the presence of microvilli on the surface of the anucleate, but not the nucleate, compartment; and (iii) the localization (segregation) of mitochondria at the periphery of the anucleate, but not the nucleate, compartment. The results presented suggest that pseudo-cleavage induced by cytochalasin B arises as a consequence of a limited interaction of the drug with the oocyte surface and/or cortex and that it may represent a topographical dissociation of transporting and non-transporting regions of the membrane. These and other features of mouse oocytes treated with cytochalasin B are of interest in view of the involvement of the oocyte zona pellucida and plasma membrane during meiotic maturation, fertilization, and early embryogenesis.

Meiotic maturation of mouse oocytes in vitro: association of newly synthesized proteins with condensing chromosomes.

The nature, intracellular distribution, and role of proteins synthesized during meiotic maturation of mouse oocytes in vitro have been examined. Proteins synthesized during the initial stages of maturation are concentrated within the nucleus (germinal vesicle) and become intimately associated with the condensing chromosomes. Inhibition of protein synthesis during this period does not prevent germinal vesicle dissolution or chromosome condensation, but meiotic progression is blocked reversibly at the circular bivalent stage. A protein is synthesized during meiotic maturation of the mouse oocyte which exhibits several of the characteristics of the very lysine-rich histone, FI; this and other histones are phosphorylated during the initial stages of maturation. These results are discussed in relation to studies of meiotic maturation of oocytes from non-mammalian species and chromosome condensation in both oocytes and mitotic cells.