Between 2001 and 2008 we experimentally manipulated atmospheric sulfate-loading to a small boreal peatland and monitored the resulting short and long-term changes in methylmercury (MeHg) production. MeHg concentrations and %MeHg (fraction of total-Hg (Hg¬T) present as MeHg) in the pore-waters of the experimental treatment reached peak values within a week of sulfate addition and then declined as the added sulfate disappeared. MeHg increased cumulatively over time in the solid-phase peat, which acted as a sink for newly produced MeHg. In 2006 a "recovery" treatment was created by discontinuing sulfate addition to a portion of the experimentally-treated section to assess how MeHg production might respond to decreased sulfate loads. Four years after sulfate additions ceased, MeHg concentrations and %MeHg had declined significantly from 2006 values in pore-waters and peat, but remained elevated relative to control levels. Mosquito larvae collected from each treatment at the end of the experiment exhibited HgT concentrations that reflect MeHg levels in the peat and pore-waters where they were collected. The proportional responses of invertebrate HgT to sulfate deposition rates demonstrates that further controls on sulfur emissions may represent as an additional means of mitigating Hg contamination in fish and wildlife across low-sulfur landscapes.

A snow cover can modify when, to what extent, and in what form atmospherically deposited mercury is released to the underlying surface media and/or back to the atmosphere. Investigations of mercury transport and transformation processes in snow packs are hampered by the difficulty in controlling experimental and melt conditions and due to the huge variability in the composition and physical structure of environmental snow packs. A method was developed that allows the detailed mechanistic investigation of mercury fate in snow that is made, aged and melted under controlled laboratory conditions. A number of control samples established that mercury in indoor air, scavenged during the snow making process, constitutes the dominant source of mercury in the artificial snow. No addition of mercury is required. The amount of mercury in fresh snow was quantitatively (102 and 106% in two experiments) recovered in the dissolved and particulate fractions of the melt water and the vessel head space, confirming a mass balance for mercury and the absence of unquantifiable mercury sources and sinks in the experimental system. In snow made from unmodified tap water, more than half of the mercury present in the snowpack was recovered from the bottom of the snow vessel after all of the snow had melted. Such late elution is indicative of mercury being mostly associated with particles that are filtered by, and retained in, the shrinking snowpack. Addition of salt to the snow-making water at an environmentally realistic pH notably shifted the distribution of mercury in the snowpack from the particulate to the dissolved phase, resulting in more than 60% of the mercury eluting in the dissolved phase of early melt water fractions.

Bottom sediments from Lake Jinzai in southwest Japan were analyzed to determine their chemical compositions and to assess the potential for ecological harm by comparison with sediment quality guidelines. The pollution status of lake sediments was evaluated by employing contamination factor (CF), pollution load index (PLI), and geoaccumulation index (I (geo)), focusing on a suite of elements in lakebed and core sediments. Elevated concentrations of As, Pb, Zn, Cu, TOC, N, and P were present in several layers of the upper core and other surface sediments. The elevated metal concentrations are likely related to the fine-grained nature of the sediments, reducing bottom conditions produced by abundant organic matter, and possibly minor non-point anthropogenic sources. Moreover, correlations between the concentrations of trace metals and organic carbon, nitrogen, phosphorus, and iron, suggest that these elements play a role in controlling abundances. Calculated CF, PLI, and I (geo) indicate that the sediments are strongly polluted with respect to As, moderately to strongly polluted with Zn, and moderately polluted with Pb and Cu. Metal concentrations exceed the New York State Department of Environmental Conservation (NYSDEC) lowest effect level and the Canadian Council of Ministers of the Environment (CCME) interim sediment quality guidelines that indicate moderate impact on aquatic organisms in the study area.

Many wetlands are sources of methylmercury (MeHg) to surface waters, yet little information exists about the distribution of MeHg within wetlands. Total mercury (THg) and MeHg in peat pore waters were studied in four peatlands in spring, summer, and fall 2005. Marked spatial variability in the distribution of MeHg, and %MeHg as a proxy for net MeHg production, was observed, with highest values occurring in discrete zones. We denote these zones "MeHg hot spots", defined as an area where the pore water %MeHg exceeded the 90th percentile of the data set (n=463) or >22% of THg as MeHg. MeHg hot spots occurred near the interface between peatland and the upland watershed with few exceptions. The %MeHg in pore water was significantly less in peatland interiors compared to upland-peatland interface zones, with the significance of these differences related to the delineation of the boundary between the two areas. Although further research is necessary, our data suggest that the occurrence of MeHg hot spots is related to the transport of solutes in upland runoff to the peatland perimeter and not to the accumulation of MeHg in this zone as a result of transport from either the peatland interior or the surrounding upland watershed. These findings augment the understanding of peatland MeHg production in upland-peatland watersheds, provide guidance for more accurate quantification of MeHg pool sizes in the landscape, and a spatial framework forthe further study of mercury methylation processes in peatlands.

BACKGROUND:: Prescription monitoring in the United States suggests that oral olanzapine is prescribed in doses that exceed the approved range of 5 to 20 mg/d. OBJECTIVE:: In this double-blind, randomized study, the pharmacokinetics and tolerability of higher-dose (30 or 40 mg/d) olanzapine were examined relative to the highest approved dose (20 mg/d) among non-treatment-resistant patients with psychiatric illnesses. METHODS:: After a 10-day period in which all patients were stabilized on 20 mg/d olanzapine, 37 patients with schizophrenia, schizoaffective disorder, or bipolar I disorder were randomized to receive treatment with olanzapine 20 mg/d for 20 days (group A, n = 12), 30 mg/d for 10 days followed by 40 mg/d for 10 days (group B, n = 11), or 40 mg/d for 20 days (group C, n = 14). On days 10, 20, and 30, blood samples were collected before dosing and at 1, 2, 5, 6, 10, 14, 18, and 24 hours after dosing. Plasma olanzapine concentrations were assayed using high-performance liquid chromatography with electrochemical detection. Tolerability was assessed by spontaneously reported treatment-emergent adverse events; changes from baseline in vital signs, electrocardiograms, and standard laboratory test values; incidences of categorically defined treatment-emergent akathisia and parkinsonism; and 2-hour standard oral glucose tolerance tests. RESULTS:: Of the 53 subjects who entered the study, 16 were excluded (7 because entry criteria were not met, 6 because of subject's decision, and 3 for other reasons). Subjects were primarily men (group A, 75%; group B, 55%; group C, 79%), approximately 40 years old (mean [SD] age: group A, 40.6 [8.6]; group B, 37.9 [8.6]; group C, 39.4 [9.2] years), and black (group A, 83%; group B, 55%; group C, 64%[the remainder were white]). Mean (SD) baseline weight was 84.0 (17.5) kg for group A, 82.1 (12.0) kg for group B, and 100.9 (23.3) kg for group C. By day 20, dose-proportional increases were observed in plasma olanzapine C(max,ss) and AUC. Geometric mean (percent coefficient of variation) values for groups A, B, and C at day 20 were as follows: C(max,ss) 57.8 (40.2), 75.6 (86.7), and 94.1 (50.2) ng/mL, respectively; and AUC: 997 (38.5), 1220 (88.0), and 1630 (53.9) ng . h/mL, respectively. The most frequently reported adverse events were weight gain (group A, 2/12 [17%]; group B, 3/11 [27%]; group C, 2/14 [14%]) and sedation (group A, 3/12 [25%]; group B, 2/11 [18%]; group C, 2/14 [14%]). Mean (SD) weight gain from baseline to end point was 3.5 (2.81) kg for group A, 3.0 (3.15) kg for group B, and 3.1 (2.22) kg for group C. Changes in glucose tolerance, vital signs, or laboratory parameters did not appear to be dose dependent. During double-blind therapy, 7 subjects experienced akathisia (spontaneously reported, n = 3 [group C]; categorically defined, n = 3 [group B]; both, n = 1 [group C]). Of the subjects with categorically defined akathisia, 2 had a history of akathisia and the other had a score of 1 (questionable) on the Barnes Akathisia Scale at baseline. No cases of parkinsonism were observed at any time. CONCLUSIONS:: Among these subjects with psychiatric illnesses, olanzapine at doses of 30 and 40 mg/d displayed a pharmacokinetic profile consistent with that of 20 mg/d. Higher-dose olanzapine exhibited a tolerance profile similar to that of 20 mg/d; however, akathisia may be more likely to occur at higher doses, particularly in subjects with a history of akathisia.

Purpose: The purpose of this study was to examine knowledge, attitudes, and behaviors regarding emergency contraception (EC) in university men and women aged 18-21. Data sources: Data sources included responses to a 25-item questionnaire and an 8-item demographic survey completed anonymously at a public site on campus. Ninety-seven university students participated in the study. Participants were asked to respond to questions relating to knowledge, attitudes, and behaviors regarding EC, perceived worthiness, objections, sources of information about EC, preferred birth-control method and usage, and perceptions of their personal risk of unintended pregnancy. Conclusions: Many respondents considered unintended pregnancy to be a major problem and considered EC a worthy option in the event of method failure or unprotected intercourse. While most participants were aware that there was a postcoital method of contraception, confusion existed between EC and RU-486 (the abortion pill). Almost half (49.5%) believed that EC was the same as RU-486. There was an association between advanced prescription for EC and its likelihood of use. Most women would be significantly more likely to use EC if they had a prescription on hand. Of the women who were less likely to choose EC, 100% indicated they would feel embarrassed or judged when asking for it. Only 34% of those women who have had a gynecological exam in the past 12 months had discussed EC with their provider. Implications for practice: Advanced practice nurses need to incorporate EC into preventive health counseling for both men and women. Providing women with an advanced prescription increases the likelihood that women will use EC.

Reelin mRNA and protein levels are reduced by approximately 50% in various cortical structures of postmortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. In addition, the mRNA encoding the methylating enzyme, DNA methyltransferase 1, is up-regulated in the same neurons that coexpress reelin and glutamic acid decarboxylase 67. We have analyzed the extent and pattern of methylation within the CpG island of the reelin promoter in genomic DNA isolated from cortices of schizophrenia patients and nonpsychiatric subjects. Ten (The Stanley Foundation Neuropathology Consortium) and five (Harvard Brain Collection) schizophrenia patients and an equal number of nonpsychiatric subjects were selected from each brain collection. Genomic DNA was isolated, amplified (from base pair -527 to base pair +322) after bisulphite treatment, and sequenced. The results show that within the promoter region there were interesting regional variations. There was increased methylation at positions -134 and 139, which is particularly important for regulation, because this portion of the promoter is functionally competent based on transient transfection assays. This promoter region binds a protein present in neuronal precursor nuclear extracts that express very low levels of reelin mRNA; i.e., an oligonucleotide corresponding to this region and that contains methylated cytosines binds more tightly to extracts from nonexpressing cells than the nonmethylated counterpart. Collectively, the data show that this promoter region has positive and negative properties and that the function of this complex cis element relates to its methylation status.

We investigated the effects of agents that induce reelin mRNA expression in vitro on the methylation status of the human reelin promoter in neural progenitor cells (NT2). NT2 cells were treated with the histone deacetylase inhibitors, trichostatin A (TSA) and valproic acid (VPA), and the methylation inhibitor aza-2'-deoxycytidine (AZA) for various times. All three drugs reduced the methylation profile of the reelin promoter relative to untreated cells. The acetylation status of histones H3 and H4 increased following treatment with VPA and TSA at times as short as 15 min following treatment; a result consistent with the reported mode of action of these drugs. Chromatin immunoprecipitation experiments showed that these changes were accompanied by changes occurring at the level of the reelin promoter as well. Interestingly, AZA decreased reelin promoter methylation without concomittantly increasing histone acetylation. In fact, after prolonged treatments with AZA, the acetylation status of histones H3 and H4 decreased relative to untreated cells. We also observed a trend towards reduced methylated H3 after 18 h treatment with TSA and VPA. Our data indicate that while TSA and VPA act to increase histone acetylation and reduce promoter methylation, AZA acts only to decrease the amount of reelin promoter methylation.

When rats experience an unexpected decrease in reward value, e.g., from 32% sucrose to 4% sucrose, consummatory behavior abruptly decreases to a level below control subjects that only experience the lesser reward, a phenomenon known as Successive Negative Contrast (SNC). In food deprived rats experiencing downshifts in sucrose concentration, SNC dissipates in 3-4 days, as consummatory behavior in shifted rats recovers to the level of unshifted controls. In Experiment 1 food deprived rats that were given 5 min daily access to a 2% glucose-0.15% saccharin mixture, and subsequently shifted to 2% glucose alone, displayed a dramatic SNC effect relative to rats that only received 2% glucose. This SNC effect was primarily manifested as a decrease in the number of consummatory bursts initiated. Interestingly, intake failed to recover to control levels during eight daily postshift sessions. However, in Experiment 2 subjects that were shifted from the same glucose-saccharin mixture to 0.15% saccharin alone failed to show SNC rather, intake fell to the level of control animals which only received 0.15% saccharin. The data from Experiment 1, in conjunction with previous studies utilizing non-deprived rats, quinine adulteration, or shifts from sucrose to saccharin, show that reductions in taste value can produce contrast effects, but suggest that a threshold caloric value is necessary for recovery. The data from Experiment 2 may suggest that saccharin and glucose do not contribute equally to the enhanced palatability of the mixture.

BACKGROUND: Gamma-aminobutyric acid (GABA)-ergic function is altered in schizophrenia. Of particular interest is the altered central nervous system expression of GABA-A receptor subunits, as changes in subunit expression account for recognized differences in mammalian brain function making them inviting targets for novel psychotropic agents. Excitotoxic neonatal lesions of the ventral hippocampal formation (NVHL) in rats reproduce numerous aspects of schizophrenia, including decreased mRNA expression of the GABA synthesizing enzyme glutamic acid decarboxylase-67, though their impact on subunit expression is unknown. METHODS: We utilized quantitative reverse transcription polymerase chain reaction to investigate mRNA expression of the alpha1, alpha5, and gamma2s GABA-A receptor subunits in the frontal pole of water-deprived adult NVHL and SHAM-lesioned animals. RESULTS: Messenger RNA expression for all three GABA-A subunits (alpha1-NVHL: 18.5 +/- 1.6 pg/mug total pooled RNA, SHAM: 11.3 +/-.4; alpha5-NVHL: 5.1 +/-.6; SHAM: 3.5 +/-.7; and gamma2s-NVHL: 10.8 +/- 1.7; SHAM: 7.2 +/- 1.5) was higher in NVHL, though only levels of alpha1 differed significantly after correction for multiple comparisons. Levels of a control mRNA, neuronal specific enolase, were similar in the two groups. CONCLUSIONS: These data indicate that NVHL reproduce changes in cortical GABA-A receptor subunit expression seen in schizophrenia, suggesting this animal model may facilitate efforts to clarify the physiologic significance of altered GABA function and to develop novel targets for therapeutic interventions.